Efficacy, Immunogenicity and Safety of GSK Biologicals' HPV GSK 580299 Vaccine in Healthy Chinese Female Subjects

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00779766
• Collaborator: (none)
• Enrollment: 6,081
• Locations: 4
• Arms: 2
• Actual Duration (Months): 88.2
• Patients Per Site: 1520.3
• Patients Per Site Per Month: 17.2

Study Details

Study Description

Brief Summary

This is a multicenter study in which women are planned to receive either the HPV vaccine or control. Study participation will last approximately 72 months and involves a total of thirteen or fourteen scheduled visits.

Originally, the study was planned for 24 months. It was then extended for 2 more years with 4 additional visits (study end at Month 48).

The protocol posting has been updated as the study was extended by additional 2 years with two or three additional visits (study end at Month 72) for subjects who consent to participate in the extension.

Condition or Disease	Intervention/Treatment	Phase
Infections, Papillomavirus	Biological: HPV GSK 580299 vaccine; Biological: Placebo control	Phase 3

Detailed Description

This protocol posting has been updated following protocol amendment 6 dated 24 April 2014.

Study Design

• Study Type: Interventional
• Actual Enrollment: 6081 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Efficacy, Immunogenicity and Safety of GlaxoSmithKline Biologicals' HPV GSK 580299 Vaccine in Healthy Chinese Female Subjects
• Actual Study Start Date: Oct 22, 2008
• Actual Primary Completion Date: Sep 6, 2011
• Actual Study Completion Date: Feb 28, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cervarix Group Subjects received 3 doses of Cervarix™ vaccine. Cervarix™ vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.	Biological: HPV GSK 580299 vaccine; Subjects were planned to receive three doses of the study vaccine administered intramuscularly according to a 0, 1, 6 month vaccination schedule.
Placebo Comparator: Placebo Group Subjects received 3 doses of placebo. Placebo was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.	Biological: Placebo control; Subjects were planned to receive three doses of the placebo control administered intramuscularly according to a 0, 1, 6 month vaccination schedule.

Outcome Measures

Primary Outcome Measures

1. Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN1+) and/or Persistent Infection (6 Month+ Definition) Associated With Human Papillomavirus (HPV)-16 and/or HPV-18 at Month 24 [At Month 24]

   CIN1+ = CIN 1, 2, and 3, low/high-grade cervical glandular intraepithelial neoplasia (L/HCGIN), adenocarcinoma in-situ (AIS) or invasive cervical cancer. Persistent infection (6-month+ definition) = at least 2 positive HPV deoxyribonucleic acid (DNA) polymerase chain reaction (PCR) assays for the same viral genotype with no negative DNA sample between the 2 positive DNA samples, over an interval of approximately 6 months. The analyses were done on subjects HPV DNA negative at baseline (Month 0) and Month 6 and seronegative at baseline (Month 0) or on subjects DNA negative at baseline (Month 0) and Month 6, regardless of initial serostatus.

2. Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN1+) and/or Persistent Infection (6 Month+ Definition) Associated With Human Papillomavirus (HPV)-16 and/or HPV-18 at Month 48 [At Month 48]

   CIN1+ = CIN 1, 2, and 3, low/high-grade cervical glandular intraepithelial neoplasia (L/HCGIN), adenocarcinoma in-situ (AIS) or invasive cervical cancer. Persistent infection (6-month+ definition) = at least 2 positive HPV deoxyribonucleic acid (DNA) polymerase chain reaction (PCR) assays for the same viral genotype with no negative DNA sample between the 2 positive DNA samples, over an interval of approximately 6 months. The analyses were done on subjects HPV DNA negative at baseline (Month 0) and Month 6 and seronegative at baseline (Month 0) or on subjects DNA negative at baseline (Month 0) and Month 6, regardless of initial serostatus.

3. Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN1+) and/or Persistent Infection (6 Month+ Definition) Associated With Human Papillomavirus (HPV)-16 and/or HPV-18 at Month 57 [At Month 57]

   CIN1+ = CIN 1, 2, and 3, low/high-grade cervical glandular intraepithelial neoplasia (L/HCGIN), adenocarcinoma in-situ (AIS) or invasive cervical cancer. Persistent infection (6-month+ definition) = at least 2 positive HPV deoxyribonucleic acid (DNA) polymerase chain reaction (PCR) assays for the same viral genotype with no negative DNA sample between the 2 positive DNA samples, over an interval of approximately 6 months. The analyses were done on subjects HPV DNA negative at baseline (Month 0) and Month 6 and seronegative at baseline (Month 0) or on subjects DNA negative at baseline (Month 0) and Month 6, regardless of initial serostatus.

4. Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN1+) and/or Persistent Infection (6 Month+ Definition) Associated With Human Papillomavirus (HPV)-16 and/or HPV-18 at Month 72 [At Month 72]

   CIN1+ = CIN 1, 2, and 3, low/high-grade cervical glandular intraepithelial neoplasia (L/HCGIN), adenocarcinoma in-situ (AIS) or invasive cervical cancer. Persistent infection (6-month+ definition) = at least 2 positive HPV deoxyribonucleic acid (DNA) polymerase chain reaction (PCR) assays for the same viral genotype with no negative DNA sample between the 2 positive DNA samples, over an interval of approximately 6 months. The analyses were done on subjects HPV DNA negative at baseline (Month 0) and Month 6 and seronegative at baseline (Month 0) or on subjects DNA negative at baseline (Month 0) and Month 6, regardless of initial serostatus.

Secondary Outcome Measures

1. Number of Subjects With Incident Cervical Infection With HPV-16 and/or HPV-18 [At Months 24,48, 57 and 72]

   HPV-16 and/or HPV-18 incident infection is defined as at least one positive HPV-16 or HPV-18 DNA PCR assay at the time point considered. - DNA- and sero-: subjects HPV DNA negative at Months 0 and 6 by PCR and seronegative at Month 0 for the corresponding HPV-type by Enzyme-linked Immunosorbent Assay (ELISA) - Overall: subjects DNA- at Months 0 and 6 for the corresponding HPV-type, regardless of initial serostatus.

2. Number of Subjects With Persistent Cervical Infection (6-month+ Definition) With HPV-16 and/or HPV-18 [At Months 24, 48, 57 and 72]

   Persistent HPV-16 and/or HPV-18 infection (6-month+ definition) = at least 2 positive HPV deoxyribonucleic acid (DNA) polymerase chain reaction (PCR) assays for the same viral genotype with no negative DNA sample between the two positive DNA samples, over an interval of approximately 6 months. Subjects had at least 5 months of follow-up after Month 12. DNA- and sero-: subjects HPV DNA negative at Months 0 and 6 by PCR and seronegative at Month 0 for the corresponding HPV-type by ELISA Overall: subjects DNA- at Months 0 and 6 for the corresponding HPV-type, regardless of initial serostatus.

3. Number of Subjects With Persistent Cervical Infection (12-month+ Definition) With HPV-16 and/or HPV-18 [At Months 24, 48, 57 and 72]

   Persistent infection (12-month+ definition) is defined as the detection of the same HPV type(s) (by PCR) in cervical samples at all available time points over an interval of approximately 12 months. Subjects had at least 10 months of follow-up after Month 12. DNA- and sero-: subjects HPV DNA negative at Months 0 and 6 by PCR and seronegative at Month 0 for the corresponding HPV-type by Enzyme-linked Immunosorbent Assay (ELISA). Overall: subjects DNA- at Months 0 and 6 for the corresponding HPV-type, regardless of initial serostatus.

4. Number of Subjects With Incident Cervical Infection With Any Oncogenic HPV Type [At Months 24, 48, 57 and 72]

   Oncogenic HPV types assessed were HPV-16, -18, -31, -33, -35, -39, -45, -51, -52, -56, -58, -59, -66 and -68 individually or in combination. Subjects were HPV DNA- at Months 0 and 6 for the corresponding HPV-type, regardless of initial serostatus. HRW-HPV=All high-risk (oncogenic) HPV types excluding HPV-16 and HPV-18 HR-HPV=High-risk (oncogenic) HPV types: HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68.

5. Number of Subjects With Persistent Cervical Infection (6-month+ Definition) With Any Oncogenic HPV Type [At Months 24, 48, 57 and 72]

   Oncogenic HPV types assessed were HPV-16, -18, -31, -33, -35, -39, -45, -51, -52, -56, -58, -59, -66 and -68 individually or in combination. Subjects were HPV DNA- at Months 0 and 6 for the corresponding HPV-type, regardless of initial serostatus. HRW-HPV=All high-risk (oncogenic) HPV types excluding HPV-16 and HPV-18 HR-HPV=High-risk (oncogenic) HPV types: HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68.

6. Number of Subjects With Persistent Cervical Infection (12-month+ Definition) With Any Oncogenic HPV Type [At Months 24,48, 57 and 72]

   Oncogenic HPV types assessed were HPV-16, -18, -31, -33, -35, -39, -45, -51, -52, -56, -58, -59, -66 and -68 individually or in combination. Subjects were HPV DNA- at Months 0 and 6 for the corresponding HPV-type, regardless of initial serostatus. HRW-HPV=All high-risk (oncogenic) HPV types excluding HPV-16 and HPV-18 HR-HPV=High-risk (oncogenic) HPV types: HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68.

7. Number of Subjects With Any Cytological Abnormality Including Atypical Squamous Cells of Undetermined Significance (ASC-US+) Associated With HPV-16 and/or HPV-18 Cervical Infection [At Months 24, 48, 57 and 72]

   Cytological abnormalities = atypical squamous cells of undetermined significance (ASC-DNA- and sero-: subjects HPV DNA negative at Months 0 and 6 by PCR and seronegative at Month 0 for the corresponding HPV-type by Enzyme-linked Immunosorbent Assay (ELISA) Overall: subjects DNA- at Months 0 and 6 for the corresponding HPV-type, regardless of initial serostatus. US).

8. Number of Subjects With Any Cytological Abnormality Including Atypical Squamous Cells of Undetermined Significance (ASC-US+) Associated With Any Oncogenic HPV Type [At Months 24, 48, 57 and 72]

   Cytological abnormalities = atypical squamous cells of undetermined significance (ASC-US). Oncogenic HPV types assessed were HPV-16, -18, -31, -33, -35, -39, -45, -51, -52, -56, -58, -59, -66 and -68 individually or in combination. Subjects were HPV DNA- at Months 0 and 6 for the corresponding HPV-type, regardless of initial serostatus. HRW-HPV=All high-risk (oncogenic) HPV types excluding HPV-16 and HPV-18 HR-HPV=High-risk (oncogenic) HPV types: HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68.

9. Number of Subjects With Histopathologically-confirmed CIN1+ Associated With HPV-16 and/or HPV-18 Cervical Infection [At Months 24, 48, 57 and 72]

   CIN1+ = CIN grades 1, 2, and3, low-grade cervical glandular intraepithelial neoplasia (LCGIN), high grade cervical glandular intraepithelial neoplasia (HCGIN), adenocarcinoma in-situ (AIS) or invasive cervical cancer. DNA- and sero-: subjects HPV DNA negative at Months 0 and 6 by PCR and seronegative at Month 0 for the corresponding HPV-type by Enzyme-linked Immunosorbent Assay (ELISA) Overall: subjects DNA- at Months 0 and 6 for the corresponding HPV-type, regardless of initial serostatus.

10. Number of Subjects With Histopathologically-confirmed CIN2+ Associated With HPV-16 and/or HPV-18 Cervical Infection [At Months 24, 48, 57 and 72]

    CIN2+ = CIN grades 2 and 3, LCGIN, HCGIN, AIS or invasive cervical cancer. DNA- and sero-: subjects HPV DNA negative at Months 0 and 6 by PCR and seronegative at Month 0 for the corresponding HPV-type by Enzyme-linked Immunosorbent Assay (ELISA) Overall: subjects DNA- at Months 0 and 6 for the corresponding HPV-type, regardless of initial serostatus.

11. Number of Subjects With Histopathologically-confirmed CIN1+ Associated With Cervical Infection With Any Oncogenic HPV Type [At Months 24, 48, 57 and 72]

    CIN1+ = CIN grades 1, 2 and 3, LCGIN, HCGIN, AIS or invasive cervical cancer. Oncogenic HPV types assessed were HPV-16, -18, -31, -33, -35, -39, -45, -51, -52, -56, -58, -59, -66 and -68 individually or in combination. Subjects were HPV DNA- at Months 0 and 6 for the corresponding HPV-type, regardless of initial serostatus. HRW-HPV=All high-risk (oncogenic) HPV types excluding HPV-16 and HPV-18 HR-HPV=High-risk (oncogenic) HPV types: HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68.

12. Number of Subjects With Histopathologically-confirmed CIN2+ Associated With Cervical Infection With Any Oncogenic HPV Type [At Months 24, 48, 57 and 72]

    CIN2+ = CIN grades 2 and 3, LCGIN, HCGIN, AIS or invasive cervical cancer. Oncogenic HPV types assessed were HPV-16, -18, -31, -33, -35, -39, -45, -51, -52, -56, -58, -59, -66 and -68 individually or in combination. Subjects were HPV DNA- at Months 0 and 6 for the corresponding HPV-type, regardless of initial serostatus. HRW-HPV=All high-risk (oncogenic) HPV types excluding HPV-16 and HPV-18 HR-HPV=High-risk (oncogenic) HPV types: HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68.

13. Number of Subjects With Any and Severe (Grade 3) Solicited Local Symptoms [Within 7 days (Days 0-6) after vaccination]

    Solicited local symptoms assessed were pain, redness and swelling. Any = solicited local symptom reported irrespective of intensity grade, Grade 3 Pain = pain that prevented normal activity, Grade 3 Swelling or Redness = swelling or redness above (>) 50 millimeter (mm). All local symptoms were considered as related to the study vaccination.

14. Number of Subjects With Any and Severe (Grade 3) Solicited Local Symptoms, for Subjects Seronegative and DNA Negative for Both HPV-16 and HPV-18 at Baseline [Within 7 days (Days 0-6) after vaccination]

    Solicited local symptoms assessed were pain, redness and swelling. Any = solicited local symptom reported irrespective of intensity grade Grade 3 Pain = pain that prevented normal activity Grade 3 Swelling or Redness = swelling/redness above (>) 50 millimeter (mm). All local symptoms were considered as related to the study vaccination.

15. Number of Subjects With Any and Severe (Grade 3) Solicited Local Symptoms, for Subjects Seropositive and/or DNA Positive for Either HPV-16 or HPV-18 at Baseline [Within 7 days (Days 0-6) after vaccination]

    Solicited local symptoms assessed were pain, redness and swelling. Any = solicited local symptom reported irrespective of intensity grade Grade 3 Pain = pain that prevented normal activity, Grade 3 Swelling or Redness = swelling/redness above (>) 50 millimeter (mm). All local symptoms were considered as related to the study vaccination.

16. Number of Subjects With Any and Severe (Grade 3) Solicited Local Symptoms, for Subjects DNA Positive for Either HPV-16 or HPV-18 at Baseline [Within 7 days (Days 0-6) after vaccination]

    Solicited local symptoms assessed were pain, redness and swelling. Any = solicited local symptom reported irrespective of intensity grade, Grade 3 Redness, Swelling = redness/swelling above 50 millimeter All local symptoms were considered as related to the study vaccination

17. Number of Subjects With Any, Severe (Grade 3) and Causally Related to Vaccination Solicited General Symptoms. [Within 7 days (Days 0-6) after vaccination]

    Solicited general symptoms assessed were arthralgia, fatigue, gastrointestinal, headache, myalgia, rash, fever (= axillary temperature above 37.0 degrees Celsius) and urticaria. Any = any solicited general symptom reported irrespective of intensity grade and relationship to vaccination, Related = symptoms assessed by the investigator as causally related to study vaccination, Grade 3 symptoms = prevented normal activity, Grade 3 urticaria = distributed on at least 4 body areas.

18. Number of Subjects With Any, Severe (Grade 3) and Causally Related to Vaccination Solicited General Symptoms, for Subjects Seronegative and DNA Negative for Both HPV-16 and HPV-18 at Baseline [Within 7 days (Days 0-6) after vaccination]

    Solicited general symptoms assessed were arthralgia, fatigue, gastrointestinal, headache, myalgia, rash, fever (= axillary temperature above 37.0°C) and urticaria. Any = any solicited general symptom reported irrespective of intensity grade and relationship to vaccination Related = symptoms assessed by the investigator as causally related to study vaccination Grade 3 symptoms = symptoms that prevented normal activity Grade 3 urticaria = urticaria distributed on at least 4 body areas.

19. Number of Subjects With Any, Severe (Grade 3) and Causally Related to Vaccination Solicited General Symptoms, for Subjects Seropositive and/or DNA Positive for Either HPV-16 or HPV-18 at Baseline [Within 7 days (Days 0-6) after vaccination]

    Solicited general symptoms assessed were arthralgia, fatigue, gastrointestinal, headache, myalgia, rash, fever (= axillary temperature above 37.0°C) and urticaria. Any = any solicited general symptom reported irrespective of intensity grade and relationship to vaccination Related = symptoms assessed by the investigator as causally related to study vaccination Grade 3 symptoms = symptoms that prevented normal activity Grade 3 urticaria = urticaria distributed on at least 4 body areas

20. Number of Subjects With Any, Severe (Grade 3) and Causally Related to Vaccination Solicited General Symptoms, for Subjects DNA Positive for Either HPV-16 or HPV-18 at Baseline [Within 7 days (Days 0-6) after vaccination]

    Solicited general symptoms assessed were arthralgia, fatigue, gastrointestinal, headache, myalgia, rash, fever (= axillary temperature above 37.0°C) and urticaria. Any = any solicited general symptom reported irrespective of intensity grade and relationship to vaccination Related = symptoms assessed by the investigator as causally related to study vaccination Grade 3 symptoms = symptoms that prevented normal activity Grade 3 urticaria = urticaria distributed on at least 4 body areas

21. Number of Subjects With Any, Severe (Grade 3) and Causally Related to Vaccination Unsolicited Adverse Events (AEs) [Within Days 0-29 after vaccination]

    An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Related = event assessed by the investigator as causally related to study vaccination Grade 3 = event that prevented normal activity

22. Number of Subjects With Unsolicited Adverse Events for Subjects Seronegative and DNA Negative for Both HPV-16 and HPV-18 at Baseline [Within Days 0-29 after vaccination]

    An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms.

23. Number of Subjects With Unsolicited Adverse Events for Subjects Seropositive and/or DNA Positive for Either HPV-16 or HPV-18 at Baseline [Within Days 0-29 after vaccination]

    An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms

24. Number of Subjects With Unsolicited Adverse Events for Subjects DNA Positive for Either HPV-16 or HPV-18 at Baseline [Within Days 0-29 after vaccination]

    An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms.

25. Number of Subjects With Serious Adverse Events (SAEs) [From Day 0 to Month 72]

    SAEs assessed include medical occurrences that results in death, are life threatening, require hospitalization or prolongation of hospitalization, results in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subjects.

26. Number of Subjects With Medically Significant Conditions (MSC) Regardless of Causal Relationship to Vaccination and Intensity [From Day 0 to Month 72]

    Medically significant conditions were defined as: adverse events (AEs) prompting emergency room or physician visits that were not (1) related to common diseases or (2) routine visits for physical examination or vaccination, or SAEs that were not related to common diseases. Common diseases included: upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervicovaginal yeast infections, menstrual cycle abnormalities and injury.

27. Number of Subjects With Medically Significant Conditions Regardless of Causal Relationship to Vaccination and Intensity for Subjects Seronegative and DNA Negative for Both HPV-16 and HPV-18 at Baseline [From Day 0 to Month 72]

    Medically significant conditions were defined as: adverse events (AEs) prompting emergency room or physician visits that were not (1) related to common diseases or (2) routine visits for physical examination or vaccination, or SAEs that were not related to common diseases. Common diseases included: upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervicovaginal yeast infections, menstrual cycle abnormalities and injury.

28. Number of Subjects With Medically Significant Conditions Regardless of Causal Relationship to Vaccination and Intensity for Subjects Seropositive and/or DNA Positive for Either HPV-16 or HPV-18 at Baseline [From Day 0 to Month 72]

    Medically significant conditions were defined as: adverse events (AEs) prompting emergency room or physician visits that were not (1) related to common diseases or (2) routine visits for physical examination or vaccination, or SAEs that were not related to common diseases. Common diseases included: upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervicovaginal yeast infections, menstrual cycle abnormalities and injury.

29. Number of Subjects With Medically Significant Conditions Regardless of Causal Relationship to Vaccination and Intensity for Subjects DNA Positive for Either HPV-16 or HPV-18 at Baseline [From Day 0 to Month 72]

    Medically significant conditions were defined as: adverse events (AEs) prompting emergency room or physician visits that were not (1) related to common diseases or (2) routine visits for physical examination or vaccination, or SAEs that were not related to common diseases. Common diseases included: upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervicovaginal yeast infections, menstrual cycle abnormalities and injury.

30. Number of Subjects With Pregnancies and Outcomes of Reported Pregnancies [From Day 0 to Month 72]

    Outcomes of pregnancies were Live infant NO apparent congenital anomaly (ACA), Live infant CA, Elective termination NO ACA, Elective termination CA, Ectopic pregnancy, Spontaneous abortion NO ACA, Stillbirth NO ACA, Stillbirth CA, Lost to follow up and Pregnancy ongoing.

31. Number of Subjects With Pregnancies and Outcomes of Reported Pregnancies for Subjects Seronegative and DNA Negative for Both HPV-16 and HPV-18 at Baseline [From Day 0 to Month 72]

    Outcomes of pregnancies were Live infant NO apparent congenital anomaly (ACA), Live infant CA, Elective termination NO ACA, Elective termination CA, Ectopic pregnancy, Spontaneous abortion NO ACA, Stillbirth NO ACA, Stillbirth CA, Lost to follow up, Pregnancy ongoing and MIssing.

32. Number of Subjects With Pregnancies and Outcomes of Reported Pregnancies Seropositive and/or DNA Positive for Either HPV-16 or HPV-18 at Baseline [From Day 0 to Month 72]

    Outcomes of pregnancies were Live infant NO apparent congenital anomaly (ACA), Live infant CA, Elective termination NO ACA, Elective termination CA, Ectopic pregnancy, Spontaneous abortion NO ACA, Stillbirth NO ACA, Stillbirth CA, Lost to follow up, Pregnancy ongoing and Missing.

33. Number of Subjects With Pregnancies and Outcomes of Reported Pregnancies for Subjects DNA Positive for Either HPV-16 or HPV-18 at Baseline [From Day 0 to Month 72]

    Outcomes of pregnancies were Live infant NO apparent congenital anomaly (ACA), Live infant CA, Elective termination NO ACA, Elective termination CA, Ectopic pregnancy, Spontaneous abortion NO ACA, Stillbirth NO ACA, Stillbirth CA, Lost to follow up and Pregnancy ongoing.

34. Number of Subjects With HPV-16 Antibody Concentration Equal to or Above the Assay Cut-off Value, by Pre-vaccination Status [at Months 0 (PRE), 7, 12, 24, 36, 48 and 72]

    HPV-16 assay cut-off value was defined as greater than or equal to (≥) 8 ELISA units per millilitre (EL.U/mL) at PRE vaccination, Month 7, 12 and 24 and ≥ 19 EL.U/mL at Month 36, 48 and 72. Seronegative (Sero-) subjects are subjects who had an antibody concentration below 8 EL.U/mL prior to vaccination. Seropositive (Sero+) subjects are subjects who had an antibody concentration ≥ 8 EL.U/mL prior to vaccination.

35. Number of Subjects With HPV-18 Antibody Concentration Equal to or Above the Assay Cut-off Value, by Pre-vaccination Status [at Months 0 (PRE), 7, 12, 24, 36, 48 and 72]

    HPV-18 assay cut-off value was defined as ≥ 7 EL.U/mL at PRE vaccination, Month 7, 12 and 24 and ≥ 18 EL.U/mL at Month 36, 48 and 72. Seronegative (Sero-) subjects are subjects who had an antibody concentration below 7 EL.U/mL and 18 EL.U/mL prior to vaccination. Seropositive (Sero+) subjects are subjects who had an antibody concentration ≥ 7 EL.U/mL and 18 EL.U/mL prior to vaccination.

36. Geometric Mean Titers for HPV-16/HPV-18 Antibodies, by Pre-vaccination Status [at Months 0 (PRE), 7, 12, 24, 36, 48 and 72]

    Titers were expressed as geometric mean titers calculated on all subjects, HPV-16 assay cut-off value was defined as greater than or equal to 8 EL.U/mL at Months 0, 7, 12 and 24 and greater than or equal to 19 EL.U/mL at Months 36, 48 and 72. HPV-18 assay cut-off value was defined as ≥ 7 EL.U/mL at Month 0, 7, 12 and 24 and ≥ 18 EL.U/mL at Months 36, 48 and 72. Seronegative (Sero-) subjects are subjects who had an antibody concentration below the assay cut-off value prior to vaccination. Seropositive (Sero+) subjects are subjects who had an antibody concentration ≥ the assay cut-off value prior to vaccination.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 25 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Healthy Chinese females between and including 18 and 25 years of age at the time of the first vaccination.

• Subjects who the investigator believes that they can and will comply with the requirements of the protocol.

• Written informed consent obtained from the subject prior to enrolment.

• Healthy subjects as established by medical history and history-directed clinical examination before entering into the study.

• Subjects must not be pregnant. Absence of pregnancy will be verified with a urine pregnancy test.

• Subjects must be of non-childbearing potential, or if of childbearing potential, they must be abstinent or have practiced adequate contraception for 30 days prior to vaccination and agree to continue such precautions for 2 months after completion of the vaccination series.

• Subject must have one single intact cervix.

Exclusion Criteria:

• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines within 30 days preceding the first dose of study vaccine, or planned use during the study period.

• Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose.

• Planned administration/administration of a vaccine not foreseen by the study protocol within 30 days before and 30 days after (i.e., Days 0-29) the first dose of vaccine.

• Concurrently participating in another clinical study, at any time during the study period (up to Month 24), in which the subject has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device).

• A subject planning to become pregnant, likely to become pregnant (as determined by the investigator) or planning to discontinue contraceptive precautions during the study period and up to two months after the last vaccine dose.

• Pregnant or breastfeeding. Subjects must be at least three months post-pregnancy and not breastfeeding to enter the study.

• Previous vaccination against HPV or planned administration of any HPV vaccine other than that foreseen by the protocol during the study period.

• Previous administration of components of the investigational vaccine.

• History of chronic condition(s) requiring treatment such as cancer or autoimmune disease.

• History of allergic disease, suspected allergy or reactions likely to be exacerbated by any component of the vaccine.

• Hypersensitivity to latex.

• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.

• Acute disease at the time of enrolment.

• Administration of immunoglobulins and/or any blood products within the three months preceding the first dose of study vaccine or planned administration during the study period.

• History of having had colposcopy or has planned a colposcopy to evaluate an abnormal cervical cytology (Pap smear) test.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Jintan	Jiangsu	China	213200
2	GSK Investigational Site	Lianshui	Jiangsu	China
3	GSK Investigational Site	Xuzhou	Jiangsu	China	221006
4	GSK Investigational Site	Yancheng	Jiangsu	China	224500

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Publications

• Zhao FH, Zhu FC, Chen W, Li J, Hu YM, Hong Y, Zhang YJ, Pan QJ, Zhu JH, Zhang X, Chen Y, Tang H, Zhang H, Durand C, Datta SK, Struyf F, Bi D; HPV-039 study group. Baseline prevalence and type distribution of human papillomavirus in healthy Chinese women aged 18-25 years enrolled in a clinical trial. Int J Cancer. 2014 Dec 1;135(11):2604-11. doi: 10.1002/ijc.28896. Epub 2014 May 20.
• Zhu FC, Chen W, Hu YM, Hong Y, Li J, Zhang X, Zhang YJ, Pan QJ, Zhao FH, Yu JX, Zhang YS, Yang X, Zhang CF, Tang H, Zhang H, Lebacq M, David MP, Datta SK, Struyf F, Bi D, Descamps D; HPV-039 study group. Efficacy, immunogenicity and safety of the HPV-16/18 AS04-adjuvanted vaccine in healthy Chinese women aged 18-25 years: results from a randomized controlled trial. Int J Cancer. 2014 Dec 1;135(11):2612-22. doi: 10.1002/ijc.28897. Epub 2014 May 20.
• Zhu FC, Hu SY, Hong Y, Hu YM, Zhang X, Zhang YJ, Pan QJ, Zhang WH, Zhao FH, Zhang CF, Yang X, Yu JX, Zhu J, Zhu Y, Chen F, Zhang Q, Wang H, Wang C, Bi J, Xue S, Shen L, Zhang YS, He Y, Tang H, Karkada N, Suryakiran P, Bi D, Struyf F. Efficacy, immunogenicity, and safety of the HPV-16/18 AS04-adjuvanted vaccine in Chinese women aged 18-25 years: event-triggered analysis of a randomized controlled trial. Cancer Med. 2017 Jan;6(1):12-25. doi: 10.1002/cam4.869. Epub 2016 Dec 20.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00779766
• Other Study ID Numbers: 107638
• First Posted: Oct 24, 2008
• Last Update Posted: Jun 10, 2019
• Last Verified: May 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by GlaxoSmithKline: Human papillomavirus; vaccine; cervical cancer; cervical infection
• Additional relevant MeSH terms: Infections

Study Results

Participant Flow

Recruitment Details	This record provides the end-of-study analysis, including analyses at Month 24, 48, 57 and 72.
Pre-assignment Detail	Out of the 6081 subjects enrolled, 2 did not have any subject or vaccine number allocated and 28 did not receive any study vaccine dose, hence only 6051 subjects started the study.

Arm/Group Title	Cervarix Group	Placebo Group
Arm/Group Description	Subjects received 3 doses of Cervarix vaccine. Cervarix vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.	Subjects received 3 doses of placebo. Placebo was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.
Period Title: Month 24
STARTED	3026	3025
COMPLETED	2694	2693
NOT COMPLETED	332	332
Period Title: Month 24
STARTED	2703	2727
COMPLETED	2529	2559
NOT COMPLETED	174	168
Period Title: Month 24
STARTED	2319	2347
COMPLETED	2134	2158
NOT COMPLETED	185	189

Baseline Characteristics

Arm/Group Title	Cervarix Group	Placebo Group	Total
Arm/Group Description	Subjects received 3 doses of Cervarix vaccine. Cervarix vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.	Subjects received 3 doses of placebo. Placebo was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.	Total of all reporting groups
Overall Participants	3026	3025	6051
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	23.0 (1.70)	23.0 (1.75)	23.0 (1.73)
Sex: Female, Male (Count of Participants)
Female	3026 100%	3025 100%	6051 100%
Male	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
Asian - Chinese Heritage	3026 100%	3025 100%	6051 100%

Outcome Measures

1. Primary Outcome

Title	Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN1+) and/or Persistent Infection (6 Month+ Definition) Associated With Human Papillomavirus (HPV)-16 and/or HPV-18 at Month 24
Description	CIN1+ = CIN 1, 2, and 3, low/high-grade cervical glandular intraepithelial neoplasia (L/HCGIN), adenocarcinoma in-situ (AIS) or invasive cervical cancer. Persistent infection (6-month+ definition) = at least 2 positive HPV deoxyribonucleic acid (DNA) polymerase chain reaction (PCR) assays for the same viral genotype with no negative DNA sample between the 2 positive DNA samples, over an interval of approximately 6 months. The analyses were done on subjects HPV DNA negative at baseline (Month 0) and Month 6 and seronegative at baseline (Month 0) or on subjects DNA negative at baseline (Month 0) and Month 6, regardless of initial serostatus.
Time Frame	At Month 24

Outcome Measure Data

Analysis Population Description

The analysis was performed on the According-To-Protocol (ATP) cohort for efficacy, which included all evaluable subjects for whom efficacy data were available and who had a normal or low-grade cytology (negative or atypical squamous cells of undetermined significance (ASC-US) or low-grade squamous intraepithelial lesion (LSIL)) at Month 0.

Arm/Group Title	Cervarix Group	Placebo Group
Arm/Group Description	Subjects received 3 doses of Cervarix vaccine. Cervarix vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.	Subjects received 3 doses of placebo. Placebo was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.
Measure Participants	2775	2764
Sero negative, DNA negative HPV-16/18	1	17
Sero negative, DNA negative HPV-16	1	15
Sero negative, DNA negative HPV-18	0	3
DNA negative, HPV-16/18	1	27
DNA negative, HPV-16	1	21
DNA negative, HPV-18	0	7

2. Primary Outcome

Title	Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN1+) and/or Persistent Infection (6 Month+ Definition) Associated With Human Papillomavirus (HPV)-16 and/or HPV-18 at Month 48
Description	CIN1+ = CIN 1, 2, and 3, low/high-grade cervical glandular intraepithelial neoplasia (L/HCGIN), adenocarcinoma in-situ (AIS) or invasive cervical cancer. Persistent infection (6-month+ definition) = at least 2 positive HPV deoxyribonucleic acid (DNA) polymerase chain reaction (PCR) assays for the same viral genotype with no negative DNA sample between the 2 positive DNA samples, over an interval of approximately 6 months. The analyses were done on subjects HPV DNA negative at baseline (Month 0) and Month 6 and seronegative at baseline (Month 0) or on subjects DNA negative at baseline (Month 0) and Month 6, regardless of initial serostatus.
Time Frame	At Month 48

Outcome Measure Data

Analysis Population Description

The analysis was performed on the ATP cohort for efficacy, which included all evaluable subjects for whom data concerning efficacy outcome measures were available and who had a normal or low-grade cytology (negative or ASC-US or LSIL) at Month 0.

Arm/Group Title	Cervarix Group	Placebo Group
Arm/Group Description	Subjects received 3 doses of Cervarix vaccine. Cervarix vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.	Subjects received 3 doses of placebo. Placebo was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.
Measure Participants	2803	2799
Sero negative, DNA negative HPV-16/18	2 0.1%	45 1.5%
Sero negative, DNA negative HPV-16	2 0.1%	33 1.1%
Sero negative, DNA negative HPV-18	0 0%	14 0.5%
DNA negative, HPV-16/18	2 0.1%	61 2%
DNA negative, HPV-16	2 0.1%	45 1.5%
DNA negative, HPV-18	0 0%	18 0.6%

3. Primary Outcome

Title	Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN1+) and/or Persistent Infection (6 Month+ Definition) Associated With Human Papillomavirus (HPV)-16 and/or HPV-18 at Month 57
Description	CIN1+ = CIN 1, 2, and 3, low/high-grade cervical glandular intraepithelial neoplasia (L/HCGIN), adenocarcinoma in-situ (AIS) or invasive cervical cancer. Persistent infection (6-month+ definition) = at least 2 positive HPV deoxyribonucleic acid (DNA) polymerase chain reaction (PCR) assays for the same viral genotype with no negative DNA sample between the 2 positive DNA samples, over an interval of approximately 6 months. The analyses were done on subjects HPV DNA negative at baseline (Month 0) and Month 6 and seronegative at baseline (Month 0) or on subjects DNA negative at baseline (Month 0) and Month 6, regardless of initial serostatus.
Time Frame	At Month 57

Outcome Measure Data

Analysis Population Description

The analysis was performed on the ATP cohort for efficacy, which included all evaluable subjects for whom data concerning efficacy outcome measures were available and who had a normal or low-grade cytology (negative or ASC-US or LSIL) at Month 0.

Arm/Group Title	Cervarix Group	Placebo Group
Arm/Group Description	Subjects received 3 doses of Cervarix vaccine. Cervarix vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.	Subjects received 3 doses of placebo. Placebo was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.
Measure Participants	2805	2802
Sero negative, DNA negative HPV-16/18	2 0.1%	60 2%
Sero negative, DNA negative HPV-16	2 0.1%	43 1.4%
Sero negative, DNA negative HPV-18	0 0%	19 0.6%
DNA negative HPV-16/18	2 0.1%	78 2.6%
DNA negative HPV-16	2 0.1%	57 1.9%
DNA negative HPV-18	0 0%	23 0.8%

4. Primary Outcome

Title	Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN1+) and/or Persistent Infection (6 Month+ Definition) Associated With Human Papillomavirus (HPV)-16 and/or HPV-18 at Month 72
Description	CIN1+ = CIN 1, 2, and 3, low/high-grade cervical glandular intraepithelial neoplasia (L/HCGIN), adenocarcinoma in-situ (AIS) or invasive cervical cancer. Persistent infection (6-month+ definition) = at least 2 positive HPV deoxyribonucleic acid (DNA) polymerase chain reaction (PCR) assays for the same viral genotype with no negative DNA sample between the 2 positive DNA samples, over an interval of approximately 6 months. The analyses were done on subjects HPV DNA negative at baseline (Month 0) and Month 6 and seronegative at baseline (Month 0) or on subjects DNA negative at baseline (Month 0) and Month 6, regardless of initial serostatus.
Time Frame	At Month 72

Outcome Measure Data

Analysis Population Description

The analysis was performed on the ATP cohort for efficacy, which included all evaluable subjects for whom data concerning efficacy outcome measures were available and who had a normal or low-grade cytology (negative or ASC-US or LSIL) at Month 0.

Arm/Group Title	Cervarix Group	Placebo Group
Arm/Group Description	Subjects received 3 doses of Cervarix vaccine. Cervarix vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.	Subjects received 3 doses of placebo. Placebo was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.
Measure Participants	2804	2801
Sero negative, DNA negative HPV-16/18	2 0.1%	69 2.3%
Sero negative, DNA negative HPV-16	2 0.1%	50 1.7%
Sero negative, DNA negative HPV-18	0 0%	21 0.7%
DNA negative HPV-16/18	2 0.1%	91 3%
DNA negative HPV-16	2 0.1%	68 2.2%
DNA negative HPV-18	0 0%	26 0.9%

5. Secondary Outcome

Title	Number of Subjects With Incident Cervical Infection With HPV-16 and/or HPV-18
Description	HPV-16 and/or HPV-18 incident infection is defined as at least one positive HPV-16 or HPV-18 DNA PCR assay at the time point considered. - DNA- and sero-: subjects HPV DNA negative at Months 0 and 6 by PCR and seronegative at Month 0 for the corresponding HPV-type by Enzyme-linked Immunosorbent Assay (ELISA) - Overall: subjects DNA- at Months 0 and 6 for the corresponding HPV-type, regardless of initial serostatus.
Time Frame	At Months 24,48, 57 and 72

Outcome Measure Data

Analysis Population Description

The analysis was performed on the ATP cohort for efficacy, which included all evaluable subjects for whom data concerning efficacy outcome measures were available and who had a normal or low-grade cytology (negative or ASC-US or LSIL) at Month 0.

Arm/Group Title	Cervarix Group	Placebo Group
Arm/Group Description	Subjects received 3 doses of Cervarix vaccine. Cervarix vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.	Subjects received 3 doses of placebo. Placebo was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.
Measure Participants	2807	2802
Sero negative, DNA negative HPV-16/18 M24	15 0.5%	49 1.6%
Sero negative, DNA negative HPV-16 M24	9 0.3%	30 1%
Sero negative, DNA negative HPV-18 M24	7 0.2%	21 0.7%
DNA negative HPV-16/18 M24	20 0.7%	70 2.3%
DNA negative HPV-16 M24	13 0.4%	43 1.4%
DNA negative HPV-18 M24	8 0.3%	30 1%
Sero negative, DNA negative HPV-16/18 M48	22 0.7%	96 3.2%
Sero negative, DNA negative HPV-16 M48	13 0.4%	62 2%
Sero negative, DNA negative HPV-18 M48	10 0.3%	39 1.3%
DNA negative HPV-16/18 M48	1 0%	21 0.7%
DNA negative HPV-18 M48	0 0%	5 0.2%
DNA negative HPV-16 M48	1 0%	16 0.5%
Sero negative, DNA negative HPV-16/18 M57	29 1%	142 4.7%
Sero negative, DNA negative HPV-16 M57	16 0.5%	92 3%
Sero negative, DNA negative HPV-18 M57	14 0.5%	57 1.9%
DNA negative HPV-16/18 M57	43 1.4%	189 6.2%
DNA negative HPV-16 M57	26 0.9%	127 4.2%
DNA negative HPV-18 M57	18 0.6%	74 2.4%
Sero negative, DNA negative HPV-16/18 M72	34 1.1%	156 5.2%
Sero negative, DNA negative HPV-16 M72	21 0.7%	103 3.4%
Sero negative, DNA negative HPV-18 M72	14 0.5%	63 2.1%
DNA negative HPV-16/18 M72	49 1.6%	204 6.7%
DNA negative HPV-16 M72	32 1.1%	139 4.6%
DNA negative HPV-18 M72	18 0.6%	81 2.7%

6. Secondary Outcome

Title	Number of Subjects With Persistent Cervical Infection (6-month+ Definition) With HPV-16 and/or HPV-18
Description	Persistent HPV-16 and/or HPV-18 infection (6-month+ definition) = at least 2 positive HPV deoxyribonucleic acid (DNA) polymerase chain reaction (PCR) assays for the same viral genotype with no negative DNA sample between the two positive DNA samples, over an interval of approximately 6 months. Subjects had at least 5 months of follow-up after Month 12. DNA- and sero-: subjects HPV DNA negative at Months 0 and 6 by PCR and seronegative at Month 0 for the corresponding HPV-type by ELISA Overall: subjects DNA- at Months 0 and 6 for the corresponding HPV-type, regardless of initial serostatus.
Time Frame	At Months 24, 48, 57 and 72

Outcome Measure Data

Analysis Population Description

The analysis was performed on the ATP cohort for efficacy, which included all evaluable subjects for whom data concerning efficacy outcome measures were available and who had a normal or low-grade cytology (negative or ASC-US or LSIL) at Month 0.

Arm/Group Title	Cervarix Group	Placebo Group
Arm/Group Description	Subjects received 3 doses of Cervarix vaccine. Cervarix vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.	Subjects received 3 doses of placebo. Placebo was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.
Measure Participants	2762	2748
Sero negative, DNA negative HPV-16/18 M24	1 0%	15 0.5%
Sero negative, DNA negative HPV-16 M24	1 0%	13 0.4%
Sero negative, DNA negative HPV-18 M24	0 0%	3 0.1%
Overall HPV-16/18 M24	1 0%	24 0.8%
Overall HPV-16 M24	1 0%	18 0.6%
Overall HPV-18 M24	0 0%	7 0.2%
Sero negative, DNA negative HPV-16/18 M48	2 0.1%	39 1.3%
Sero negative, DNA negative HPV-16 M48	2 0.1%	30 1%
Sero negative, DNA negative HPV-18 M48	0 0%	11 0.4%
Overall HPV-16/18 M48	2 0.1%	53 1.8%
Overall HPV-16 M48	2 0.1%	40 1.3%
Overall HPV-18 M48	0 0%	15 0.5%
Sero negative, DNA negative HPV-16/18 M57	2 0.1%	54 1.8%
Sero negative, DNA negative HPV-16 M57	2 0.1%	39 1.3%
Sero negative, DNA negative HPV-18 M57	0 0%	17 0.6%
Overall HPV-16/18 M57	2 0.1%	70 2.3%
Overall HPV-16 M57	2 0.1%	51 1.7%
Overall HPV-18 M57	0 0%	21 0.7%
Sero negative, DNA negative HPV-16/18 M72	2 0.1%	63 2.1%
Sero negative, DNA negative HPV-16 M72	2 0.1%	46 1.5%
Sero negative, DNA negative HPV-18 M72	0 0%	19 0.6%
Overall HPV-16/18 M72	2 0.1%	83 2.7%
Overall HPV-16 M72	2 0.1%	62 2%
Overall HPV-18 M72	0 0%	24 0.8%

7. Secondary Outcome

Title	Number of Subjects With Persistent Cervical Infection (12-month+ Definition) With HPV-16 and/or HPV-18
Description	Persistent infection (12-month+ definition) is defined as the detection of the same HPV type(s) (by PCR) in cervical samples at all available time points over an interval of approximately 12 months. Subjects had at least 10 months of follow-up after Month 12. DNA- and sero-: subjects HPV DNA negative at Months 0 and 6 by PCR and seronegative at Month 0 for the corresponding HPV-type by Enzyme-linked Immunosorbent Assay (ELISA). Overall: subjects DNA- at Months 0 and 6 for the corresponding HPV-type, regardless of initial serostatus.
Time Frame	At Months 24, 48, 57 and 72

Outcome Measure Data

Analysis Population Description

The analysis was performed on the ATP cohort for efficacy, which included all evaluable subjects for whom data concerning efficacy outcome measures were available and who had a normal or low-grade cytology (negative or ASC-US or LSIL) at Month 0.

Arm/Group Title	Cervarix Group	Placebo Group
Arm/Group Description	Subjects received 3 doses of Cervarix vaccine. Cervarix vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.	Subjects received 3 doses of placebo. Placebo was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.
Measure Participants	2702	2709
Sero negative, DNA negative HPV-16/18 M24	0	2
Sero negative, DNA negative HPV-16 M24	0	2
Sero negative, DNA negative HPV-18 M24	0	0
Overall, HPV-16/18 M24	0	2
Overall, HPV-16 M24	0	2
Overall, HPV-18 M24	0	0
Sero negative, DNA negative HPV-16/18 M48	1	21
Sero negative, DNA negative HPV-16 M48	1	16
Sero negative, DNA negative HPV-18 M48	0	5
Overall, HPV-16/18 M48	1	22
Overall, HPV-16 M48	1	17
Overall, HPV-18 M48	0	5
Sero negative, DNA negative HPV-16/18 M57	1	32
Sero negative, DNA negative HPV-16 M57	1	24
Sero negative, DNA negative HPV-18 M57	0	8
Overall, HPV-16/18 M57	1	37
Overall, HPV-16 M57	1	29
Overall, HPV-18 M57	0	8
Sero negative, DNA negative HPV-16/18 M72	1	32
Sero negative, DNA negative HPV-16 M72	1	24
Sero negative, DNA negative HPV-18 M72	0	8
Overall, HPV-16/18 M72	1	38
Overall, HPV-16 M72	1	30
Overall, HPV-18 M72	0	8

8. Secondary Outcome

Title	Number of Subjects With Incident Cervical Infection With Any Oncogenic HPV Type
Description	Oncogenic HPV types assessed were HPV-16, -18, -31, -33, -35, -39, -45, -51, -52, -56, -58, -59, -66 and -68 individually or in combination. Subjects were HPV DNA- at Months 0 and 6 for the corresponding HPV-type, regardless of initial serostatus. HRW-HPV=All high-risk (oncogenic) HPV types excluding HPV-16 and HPV-18 HR-HPV=High-risk (oncogenic) HPV types: HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68.
Time Frame	At Months 24, 48, 57 and 72

Outcome Measure Data

Analysis Population Description

The analysis was performed on the ATP cohort for efficacy, which included all evaluable subjects for whom data concerning efficacy outcome measures were available and who had a normal or low-grade cytology (negative or ASC-US or LSIL) at Month 0.

Arm/Group Title	Cervarix Group	Placebo Group
Arm/Group Description	Subjects received 3 doses of Cervarix vaccine. Cervarix vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.	Subjects received 3 doses of placebo. Placebo was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.
Measure Participants	2812	2812
HPV-16 M24	13	43
HPV-18 M24	8	30
HPV-31 M24	14	25
HPV-33 M24	19	22
HPV-35 M24	17	15
HPV-39 M24	42	32
HPV-45 M24	8	17
HPV-51 M24	69	57
HPV-52 M24	90	87
HPV-56 M24	34	37
HPV-58 M24	28	34
HPV-59 M24	16	20
HPV-66 M24	37	33
HPV-68 M24	33	32
HPV-31/33/45 M24	36	60
HPV-16/18/31/33/45 M24	54	126
HRW-HPV M24	313	324
HR-HPV M24	323	364
HPV-16 M48	18	88
HPV-18 M48	13	50
HPV-31 M48	29	59
HPV-33 M48	29	52
HPV-35 M48	35	38
HPV-39 M48	80	78
HPV-45 M48	13	25
HPV-51 M48	117	131
HPV-52 M48	168	176
HPV-56 M48	63	70
HPV-58 M48	56	62
HPV-59 M48	35	44
HPV-66 M48	74	73
HPV-68 M48	59	61
HPV-31/33/45 M48	62	119
HPV-16/18/31/33/45 M48	89	239
HRW-HPV M48	536	591
HR-HPV M48	552	646
HPV-16 M57	26	127
HPV-18 M57	18	74
HPV-31 M57	33	74
HPV-33 M57	40	69
HPV-35 M57	49	55
HPV-39 M57	136	121
HPV-45 M57	18	38
HPV-51 M57	152	187
HPV-52 M57	227	264
HPV-56 M57	93	106
HPV-58 M57	77	99
HPV-59 M57	47	62
HPV-66 M57	96	111
HPV-68 M57	91	95
HPV-31/33/45 M57	80	159
HPV-16/18/31/33/45 M57	120	329
HRW-HPV M57	692	800
HR-HPV M57	710	862
HPV-16 M72	32	139
HPV-18 M72	18	81
HPV-31 M72	35	86
HPV-33 M72	43	75
HPV-35 M72	53	65
HPV-39 M72	154	133
HPV-45 M72	18	40
HPV-51 M72	166	204
HPV-52 M72	251	284
HPV-56 M72	104	113
HPV-58 M72	83	111
HPV-59 M72	52	65
HPV-66 M72	103	124
HPV-68 M72	101	107
HPV-31/33/45 M72	85	175
HPV-16/18/31/33/45 M72	131	356
HRW-HPV M72	744	852
HR-HPV M72	764	914

9. Secondary Outcome

Title	Number of Subjects With Persistent Cervical Infection (6-month+ Definition) With Any Oncogenic HPV Type
Description	Oncogenic HPV types assessed were HPV-16, -18, -31, -33, -35, -39, -45, -51, -52, -56, -58, -59, -66 and -68 individually or in combination. Subjects were HPV DNA- at Months 0 and 6 for the corresponding HPV-type, regardless of initial serostatus. HRW-HPV=All high-risk (oncogenic) HPV types excluding HPV-16 and HPV-18 HR-HPV=High-risk (oncogenic) HPV types: HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68.
Time Frame	At Months 24, 48, 57 and 72

Outcome Measure Data

Analysis Population Description

The analysis was performed on the ATP cohort for efficacy, which included all evaluable subjects for whom data concerning efficacy outcome measures were available and who had a normal or low-grade cytology (negative or ASC-US or LSIL) at Month 0.

Arm/Group Title	Cervarix Group	Placebo Group
Arm/Group Description	Subjects received 3 doses of Cervarix vaccine. Cervarix vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.	Subjects received 3 doses of placebo. Placebo was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.
Measure Participants	2767	2756
HPV-16 M24	1 0%	18 0.6%
HPV-18 M24	0 0%	7 0.2%
HPV-31 M24	5 0.2%	6 0.2%
HPV-33 M24	7 0.2%	8 0.3%
HPV-35 M24	4 0.1%	7 0.2%
HPV-39 M24	11 0.4%	9 0.3%
HPV-45 M24	1 0%	5 0.2%
HPV-51 M24	21 0.7%	14 0.5%
HPV-52 M24	36 1.2%	23 0.8%
HPV-56 M24	13 0.4%	5 0.2%
HPV-58 M24	8 0.3%	12 0.4%
HPV-59 M24	6 0.2%	7 0.2%
HPV-66 M24	5 0.2%	8 0.3%
HPV-68 M24	11 0.4%	7 0.2%
HPV-31/33/45 M24	12 0.4%	19 0.6%
HPV-16/18/31/33/45 M24	13 0.4%	42 1.4%
HRW-HPV M24	114 3.8%	98 3.2%
HR-HPV M24	115 3.8%	116 3.8%
HPV-16 M48	2 0.1%	40 1.3%
HPV-18 M48	0 0%	15 0.5%
HPV-31 M48	10 0.3%	23 0.8%
HPV-33 M48	12 0.4%	19 0.6%
HPV-35 M48	13 0.4%	15 0.5%
HPV-39 M48	34 1.1%	29 1%
HPV-45 M48	7 0.2%	7 0.2%
HPV-51 M48	49 1.6%	42 1.4%
HPV-52 M48	84 2.8%	72 2.4%
HPV-56 M48	25 0.8%	29 1%
HPV-58 M48	25 0.8%	29 1%
HPV-59 M48	14 0.5%	13 0.4%
HPV-66 M48	19 0.6%	25 0.8%
HPV-68 M48	21 0.7%	20 0.7%
HPV-31/33/45 M48	27 0.9%	46 1.5%
HPV-16/18/31/33/45 M48	29 1%	97 3.2%
HRW-HPV M48	257 8.5%	275 9.1%
HR-HPV M48	258 8.5%	312 10.3%
HPV-16 M57	2 0.1%	51 1.7%
HPV-18 M57	0 0%	21 0.7%
HPV-31 M57	10 0.3%	29 1%
HPV-33 M57	13 0.4%	25 0.8%
HPV-35 M57	17 0.6%	18 0.6%
HPV-39 M57	47 1.6%	41 1.4%
HPV-45 M57	7 0.2%	8 0.3%
HPV-51 M57	59 1.9%	58 1.9%
HPV-52 M57	109 3.6%	97 3.2%
HPV-56 M57	32 1.1%	36 1.2%
HPV-58 M57	32 1.1%	40 1.3%
HPV-59 M57	15 0.5%	15 0.5%
HPV-66 M57	31 1%	29 1%
HPV-68 M57	28 0.9%	30 1%
HPV-31/33/45 M57	28 0.9%	59 2%
HPV-16/18/31/33/45 M57	30 1%	126 4.2%
HRW-HPV M57	319 10.5%	357 11.8%
HR-HPV M57	320 10.6%	400 13.2%
HPV-16 M72	2 0.1%	62 2%
HPV-18 M72	0 0%	24 0.8%
HPV-31 M72	11 0.4%	31 1%
HPV-33 M72	16 0.5%	30 1%
HPV-35 M72	19 0.6%	18 0.6%
HPV-39 M72	63 2.1%	50 1.7%
HPV-45 M72	8 0.3%	10 0.3%
HPV-51 M72	69 2.3%	73 2.4%
HPV-52 M72	128 4.2%	117 3.9%
HPV-56 M72	43 1.4%	41 1.4%
HPV-58 M72	38 1.3%	49 1.6%
HPV-59 M72	16 0.5%	16 0.5%
HPV-66 M72	36 1.2%	37 1.2%
HPV-68 M72	32 1.1%	36 1.2%
HPV-31/33/45 M72	33 1.1%	68 2.2%
HPV-16/18/31/33/45 M72	35 1.2%	146 4.8%
HRW-HPV M72	381 12.6%	418 13.8%
HR-HPV M72	382 12.6%	466 15.4%

10. Secondary Outcome

Title	Number of Subjects With Persistent Cervical Infection (12-month+ Definition) With Any Oncogenic HPV Type
Description	Oncogenic HPV types assessed were HPV-16, -18, -31, -33, -35, -39, -45, -51, -52, -56, -58, -59, -66 and -68 individually or in combination. Subjects were HPV DNA- at Months 0 and 6 for the corresponding HPV-type, regardless of initial serostatus. HRW-HPV=All high-risk (oncogenic) HPV types excluding HPV-16 and HPV-18 HR-HPV=High-risk (oncogenic) HPV types: HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68.
Time Frame	At Months 24,48, 57 and 72

Outcome Measure Data

Analysis Population Description

The analysis was performed on the ATP cohort for efficacy, which included all evaluable subjects for whom data concerning efficacy outcome measures were available and who had a normal or low-grade cytology (negative or ASC-US or LSIL) at Month 0.

Arm/Group Title	Cervarix Group	Placebo Group
Arm/Group Description	Subjects received 3 doses of Cervarix vaccine. Cervarix vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.	Subjects received 3 doses of placebo. Placebo was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.
Measure Participants	2706	2717
HPV-16 M24	0 0%	2 0.1%
HPV-18 M24	0 0%	0 0%
HPV-31 M24	0 0%	0 0%
HPV-33 M24	2 0.1%	1 0%
HPV-35 M24	1 0%	0 0%
HPV-39 M24	1 0%	3 0.1%
HPV-45 M24	1 0%	0 0%
HPV-51 M24	6 0.2%	2 0.1%
HPV-52 M24	7 0.2%	5 0.2%
HPV-56 M24	0 0%	0 0%
HPV-58 M24	0 0%	1 0%
HPV-59 M24	1 0%	1 0%
HPV-66 M24	0 0%	1 0%
HPV-68 M24	2 0.1%	0 0%
HPV-31/33/45 M24	3 0.1%	1 0%
HPV-16/18/31/33/45 M24	3 0.1%	3 0.1%
HRW-HPV M24	21 0.7%	14 0.5%
HR-HPV M24	21 0.7%	15 0.5%
HPV-16 M48	1 0%	17 0.6%
HPV-18 M48	0 0%	5 0.2%
HPV-31 M48	3 0.1%	11 0.4%
HPV-33 M48	6 0.2%	6 0.2%
HPV-35 M48	5 0.2%	7 0.2%
HPV-39 M48	12 0.4%	16 0.5%
HPV-45 M48	4 0.1%	1 0%
HPV-51 M48	20 0.7%	16 0.5%
HPV-52 M48	41 1.4%	40 1.3%
HPV-56 M48	11 0.4%	5 0.2%
HPV-58 M48	4 0.1%	9 0.3%
HPV-59 M48	5 0.2%	2 0.1%
HPV-66 M48	8 0.3%	7 0.2%
HPV-68 M48	9 0.3%	4 0.1%
HPV-31/33/45 M48	12 0.4%	18 0.6%
HPV-16/18/31/33/45 M48	13 0.4%	40 1.3%
HRW-HPV M48	122 4%	119 3.9%
HR-HPV M48	122 4%	137 4.5%
HPV-16 M57	1 0%	29 1%
HPV-18 M57	0 0%	8 0.3%
HPV-31 M57	3 0.1%	16 0.5%
HPV-33 M57	8 0.3%	9 0.3%
HPV-35 M57	11 0.4%	9 0.3%
HPV-39 M57	25 0.8%	22 0.7%
HPV-45 M57	5 0.2%	2 0.1%
HPV-51 M57	28 0.9%	24 0.8%
HPV-52 M57	70 2.3%	63 2.1%
HPV-56 M57	14 0.5%	11 0.4%
HPV-58 M57	15 0.5%	18 0.6%
HPV-59 M57	7 0.2%	2 0.1%
HPV-66 M57	17 0.6%	10 0.3%
HPV-68 M57	12 0.4%	12 0.4%
HPV-31/33/45 M57	15 0.5%	27 0.9%
HPV-16/18/31/33/45 M57	16 0.5%	63 2.1%
HRW-HPV M57	192 6.3%	188 6.2%
HR-HPV M57	192 6.3%	215 7.1%
HPV-16 M72	1 0%	30 1%
HPV-18 M72	0 0%	8 0.3%
HPV-31 M72	3 0.1%	16 0.5%
HPV-33 M72	9 0.3%	9 0.3%
HPV-35 M72	12 0.4%	9 0.3%
HPV-39 M72	25 0.8%	22 0.7%
HPV-45 M72	5 0.2%	2 0.1%
HPV-51 M72	28 0.9%	25 0.8%
HPV-52 M72	72 2.4%	65 2.1%
HPV-56 M72	14 0.5%	12 0.4%
HPV-58 M72	15 0.5%	18 0.6%
HPV-59 M72	8 0.3%	2 0.1%
HPV-66 M72	17 0.6%	10 0.3%
HPV-68 M72	12 0.4%	12 0.4%
HPV-31/33/45 M72	16 0.5%	27 0.9%
HPV-16/18/31/33/45 M72	17 0.6%	64 2.1%
HRW-HPV M72	196 6.5%	192 6.3%
HR-HPV M72	196 6.5%	219 7.2%

11. Secondary Outcome

Title	Number of Subjects With Any Cytological Abnormality Including Atypical Squamous Cells of Undetermined Significance (ASC-US+) Associated With HPV-16 and/or HPV-18 Cervical Infection
Description	Cytological abnormalities = atypical squamous cells of undetermined significance (ASC-DNA- and sero-: subjects HPV DNA negative at Months 0 and 6 by PCR and seronegative at Month 0 for the corresponding HPV-type by Enzyme-linked Immunosorbent Assay (ELISA) Overall: subjects DNA- at Months 0 and 6 for the corresponding HPV-type, regardless of initial serostatus. US).
Time Frame	At Months 24, 48, 57 and 72

Outcome Measure Data

Analysis Population Description

The analysis was performed on the ATP cohort for efficacy, which included all evaluable subjects for whom data concerning efficacy outcome measures were available and who had a normal or low-grade cytology (negative or ASC-US or LSIL) at Month 0.

Arm/Group Title	Cervarix Group	Placebo Group
Arm/Group Description	Subjects received 3 doses of Cervarix vaccine. Cervarix vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.	Subjects received 3 doses of placebo. Placebo was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.
Measure Participants	2803	2802
Sero negative, DNA negative HPV-16/18 M24	1 0%	16 0.5%
Sero negative, DNA negative HPV-16 M24	1 0%	12 0.4%
Sero negative, DNA negative HPV-18 M24	0 0%	5 0.2%
Overall, HPV-16/18 M24	3 0.1%	24 0.8%
Overall, HPV-16 M24	3 0.1%	17 0.6%
Overall, HPV-18 M24	0 0%	8 0.3%
Sero negative, DNA negative HPV-16/18 M48	2 0.1%	39 1.3%
Sero negative, DNA negative HPV-16 M48	2 0.1%	28 0.9%
Sero negative, DNA negative HPV-18 M48	0 0%	12 0.4%
Overall, HPV-16/18 M48	5 0.2%	53 1.8%
Overall, HPV-16 M48	4 0.1%	39 1.3%
Overall, HPV-18 M48	1 0%	16 0.5%
Sero negative, DNA negative HPV-16/18 M57	4 0.1%	53 1.8%
Sero negative, DNA negative HPV-16 M57	3 0.1%	38 1.3%
Sero negative, DNA negative HPV-18 M57	1 0%	16 0.5%
Overall, HPV-16/18 M57	10 0.3%	71 2.3%
Overall, HPV-16 M57	7 0.2%	52 1.7%
Overall, HPV-18 M57	3 0.1%	21 0.7%
Sero negative, DNA negative HPV-16/18 M72	5 0.2%	60 2%
Sero negative, DNA negative HPV-16 M72	4 0.1%	44 1.5%
Sero negative, DNA negative HPV-18 M72	1 0%	17 0.6%
Overall, HPV-16/18 M72	12 0.4%	83 2.7%
Overall, HPV-16 M72	9 0.3%	62 2%
Overall, HPV-18 M72	3 0.1%	24 0.8%

12. Secondary Outcome

Title	Number of Subjects With Any Cytological Abnormality Including Atypical Squamous Cells of Undetermined Significance (ASC-US+) Associated With Any Oncogenic HPV Type
Description	Cytological abnormalities = atypical squamous cells of undetermined significance (ASC-US). Oncogenic HPV types assessed were HPV-16, -18, -31, -33, -35, -39, -45, -51, -52, -56, -58, -59, -66 and -68 individually or in combination. Subjects were HPV DNA- at Months 0 and 6 for the corresponding HPV-type, regardless of initial serostatus. HRW-HPV=All high-risk (oncogenic) HPV types excluding HPV-16 and HPV-18 HR-HPV=High-risk (oncogenic) HPV types: HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68.
Time Frame	At Months 24, 48, 57 and 72

Outcome Measure Data

Analysis Population Description

The analysis was performed on the ATP cohort for efficacy, which included all evaluable subjects for whom data concerning efficacy outcome measures were available and who had a normal or low-grade cytology (negative or ASC-US or LSIL) at Month 0.

Arm/Group Title	Cervarix Group	Placebo Group
Arm/Group Description	Subjects received 3 doses of Cervarix vaccine. Cervarix vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.	Subjects received 3 doses of placebo. Placebo was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.
Measure Participants	2808	2812
HPV-16 M24	3 0.1%	17 0.6%
HPV-18 M24	0 0%	8 0.3%
HPV-31 M24	5 0.2%	7 0.2%
HPV-33 M24	5 0.2%	7 0.2%
HPV-35 M24	6 0.2%	4 0.1%
HPV-39 M24	11 0.4%	8 0.3%
HPV-45 M24	4 0.1%	5 0.2%
HPV-51 M24	19 0.6%	17 0.6%
HPV-52 M24	29 1%	16 0.5%
HPV-56 M24	9 0.3%	13 0.4%
HPV-58 M24	9 0.3%	11 0.4%
HPV-59 M24	8 0.3%	4 0.1%
HPV-66 M24	12 0.4%	9 0.3%
HPV-68 M24	10 0.3%	10 0.3%
HPV-31/33/45 M24	13 0.4%	18 0.6%
HPV-16/18/31/33/45 M24	15 0.5%	42 1.4%
HRW-HPV M24	88 2.9%	90 3%
HR-HPV M24	90 3%	105 3.5%
HPV-16 M48	4 0.1%	39 1.3%
HPV-18 M48	1 0%	16 0.5%
HPV-31 M48	10 0.3%	21 0.7%
HPV-33 M48	11 0.4%	20 0.7%
HPV-35 M48	12 0.4%	15 0.5%
HPV-39 M48	29 1%	21 0.7%
HPV-45 M48	6 0.2%	6 0.2%
HPV-51 M48	42 1.4%	47 1.6%
HPV-52 M48	54 1.8%	45 1.5%
HPV-56 M48	25 0.8%	27 0.9%
HPV-58 M48	20 0.7%	20 0.7%
HPV-59 M48	17 0.6%	10 0.3%
HPV-66 M48	27 0.9%	20 0.7%
HPV-68 M48	22 0.7%	19 0.6%
HPV-31/33/45 M48	24 0.8%	41 1.4%
HPV-16/18/31/33/45 M48	28 0.9%	92 3%
HRW-HPV M48	196 6.5%	212 7%
HR-HPV M48	199 6.6%	238 7.9%
HPV-16 M57	7 0.2%	52 1.7%
HPV-18 M57	3 0.1%	21 0.7%
HPV-31 M57	12 0.4%	28 0.9%
HPV-33 M57	15 0.5%	29 1%
HPV-35 M57	18 0.6%	19 0.6%
HPV-39 M57	40 1.3%	31 1%
HPV-45 M57	9 0.3%	12 0.4%
HPV-51 M57	57 1.9%	64 2.1%
HPV-52 M57	71 2.3%	74 2.4%
HPV-56 M57	39 1.3%	43 1.4%
HPV-58 M57	34 1.1%	42 1.4%
HPV-59 M57	19 0.6%	15 0.5%
HPV-66 M57	39 1.3%	39 1.3%
HPV-68 M57	28 0.9%	30 1%
HPV-31/33/45 M57	32 1.1%	61 2%
HPV-16/18/31/33/45 M57	41 1.4%	127 4.2%
HRW-HPV M57	127 4.2%	274 9.1%
HR-HPV M57	278 9.2%	343 11.3%
HPV-16 M72	9 0.3%	62 2%
HPV-18 M72	3 0.1%	25 0.8%
HPV-31 M72	12 0.4%	32 1.1%
HPV-33 M72	17 0.6%	32 1.1%
HPV-35 M72	20 0.7%	21 0.7%
HPV-39 M72	49 1.6%	35 1.2%
HPV-45 M72	9 0.3%	12 0.4%
HPV-51 M72	64 2.1%	78 2.6%
HPV-52 M72	83 2.7%	81 2.7%
HPV-56 M72	46 1.5%	51 1.7%
HPV-58 M72	36 1.2%	49 1.6%
HPV-59 M72	20 0.7%	17 0.6%
HPV-66 M72	42 1.4%	46 1.5%
HPV-68 M72	30 1%	37 1.2%
HPV-31/33/45 M72	34 1.1%	66 2.2%
HPV-16/18/31/33/45 M72	45 1.5%	144 4.8%
HRW-HPV M72	309 10.2%	352 11.6%
HR-HPV M72	313 10.3%	386 12.8%

13. Secondary Outcome

Title	Number of Subjects With Histopathologically-confirmed CIN1+ Associated With HPV-16 and/or HPV-18 Cervical Infection
Description	CIN1+ = CIN grades 1, 2, and3, low-grade cervical glandular intraepithelial neoplasia (LCGIN), high grade cervical glandular intraepithelial neoplasia (HCGIN), adenocarcinoma in-situ (AIS) or invasive cervical cancer. DNA- and sero-: subjects HPV DNA negative at Months 0 and 6 by PCR and seronegative at Month 0 for the corresponding HPV-type by Enzyme-linked Immunosorbent Assay (ELISA) Overall: subjects DNA- at Months 0 and 6 for the corresponding HPV-type, regardless of initial serostatus.
Time Frame	At Months 24, 48, 57 and 72

Outcome Measure Data

Analysis Population Description

The analysis was performed on the ATP cohort for efficacy, which included all evaluable subjects for whom data concerning efficacy outcome measures were available and who had a normal or low-grade cytology (negative or ASC-US or LSIL) at Month 0.

Arm/Group Title	Cervarix Group	Placebo Group
Arm/Group Description	Subjects received 3 doses of Cervarix vaccine. Cervarix vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.	Subjects received 3 doses of placebo. Placebo was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.
Measure Participants	2805	2802
Sero negative, DNA negative HPV-16/18 M24	0 0%	4 0.1%
Sero negative, DNA negative HPV-16 M24	0 0%	4 0.1%
Sero negative, DNA negative HPV-18 M24	0 0%	0 0%
Overall, HPV-16/18 M24	0 0%	5 0.2%
Overall, HPV-16 M24	0 0%	5 0.2%
Overall, HPV-18 M24	0 0%	0 0%
Sero negative, DNA negative HPV-16/18 M48	1 0%	12 0.4%
Sero negative, DNA negative HPV-16 M48	1 0%	8 0.3%
Sero negative, DNA negative HPV-18 M48	0 0%	4 0.1%
Overall, HPV-16/18 M48	1 0%	14 0.5%
Overall, HPV-16 M48	1 0%	10 0.3%
Overall, HPV-18 M48	0 0%	4 0.1%
Sero negative, DNA negative HPV-16/18 M57	1 0%	15 0.5%
Sero negative, DNA negative HPV-16 M57	1 0%	10 0.3%
Sero negative, DNA negative HPV-18 M57	0 0%	5 0.2%
Overall, HPV-16/18 M57	1 0%	18 0.6%
Overall, HPV-16 M57	1 0%	13 0.4%
Overall, HPV-18 M57	0 0%	5 0.2%
Sero negative, DNA negative HPV-16/18 M72	1 0%	15 0.5%
Sero negative, DNA negative HPV-16 M72	1 0%	10 0.3%
Sero negative, DNA negative HPV-18 M72	0 0%	5 0.2%
Overall, HPV-16/18 M72	1 0%	18 0.6%
Overall, HPV-16 M72	1 0%	13 0.4%
Overall, HPV-18 M72	0 0%	5 0.2%

14. Secondary Outcome

Title	Number of Subjects With Histopathologically-confirmed CIN2+ Associated With HPV-16 and/or HPV-18 Cervical Infection
Description	CIN2+ = CIN grades 2 and 3, LCGIN, HCGIN, AIS or invasive cervical cancer. DNA- and sero-: subjects HPV DNA negative at Months 0 and 6 by PCR and seronegative at Month 0 for the corresponding HPV-type by Enzyme-linked Immunosorbent Assay (ELISA) Overall: subjects DNA- at Months 0 and 6 for the corresponding HPV-type, regardless of initial serostatus.
Time Frame	At Months 24, 48, 57 and 72

Outcome Measure Data

Analysis Population Description

The analysis was performed on the ATP cohort for efficacy, which included all evaluable subjects for whom data concerning efficacy outcome measures were available and who had a normal or low-grade cytology (negative or ASC-US or LSIL) at Month 0.

Arm/Group Title	Cervarix Group	Placebo Group
Arm/Group Description	Subjects received 3 doses of Cervarix vaccine. Cervarix vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.	Subjects received 3 doses of placebo. Placebo was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.
Measure Participants	2805	2802
Sero negative, DNA negative HPV-16/18 M24	0 0%	3 0.1%
Sero negative, DNA negative HPV-16 M24	0 0%	3 0.1%
Sero negative, DNA negative HPV-18 M24	0 0%	0 0%
Overall, HPV-16/18 M24	0 0%	4 0.1%
Overall, HPV-16 M24	0 0%	4 0.1%
Overall, HPV-18 M24	0 0%	0 0%
Sero negative, DNA negative HPV-16/18 M48	1 0%	6 0.2%
Sero negative, DNA negative HPV-16 M48	1 0%	6 0.2%
Sero negative, DNA negative HPV-18 M48	0 0%	0 0%
Overall, HPV-16/18 M48	1 0%	7 0.2%
Overall, HPV-16 M48	1 0%	7 0.2%
Overall, HPV-18 M48	0 0%	0 0%
Sero negative, DNA negative HPV-16/18 M57	1 0%	8 0.3%
Sero negative, DNA negative HPV-16 M57	1 0%	8 0.3%
Sero negative, DNA negative HPV-18 M57	0 0%	0 0%
Overall, HPV-16/18 M57	1 0%	10 0.3%
Overall, HPV-16 M57	1 0%	10 0.3%
Overall, HPV-18 M57	0 0%	0 0%
Sero negative, DNA negative HPV-16/18 M72	1 0%	8 0.3%
Sero negative, DNA negative HPV-16 M72	1 0%	8 0.3%
Sero negative, DNA negative HPV-18 M72	0 0%	0 0%
Overall, HPV-16/18 M72	1 0%	10 0.3%
Overall, HPV-16 M72	1 0%	10 0.3%
Overall, HPV-18 M72	0 0%	0 0%

15. Secondary Outcome

Title	Number of Subjects With Histopathologically-confirmed CIN1+ Associated With Cervical Infection With Any Oncogenic HPV Type
Description	CIN1+ = CIN grades 1, 2 and 3, LCGIN, HCGIN, AIS or invasive cervical cancer. Oncogenic HPV types assessed were HPV-16, -18, -31, -33, -35, -39, -45, -51, -52, -56, -58, -59, -66 and -68 individually or in combination. Subjects were HPV DNA- at Months 0 and 6 for the corresponding HPV-type, regardless of initial serostatus. HRW-HPV=All high-risk (oncogenic) HPV types excluding HPV-16 and HPV-18 HR-HPV=High-risk (oncogenic) HPV types: HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68.
Time Frame	At Months 24, 48, 57 and 72

Outcome Measure Data

Analysis Population Description

The analysis was performed on the ATP cohort for efficacy, which included all evaluable subjects for whom data concerning efficacy outcome measures were available and who had a normal or low-grade cytology (negative or ASC-US or LSIL) at Month 0.

Arm/Group Title	Cervarix Group	Placebo Group
Arm/Group Description	Subjects received 3 doses of Cervarix vaccine. Cervarix vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.	Subjects received 3 doses of placebo. Placebo was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.
Measure Participants	2810	2812
HPV-16 M24	0 0%	5 0.2%
HPV-18 M24	0 0%	0 0%
HPV-31 M24	0 0%	1 0%
HPV-33 M24	2 0.1%	1 0%
HPV-35 M24	1 0%	1 0%
HPV-39 M24	2 0.1%	0 0%
HPV-45 M24	2 0.1%	1 0%
HPV-51 M24	1 0%	3 0.1%
HPV-52 M24	2 0.1%	3 0.1%
HPV-56 M24	0 0%	2 0.1%
HPV-58 M24	0 0%	1 0%
HPV-59 M24	1 0%	0 0%
HPV-66 M24	3 0.1%	2 0.1%
HPV-68 M24	0 0%	2 0.1%
HPV-31/33/45 M24	3 0.1%	3 0.1%
HPV-16/18/31/33/45 M24	3 0.1%	8 0.3%
HRW-HPV M24	11 0.4%	14 0.5%
HR-HPV M24	11 0.4%	17 0.6%
HPV-16 M48	1 0%	10 0.3%
HPV-18 M48	0 0%	4 0.1%
HPV-31 M48	0 0%	4 0.1%
HPV-33 M48	3 0.1%	2 0.1%
HPV-35 M48	1 0%	3 0.1%
HPV-39 M48	4 0.1%	1 0%
HPV-45 M48	3 0.1%	1 0%
HPV-51 M48	1 0%	8 0.3%
HPV-52 M48	7 0.2%	9 0.3%
HPV-56 M48	1 0%	3 0.1%
HPV-58 M48	4 0.1%	4 0.1%
HPV-59 M48	1 0%	0 0%
HPV-66 M48	6 0.2%	3 0.1%
HPV-68 M48	2 0.1%	2 0.1%
HPV-31/33/45 M48	5 0.2%	7 0.2%
HPV-16/18/31/33/45 M48	6 0.2%	21 0.7%
HRW-HPV M48	27 0.9%	35 1.2%
HR-HPV M48	27 0.9%	44 1.5%
HPV-16 M57	1 0%	13 0.4%
HPV-18 M57	0 0%	5 0.2%
HPV-31 M57	0 0%	6 0.2%
HPV-33 M57	3 0.1%	2 0.1%
HPV-35 M57	2 0.1%	3 0.1%
HPV-39 M57	7 0.2%	1 0%
HPV-45 M57	3 0.1%	3 0.1%
HPV-51 M57	2 0.1%	9 0.3%
HPV-52 M57	11 0.4%	11 0.4%
HPV-56 M57	2 0.1%	4 0.1%
HPV-58 M57	4 0.1%	9 0.3%
HPV-59 M57	1 0%	0 0%
HPV-66 M57	6 0.2%	5 0.2%
HPV-68 M57	3 0.1%	3 0.1%
HPV-31/33/45 M57	5 0.2%	10 0.3%
HPV-16/18/31/33/45 M57	6 0.2%	27 0.9%
HRW-HPV M57	37 1.2%	49 1.6%
HR-HPV M57	37 1.2%	60 2%
HPV-16 M72	1 0%	13 0.4%
HPV-18 M72	0 0%	5 0.2%
HPV-31 M72	0 0%	6 0.2%
HPV-33 M72	5 0.2%	3 0.1%
HPV-35 M72	2 0.1%	3 0.1%
HPV-39 M72	7 0.2%	1 0%
HPV-45 M72	3 0.1%	3 0.1%
HPV-51 M72	3 0.1%	9 0.3%
HPV-52 M72	11 0.4%	12 0.4%
HPV-56 M72	2 0.1%	4 0.1%
HPV-58 M72	6 0.2%	9 0.3%
HPV-59 M72	1 0%	0 0%
HPV-66 M72	6 0.2%	8 0.3%
HPV-68 M72	3 0.1%	3 0.1%
HPV-31/33/45 M72	7 0.2%	11 0.4%
HPV-16/18/31/33/45 M72	8 0.3%	28 0.9%
HRW-HPV M72	42 1.4%	53 1.8%
HR-HPV M72	42 1.4%	64 2.1%

16. Secondary Outcome

Title	Number of Subjects With Histopathologically-confirmed CIN2+ Associated With Cervical Infection With Any Oncogenic HPV Type
Description	CIN2+ = CIN grades 2 and 3, LCGIN, HCGIN, AIS or invasive cervical cancer. Oncogenic HPV types assessed were HPV-16, -18, -31, -33, -35, -39, -45, -51, -52, -56, -58, -59, -66 and -68 individually or in combination. Subjects were HPV DNA- at Months 0 and 6 for the corresponding HPV-type, regardless of initial serostatus. HRW-HPV=All high-risk (oncogenic) HPV types excluding HPV-16 and HPV-18 HR-HPV=High-risk (oncogenic) HPV types: HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68.
Time Frame	At Months 24, 48, 57 and 72

Outcome Measure Data

Analysis Population Description

The analysis was performed on the ATP cohort for efficacy, which included all evaluable subjects for whom data concerning efficacy outcome measures were available and who had a normal or low-grade cytology (negative or ASC-US or LSIL) at Month 0.

Arm/Group Title	Cervarix Group	Placebo Group
Arm/Group Description	Subjects received 3 doses of Cervarix vaccine. Cervarix vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.	Subjects received 3 doses of placebo. Placebo was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.
Measure Participants	2810	2812
HPV-16 M24	0 0%	4 0.1%
HPV-18 M24	0 0%	0 0%
HPV-31 M24	0 0%	0 0%
HPV-33 M24	1 0%	1 0%
HPV-35 M24	0 0%	0 0%
HPV-39 M24	0 0%	0 0%
HPV-45 M24	0 0%	0 0%
HPV-51 M24	0 0%	0 0%
HPV-52 M24	0 0%	0 0%
HPV-56 M24	0 0%	0 0%
HPV-58 M24	0 0%	1 0%
HPV-59 M24	0 0%	0 0%
HPV-66 M24	1 0%	1 0%
HPV-68 M24	0 0%	0 0%
HPV-31/33/45 M24	1 0%	1 0%
HPV-16/18/31/33/45 M24	1 0%	5 0.2%
HRW-HPV M24	2 0.1%	3 0.1%
HR-HPV M24	2 0.1%	6 0.2%
HPV-16 M48	1 0%	7 0.2%
HPV-18 M48	0 0%	0 0%
HPV-31 M48	0 0%	2 0.1%
HPV-33 M48	1 0%	2 0.1%
HPV-35 M48	0 0%	2 0.1%
HPV-39 M48	1 0%	0 0%
HPV-45 M48	0 0%	0 0%
HPV-51 M48	0 0%	0 0%
HPV-52 M48	2 0.1%	1 0%
HPV-56 M48	0 0%	0 0%
HPV-58 M48	4 0.1%	2 0.1%
HPV-59 M48	0 0%	0 0%
HPV-66 M48	2 0.1%	1 0%
HPV-68 M48	0 0%	0 0%
HPV-31/33/45 M48	1 0%	4 0.1%
HPV-16/18/31/33/45 M48	2 0.1%	11 0.4%
HRW-HPV M48	8 0.3%	9 0.3%
HR-HPV M48	8 0.3%	15 0.5%
HPV-16 M57	1 0%	10 0.3%
HPV-18 M57	0 0%	0 0%
HPV-31 M57	0 0%	4 0.1%
HPV-33 M57	1 0%	2 0.1%
HPV-35 M57	1 0%	2 0.1%
HPV-39 M57	2 0.1%	0 0%
HPV-45 M57	0 0%	2 0.1%
HPV-51 M57	0 0%	0 0%
HPV-52 M57	2 0.1%	2 0.1%
HPV-56 M57	0 0%	1 0%
HPV-58 M57	4 0.1%	5 0.2%
HPV-59 M57	0 0%	0 0%
HPV-66 M57	2 0.1%	1 0%
HPV-68 M57	0 0%	0 0%
HPV-31/33/45 M57	1 0%	7 0.2%
HPV-16/18/31/33/45 M57	2 0.1%	17 0.6%
HRW-HPV M57	10 0.3%	16 0.5%
HR-HPV M57	10 0.3%	25 0.8%
HPV-16 M72	1 0%	10 0.3%
HPV-18 M72	0 0%	0 0%
HPV-31 M72	0 0%	4 0.1%
HPV-33 M72	2 0.1%	3 0.1%
HPV-35 M72	1 0%	2 0.1%
HPV-39 M72	2 0.1%	0 0%
HPV-45 M72	0 0%	2 0.1%
HPV-51 M72	1 0%	0 0%
HPV-52 M72	2 0.1%	2 0.1%
HPV-56 M72	0 0%	1 0%
HPV-58 M72	5 0.2%	5 0.2%
HPV-59 M72	0 0%	0 0%
HPV-66 M72	2 0.1%	1 0%
HPV-68 M72	0 0%	0 0%
HPV-31/33/45 M72	2 0.1%	8 0.3%
HPV-16/18/31/33/45 M72	3 0.1%	18 0.6%
HRW-HPV M72	13 0.4%	17 0.6%
HR-HPV M72	13 0.4%	26 0.9%

17. Secondary Outcome

Title	Number of Subjects With Any and Severe (Grade 3) Solicited Local Symptoms
Description	Solicited local symptoms assessed were pain, redness and swelling. Any = solicited local symptom reported irrespective of intensity grade, Grade 3 Pain = pain that prevented normal activity, Grade 3 Swelling or Redness = swelling or redness above (>) 50 millimeter (mm). All local symptoms were considered as related to the study vaccination.
Time Frame	Within 7 days (Days 0-6) after vaccination

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects for whom data were available.

Arm/Group Title	Cervarix Group	Placebo Group
Arm/Group Description	Subjects received 3 doses of Cervarix vaccine. Cervarix vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.	Subjects received 3 doses of placebo. Placebo was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.
Measure Participants	3005	3001
Any Pain - Dose 1	2439 80.6%	1815 60%
Grade 3 Pain - Dose 1	105 3.5%	23 0.8%
Any Pain - Dose 2	1650 54.5%	1062 35.1%
Grade 3 Pain - Dose 2	53 1.8%	17 0.6%
Any Pain - Dose 3	1499 49.5%	918 30.3%
Grade 3 Pain - Dose 3	86 2.8%	26 0.9%
Any Pain - Across doses	2634 87%	2166 71.6%
Grade 3 Pain - Across doses	211 7%	64 2.1%
Any Redness - Dose 1	512 16.9%	326 10.8%
Grade 3 Redness - Dose 1	1 0%	1 0%
Any Redness - Dose 2	350 11.6%	182 6%
Grade 3 Redness - Dose 2	2 0.1%	0 0%
Any Redness - Dose 3	432 14.3%	173 5.7%
Grade 3 Redness - Dose 3	2 0.1%	0 0%
Any Redness - Across Doses	838 27.7%	517 17.1%
Grade 3 Redness - Across Doses	5 0.2%	1 0%
Any Swelling - Dose 1	514 17%	215 7.1%
Grade 3 Swelling - Dose 1	34 1.1%	4 0.1%
Any Swelling - Dose 2	323 10.7%	120 4%
Grade 3 Swelling - Dose 2	19 0.6%	2 0.1%
Any Swelling - Dose 3	447 14.8%	149 4.9%
Grade 3 Swelling - Dose 3	10 0.3%	1 0%
Any Swelling - Across Doses	853 28.2%	408 13.5%
Grade 3 Swelling - Across Doses	48 1.6%	5 0.2%

18. Secondary Outcome

Title	Number of Subjects With Any and Severe (Grade 3) Solicited Local Symptoms, for Subjects Seronegative and DNA Negative for Both HPV-16 and HPV-18 at Baseline
Description	Solicited local symptoms assessed were pain, redness and swelling. Any = solicited local symptom reported irrespective of intensity grade Grade 3 Pain = pain that prevented normal activity Grade 3 Swelling or Redness = swelling/redness above (>) 50 millimeter (mm). All local symptoms were considered as related to the study vaccination.
Time Frame	Within 7 days (Days 0-6) after vaccination

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects for whom data were available.

Arm/Group Title	Cervarix Group	Placebo Group
Arm/Group Description	Subjects received 3 doses of Cervarix vaccine. Cervarix vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.	Subjects received 3 doses of placebo. Placebo was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.
Measure Participants	1879	1831
Any Pain - Dose 1	1519 50.2%	1079 35.7%
Grade 3 Pain - Dose 1	65 2.1%	11 0.4%
Any Pain - Dose 2	1029 34%	627 20.7%
Grade 3 Pain - Dose 2	35 1.2%	10 0.3%
Any Pain - Dose 3	923 30.5%	530 17.5%
Grade 3 Pain - Dose 3	54 1.8%	14 0.5%
Any Pain - Across doses	1633 54%	1286 42.5%
Grade 3 Pain - Across doses	131 4.3%	22 0.7%
Any Redness - Dose 1	290 9.6%	174 5.8%
Grade 3 Redness - Dose 1	1 0%	1 0%
Any Redness - Dose 2	201 6.6%	99 3.3%
Grade 3 Redness - Dose 2	0 0%	0 0%
Any Redness - Dose 3	240 7.9%	95 3.1%
Grade 3 Redness - Dose 3	0 0%	0 0%
Any Redness - Across doses	486 16.1%	280 9.3%
Grade 3 Redness - Across doses	1 0%	1 0%
Any Swelling - Dose 1	293 9.7%	138 4.6%
Grade 3 Swelling - Dose 1	18 0.6%	4 0.1%
Any Swelling - Dose 2	196 6.5%	65 2.1%
Grade 3 Swelling - Dose 2	12 0.4%	1 0%
Any Swelling - Dose 3	248 8.2%	85 2.8%
Grade 3 Swelling - Dose 3	7 0.2%	1 0%
Any Swelling - Across doses	493 16.3%	228 7.5%
Grade 3 Swelling - Across doses	28 0.9%	4 0.1%

19. Secondary Outcome

Title	Number of Subjects With Any and Severe (Grade 3) Solicited Local Symptoms, for Subjects Seropositive and/or DNA Positive for Either HPV-16 or HPV-18 at Baseline
Description	Solicited local symptoms assessed were pain, redness and swelling. Any = solicited local symptom reported irrespective of intensity grade Grade 3 Pain = pain that prevented normal activity, Grade 3 Swelling or Redness = swelling/redness above (>) 50 millimeter (mm). All local symptoms were considered as related to the study vaccination.
Time Frame	Within 7 days (Days 0-6) after vaccination

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects for whom data were available.

Arm/Group Title	Cervarix Group	Placebo Group
Arm/Group Description	Subjects received 3 doses of Cervarix vaccine. Cervarix vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.	Subjects received 3 doses of placebo. Placebo was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.
Measure Participants	1124	1167
Any Pain - Dose 1	919 30.4%	733 24.2%
Grade 3 Pain - Dose 1	40 1.3%	11 0.4%
Any Pain - Dose 2	620 20.5%	434 14.3%
Grade 3 Pain - Dose 2	18 0.6%	7 0.2%
Any Pain - Dose 3	576 19%	386 12.8%
Grade 3 Pain - Dose 3	32 1.1%	12 0.4%
Any Pain - Across doses	1000 33%	877 29%
Grade 3 Pain - Across doses	80 2.6%	30 1%
Any Redness - Dose 1	222 7.3%	151 5%
Grade 3 Redness - Dose 1	0 0%	0 0%
Any Redness - Dose 2	148 4.9%	83 2.7%
Grade 3 Redness - Dose 2	2 0.1%	0 0%
Any Redness - Dose 3	192 6.3%	78 2.6%
Grade 3 Redness - Dose 3	2 0.1%	0 0%
Any Redness - Across doses	351 11.6%	236 7.8%
Grade 3 Redness - Across doses	4 0.1%	0 0%
Any Swelling - Dose 1	220 7.3%	112 3.7%
Grade 3 Swelling - Dose 1	16 0.5%	0 0%
Any Swelling - Dose 2	126 4.2%	55 1.8%
Grade 3 Swelling - Dose 2	7 0.2%	1 0%
Any Swelling - Dose 3	199 6.6%	64 2.1%
Grade 3 Swelling - Dose 3	3 0.1%	0 0%
Any Swelling - Across doses	359 11.9%	179 5.9%
Grade 3 Swelling - Across doses	20 0.7%	1 0%

20. Secondary Outcome

Title	Number of Subjects With Any and Severe (Grade 3) Solicited Local Symptoms, for Subjects DNA Positive for Either HPV-16 or HPV-18 at Baseline
Description	Solicited local symptoms assessed were pain, redness and swelling. Any = solicited local symptom reported irrespective of intensity grade, Grade 3 Redness, Swelling = redness/swelling above 50 millimeter All local symptoms were considered as related to the study vaccination
Time Frame	Within 7 days (Days 0-6) after vaccination

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects for whom data were available.

Arm/Group Title	Cervarix Group	Placebo Group
Arm/Group Description	Subjects received 3 doses of Cervarix vaccine. Cervarix vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.	Subjects received 3 doses of placebo. Placebo was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.
Measure Participants	151	127
Any Pain - Dose 1	123 4.1%	82 2.7%
Grade 3 Pain - Dose 1	5 0.2%	0 0%
Any Pain - Dose 2	78 2.6%	55 1.8%
Grade 3 Pain - Dose 2	2 0.1%	1 0%
Any Pain - Dose 3	74 2.4%	43 1.4%
Grade 3 Pain - Dose 3	5 0.2%	1 0%
Any Pain - Across doses	133 4.4%	97 3.2%
Grade 3 Pain - Across doses	11 0.4%	3 0.1%
Any Redness - Dose 1	41 1.4%	16 0.5%
Grade 3 Redness - Dose 1	0 0%	0 0%
Any Redness - Dose 2	24 0.8%	11 0.4%
Grade 3 Redness - Dose 2	0 0%	0 0%
Any Redness - Dose 3	23 0.8%	6 0.2%
Grade 3 Redness - Dose 3	0 0%	0 0%
Any Redness - Across doses	55 1.8%	28 0.9%
Grade 3 Redness - Across doses	0 0%	0 0%
Any Swelling - Dose 1	40 1.3%	14 0.5%
Grade 3 Swelling - Dose 1	0 0%	0 0%
Any Swelling - Dose 2	21 0.7%	8 0.3%
Grade 3 Swelling - Dose 2	0 0%	0 0%
Any Swelling - Dose 3	29 1%	5 0.2%
Grade 3 Swelling - Dose 3	0 0%	0 0%
Any Swelling - Across doses	58 1.9%	21 0.7%
Grade 3 Swelling - Across doses	0 0%	0 0%

21. Secondary Outcome

Title	Number of Subjects With Any, Severe (Grade 3) and Causally Related to Vaccination Solicited General Symptoms.
Description	Solicited general symptoms assessed were arthralgia, fatigue, gastrointestinal, headache, myalgia, rash, fever (= axillary temperature above 37.0 degrees Celsius) and urticaria. Any = any solicited general symptom reported irrespective of intensity grade and relationship to vaccination, Related = symptoms assessed by the investigator as causally related to study vaccination, Grade 3 symptoms = prevented normal activity, Grade 3 urticaria = distributed on at least 4 body areas.
Time Frame	Within 7 days (Days 0-6) after vaccination

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects for whom data were available.

Arm/Group Title	Cervarix Group	Placebo Group
Arm/Group Description	Subjects received 3 doses of Cervarix vaccine. Cervarix vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.	Subjects received 3 doses of placebo. Placebo was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.
Measure Participants	3005	3001
Any Arthralgia - Dose 1	199 6.6%	163 5.4%
Any Arthralgia - Dose 2	63 2.1%	51 1.7%
Any Arthralgia - Dose 3	67 2.2%	32 1.1%
Any Arthralgia - Across doses	270 8.9%	213 7%
Grade 3 Arthralgia - Dose 1	0 0%	3 0.1%
Grade 3 Arthralgia - Dose 2	1 0%	0 0%
Grade 3 Arthralgia - Dose 3	1 0%	1 0%
Grade 3 Arthralgia - Across doses	2 0.1%	4 0.1%
Related Arthralgia - Dose 1	143 4.7%	109 3.6%
Related Arthralgia - Dose 2	51 1.7%	32 1.1%
Related Arthralgia - Dose 3	61 2%	26 0.9%
Related Arthralgia - Across doses	210 6.9%	149 4.9%
Any Fatigue - Dose 1	817 27%	769 25.4%
Any Fatigue - Dose 2	447 14.8%	367 12.1%
Any Fatigue - Dose 3	443 14.6%	309 10.2%
Any Fatigue - Across doses	1142 37.7%	1018 33.7%
Grade 3 Fatigue - Dose 1	14 0.5%	18 0.6%
Grade 3 Fatigue - Dose 2	1 0%	0 0%
Grade 3 Fatigue - Dose 3	5 0.2%	5 0.2%
Grade 3 Fatigue - Across doses	26 0.9%	29 1%
Related Fatigue - Dose 1	634 21%	581 19.2%
Related Fatigue - Dose 2	51 1.7%	32 1.1%
Related Fatigue - Dose 3	390 12.9%	256 8.5%
Related Fatigue - Across doses	968 32%	833 27.5%
Any Gastrointestinal - Dose 1	295 9.7%	368 12.2%
Any Gastrointestinal - Dose 2	123 4.1%	111 3.7%
Any Gastrointestinal - Dose 3	64 2.1%	61 2%
Any Gastrointestinal - Across doses	409 13.5%	473 15.6%
Grade 3 Gastrointestinal - Dose 1	10 0.3%	18 0.6%
Grade 3 Gastrointestinal - Dose 2	2 0.1%	5 0.2%
Grade 3 Gastrointestinal - Dose 3	3 0.1%	1 0%
Grade 3 Gastrointestinal - Across doses	15 0.5%	22 0.7%
Related Gastrointestinal - Dose 1	177 5.8%	200 6.6%
Related Gastrointestinal - Dose 2	79 2.6%	65 2.1%
Related Gastrointestinal - Dose 3	50 1.7%	43 1.4%
Related Gastrointestinal - Across doses	267 8.8%	275 9.1%
Any Headache - Dose 1	476 15.7%	509 16.8%
Any Headache - Dose 2	229 7.6%	208 6.9%
Any Headache - Dose 3	191 6.3%	146 4.8%
Any Headache - Across doses	684 22.6%	682 22.5%
Grade 3 Headache - Dose 1	332 11%	347 11.5%
Grade 3 Headache - Dose 2	5 0.2%	4 0.1%
Grade 3 Headache - Dose 3	6 0.2%	5 0.2%
Grade 3 Headache - Across doses	25 0.8%	20 0.7%
Related Headache - Dose 1	332 11%	347 11.5%
Related Headache - Dose 2	180 5.9%	161 5.3%
Related Headache - Dose 3	164 5.4%	107 3.5%
Related Headache - Across doses	526 17.4%	505 16.7%
Any Myalgia - Dose 1	362 12%	249 8.2%
Any Myalgia - Dose 2	118 3.9%	73 2.4%
Any Myalgia - Dose 3	175 5.8%	109 3.6%
Any Myalgia - Across doses	523 17.3%	360 11.9%
Grade 3 Myalgia - Dose 1	5 0.2%	2 0.1%
Grade 3 Myalgia - Dose 2	2 0.1%	1 0%
Grade 3 Myalgia - Dose 3	2 0.1%	3 0.1%
Grade 3 Myalgia - Across doses	9 0.3%	5 0.2%
Related Myalgia - Dose 1	303 10%	188 6.2%
Related Myalgia - Dose 2	98 3.2%	57 1.9%
Related Myalgia - Dose 3	153 5.1%	92 3%
Related Myalgia - Across doses	449 14.8%	287 9.5%
Any Rash - Dose 1	28 0.9%	42 1.4%
Any Rash - Dose 2	9 0.3%	13 0.4%
Any Rash - Dose 3	12 0.4%	7 0.2%
Any Rash - Across doses	47 1.6%	59 2%
Grade 3 Rash - Dose 1	1 0%	1 0%
Grade 3 Rash - Dose 2	0 0%	0 0%
Grade 3 Rash - Dose 3	2 0.1%	1 0%
Grade 3 Rash - Across doses	3 0.1%	2 0.1%
Related Rash - Dose 1	15 0.5%	19 0.6%
Related Rash - Dose 2	1 0%	9 0.3%
Related Rash - Dose 3	5 0.2%	5 0.2%
Related Rash - Across doses	21 0.7%	33 1.1%
>37.0°C Fever - Dose 1	480 15.9%	433 14.3%
>37.0°C Fever - Dose 2	232 7.7%	236 7.8%
>37.0°C Fever - Dose 3	182 6%	175 5.8%
>37.0°C Fever - Across doses	744 24.6%	697 23%
>39.0°C Fever - Dose 1	2 0.1%	0 0%
>39.0°C Fever - Dose 2	6 0.2%	0 0%
>39.0°C Fever - Dose 3	3 0.1%	2 0.1%
>39.0°C Fever - Across doses	11 0.4%	2 0.1%
Related Fever - Dose 1	386 12.8%	344 11.4%
Related Fever - Dose 2	175 5.8%	168 5.6%
Related Fever - Dose 3	124 4.1%	117 3.9%
Related Fever - Across doses	588 19.4%	539 17.8%
Any Urticaria - Dose 1	22 0.7%	20 0.7%
Any Urticaria - Dose 2	6 0.2%	6 0.2%
Any Urticaria - Dose 3	4 0.1%	4 0.1%
Any Urticaria - Across doses	29 1%	28 0.9%
Grade 3 Urticaria - Dose 1	4 0.1%	2 0.1%
Grade 3 Urticaria - Dose 2	0 0%	0 0%
Grade 3 Urticaria - Dose 3	1 0%	1 0%
Grade 3 Urticaria - Across doses	5 0.2%	3 0.1%
Related Urticaria - Dose 1	10 0.3%	12 0.4%
Related Urticaria - Dose 2	6 0.2%	5 0.2%
Related Urticaria - Dose 3	1 0%	1 0%
Related Urticaria - Across doses	16 0.5%	16 0.5%

22. Secondary Outcome

Title	Number of Subjects With Any, Severe (Grade 3) and Causally Related to Vaccination Solicited General Symptoms, for Subjects Seronegative and DNA Negative for Both HPV-16 and HPV-18 at Baseline
Description	Solicited general symptoms assessed were arthralgia, fatigue, gastrointestinal, headache, myalgia, rash, fever (= axillary temperature above 37.0°C) and urticaria. Any = any solicited general symptom reported irrespective of intensity grade and relationship to vaccination Related = symptoms assessed by the investigator as causally related to study vaccination Grade 3 symptoms = symptoms that prevented normal activity Grade 3 urticaria = urticaria distributed on at least 4 body areas.
Time Frame	Within 7 days (Days 0-6) after vaccination

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects for whom data were available.

Arm/Group Title	Cervarix Group	Placebo Group
Arm/Group Description	Subjects received 3 doses of Cervarix vaccine. Cervarix vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.	Subjects received 3 doses of placebo. Placebo was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.
Measure Participants	1879	1831
Any Arthralgia - Dose 1	124 4.1%	96 3.2%
Any Arthralgia - Dose 2	33 1.1%	34 1.1%
Any Arthralgia - Dose 3	40 1.3%	18 0.6%
Any Arthralgia - Across doses	164 5.4%	128 4.2%
Grade 3 Arthralgia - Dose 1	0 0%	2 0.1%
Grade 3 Arthralgia - Dose 2	0 0%	0 0%
Grade 3 Arthralgia - Dose 3	0 0%	0 0%
Grade 3 Arthralgia - Across doses	0 0%	2 0.1%
Related Arthralgia - Dose 1	89 2.9%	62 2%
Related Arthralgia - Dose 2	29 1%	20 0.7%
Related Arthralgia - Dose 3	37 1.2%	16 0.5%
Related Arthralgia - Across doses	128 4.2%	87 2.9%
Any Fatigue - Dose 1	509 16.8%	443 14.6%
Any Fatigue - Dose 2	255 8.4%	219 7.2%
Any Fatigue - Dose 3	278 9.2%	165 5.5%
Any Fatigue - Across doses	711 23.5%	588 19.4%
Grade 3 Fatigue - Dose 1	10 0.3%	13 0.4%
Grade 3 Fatigue - Dose 2	4 0.1%	3 0.1%
Grade 3 Fatigue - Dose 3	3 0.1%	2 0.1%
Grade 3 Fatigue - Across doses	16 0.5%	18 0.6%
Related Fatigue - Dose 1	386 12.8%	321 10.6%
Related Fatigue - Dose 2	223 7.4%	185 6.1%
Related Fatigue - Dose 3	248 8.2%	135 4.5%
Related Fatigue - Across doses	592 19.6%	471 15.6%
Any Gastrointestinal - Dose 1	182 6%	227 7.5%
Any Gastrointestinal - Dose 2	66 2.2%	65 2.1%
Any Gastrointestinal - Dose 3	33 1.1%	35 1.2%
Any Gastrointestinal - Across doses	240 7.9%	287 9.5%
Grade 3 Gastrointestinal - Dose 1	5 0.2%	9 0.3%
Grade 3 Gastrointestinal - Dose 2	0 0%	3 0.1%
Grade 3 Gastrointestinal - Dose 3	1 0%	0 0%
Grade 3 Gastrointestinal - Across doses	6 0.2%	10 0.3%
Related Gastrointestinal - Dose 1	114 3.8%	122 4%
Related Gastrointestinal - Dose 2	40 1.3%	40 1.3%
Related Gastrointestinal - Dose 3	25 0.8%	27 0.9%
Related Gastrointestinal - Across doses	154 5.1%	170 5.6%
Any Headache - Dose 1	284 9.4%	315 10.4%
Any Headache - Dose 2	118 3.9%	120 4%
Any Headache - Dose 3	111 3.7%	85 2.8%
Any Headache - Across doses	408 13.5%	404 13.4%
Grade 3 Headache - Dose 1	7 0.2%	10 0.3%
Grade 3 Headache - Dose 2	2 0.1%	2 0.1%
Grade 3 Headache - Dose 3	2 0.1%	2 0.1%
Grade 3 Headache - Across doses	11 0.4%	12 0.4%
Related Headache - Dose 1	186 6.1%	212 7%
Related Headache - Dose 2	89 2.9%	96 3.2%
Related Headache - Dose 3	97 3.2%	60 2%
Related Headache - Across doses	300 9.9%	298 9.9%
Any Myalgia - Dose 1	233 7.7%	154 5.1%
Any Myalgia - Dose 2	73 2.4%	38 1.3%
Any Myalgia - Dose 3	114 3.8%	74 2.4%
Any Myalgia - Across doses	328 10.8%	214 7.1%
Grade 3 Myalgia - Dose 1	4 0.1%	2 0.1%
Grade 3 Myalgia - Dose 2	0 0%	1 0%
Grade 3 Myalgia - Dose 3	0 0%	1 0%
Grade 3 Myalgia - Across doses	4 0.1%	3 0.1%
Related Myalgia - Dose 1	194 6.4%	117 3.9%
Related Myalgia - Dose 2	59 1.9%	33 1.1%
Related Myalgia - Dose 3	100 3.3%	62 2%
Related Myalgia - Across doses	280 9.3%	173 5.7%
Any Rash - Dose 1	19 0.6%	26 0.9%
Any Rash - Dose 2	6 0.2%	7 0.2%
Any Rash - Dose 3	7 0.2%	7 0.2%
Any Rash - Across doses	32 1.1%	37 1.2%
Grade 3 Rash - Dose 1	1 0%	1 0%
Grade 3 Rash - Dose 2	0 0%	0 0%
Grade 3 Rash - Dose 3	1 0%	1 0%
Grade 3 Rash - Across doses	2 0.1%	2 0.1%
Related Rash - Dose 1	8 0.3%	11 0.4%
Related Rash - Dose 2	1 0%	6 0.2%
Related Rash - Dose 3	2 0.1%	5 0.2%
Related Rash - Across doses	11 0.4%	22 0.7%
>37.0°C Fever - Dose 1	296 9.8%	261 8.6%
>37.0°C Fever - Dose 2	146 4.8%	149 4.9%
>37.0°C Fever - Dose 3	107 3.5%	108 3.6%
>37.0°C Fever - Across doses	464 15.3%	427 14.1%
>39.0°C Fever - Dose 1	2 0.1%	0 0%
>39.0°C Fever - Dose 2	4 0.1%	0 0%
>39.0°C Fever - Dose 3	0 0%	0 0%
>39.0°C Fever - Across doses	6 0.2%	0 0%
Related Fever - Dose 1	226 7.5%	211 7%
Related Fever - Dose 2	106 3.5%	109 3.6%
Related Fever - Dose 3	74 2.4%	72 2.4%
Related Fever - Across doses	355 11.7%	333 11%
Any Urticaria - Dose 1	13 0.4%	15 0.5%
Any Urticaria - Dose 2	5 0.2%	4 0.1%
Any Urticaria - Dose 3	2 0.1%	2 0.1%
Any Urticaria - Across doses	18 0.6%	19 0.6%
Grade 3 Urticaria - Dose 1	2 0.1%	2 0.1%
Grade 3 Urticaria - Dose 2	0 0%	0 0%
Grade 3 Urticaria - Dose 3	1 0%	0 0%
Grade 3 Urticaria - Across doses	3 0.1%	2 0.1%
Related Urticaria - Dose 1	7 0.2%	8 0.3%
Related Urticaria - Dose 2	5 0.2%	4 0.1%
Related Urticaria - Dose 3	0 0%	1 0%
Related Urticaria - Across doses	11 0.4%	11 0.4%

23. Secondary Outcome

Title	Number of Subjects With Any, Severe (Grade 3) and Causally Related to Vaccination Solicited General Symptoms, for Subjects Seropositive and/or DNA Positive for Either HPV-16 or HPV-18 at Baseline
Description	Solicited general symptoms assessed were arthralgia, fatigue, gastrointestinal, headache, myalgia, rash, fever (= axillary temperature above 37.0°C) and urticaria. Any = any solicited general symptom reported irrespective of intensity grade and relationship to vaccination Related = symptoms assessed by the investigator as causally related to study vaccination Grade 3 symptoms = symptoms that prevented normal activity Grade 3 urticaria = urticaria distributed on at least 4 body areas
Time Frame	Within 7 days (Days 0-6) after vaccination

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects for whom data were available.

Arm/Group Title	Cervarix Group	Placebo Group
Arm/Group Description	Subjects received 3 doses of Cervarix vaccine. Cervarix vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.	Subjects received 3 doses of placebo. Placebo was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.
Measure Participants	1124	1167
Any Arthralgia - Dose 1	75 2.5%	67 2.2%
Any Arthralgia - Dose 2	30 1%	17 0.6%
Any Arthralgia - Dose 3	27 0.9%	14 0.5%
Any Arthralgia - Across doses	106 3.5%	85 2.8%
Grade 3 Arthralgia - Dose 1	0 0%	1 0%
Grade 3 Arthralgia - Dose 2	1 0%	0 0%
Grade 3 Arthralgia - Dose 3	1 0%	1 0%
Grade 3 Arthralgia - Across doses	2 0.1%	2 0.1%
Related Arthralgia - Dose 1	54 1.8%	47 1.6%
Related Arthralgia - Dose 2	22 0.7%	12 0.4%
Related Arthralgia - Dose 3	24 0.8%	10 0.3%
Related Arthralgia - Across doses	82 2.7%	62 2%
Any Fatigue - Dose 1	307 10.1%	325 10.7%
Any Fatigue - Dose 2	191 6.3%	147 4.9%
Any Fatigue - Dose 3	27 0.9%	14 0.5%
Any Fatigue - Across doses	430 14.2%	429 14.2%
Grade 3 Fatigue - Dose 1	4 0.1%	5 0.2%
Grade 3 Fatigue - Dose 2	5 0.2%	3 0.1%
Grade 3 Fatigue - Dose 3	2 0.1%	3 0.1%
Grade 3 Fatigue - Across doses	10 0.3%	11 0.4%
Related Fatigue - Dose 1	247 8.2%	259 8.6%
Related Fatigue - Dose 2	170 5.6%	118 3.9%
Related Fatigue - Dose 3	142 4.7%	120 4%
Related Fatigue - Across doses	375 12.4%	361 11.9%
Any Gastrointestinal - Dose 1	112 3.7%	140 4.6%
Any Gastrointestinal - Dose 2	57 1.9%	46 1.5%
Any Gastrointestinal - Dose 3	31 1%	26 0.9%
Any Gastrointestinal - Across doses	168 5.6%	185 6.1%
Grade 3 Gastrointestinal - Dose 1	5 0.2%	9 0.3%
Grade 3 Gastrointestinal - Dose 2	2 0.1%	2 0.1%
Grade 3 Gastrointestinal - Dose 3	2 0.1%	1 0%
Grade 3 Gastrointestinal - Across doses	9 0.3%	12 0.4%
Related Gastrointestinal - Dose 1	62 2%	78 2.6%
Related Gastrointestinal - Dose 2	39 1.3%	25 0.8%
Related Gastrointestinal - Dose 3	25 0.8%	16 0.5%
Related Gastrointestinal - Across doses	112 3.7%	105 3.5%
Any Headache - Dose 1	191 6.3%	193 6.4%
Any Headache - Dose 2	111 3.7%	88 2.9%
Any Headache - Dose 3	80 2.6%	61 2%
Any Headache - Across doses	275 9.1%	277 9.2%
Grade 3 Headache - Dose 1	7 0.2%	3 0.1%
Grade 3 Headache - Dose 2	3 0.1%	2 0.1%
Grade 3 Headache - Dose 3	4 0.1%	3 0.1%
Grade 3 Headache - Across doses	14 0.5%	8 0.3%
Related Headache - Dose 1	145 4.8%	134 4.4%
Related Headache - Dose 2	91 3%	65 2.1%
Related Headache - Dose 3	67 2.2%	47 1.6%
Related Headache - Across doses	225 7.4%	206 6.8%
Any Myalgia - Dose 1	129 4.3%	94 3.1%
Any Myalgia - Dose 2	45 1.5%	35 1.2%
Any Myalgia - Dose 3	61 2%	35 1.2%
Any Myalgia - Across doses	195 6.4%	145 4.8%
Grade 3 Myalgia - Dose 1	1 0%	0 0%
Grade 3 Myalgia - Dose 2	2 0.1%	0 0%
Grade 3 Myalgia - Dose 3	2 0.1%	2 0.1%
Grade 3 Myalgia - Across doses	5 0.2%	2 0.1%
Related Myalgia - Dose 1	109 3.6%	70 2.3%
Related Myalgia - Dose 2	39 1.3%	24 0.8%
Related Myalgia - Dose 3	53 1.8%	30 1%
Related Myalgia - Across doses	169 5.6%	113 3.7%
Any Rash - Dose 1	9 0.3%	16 0.5%
Any Rash - Dose 2	3 0.1%	6 0.2%
Any Rash - Dose 3	5 0.2%	0 0%
Any Rash - Across doses	15 0.5%	22 0.7%
Grade 3 Rash - Dose 1	0 0%	0 0%
Grade 3 Rash - Dose 2	0 0%	0 0%
Grade 3 Rash - Dose 3	1 0%	0 0%
Grade 3 Rash - Across doses	1 0%	0 0%
Related Rash - Dose 1	7 0.2%	8 0.3%
Related Rash - Dose 2	0 0%	0 0%
Related Rash - Dose 3	3 0.1%	0 0%
Related Rash - Across doses	10 0.3%	11 0.4%
>37.0°C Fever - Dose 1	183 6%	172 5.7%
>37.0°C Fever - Dose 2	85 2.8%	87 2.9%
>37.0°C Fever - Dose 3	73 2.4%	67 2.2%
>37.0°C Fever - Across doses	278 9.2%	270 8.9%
>39.0°C Fever - Dose 1	0 0%	0 0%
>39.0°C Fever - Dose 2	2 0.1%	0 0%
>39.0°C Fever - Dose 3	3 0.1%	2 0.1%
>39.0°C Fever - Across doses	5 0.2%	2 0.1%
Related Fever - Dose 1	159 5.3%	133 4.4%
Related Fever - Dose 2	68 2.2%	59 2%
Related Fever - Dose 3	49 1.6%	45 1.5%
Related Fever - Across doses	232 7.7%	206 6.8%
Any Urticaria - Dose 1	9 0.3%	5 0.2%
Any Urticaria - Dose 2	1 0%	2 0.1%
Any Urticaria - Dose 3	2 0.1%	2 0.1%
Any Urticaria - Across doses	11 0.4%	9 0.3%
Grade 3 Urticaria - Dose 1	2 0.1%	0 0%
Grade 3 Urticaria - Dose 2	0 0%	0 0%
Grade 3 Urticaria - Dose 3	0 0%	1 0%
Grade 3 Urticaria - Across doses	2 0.1%	1 0%
Related Urticaria - Dose 1	3 0.1%	4 0.1%
Related Urticaria - Dose 2	1 0%	1 0%
Related Urticaria - Dose 3	1 0%	0 0%
Related Urticaria - Across doses	5 0.2%	5 0.2%

24. Secondary Outcome

Title	Number of Subjects With Any, Severe (Grade 3) and Causally Related to Vaccination Solicited General Symptoms, for Subjects DNA Positive for Either HPV-16 or HPV-18 at Baseline
Description	Solicited general symptoms assessed were arthralgia, fatigue, gastrointestinal, headache, myalgia, rash, fever (= axillary temperature above 37.0°C) and urticaria. Any = any solicited general symptom reported irrespective of intensity grade and relationship to vaccination Related = symptoms assessed by the investigator as causally related to study vaccination Grade 3 symptoms = symptoms that prevented normal activity Grade 3 urticaria = urticaria distributed on at least 4 body areas
Time Frame	Within 7 days (Days 0-6) after vaccination

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects for whom data were available.

Arm/Group Title	Cervarix Group	Placebo Group
Arm/Group Description	Subjects received 3 doses of Cervarix vaccine. Cervarix vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.	Subjects received 3 doses of placebo. Placebo was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.
Measure Participants	151	127
Any Arthralgia - Dose 1	12 0.4%	8 0.3%
Any Arthralgia - Dose 2	3 0.1%	1 0%
Any Arthralgia - Dose 3	1 0%	1 0%
Any Arthralgia - Across doses	14 0.5%	10 0.3%
Grade 3 Arthralgia - Dose 1	0 0%	0 0%
Grade 3 Arthralgia - Dose 2	0 0%	0 0%
Grade 3 Arthralgia - Dose 3	0 0%	0 0%
Grade 3 Arthralgia - Across doses	0 0%	0 0%
Related Arthralgia - Dose 1	7 0.2%	5 0.2%
Related Arthralgia - Dose 2	1 0%	1 0%
Related Arthralgia - Dose 3	1 0%	0 0%
Related Arthralgia - Across doses	8 0.3%	6 0.2%
Any Fatigue - Dose 1	44 1.5%	46 1.5%
Any Fatigue - Dose 2	29 1%	18 0.6%
Any Fatigue - Dose 3	24 0.8%	14 0.5%
Any Fatigue - Across doses	66 2.2%	53 1.8%
Grade 3 Fatigue - Dose 1	0 0%	0 0%
Grade 3 Fatigue - Dose 2	1 0%	0 0%
Grade 3 Fatigue - Dose 3	1 0%	1 0%
Grade 3 Fatigue - Across doses	1 0%	1 0%
Related Fatigue - Dose 1	35 1.2%	36 1.2%
Related Fatigue - Dose 2	26 0.9%	13 0.4%
Related Fatigue - Dose 3	20 0.7%	14 0.5%
Related Fatigue - Across doses	58 1.9%	47 1.6%
Any Gastrointestinal - Dose 1	14 0.5%	20 0.7%
Any Gastrointestinal - Dose 2	10 0.3%	5 0.2%
Any Gastrointestinal - Dose 3	3 0.1%	1 0%
Any Gastrointestinal - Across doses	22 0.7%	24 0.8%
Grade 3 Gastrointestinal - Dose 1	0 0%	2 0.1%
Grade 3 Gastrointestinal - Dose 2	1 0%	0 0%
Grade 3 Gastrointestinal - Dose 3	0 0%	1 0%
Grade 3 Gastrointestinal - Across doses	1 0%	3 0.1%
Related Gastrointestinal - Dose 1	7 0.2%	8 0.3%
Related Gastrointestinal - Dose 2	7 0.2%	3 0.1%
Related Gastrointestinal - Dose 3	2 0.1%	1 0%
Related Gastrointestinal - Across doses	14 0.5%	12 0.4%
Any Headache - Dose 1	25 0.8%	20 0.7%
Any Headache - Dose 2	17 0.6%	9 0.3%
Any Headache - Dose 3	8 0.3%	6 0.2%
Any Headache - Across doses	36 1.2%	31 1%
Grade 3 Headache - Dose 1	1 0%	0 0%
Grade 3 Headache - Dose 2	1 0%	0 0%
Grade 3 Headache - Dose 3	1 0%	0 0%
Grade 3 Headache - Across doses	3 0.1%	0 0%
Related Headache - Dose 1	15 0.5%	11 0.4%
Related Headache - Dose 2	16 0.5%	7 0.2%
Related Headache - Dose 3	7 0.2%	5 0.2%
Related Headache - Across doses	29 1%	22 0.7%
Any Myalgia - Dose 1	17 0.6%	10 0.3%
Any Myalgia - Dose 2	5 0.2%	4 0.1%
Any Myalgia - Dose 3	7 0.2%	2 0.1%
Any Myalgia - Across doses	25 0.8%	15 0.5%
Grade 3 Myalgia - Dose 1	0 0%	0 0%
Grade 3 Myalgia - Dose 2	0 0%	0 0%
Grade 3 Myalgia - Dose 3	0 0%	0 0%
Grade 3 Myalgia - Across doses	0 0%	0 0%
Related Myalgia - Dose 1	11 0.4%	9 0.3%
Related Myalgia - Dose 2	5 0.2%	4 0.1%
Related Myalgia - Dose 3	7 0.2%	1 0%
Related Myalgia - Across doses	19 0.6%	13 0.4%
Any Rash - Dose 1	1 0%	0 0%
Any Rash - Dose 2	2 0.1%	2 0.1%
Any Rash - Dose 3	1 0%	0 0%
Any Rash - Across doses	4 0.1%	2 0.1%
Grade 3 Rash - Dose 1	0 0%	0 0%
Grade 3 Rash - Dose 2	0 0%	0 0%
Grade 3 Rash - Dose 3	0 0%	0 0%
Grade 3 Rash - Across doses	0 0%	0 0%
Related Rash - Dose 1	1 0%	0 0%
Related Rash - Dose 2	0 0%	2 0.1%
Related Rash - Dose 3	0 0%	0 0%
Related Rash - Across doses	1 0%	2 0.1%
>37.0°C Fever - Dose 1	16 0.5%	18 0.6%
>37.0°C Fever - Dose 2	11 0.4%	12 0.4%
>37.0°C Fever - Dose 3	15 0.5%	3 0.1%
>37.0°C Fever - Across doses	32 1.1%	26 0.9%
>39.0°C Fever - Dose 1	0 0%	0 0%
>39.0°C Fever - Dose 2	0 0%	0 0%
>39.0°C Fever - Dose 3	2 0.1%	0 0%
>39.0°C Fever - Across doses	2 0.1%	0 0%
Related Fever - Dose 1	13 0.4%	13 0.4%
Related Fever - Dose 2	8 0.3%	7 0.2%
Related Fever - Dose 3	8 0.3%	2 0.1%
Related Fever - Across doses	23 0.8%	18 0.6%
Any Urticaria - Dose 1	1 0%	0 0%
Any Urticaria - Dose 2	0 0%	0 0%
Any Urticaria - Dose 3	0 0%	0 0%
Any Urticaria - Across doses	1 0%	0 0%
Grade 3 Urticaria - Dose 1	0 0%	0 0%
Grade 3 Urticaria - Dose 2	0 0%	0 0%
Grade 3 Urticaria - Dose 3	0 0%	0 0%
Grade 3 Urticaria - Across doses	0 0%	0 0%
Related Urticaria - Dose 1	0 0%	0 0%
Related Urticaria - Dose 2	0 0%	0 0%
Related Urticaria - Dose 3	0 0%	0 0%
Related Urticaria - Across doses	0 0%	0 0%

25. Secondary Outcome

Title	Number of Subjects With Any, Severe (Grade 3) and Causally Related to Vaccination Unsolicited Adverse Events (AEs)
Description	An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Related = event assessed by the investigator as causally related to study vaccination Grade 3 = event that prevented normal activity
Time Frame	Within Days 0-29 after vaccination

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects for whom data were available.

Arm/Group Title	Cervarix Group	Placebo Group
Arm/Group Description	Subjects received 3 doses of Cervarix vaccine. Cervarix vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.	Subjects received 3 doses of placebo. Placebo was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.
Measure Participants	3026	3025
Any AEs	793 26.2%	775 25.6%
Grade 3 AEs	18 0.6%	18 0.6%
Related AEs	35 1.2%	32 1.1%

26. Secondary Outcome

Title	Number of Subjects With Unsolicited Adverse Events for Subjects Seronegative and DNA Negative for Both HPV-16 and HPV-18 at Baseline
Description	An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms.
Time Frame	Within Days 0-29 after vaccination

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects for whom data were available.

Arm/Group Title	Cervarix Group	Placebo Group
Arm/Group Description	Subjects received 3 doses of Cervarix vaccine. Cervarix vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.	Subjects received 3 doses of placebo. Placebo was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.
Measure Participants	1892	1843
Count of Participants [Participants]	497 16.4%	468 15.5%

27. Secondary Outcome

Title	Number of Subjects With Unsolicited Adverse Events for Subjects Seropositive and/or DNA Positive for Either HPV-16 or HPV-18 at Baseline
Description	An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms
Time Frame	Within Days 0-29 after vaccination

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects for whom data were available.

Arm/Group Title	Cervarix Group	Placebo Group
Arm/Group Description	Subjects received 3 doses of Cervarix vaccine. Cervarix vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.	Subjects received 3 doses of placebo. Placebo was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.
Measure Participants	1131	1179
Count of Participants [Participants]	295 9.7%	307 10.1%

28. Secondary Outcome

Title	Number of Subjects With Unsolicited Adverse Events for Subjects DNA Positive for Either HPV-16 or HPV-18 at Baseline
Description	An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms.
Time Frame	Within Days 0-29 after vaccination

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects for whom data were available.

Arm/Group Title	Cervarix Group	Placebo Group
Arm/Group Description	Subjects received 3 doses of Cervarix vaccine. Cervarix vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.	Subjects received 3 doses of placebo. Placebo was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule
Measure Participants	151	128
Count of Participants [Participants]	32 1.1%	40 1.3%

29. Secondary Outcome

Title	Number of Subjects With Serious Adverse Events (SAEs)
Description	SAEs assessed include medical occurrences that results in death, are life threatening, require hospitalization or prolongation of hospitalization, results in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subjects.
Time Frame	From Day 0 to Month 72

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects for whom data were available.

Arm/Group Title	Cervarix Group	Placebo Group
Arm/Group Description	Subjects received 3 doses of Cervarix vaccine. Cervarix vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.	Subjects received 3 doses of placebo. Placebo was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.
Measure Participants	3026	3025
Count of Participants [Participants]	56 1.9%	81 2.7%

30. Secondary Outcome

Title	Number of Subjects With Medically Significant Conditions (MSC) Regardless of Causal Relationship to Vaccination and Intensity
Description	Medically significant conditions were defined as: adverse events (AEs) prompting emergency room or physician visits that were not (1) related to common diseases or (2) routine visits for physical examination or vaccination, or SAEs that were not related to common diseases. Common diseases included: upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervicovaginal yeast infections, menstrual cycle abnormalities and injury.
Time Frame	From Day 0 to Month 72

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects for whom data were available.

Arm/Group Title	Cervarix Group	Placebo Group
Arm/Group Description	Subjects received 3 doses of Cervarix vaccine. Cervarix vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.	Subjects received 3 doses of placebo. Placebo was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.
Measure Participants	3026	3025
Count of Participants [Participants]	186 6.1%	185 6.1%

31. Secondary Outcome

Title	Number of Subjects With Medically Significant Conditions Regardless of Causal Relationship to Vaccination and Intensity for Subjects Seronegative and DNA Negative for Both HPV-16 and HPV-18 at Baseline
Description	Medically significant conditions were defined as: adverse events (AEs) prompting emergency room or physician visits that were not (1) related to common diseases or (2) routine visits for physical examination or vaccination, or SAEs that were not related to common diseases. Common diseases included: upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervicovaginal yeast infections, menstrual cycle abnormalities and injury.
Time Frame	From Day 0 to Month 72

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects for whom data were available.

Arm/Group Title	Cervarix Group	Placebo Group
Arm/Group Description	Subjects received 3 doses of Cervarix vaccine. Cervarix vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.	Subjects received 3 doses of placebo. Placebo was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.
Measure Participants	1892	1843
Count of Participants [Participants]	122 4%	110 3.6%

32. Secondary Outcome

Title	Number of Subjects With Medically Significant Conditions Regardless of Causal Relationship to Vaccination and Intensity for Subjects Seropositive and/or DNA Positive for Either HPV-16 or HPV-18 at Baseline
Description	Medically significant conditions were defined as: adverse events (AEs) prompting emergency room or physician visits that were not (1) related to common diseases or (2) routine visits for physical examination or vaccination, or SAEs that were not related to common diseases. Common diseases included: upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervicovaginal yeast infections, menstrual cycle abnormalities and injury.
Time Frame	From Day 0 to Month 72

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects for whom data were available.

Arm/Group Title	Cervarix Group	Placebo Group
Arm/Group Description	Subjects received 3 doses of Cervarix vaccine. Cervarix vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.	Subjects received 3 doses of placebo. Placebo was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.
Measure Participants	1131	1179
Count of Participants [Participants]	64 2.1%	75 2.5%

33. Secondary Outcome

Title	Number of Subjects With Medically Significant Conditions Regardless of Causal Relationship to Vaccination and Intensity for Subjects DNA Positive for Either HPV-16 or HPV-18 at Baseline
Description	Medically significant conditions were defined as: adverse events (AEs) prompting emergency room or physician visits that were not (1) related to common diseases or (2) routine visits for physical examination or vaccination, or SAEs that were not related to common diseases. Common diseases included: upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervicovaginal yeast infections, menstrual cycle abnormalities and injury.
Time Frame	From Day 0 to Month 72

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects for whom data were available.

Arm/Group Title	Cervarix Group	Placebo Group
Arm/Group Description	Subjects received 3 doses of Cervarix vaccine. Cervarix vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.	Subjects received 3 doses of placebo. Placebo was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.
Measure Participants	151	128
Count of Participants [Participants]	10 0.3%	9 0.3%

34. Secondary Outcome

Title	Number of Subjects With Pregnancies and Outcomes of Reported Pregnancies
Description	Outcomes of pregnancies were Live infant NO apparent congenital anomaly (ACA), Live infant CA, Elective termination NO ACA, Elective termination CA, Ectopic pregnancy, Spontaneous abortion NO ACA, Stillbirth NO ACA, Stillbirth CA, Lost to follow up and Pregnancy ongoing.
Time Frame	From Day 0 to Month 72

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects for whom data were available.

Arm/Group Title	Cervarix Group	Placebo Group
Arm/Group Description	Subjects received 3 doses of Cervarix vaccine. Cervarix vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.	Subjects received 3 doses of placebo. Placebo was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.
Measure Participants	837	853
Live infant NO ACA	648 21.4%	657 21.7%
Live infant CA	5 0.2%	0 0%
Elective termination NO ACA	139 4.6%	158 5.2%
Elective termination CA	1 0%	2 0.1%
Ectopic pregnancy	7 0.2%	7 0.2%
Spontaneous abortion NO ACA	16 0.5%	13 0.4%
Stillbirth NO ACA	0 0%	2 0.1%
Stillbirth CA	0 0%	1 0%
Lost to follow up	20 0.7%	13 0.4%
Pregnancy ongoing	1 0%	0 0%

35. Secondary Outcome

Title	Number of Subjects With Pregnancies and Outcomes of Reported Pregnancies for Subjects Seronegative and DNA Negative for Both HPV-16 and HPV-18 at Baseline
Description	Outcomes of pregnancies were Live infant NO apparent congenital anomaly (ACA), Live infant CA, Elective termination NO ACA, Elective termination CA, Ectopic pregnancy, Spontaneous abortion NO ACA, Stillbirth NO ACA, Stillbirth CA, Lost to follow up, Pregnancy ongoing and MIssing.
Time Frame	From Day 0 to Month 72

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects for whom data were available.

Arm/Group Title	Cervarix Group	Placebo Group
Arm/Group Description	Subjects received 3 doses of Cervarix vaccine. Cervarix vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.	Subjects received 3 doses of placebo. Placebo was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.
Measure Participants	555	529
Live infant NO ACA	436 14.4%	411 13.6%
Live infant CA	5 0.2%	0 0%
Elective termination NO ACA	87 2.9%	97 3.2%
Elective termination CA	0 0%	0 0%
Ectopic pregnancy	2 0.1%	3 0.1%
Spontaneous abortion NO ACA	10 0.3%	8 0.3%
Spontaneous abortion CA [Month 24]	0 0%	0 0%
Stillbirth NO ACA	0 0%	1 0%
Stillbirth CA	0 0%	0 0%
Lost to follow up	14 0.5%	9 0.3%
Pregnancy ongoing	1 0%	0 0%
Missing	0 0%	0 0%

36. Secondary Outcome

Title	Number of Subjects With Pregnancies and Outcomes of Reported Pregnancies Seropositive and/or DNA Positive for Either HPV-16 or HPV-18 at Baseline
Description	Outcomes of pregnancies were Live infant NO apparent congenital anomaly (ACA), Live infant CA, Elective termination NO ACA, Elective termination CA, Ectopic pregnancy, Spontaneous abortion NO ACA, Stillbirth NO ACA, Stillbirth CA, Lost to follow up, Pregnancy ongoing and Missing.
Time Frame	From Day 0 to Month 72

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects for whom data were available.

Arm/Group Title	Cervarix Group	Placebo Group
Arm/Group Description	Subjects received 3 doses of Cervarix vaccine. Cervarix vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.	Subjects received 3 doses of placebo. Placebo was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule
Measure Participants	282	324
Live infant NO ACA	212 7%	246 8.1%
Live infant CA	0 0%	0 0%
Elective termination NO ACA	52 1.7%	61 2%
Elective termination CA	1 0%	2 0.1%
Ectopic pregnancy	5 0.2%	4 0.1%
Spontaneous abortion NO ACA	6 0.2%	5 0.2%
Stillbirth NO ACA	0 0%	1 0%
Stillbirth CA	0 0%	1 0%
Lost to follow up	6 0.2%	4 0.1%
Pregnancy ongoing	0 0%	0 0%
Missing	0 0%	0 0%

37. Secondary Outcome

Title	Number of Subjects With Pregnancies and Outcomes of Reported Pregnancies for Subjects DNA Positive for Either HPV-16 or HPV-18 at Baseline
Description	Outcomes of pregnancies were Live infant NO apparent congenital anomaly (ACA), Live infant CA, Elective termination NO ACA, Elective termination CA, Ectopic pregnancy, Spontaneous abortion NO ACA, Stillbirth NO ACA, Stillbirth CA, Lost to follow up and Pregnancy ongoing.
Time Frame	From Day 0 to Month 72

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects for whom data were available.

Arm/Group Title	Cervarix Group	Placebo Group
Arm/Group Description	Subjects received 3 doses of Cervarix vaccine. Cervarix vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.	Subjects received 3 doses of placebo. Placebo was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.
Measure Participants	40	39
Live infant NO ACA	29 1%	26 0.9%
Live infant CA	0 0%	0 0%
Elective termination NO ACA	6 0.2%	12 0.4%
Elective termination CA	1 0%	0 0%
Ectopic pregnancy	3 0.1%	1 0%
Spontaneous abortion NO ACA	0 0%	0 0%
Stillbirth NO ACA	0 0%	0 0%
Stillbirth CA	0 0%	0 0%
Lost to follow up	1 0%	0 0%
Pregnancy ongoing	0 0%	0 0%
Missing	0 0%	0 0%

38. Secondary Outcome

Title	Number of Subjects With HPV-16 Antibody Concentration Equal to or Above the Assay Cut-off Value, by Pre-vaccination Status
Description	HPV-16 assay cut-off value was defined as greater than or equal to (≥) 8 ELISA units per millilitre (EL.U/mL) at PRE vaccination, Month 7, 12 and 24 and ≥ 19 EL.U/mL at Month 36, 48 and 72. Seronegative (Sero-) subjects are subjects who had an antibody concentration below 8 EL.U/mL prior to vaccination. Seropositive (Sero+) subjects are subjects who had an antibody concentration ≥ 8 EL.U/mL prior to vaccination.
Time Frame	at Months 0 (PRE), 7, 12, 24, 36, 48 and 72

Outcome Measure Data

Analysis Population Description

The analysis was performed on the ATP cohort for analysis of immunogenicity, which included all evaluable subjects in the immunogenicity subset for whom data concerning immunogenicity endpoint measures were available at the specified time points.

Arm/Group Title	Cervarix Group	Placebo Group
Arm/Group Description	Subjects received 3 doses of Cervarix vaccine. Cervarix vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.	Subjects received 3 doses of placebo. Placebo was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.
Measure Participants	236	220
≥8 EL.U/mL, sero- [pre-vaccination]	0 0%	0 0%
≥8 EL.U/mL, sero+ [pre-vaccination]	103 3.4%	105 3.5%
≥8 EL.U/mL, sero- [Month 7]	236 7.8%	17 0.6%
≥8 EL.U/mL, sero+ [Month 7]	103 3.4%	97 3.2%
≥8 EL.U/mL, sero-, [Month12]	222 7.3%	39 1.3%
≥8 EL.U/mL, sero+, [Month12]	99 3.3%	93 3.1%
≥8 EL.U/mL, sero-, [Month24]	207 6.8%	31 1%
≥8 EL.U/mL, sero+, [Month24]	94 3.1%	85 2.8%
≥19 EL.U/mL, sero-, [Month 36]	183 6%	4 0.1%
≥19 EL.U/mL, sero+, [Month 36]	76 2.5%	44 1.5%
≥19 EL.U/mL, sero-, [Month 48]	195 6.4%	12 0.4%
≥19 EL.U/mL, sero+, [Month 48]	83 2.7%	48 1.6%
≥19 EL.U/mL, sero-, [Month 72]	153 5.1%	10 0.3%
≥19 EL.U/mL, sero+, [Month 72]	65 2.1%	22 0.7%

39. Secondary Outcome

Title	Number of Subjects With HPV-18 Antibody Concentration Equal to or Above the Assay Cut-off Value, by Pre-vaccination Status
Description	HPV-18 assay cut-off value was defined as ≥ 7 EL.U/mL at PRE vaccination, Month 7, 12 and 24 and ≥ 18 EL.U/mL at Month 36, 48 and 72. Seronegative (Sero-) subjects are subjects who had an antibody concentration below 7 EL.U/mL and 18 EL.U/mL prior to vaccination. Seropositive (Sero+) subjects are subjects who had an antibody concentration ≥ 7 EL.U/mL and 18 EL.U/mL prior to vaccination.
Time Frame	at Months 0 (PRE), 7, 12, 24, 36, 48 and 72

Outcome Measure Data

Analysis Population Description

The analysis was performed on the ATP cohort for analysis of immunogenicity, which included all evaluable subjects in the immunogenicity subset for whom data concerning immunogenicity endpoint measures were available at the specified time points.

Arm/Group Title	Cervarix Group	Placebo Group
Arm/Group Description	Subjects received 3 doses of Cervarix vaccine. Cervarix vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.	Subjects received 3 doses of placebo. Placebo was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.
Measure Participants	279	278
≥ 7 EL.U/mL, sero- PRE	0 0%	0 0%
≥ 7 EL.U/mL, sero+ PRE	60 2%	47 1.6%
≥ 7 EL.U/mL, sero- [Month 7]	278 9.2%	14 0.5%
≥ 7 EL.U/mL, sero+ [Month 7]	60 2%	39 1.3%
≥ 7 EL.U/mL, sero- [Month 12]	263 8.7%	34 1.1%
≥ 7 EL.U/mL, sero+ [Month 12]	57 1.9%	32 1.1%
≥ 7 EL.U/mL, sero- [Month 24]	249 8.2%	63 2.1%
≥ 7 EL.U/mL, sero+ [Month 24]	51 1.7%	33 1.1%
≥ 18 EL.U/mL, sero- [Month 36]	218 7.2%	13 0.4%
≥ 18 EL.U/mL, sero+ [Month 36]	41 1.4%	22 0.7%
≥ 18 EL.U/mL, sero- [Month 48]	231 7.6%	14 0.5%
≥ 18 EL.U/mL, sero+ [Month 48]	47 1.6%	23 0.8%
≥ 18 EL.U/mL, sero- [Month 72]	183 6%	14 0.5%
≥ 18 EL.U/mL, sero+ [Month 72]	37 1.2%	19 0.6%

40. Secondary Outcome

Title	Geometric Mean Titers for HPV-16/HPV-18 Antibodies, by Pre-vaccination Status
Description	Titers were expressed as geometric mean titers calculated on all subjects, HPV-16 assay cut-off value was defined as greater than or equal to 8 EL.U/mL at Months 0, 7, 12 and 24 and greater than or equal to 19 EL.U/mL at Months 36, 48 and 72. HPV-18 assay cut-off value was defined as ≥ 7 EL.U/mL at Month 0, 7, 12 and 24 and ≥ 18 EL.U/mL at Months 36, 48 and 72. Seronegative (Sero-) subjects are subjects who had an antibody concentration below the assay cut-off value prior to vaccination. Seropositive (Sero+) subjects are subjects who had an antibody concentration ≥ the assay cut-off value prior to vaccination.
Time Frame	at Months 0 (PRE), 7, 12, 24, 36, 48 and 72

Outcome Measure Data

Analysis Population Description

The analysis was performed on the ATP cohort for analysis of immunogenicity, which included all evaluable subjects in the immunogenicity subset for whom data concerning immunogenicity endpoint measures were available at the specified time points.

Arm/Group Title	Cervarix Group	Placebo Group
Arm/Group Description	Subjects received 3 doses of Cervarix vaccine. Cervarix vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.	Subjects received 3 doses of placebo. Placebo was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.
Measure Participants	279	362
HPV-16, sero- [pre-vaccination]	4.0	4.0
HPV-16, sero- [Month 7]	6964.3	4.6
HPV-16, sero-, [Month 12]	3451.3	5.0
HPV-16, sero-, [Month 24]	1253.2	4.7
HPV-16, sero-, [Month 36]	1074.6	9.8
HPV-16, sero-, [Month 48]	828.4	10.7
HPV-16, sero-, [Month 72]	678.1	10.5
HPV-16, sero+ [pre-vaccination]	27.4	25.2
HPV-16, sero+ [Month 7]	5672.0	25.6
HPV-16, sero+, [Month 12]	3219.8	28.5
HPV-16, sero+, [Month 24]	1317.7	19.7
HPV-16, sero+, [Month 36]	1290.3	24.6
HPV-16, sero+, [Month 48]	1006.0	25.1
HPV-16, sero+, [Month 72]	724.4	17.3
HPV-18, sero- [pre-vaccination]	3.5	3.5
HPV-18, sero- [Month 7]	3357.4	3.9
HPV-18, sero-, [Month 12]	1318.9	4.2
HPV-18, sero-, [Month 24]	711.7	5.0
HPV-18, sero-, [Month 36]	525.1	9.7
HPV-18, sero-, [Month 48]	387.7	9.8
HPV-18, sero-, [Month 72]	343.7	10.1
HPV-18, sero+ [pre-vaccination]	19.9	25.8
HPV-18, sero+ [Month 7]	3200.2	24.2
HPV-18, sero+, [Month 12]	1152.9	20.2
HPV-18, sero+, [Month 24]	831.6	21.9
HPV-18, sero+, [Month 36]	601.8	33.4
HPV-18, sero+, [Month 48]	523.0	25.5
HPV-18, sero+, [Month 72]	420.0	28.3

Adverse Events

Time Frame	SAEs: up to Month 72. Unsolicited AEs: Within Days 0-29 after vaccination. Solicited local and general symptoms: Within 7 days (Days 0-6) after vaccination
Adverse Event Reporting Description	Safety data presented here were assessed for all vaccinated subjects for whom data were available at the time of the event-triggered analysis irrespective of the initial (Month 0) HPV-16 or HPV-18 serostatus and DNA status.
Arm/Group Title	Cervarix Group		Placebo Group
Arm/Group Description	Subjects received 3 doses of Cervarix vaccine. Cervarix vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.		Subjects received 3 doses of placebo. Placebo was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.
All Cause Mortality
	Cervarix Group		Placebo Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3026 (0%)		3/3025 (0.1%)
Serious Adverse Events
	Cervarix Group		Placebo Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	56/3026 (1.9%)		81/3025 (2.7%)
Blood and lymphatic system disorders
Anaemia	1/3026 (0%)		0/3025 (0%)
Hypersplenism	0/3026 (0%)		1/3025 (0%)
Cardiac disorders
Myocarditis	0/3026 (0%)		1/3025 (0%)
Supraventricular tachycardia	1/3026 (0%)		0/3025 (0%)
Congenital, familial and genetic disorders
Cleft lip and palate	2/3026 (0.1%)		0/3025 (0%)
Congenital torticollis	2/3026 (0.1%)		0/3025 (0%)
Atrial septal defect	1/3026 (0%)		0/3025 (0%)
Chondrodystrophy	1/3026 (0%)		0/3025 (0%)
Pulmonary hypoplasia	0/3026 (0%)		1/3025 (0%)
Trisomy 21	0/3026 (0%)		1/3025 (0%)
Gastrointestinal disorders
Cholelithiasis	0/3026 (0%)		2/3025 (0.1%)
Anal fissure	0/3026 (0%)		1/3025 (0%)
Diaphragmatic hernia	0/3026 (0%)		1/3025 (0%)
Gastritis	0/3026 (0%)		1/3025 (0%)
Gastrointestinal disorder	0/3026 (0%)		1/3025 (0%)
Intra-abdominal haemorrhage	1/3026 (0%)		0/3025 (0%)
General disorders
Ectopic pregnancy	6/3026 (0.2%)		6/3025 (0.2%)
Ectopic pregnancy with intrauterine device	1/3026 (0%)		1/3025 (0%)
Cyst	0/3026 (0%)		1/3025 (0%)
Hepatobiliary disorders
Cholecystitis chronic	0/3026 (0%)		1/3025 (0%)
Infections and infestations
Appendicitis	4/3026 (0.1%)		12/3025 (0.4%)
Chronic tonsillitis	0/3026 (0%)		2/3025 (0.1%)
Neonatal pneumonia	1/3026 (0%)		1/3025 (0%)
Erysipelas	0/3026 (0%)		1/3025 (0%)
Pelvic infection	0/3026 (0%)		1/3025 (0%)
Pelvic inflammatory disease	1/3026 (0%)		0/3025 (0%)
Rhinitis	0/3026 (0%)		1/3025 (0%)
Injury, poisoning and procedural complications
Comminuted fracture	0/3026 (0%)		3/3025 (0.1%)
Concussion	0/3026 (0%)		2/3025 (0.1%)
Abdominal injury	1/3026 (0%)		0/3025 (0%)
Ankle fracture	0/3026 (0%)		1/3025 (0%)
Craniocerebral injury	1/3026 (0%)		0/3025 (0%)
Fibula fracture	0/3026 (0%)		1/3025 (0%)
Hand fracture	1/3026 (0%)		0/3025 (0%)
Iris injury	1/3026 (0%)		0/3025 (0%)
Laceration	1/3026 (0%)		0/3025 (0%)
Lumbar vertebral fracture	1/3026 (0%)		0/3025 (0%)
Muscle rupture	1/3026 (0%)		0/3025 (0%)
Post procedural haemorrhage	1/3026 (0%)		0/3025 (0%)
Road traffic accident	0/3026 (0%)		1/3025 (0%)
Soft tissue injury	1/3026 (0%)		0/3025 (0%)
Wound	1/3026 (0%)		0/3025 (0%)
Metabolism and nutrition disorders
Hypoproteinaemia	1/3026 (0%)		1/3025 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Thyroid cancer	0/3026 (0%)		1/3025 (0%)
Papillary thyroid cancer	1/3026 (0%)		1/3025 (0%)
Teratoma	1/3026 (0%)		1/3025 (0%)
Adenoma benign	0/3026 (0%)		1/3025 (0%)
Angiomyolipoma	0/3026 (0%)		1/3025 (0%)
Benign gastric neoplasm	0/3026 (0%)		1/3025 (0%)
Brain neoplasm	1/3026 (0%)		0/3025 (0%)
Breast fibroma	0/3026 (0%)		1/3025 (0%)
Gastric neoplasm	0/3026 (0%)		1/3025 (0%)
Pituitary tumour	1/3026 (0%)		0/3025 (0%)
Nervous system disorders
Haemorrhage intracranial	1/3026 (0%)		2/3025 (0.1%)
Hydrocephalus	0/3026 (0%)		1/3025 (0%)
Subarachnoid haemorrhage	1/3026 (0%)		0/3025 (0%)
Pregnancy, puerperium and perinatal conditions
Abortion missed	5/3026 (0.2%)		3/3025 (0.1%)
Abortion spontaneous	5/3026 (0.2%)		3/3025 (0.1%)
Abortion spontaneous complete	2/3026 (0.1%)		5/3025 (0.2%)
Premature baby	1/3026 (0%)		5/3025 (0.2%)
Umbilical cord around neck	1/3026 (0%)		2/3025 (0.1%)
Foetal death	1/3026 (0%)		1/3025 (0%)
Low birth weight baby	1/3026 (0%)		1/3025 (0%)
Premature separation of placenta	2/3026 (0.1%)		0/3025 (0%)
Stillbirth	0/3026 (0%)		2/3025 (0.1%)
Abortion	0/3026 (0%)		1/3025 (0%)
Abortion spontaneous incomplete	0/3026 (0%)		1/3025 (0%)
Abortion threatened	1/3026 (0%)		0/3025 (0%)
Blighted ovum	1/3026 (0%)		0/3025 (0%)
Foetal distress syndrome	1/3026 (0%)		0/3025 (0%)
Gestational diabetes	0/3026 (0%)		1/3025 (0%)
Gestational hypertension	0/3026 (0%)		1/3025 (0%)
Imminent abortion	1/3026 (0%)		0/3025 (0%)
Placental insufficiency	1/3026 (0%)		0/3025 (0%)
Pre-eclampsia	0/3026 (0%)		1/3025 (0%)
Psychiatric disorders
Completed suicide	0/3026 (0%)		2/3025 (0.1%)
Renal and urinary disorders
IgA nephropathy	1/3026 (0%)		0/3025 (0%)
Renal disorder	0/3026 (0%)		1/3025 (0%)
Urethral cyst	0/3026 (0%)		1/3025 (0%)
Reproductive system and breast disorders
Breast cyst	1/3026 (0%)		1/3025 (0%)
Ovarian cyst ruptured	1/3026 (0%)		1/3025 (0%)
Ovarian cyst torsion	1/3026 (0%)		1/3025 (0%)
Ovarian cyst	2/3026 (0.1%)		1/3025 (0%)
Cervical dysplasia	0/3026 (0%)		1/3025 (0%)
Pelvic adhesions	1/3026 (0%)		0/3025 (0%)
Uterine cyst	0/3026 (0%)		1/3025 (0%)
Uterine polyp	1/3026 (0%)		0/3025 (0%)
Respiratory, thoracic and mediastinal disorders
Neonatal respiratory distress syndrome	1/3026 (0%)		1/3025 (0%)
Asphyxia	1/3026 (0%)		0/3025 (0%)
Surgical and medical procedures
Abortion induced	1/3026 (0%)		2/3025 (0.1%)
Amputation	1/3026 (0%)		0/3025 (0%)
Vascular disorders
Vascular rupture	0/3026 (0%)		1/3025 (0%)
Other (Not Including Serious) Adverse Events
	Cervarix Group		Placebo Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2786/3026 (92.1%)		2548/3025 (84.2%)
Gastrointestinal disorders
Gastrointestinal	409/3005 (13.6%)		473/3001 (15.8%)
General disorders
Pain	2634/3005 (87.7%)		2166/3001 (72.2%)
Swelling	853/3005 (28.4%)		408/3001 (13.6%)
Fatigue	1142/3005 (38%)		1018/3001 (33.9%)
Pyrexia	749/3005 (24.9%)		703/3001 (23.4%)
Infections and infestations
Upper respiratory tract infection	276/3026 (9.1%)		290/3025 (9.6%)
Musculoskeletal and connective tissue disorders
Arthralgia	270/3005 (9%)		213/3001 (7.1%)
Myalgia	523/3005 (17.4%)		360/3001 (12%)
Nervous system disorders
Headache	691/3005 (23%)		690/3001 (23%)
Skin and subcutaneous tissue disorders
Erythema	838/3005 (27.9%)		517/3001 (17.2%)

Limitations/Caveats

At the time of the event-triggered analysis at Month 24, some safety results remain blinded and are not presented here since the study is still ongoing. These results will be updated once they become available.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.