Natural History of HPV From Infection to Neoplasia in Adolescents and Young Women

Study Details

Study Description

Brief Summary

The natural history of human papillomavirus (HPV) is most likely influenced by both innate and adaptive mucosal immunity. More specifically, we hypothesize that Toll like receptors (TLR) play an important role in cervical innate immunity to HPV through secretions of proinflammatory, chemotactic and anti-viral cytokines. Up-regulated TLR expression will also result in activation of dendritic cells and T cells that in turn will promote a T helper (Th) l like response through secretion of several cytokines and consequently, the induction of a successful cell mediated immune (CMI) response.

Condition or Disease	Intervention/Treatment	Phase
Human Papillomavirus CIN 2 CIN 3

Detailed Description

The natural history of HPV is most likely influenced by both innate and adaptive mucosal immunity. More specifically, we hypothesize that Toll like receptors (TLRs) play an important role in cervical innate immunity to HPV through secretions of proinflammatory, chemotactic and anti-viral cytokines. Up-regulated TLR expression will also result in activation of dendritic cells and T cells that in turn will promote a Thl like response through secretion of several cytokines and consequently, the induction of a successful cell mediated immune (CMI) response.

We propose to: 1) examine, in cervical cell samples, the association among TRL expression, TRL-associated cytokines that mediate innate immunity and clearance of incident HPV infection; 2) examine, in cervical cell samples, the association among TRL expression, TRL-associated cytokines that induce and mediate adaptive immunity and HPV clearance; and 3) examine the association among TLR induced Th-1 responses measured in cervical cell samples, HPV specific CMI responses detected in peripheral blood (PB) and HPV clearance. Adolescent and young women who were a) entered into the cohort during the initial 1990-1995 period and have continued to be followed and b) entered into the cohort during the last recruitment wave (2000-2005) will be asked to continue followup for an additional five years (2005-2010). These women will have been well characterized at the time of the initiation of this study with HPV at their entry visit and 4-month interval sampling for HPV DNA, cytology, bacterial vaginosis, colpophotographs (assessment of cervical maturation), C. trachomatis and N. gonorrhea testing, cervical cell cytokines by reverse transcriptase polymerase chain reaction (RT-PCR) and peripheral blood (PB) CMI for HPV 16 positive women. Women will be continued to be characterized for the above at the same intervals through-out the follow-up. Measures of innate and adaptive immunity by RT PCR using cervical cells and by Luminex technology have been added to the same 4 month interval testing as HPV DNA, cytology and other cervical cytokines described. Women positive for HPV 16 will get additional blood for CMI using Interferon (IFN)-y Enzyme linked immunospot (EliSpot) technique for detection of anti-E6 and E7 responses. We also examine the natural history of anal HPV in these women. We acknowledge that this design simplifies the pleiotropic nature of cytokines. However, we feel that this model reflects plausible mechanisms involved in HPV control and is feasible to test in our cohort. Information garnered from this type of study will be critical in developing vaccine strategies and therapies as well as illuminating immune responses developed in the mucosal epithelium.

Study Design

Study Type:

Observational

Actual Enrollment :

900 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Natural History of Human Papillomavirus From Infection to Neoplasia in Adolescents and Young Women - Effect of Tobacco on Cervical Neoplasia in Young Women

Study Start Date :

Dec 1, 1987

Actual Primary Completion Date :

May 1, 2016

Actual Study Completion Date :

May 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
HPV Cohort Sexually active young women aged 12 to 22 years of age without a previous history of CIN. Women are not eligible for entry if pregnant or known immunosuppression.

Outcome Measures

Primary Outcome Measures

Cervical Intraepithelial neoplasia (CIN) 2/3 [1990 to current]
Observational study of women with HPV

Secondary Outcome Measures

HPV persistence [1990 to present]
observational study of women with HPV

Eligibility Criteria

Criteria

Ages Eligible for Study:

13 Years to 22 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

Inclusion:

Age 12 to 22 years
Sexually active less than 6 years
Received one dose of the HPV vaccine

Exclusion:

Planning on moving in 3 years
Prior history of treatment for CIN
Immunocompromised (ie transplant patient, HIV)
Pregnant

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	SFSU Student Health Center	San Francisco	California	United States	94132
2	HPV Study - San Leandro Office	San Leandro	California	United States	94577

Sponsors and Collaborators

University of California, Los Angeles
National Institutes of Health (NIH)
National Cancer Institute (NCI)

Investigators

Principal Investigator: Anna-Barbara Moscicki, MD, University of California, San Francisco

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

University of California, Los Angeles

ClinicalTrials.gov Identifier:

NCT01366742

Other Study ID Numbers:

11-05580
R37CA051323

First Posted:

Jun 6, 2011

Last Update Posted:

May 17, 2016

Last Verified:

May 1, 2016

Additional relevant MeSH terms:

Neoplasms

Study Results

No Results Posted as of May 17, 2016