Adenocarcinoma of the Uterine Cervix and HPV
Study Details
Study Description
Brief Summary
The present study will mainly aim to review and characterize the pathologic features, treatment options, and follow-up outcomes of women with in situ/microinvasive adenocarcinoma of the uterine cervix according to HPV status (positive versus negative high-risk HPV). It will evaluate the impact of HPV status on the recurrence and survival during a follow-up of five years. The present study will be a multi-institutional study including several oncological Italian Centers. Data will be retrospectively collected from January 2012 to December 2016 with a total follow-up of 5 years.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Detailed Description
The incidence of cervical cancer in developed countries declined considerably in the last few decades. This has been possible for efficient screening programs to which HPV vaccines have been added over the past 15 years. Despite this global reduction in cervical lesions, the incidence of adenocarcinoma of the uterine cervix (AC) increases in invasive and in situ stages. This increase mainly affects women aged 30-40, with an incidence of 11.2 per 100.000 women. On the contrary, the squamous histological lesions revealed an increase in the incidence of in situ lesions and a concomitant reduction of invasive stages. These data would seem to suggest a delay in the diagnosis of cervical glandular lesions, a shorter interval of disease progression from the adenocarcinoma in situ (AIS) to infiltrating stages, or a different process of carcinogenesis.
Most glandular cervical lesions occur at an early stage. The standard of treatment for in situ or micro-invasive lesions is extra fascial hysterectomy (AIS or stage 1A1 with no LVSI) or modified radical hysterectomy with pelvic lymph node dissection (stage 1A1 with LVSI, or 1A2). In fertility-sparing treatment, conization or radical trachelectomy with pelvic lymph node dissection is an option.
Another aspect that differentiates cervical adenocarcinoma from squamous lesions is the link with HPV infection. In 2018, the International Endocervical Criteria and Classification categorized cervical glandular lesions into HPV-associated and non-HPV-associated AC. Unlike cervical squamous lesions, which are almost all linked to high-risk HPV types, AC can be HPV negative in up to 15-20% of cases. The HPV 18 genotype is the most represented in AC with a rate of 38-50% in AIS and 50% in invasive stages. Based on some studies, it appears that non-HPV-related lesions have worse outcomes. This can significantly impact screening programs where 14 high-risk HPVs are tested.
In a recent study including 341 surgical specimens of AC, 100% of non-HPV-related lesions were classified as Silva Pattern C (the worst prognostic pattern). Instead, no impact of the HPV genotype was found on 113 women with AC during a follow-up of 5 years. HPV 45 showed a shorter 5-year survival than HPV 16 or 18.
While for advanced lesions, the stage itself represents the most important prognostic factor of recurrence or survival, in situ or micro-invasive lesions may represent the best target for evaluating other prognostic factors.
Give the pivotal role of HPV testing in screening programs, availability of large multicenter studies on HPV-type related AC will provide more robust evidence regarding screening policies and hence, improve prevention, treatment and follow-up outcome and prognosis of an increasing cervical pathology.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Positive high-risk HPV Women with adenocarcinoma of the uterine cervix and positive for high-risk HPV (genotype16/18/31/33/35/39/45/51/52/56/58/59/66/68). |
Procedure: Conization and/or Hysterectomy
Women undergoing loop electrosurgical excision procedure or simple/modified/radical hysterectomy
|
| Negative high-risk HPV Women with adenocarcinoma of the uterine cervix and negative for high-risk HPV (genotype16/18/31/33/35/39/45/51/52/56/58/59/66/68). |
Procedure: Conization and/or Hysterectomy
Women undergoing loop electrosurgical excision procedure or simple/modified/radical hysterectomy
|
Outcome Measures
Primary Outcome Measures
- Overall recurrence at 1 year in HPV positive vs HPV negative women [At 1 years]
Number of women who have recurrence after treatment divided by total number of patients at onset
- Overall recurrence at 3 years in HPV positive vs HPV negative women [At 3 years]
Number of women who have recurrence after treatment divided by total number of patients at onset
- Overall recurrence at 5 year in HPV positive vs HPV negative women [At 5 years]
Number of women who have recurrence after treatment divided by total number of patients at onset
- Overall survival at 5 year in HPV positive vs HPV negative women [At 5 years]
Number of women who are alive after treatment divided by total number of patients at onset
- Rate of histological outcomes (Usual type, Villoglandular, Mucinous-NOS, Mucinous-intestinal, Invasive stratified mucin-producing, Micropapillary, 'Serous'-like, Gastric type, Clear cell, Mesonephric, Endometrioid) in HPV positive vs HPV negative women [at enrollment]
Number of women with specific histological findings in HPV positive vs HPV negative patients
- Rate of colposcopic features (negative colposcopy, minor colposcopic changes, major colposcopic changes) in HPV positive vs HPV negative women [at enrollment]
Number of women with specific colposcopic findings in HPV positive vs HPV negative patients
- Treatment modality rate (conization, hysterectomy) in HPV positive vs HPV negative women [at enrollment]
Number of women undergoing conization or hysterectomy in HPV positive vs HPV negative patients
Secondary Outcome Measures
- Overall recurrence at 1 year in HPV-16/18 vs non-HPV-16/18 positive women [At 1 years]
Number of women who have recurrence after treatment divided by total number of patients at onset
- Overall recurrence at 3 years in HPV-16/18 vs non-HPV-16/18 positive women [At 3 years]
Number of women who have recurrence after treatment divided by total number of patients at onset
- Overall recurrence at 5 year in HPV-16/18 vs non-HPV-16/18 positive women [At 5 years]
Number of women who have recurrence after treatment divided by total number of patients at onset
- Overall survival at 5 year in HPV-16/18 vs non-HPV-16/18 positive women [At 5 years]
Number of women who are alive after treatment divided by total number of patients at onset
Eligibility Criteria
Criteria
Inclusion Criteria:
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Women with in-situ or microinvasive (stage 1A) adenocarcinoma of the uterine cervix undergoing conization or hysterectomy, between January 2012 and December 2016.
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Women with HPV testing within 2 months before conization.
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Women should be diagnosed and managed by the corresponding center.
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Patients with adequate clinical and pathological data.
Exclusion Criteria:
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Women with previous cervical treatments.
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Women with immunological disease (e.g. HIV).
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Unavailable HPV genotyping or testing before surgery.
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Women with inadequate follow-up.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Università Politecnica delle Marche
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- AC-HPV2