Extended Follow Up of Young Women in Costa Rica Who Received Vaccine for Human Papillomavirus Types 16 and 18 and Unvaccinated Controls

Study Overview
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Brief Summary
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This research trial studies extended follow up of young women in Costa Rica who received vaccine for human papillomavirus types 16 and 18 and unvaccinated controls. Collecting information from young women in Costa Rica who have received vaccine for human papillomavirus types 16 and 18 and a new group of unvaccinated controls enrolled for the follow-up period, may help doctors learn more about the risks and benefits of prophylactic human papillomavirus vaccine.

Detailed Description
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PRIMARY OBJECTIVES: I. To evaluate the 10-year global impact of human papillomavirus (HPV)-16/18 vaccination of young adult women. II. To evaluate determinants of the immune response to HPV and the vaccine, and markers of long-term protection. III. To evaluate the natural history of HPV and cervical disease in vaccinated and unvaccinated populations. OUTLINE: Participants undergo long term follow-up comprising risk factor questionnaire, pelvic examination for all sexually experienced women, and specimen collection at years 6, 8, and 10.

Official Title
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Extended Follow-Up of Young Women in Costa Rica Who Received Vaccination Against Human Papillomavirus Types 16 and 18 and Unvaccinated Controls

Conditions
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Anal Carcinoma, Cervical Carcinoma, Human Papillomavirus Infection, Human Papillomavirus-Related Cervical Carcinoma, Oral Cavity Carcinoma

Intervention / Treatment
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* Other: Cytology Specimen Collection Procedure
* Other: Laboratory Biomarker Analysis
* Other: Long-term Follow-up
* Other: Questionnaire Administration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women who participated in the Costa Rica Vaccine Trial (CVT) and lived in the Guanacaste province and a few areas of Puntarenas closest to Guanacaste will be eligible for the long-term follow up LTFU study Women who received the HPV-16/18 vaccine at the start of CVT will be invited for up to 6 years of additional follow-up, and women who were originally in the control arm of CVT and were offered the HPV-16/18 vaccine at crossover will be invited for an additional 2 years of follow-up A subset of the control arm women who are in the crossover immunogenicity subcohort will be followed the full 6 years Some women who received HPV vaccination and were not invited into the LTFU protocol (stopped attending their screening visits during CVT, discontinued their study participation during CVT or lived outside the study area) will be invited to participate in the LTFU protocol, particularly those who received an incomplete vaccination schedule UNVACCINATED CONTROL GROUP: Born in or between July 1978 and November 1987 Residents of Guanacaste Province and a few areas of Puntarenas closest to Guanacaste at some point during 2005 Able to speak/understand Spanish Apparently mentally competent Written informed consent obtained prior to enrollment Exclusion Criteria: History of cervical cancer History of hysterectomy Any important medical condition or other criteria that the investigator considers that precludes enrollment Vaccination with Gardasil or Cervarix will be an exclusionary criterion, but few women are expected to have received these vaccines at the time of enrollment; use of these vaccines after enrollment is not a criterion for study interruption but we plan to collect information on vaccination history so that the few women who report having been vaccinated with one of the HPV vaccines after enrollment can be evaluated separately at analysis
Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Observational (long term follow-up)<br>Participants undergo long term follow-up comprising risk factor questionnaire, pelvic examination for all sexually experienced women, and specimen collection at years 6, 8, and 10. | Other: Cytology Specimen Collection Procedure<br>* Correlative studies<br>* Other names: Cytologic Sampling;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Other: Long-term Follow-up<br>* Undergo extended follow-up<br>* Other names: LTFU;Other: Questionnaire Administration<br>* Ancillary studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative rate of cervical intraepithelial neoplasia 3 (CIN3) | Both absolute rate differences and percent reduction in rates will be evaluated. | At 10 years | 
| Level of immune response markers as prediction of long-term success of HPV vaccine | For efficiency, a nested case-control approach is envisioned to evaluate this question. We propose to compare women who become infected against a subset of those who do not (non-failures) with respect to immune response markers of interest. | Up to 10 years | 
| Increase in the rate of cervical lesions associated with other carcinogenic HPV types that the vaccine does not protect against from prevention of HPV-16/18 associated cervical lesions through vaccination | The 10-year cumulative rate of incident CIN2+ associated with HPV types other than HPV-16/18 and closely related HPV types in the alpha-7/9 species for which evidence of vaccine cross-protection is demonstrated will be compared between vaccinated and unvaccinated women. | Up to 10 years |