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

This study is currently recruiting participants.
Verified June 2013 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00867464
First received: March 20, 2009
Last updated: March 14, 2014
Last verified: June 2013
  Purpose

Background:

  • Human papillomavirus (HPV) infection is necessary for the development of cervical cancer. Worldwide, infection with HPV types 16 and 18 accounts for approximately 70 percent of cervical cancer cases. Available data suggest that prophylactic vaccination against HPV types 16 and 18 is nearly 100 percent effective in preventing persistent cervical infections and resultant disease from these types for at least 5 years following vaccination. This study is extension of a 2004 study in which 7,466 women in Costa Rica were randomized into vaccinated and control groups. The study described here proposes to extend follow-up of women recruited into this trial and vaccinated with the HPV-16/18 vaccine at the start of CVT for up to an additional 6 years, for a total of up to 10 years of follow-up. We expect to provide the HPV-16/18 vaccine to women in the control arm of the trial after the initial 4 years of follow-up are completed, and propose to follow them for an additional period as well. We will also enroll and follow a new group of approximately 3000 women who will be followed with state-of-the-art screening and will serve as an unvaccinated control group (UCG) during the extended follow-up period.

Objectives:

  • To evaluate the 10-year global impact of HPV-16/18 vaccination of young adult women.
  • To evaluate determinants of the immune response to HPV and the vaccine and markers of long-term protection.
  • To evaluate the natural history of HPV and cervical disease in vaccinated and unvaccinated populations.

Eligibility:

  • Participants in the original 2004 study who lived in the Guanacaste province and few areas of Puntarenas close to Guanacaste will be eligible for the 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 also be invited for additional follow-up. Newly recruited controls (3,000) will be matched to the participants of the original study. Women in the original study were born between July 1978 and November 1987, lived in Guanacaste or nearby Puntarenas province, and had no history of cervical cancer or hysterectomy.

Design:

  • At enrollment, newly recruited controls will receive extensive screening and treatment for cervical neoplasia.
  • All women (vaccinated and controls) will be followed at 2-year intervals for up to 6 years. Questionnaire data will be collected. Pelvic examinations will be performed at each visit. Cervical secretions and cells will be collected. Women with evidence of cervical abnormalities will have accelerated screening and will be referred to colposcopy for evaluation and treatment if needed.
  • A subset of women will have extra clinic visits and extra blood and saliva samples collected to allow study of the immune response to the vaccine and to the disease itself.

Condition
Cervical Neoplasia
HPV Infections

Study Type: Observational
Official Title: Extended Follow-up of Young Women in Costa Rica Who Received Vaccination Against Human Papillomavirus Types 16 and 18 and Unvaccinated Controls

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Infection with cervical, oral, vulvar and anal HPV, development of cervical neoplasia

Estimated Enrollment: 10000
Study Start Date: March 2009
Detailed Description:

Human papillomavirus (HPV) infection is necessary for the development of cervical cancer. Worldwide, infection with HPV types 16 and 18 account for approximately 70% of cervical cancer cases. Currently available data suggest that prophylactic vaccination against HPV types-16 and 18 is nearly 100% effective in preventing persistent cervical infections and resultant disease from these types for at least five years following vaccination. Intramural NCI and a group of Costa Rican investigators have had long-time involvement in studies to elucidate the natural history of HPV and cervical cancer, and in the development of prophylactic HPV vaccines. In 2004, we initiated a community-based randomized clinical trial in Costa Rica to evaluate the safety and efficacy of a bivalent virus-like particle HPV-16/18 vaccine. The study successfully randomized 7,466 women; active follow-up of these women is underway and is planned for 4 years. Herein, we propose to extend follow-up of women recruited into this trial and vaccinated with the HPV- 16/18 vaccine at the start of CVT for up to an additional 6 years, for a total of up to 10 years of follow-up. We expect to provide the HPV-16/18 vaccine to women in the control arm of the trial after the initial 4 years of follow-up are completed, and propose to follow them for an additional 2 years, to monitor vaccine safety and to maximize detection of persistent infections and lesions resultant from HPV exposure that occurred before cross-over to the HPV vaccination (a subset of these women will be followed for the entire 10 years). We will also enroll and follow a new group of approximately 3000 women who will be followed with state-of-the-art screening and will serve as an unvaccinated control group (UCG) during the extended follow-up period. Women will be screened at two year intervals. Women with evidence of cervical abnormalities will have accelerated screening and will be referred to colposcopy for evaluation and treatment if needed. Questionnaires and biological specimens collected during this follow-up period will allow for many unique scientific and women's health questions to be addressed.

There are three overarching objectives for this effort. They are as follows:

  1. To evaluate the 1 O-year global impact of HPV-16/18 vaccination of young adult women;
  2. To evaluate determinants of the immune response to HPV and the vaccine, and markers of long-term protection; and,
  3. To evaluate the natural history of HPV and cervical disease in vaccinated and unvaccinated populations.

This research will provide invaluable data that will allow for the continued investigation into the risks and benefits of the prophylactic HPV vaccine.

  Eligibility

Ages Eligible for Study:   20 Years to 32 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:
  • Gender: Female
  • Age: Women born in or between July 1978 and November 1987
  • Residence: Residents of Guancaste Province and a few areas of Puntarenas closest to Guanacaste at some point during 2005
  • Language: Able to speak/understand Spanish
  • Mental Competence: Apparently mentally competent
  • Consent: Written informed consent obtained prior to enrollment

EXCLUSION CRITERIA:

The following criteria will be checked at the time of enrollment for potential participants of the unvaccinated control group. If any apply, the participant will not be included in the study.

  • 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 expect ed to have received these vaccines at the time of enrollment. Use of these vaccines after enrollment is not a criteria 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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00867464

Contacts
Contact: Allan Hildesheim, Ph.D. (301) 451-3984 hildesha@exchange.nih.gov

Locations
United States, Maryland
National Cancer Institute (NCI), 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: Allan Hildesheim, Ph.D.    301-451-3984    hildesha@exchange.nih.gov   
Sponsors and Collaborators
Investigators
Principal Investigator: Allan Hildesheim, Ph.D. National Cancer Institute (NCI)