Trial Information

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

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.