Trial Information

Crossover Vaccination of Women Previously Randomized Into Protocol 04-C-N191(NCI)/IC-200403(INCIENSA)

Since the mid 1980's, the Division of Cancer Epidemiology and Genetics of the National
Cancer Institute in collaboration with investigators in Costa Rica has conducted studies
regarding cervical cancer and HPV infection. The first effort was a case control study
where Costa Rica was one of the Latin American countries included, and it was the first
large epidemiological study to show the association between HPV and cervical cancer. The
second study, consisting of a 10,049 women population-based cohort, the Guanacaste cohort,
was carried out from 1993 until 2004, and has greatly contributed to the understanding of
the natural history of HPV infection and its relationship with precancerous cervical
lesions.

The profound knowledge of the natural history of HPV infection and cervical neoplasia in
Guanacaste, Costa Rica together with the promising results of the different HPV vaccine
trials led the National Cancer Institute, in collaboration with investigators in Costa Rica,
to launch a community-based randomized phase III clinical trial to evaluate the efficacy of
a virus-like particle HPV vaccine (henceforth referred to as the Costa Rica Vaccine Trial
(CVT)).

The main objectives of the Costa Rica Vaccine Trial were to evaluate the efficacy of the
candidate vaccine to prevent persisting HPV-16/18 infections and related histopathologically
confirmed CIN2+ lesions among the according to protocol subcohort and the overall population
enrolled in the study. In contrast, the objectives of this protocol are aimed at offering
beneficial complementary vaccination to women enrolled in the trial with an additional
objective to collect biological specimens from women receiving the HPV-16/18 vaccine to
complement the information obtained during the masked phase of the trial. As an additional
objective, we propose to collect information regarding exposure to known and suspected risk
factors for HPV infection and cervical cancer and biological specimens during this crossover
phase that will complement those collected during the masked phase of the Costa Rica Vaccine
Trial.

Collection of risk factor information and biological specimens during this crossover phase
will be restricted to women receiving vaccination against HPV 16/18 at crossover. These
samples will permit a more complete and comprehensive evaluation of the vaccine
immunogenicity. Also, those specimens will allow for ancillary analyses and studies (e.g.,
natural history of HPV infection acquisition/clearance) and to assist ongoing efforts to
evaluate the longer-term impact of HPV-16/18 vaccination.