Crossover Vaccination of Women Previously Randomized Into Protocol 04-C-N191

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.

• INCLUSION CRITERIA:

To be eligible to receive crossover vaccination, participants must fulfill all of the following inclusion criteria:

• Participation Status: Women previously randomized into the HPV-16/18 vaccine trial 04-C-N191, also known as the Costa Rica Vaccine Trial.
• Planned Residence: Residents of Guanacaste or Puntarenas Province or willingness to visit one of the study clinics for participation.
• Consent: Written informed consent obtained prior to enrollment into the crossover protocol.

Exclusion criteria

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

• History of (a) allergic reaction (e.g., difficulty breathing) after receipt of any vaccine, (b) hypersensitivity to latex.
• History of vaccine related adverse events during the vaccination phase that, at the discretion of the investigators, preclude vaccination during the crossover phase.
• Are receiving vaccination with Cervarix , are sexually experienced and of childbearing potential (i.e., not surgically sterilized), and are unwilling to use an effective method of birth control for 30 days before vaccination until 60 days after the last Cervarix vaccination (approximately 9 months). Acceptable forms of birth control include abstinence, surgical sterilization, hormonal contraceptives (e.g., oral, injectable, implant, and patch), intrauterine devices, and diaphragm or condom.
• History of chronic condition that per attending doctor opinion precludes her from receiving vaccination (e.g., no proper treatment available or participant is unwilling to stay under proper treatment).
• The participant has a diagnosed autoimmune illness (per the specific requirement of the INCIENSA IRB).
• The vaccine or vaccines the participant is interested in receiving are contraindicated in her case.