Crossover Vaccination of Women Previously Randomized Into Protocol 04-C-N191
Condition: Cervical Neoplasia; HPV Infections
MeSH terms: Papillomavirus Infections
Study type: Observational

Summary: 
      Background:

      - National Cancer Institute Protocol 04-C-N191, also known as the Costa Rica Vaccine Trial,
      was a double-blind controlled study of the effectiveness of an experimental human
      papillomavirus (HPV) vaccine in preventing cervical cancer in young women in Costa Rica.
      Costa Rica was part of the first large study to show the association between HPV and cervical
      cancer, and the study contributed greatly to the understanding of this association. The women
      who have participated in the vaccine trial in Costa Rica are reaching the end of the
      follow-up period offered in the vaccine trial protocol, and as a result they are being
      offered the chance to have complementary vaccinations against HPV, hepatitis A, and hepatitis
      B.

      Objectives:

        -  To offer participants in the Costa Rica Vaccine Trial the vaccine that they did not
           receive during the masked portion of the trial (HPV vaccine or hepatitis A vaccine) and
           hepatitis B vaccination.

        -  To collect information about exposure to known and suspected risk factors for HPV
           infection and cervical cancer from women who are receiving vaccination against HPV at
           crossover.

      Eligibility:

      - Women who participated in National Cancer Institute Protocol 04-C-N191.

      Design:

        -  All participants will be offered vaccination against hepatitis B.

        -  Women who received the hepatitis A vaccine during the trial will be offered vaccination
           against HPV.

        -  Women who received the HPV vaccine during the trial will be offered vaccination against
           hepatitis A.

        -  Appropriate vaccinations (including a combined hepatitis A and hepatitis B vaccine) will
           be available to reduce the number of injections that participants will be asked to
           receive.

        -  All vaccines will be given according to the manufacturer's specifications for
           appropriate length of time between vaccine doses.
    

Detailed description: 
      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.
    

Time perspective: Prospective
Keywords: Human Papillomavirus; Vaccine; Crossover; Hepatitis A; Hepatitis B