Rationale and design of a long term follow-up study of women who did and did not receive HPV 16/18 vaccination in Guanacaste, Costa Rica

Vaccine. 2015 Apr 27;33(18):2141-51. doi: 10.1016/j.vaccine.2015.03.015. Epub 2015 Mar 18.

Abstract

The Costa Rica Vaccine Trial (CVT) was a randomized clinical trial conducted between 2004 and 2010, which randomized 7466 women aged 18 to 25 to receive the bivalent HPV-16/18 vaccine or control Hepatitis-A vaccine. Participants were followed for 4 years with cross-over vaccination at the study end. In 2010 the long term follow-up (LTFU) study was initiated to evaluate the 10-year impact of HPV-16/18 vaccination, determinants of the immune response, and HPV natural history in a vaccinated population. Herein, the rationale, design and methods of the LTFU study are described, which actively follows CVT participants in the HPV-arm 6 additional years at biennial intervals (3 additional study visits for 10 years of total follow-up), or more often if clinically indicated. According to the initial commitment, women in the Hepatitis-A arm were offered HPV vaccination at cross-over; they were followed 2 additional years and exited from the study. 92% of eligible CVT women accepted participation in LTFU. To provide underlying rates of HPV acquisition and cervical disease among unvaccinated women to compare with the HPV-arm during LTFU, a new unvaccinated control group (UCG) of women who are beyond the age generally recommended for routine vaccination was enrolled, and will be followed by cervical cancer screening over 6 years. To form the UCG, 5000 women were selected from a local census, of whom 2836 women (61% of eligible women) agreed to participate. Over 90% of participants complied with an interview, blood and cervical specimen collection. Evaluation of comparability between the original (Hepatitis-A arm of CVT) and new (UCG) control groups showed that women's characteristics, as well as their predicted future risk for cervical HPV acquisition, were similar, thus validating use of the UCG. LTFU is poised to comprehensively address many important questions related to long-term effects of prophylactic HPV vaccines.

Trial registration: ClinicalTrials.gov NCT00128661.

Keywords: Human papillomavirus; Long term follow-up; Methods; Vaccines.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Cervical Intraepithelial Neoplasia / epidemiology
  • Cervical Intraepithelial Neoplasia / prevention & control
  • Costa Rica / epidemiology
  • Cross-Over Studies
  • Early Detection of Cancer
  • Female
  • Follow-Up Studies
  • Hepatitis A Vaccines / administration & dosage
  • Human papillomavirus 16 / immunology
  • Human papillomavirus 16 / isolation & purification
  • Human papillomavirus 18 / immunology*
  • Human papillomavirus 18 / isolation & purification
  • Humans
  • Papillomavirus Infections / epidemiology
  • Papillomavirus Infections / prevention & control*
  • Papillomavirus Vaccines* / administration & dosage
  • Papillomavirus Vaccines* / adverse effects
  • Papillomavirus Vaccines* / immunology
  • Research Design
  • Time Factors
  • Uterine Cervical Diseases / epidemiology
  • Uterine Cervical Diseases / prevention & control
  • Uterine Cervical Neoplasms / epidemiology
  • Uterine Cervical Neoplasms / prevention & control*
  • Vaccination
  • Young Adult

Substances

  • Hepatitis A Vaccines
  • Papillomavirus Vaccines

Associated data

  • ClinicalTrials.gov/NCT00128661