title: 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.
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.
authors: Proyecto Epidemiológico Guanacaste, Fundación INCIENSA, Guanacaste, Costa Rica; International Agency for Research on Cancer, Lyon, France. Electronic address: pgonzalez@proyectoguanacaste.org.
authors: Paula
authors: P
authors: Gonzalez
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
authors: Allan
authors: A
authors: Hildesheim
authors: International Agency for Research on Cancer, Lyon, France.
authors: Rolando
authors: R
authors: Herrero
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
authors: Hormuzd
authors: H
authors: Katki
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
authors: Sholom
authors: S
authors: Wacholder
authors: Proyecto Epidemiológico Guanacaste, Fundación INCIENSA, Guanacaste, Costa Rica.
authors: Carolina
authors: C
authors: Porras
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
authors: Mahboobeh
authors: M
authors: Safaeian
authors: International Agency for Research on Cancer, Lyon, France.
authors: Silvia
authors: S
authors: Jimenez
authors: University of California, San Francisco (UCSF), San Francisco, CA, USA.
authors: Teresa M
authors: TM
authors: Darragh
authors: Proyecto Epidemiológico Guanacaste, Fundación INCIENSA, Guanacaste, Costa Rica.
authors: Bernal
authors: B
authors: Cortes
authors: Information Management Services (IMS), Calverton, MD, USA.
authors: Brian
authors: B
authors: Befano
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
authors: Mark
authors: M
authors: Schiffman
authors: Proyecto Epidemiológico Guanacaste, Fundación INCIENSA, Guanacaste, Costa Rica.
authors: Loreto
authors: L
authors: Carvajal
authors: University of California, San Francisco (UCSF), San Francisco, CA, USA.
authors: Joel
authors: J
authors: Palefsky
authors: Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors: John
authors: J
authors: Schiller
authors: Proyecto Epidemiológico Guanacaste, Fundación INCIENSA, Guanacaste, Costa Rica.
authors: Rebeca
authors: R
authors: Ocampo
authors: Information Management Services (IMS), Calverton, MD, USA.
authors: John
authors: J
authors: Schussler
authors: Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors: Douglas
authors: D
authors: Lowy
authors: Proyecto Epidemiológico Guanacaste, Fundación INCIENSA, Guanacaste, Costa Rica.
authors: Diego
authors: D
authors: Guillen
authors: Department of Pathology, University of Virginia, Charlottesville, VA, USA.
authors: Mark H
authors: MH
authors: Stoler
authors: DDL Diagnostic Laboratory, Rijswijk, The Netherlands.
authors: Wim
authors: W
authors: Quint
authors: Proyecto Epidemiológico Guanacaste, Fundación INCIENSA, Guanacaste, Costa Rica.
authors: Jorge
authors: J
authors: Morales
authors: Proyecto Epidemiológico Guanacaste, Fundación INCIENSA, Guanacaste, Costa Rica.
authors: Carlos
authors: C
authors: Avila
authors: Proyecto Epidemiológico Guanacaste, Fundación INCIENSA, Guanacaste, Costa Rica.
authors: Ana Cecilia
authors: AC
authors: Rodriguez
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
authors: Aimée R
authors: AR
authors: Kreimer
mesh_terms: D000328:Adult; D003364:Costa Rica / Q000453:epidemiology; D018592:Cross-Over Studies; D055088:Early Detection of Cancer; D005260:Female; D005500:Follow-Up Studies; D022362:Hepatitis A Vaccines / Q000008:administration & dosage; D052162:Human papillomavirus 16 / Q000276:immunology / Q000302:isolation & purification; D052161:Human papillomavirus 18 / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D030361:Papillomavirus Infections / Q000453:epidemiology / Q000517:prevention & control*; D053918:Papillomavirus Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D012107:Research Design; D013997:Time Factors; D002577:Uterine Cervical Diseases / Q000453:epidemiology / Q000517:prevention & control; D002583:Uterine Cervical Neoplasms / Q000453:epidemiology / Q000517:prevention & control*; D014611:Vaccination; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000453:epidemiology / Q000517:prevention & control
chemical_list: D022362:Hepatitis A Vaccines; D053918:Papillomavirus Vaccines
keywords: Human papillomavirus; Long term follow-up; Methods; Vaccines