Extended Follow Up of Young Women in Costa Rica Who Received Vaccine for Human Papillomavirus Types 16 and 18 and Unvaccinated Controls

Extended Follow-Up of Young Women in Costa Rica Who Received Vaccination Against Human Papillomavirus Types 16 and 18 and Unvaccinated Controls

This research trial studies extended follow up of young women in Costa Rica who received vaccine for human papillomavirus types 16 and 18 and unvaccinated controls. Collecting information from young women in Costa Rica who have received vaccine for human papillomavirus types 16 and 18 and a new group of unvaccinated controls enrolled for the follow-up period, may help doctors learn more about the risks and benefits of prophylactic human papillomavirus vaccine.

Study Overview

• Status: Active, not recruiting
• Conditions: Cervical Carcinoma; Oral Cavity Carcinoma; Human Papillomavirus Infection; Anal Carcinoma; Human Papillomavirus-Related Cervical Carcinoma
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Other: Questionnaire Administration; Other: Cytology Specimen Collection Procedure; Other: Long-term Follow-up

Detailed Description

PRIMARY OBJECTIVES:

I. To evaluate the 10-year global impact of human papillomavirus (HPV)-16/18 vaccination of young adult women.

II. To evaluate determinants of the immune response to HPV and the vaccine, and markers of long-term protection.

III. To evaluate the natural history of HPV and cervical disease in vaccinated and unvaccinated populations.

OUTLINE:

Participants undergo long term follow-up comprising risk factor questionnaire, pelvic examination for all sexually experienced women, and specimen collection at years 6, 8, and 10.

• Study Type: Observational
• Enrollment (Estimated): 8670

Contacts and Locations

Study Locations

• Costa Rica
  • Guanacaste Province
    • Liberia, Guanacaste Province, Costa Rica, 50101
      • Agencia Costarricense de Investigaciones Biomédicas (ACIB)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Young women in Costa Rica who received vaccination against human papillomavirus types 16 and 18 and unvaccinated controls.

Description

Inclusion Criteria:

• Women who participated in the Costa Rica Vaccine Trial (CVT) and lived in the Guanacaste province and a few areas of Puntarenas closest to Guanacaste will be eligible for the long-term follow up LTFU study
• Women who received the HPV-16/18 vaccine at the start of CVT will be invited for up to 6 years of additional follow-up, and women who were originally in the control arm of CVT and were offered the HPV-16/18 vaccine at crossover will be invited for an additional 2 years of follow-up
• A subset of the control arm women who are in the crossover immunogenicity subcohort will be followed the full 6 years
• Some women who received HPV vaccination and were not invited into the LTFU protocol (stopped attending their screening visits during CVT, discontinued their study participation during CVT or lived outside the study area) will be invited to participate in the LTFU protocol, particularly those who received an incomplete vaccination schedule
• UNVACCINATED CONTROL GROUP:
• Born in or between July 1978 and November 1987
• Residents of Guanacaste Province and a few areas of Puntarenas closest to Guanacaste at some point during 2005
• Able to speak/understand Spanish
• Apparently mentally competent
• Written informed consent obtained prior to enrollment

Exclusion Criteria:

• History of cervical cancer
• History of hysterectomy
• Any important medical condition or other criteria that the investigator considers that precludes enrollment
• Vaccination with Gardasil or Cervarix will be an exclusionary criterion, but few women are expected to have received these vaccines at the time of enrollment; use of these vaccines after enrollment is not a criterion for study interruption but we plan to collect information on vaccination history so that the few women who report having been vaccinated with one of the HPV vaccines after enrollment can be evaluated separately at analysis

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Observational (long term follow-up); Participants undergo long term follow-up comprising risk factor questionnaire, pelvic examination for all sexually experienced women, and specimen collection at years 6, 8, and 10.	Other: Laboratory Biomarker Analysis; Correlative studies; Other: Questionnaire Administration; Ancillary studies; Other: Cytology Specimen Collection Procedure; Correlative studies; Other Names: Cytologic Sampling; Other: Long-term Follow-up; Undergo extended follow-up; Other Names: long term follow-up (clinical study); LTFU; long-term follow-up (research)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative rate of cervical intraepithelial neoplasia 3 (CIN3)	Both absolute rate differences and percent reduction in rates will be evaluated.	At 10 years
Level of immune response markers as prediction of long-term success of HPV vaccine	For efficiency, a nested case-control approach is envisioned to evaluate this question. We propose to compare women who become infected against a subset of those who do not (non-failures) with respect to immune response markers of interest.	Up to 10 years
Increase in the rate of cervical lesions associated with other carcinogenic HPV types that the vaccine does not protect against from prevention of HPV-16/18 associated cervical lesions through vaccination	The 10-year cumulative rate of incident CIN2+ associated with HPV types other than HPV-16/18 and closely related HPV types in the alpha-7/9 species for which evidence of vaccine cross-protection is demonstrated will be compared between vaccinated and unvaccinated women.	Up to 10 years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Aimee Kreimer, National Cancer Institute (NCI)

Publications and helpful links

General Publications

• Shing JZ, Hu S, Herrero R, Hildesheim A, Porras C, Sampson JN, Schussler J, Schiller JT, Lowy DR, Sierra MS, Carvajal L, Kreimer AR; Costa Rica HPV Vaccine Trial Group. Precancerous cervical lesions caused by non-vaccine-preventable HPV types after vaccination with the bivalent AS04-adjuvanted HPV vaccine: an analysis of the long-term follow-up study from the randomised Costa Rica HPV Vaccine Trial. Lancet Oncol. 2022 Jul;23(7):940-949. doi: 10.1016/S1470-2045(22)00291-1. Epub 2022 Jun 13.
• Porras C, Tsang SH, Herrero R, Guillen D, Darragh TM, Stoler MH, Hildesheim A, Wagner S, Boland J, Lowy DR, Schiller JT, Schiffman M, Schussler J, Gail MH, Quint W, Ocampo R, Morales J, Rodriguez AC, Hu S, Sampson JN, Kreimer AR; Costa Rica Vaccine Trial Group. Efficacy of the bivalent HPV vaccine against HPV 16/18-associated precancer: long-term follow-up results from the Costa Rica Vaccine Trial. Lancet Oncol. 2020 Dec;21(12):1643-1652. doi: 10.1016/S1470-2045(20)30524-6.

Study record dates

Study Major Dates

• Study Start (Actual): March 30, 2009
• Primary Completion (Estimated): December 23, 2026
• Study Completion (Estimated): December 23, 2026

Study Registration Dates

• First Submitted: March 20, 2009
• First Submitted That Met QC Criteria: March 20, 2009
• First Posted (Estimated): March 23, 2009

Study Record Updates

• Last Update Posted (Actual): August 28, 2026
• Last Update Submitted That Met QC Criteria: August 27, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Mouth Diseases; Stomatognathic Diseases; Pathologic Processes; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Disease Attributes; Intestinal Diseases; Infections; Virus Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Rectal Diseases; Uterine Diseases; Genital Diseases, Female; Head and Neck Neoplasms; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; DNA Virus Infections; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Neoplasms; Tumor Virus Infections; Anus Diseases; Rectal Neoplasms; Pathological Conditions, Signs and Symptoms; Uterine Cervical Neoplasms; Papillomavirus Infections; Mouth Neoplasms; Anus Neoplasms
• Other Study ID Numbers: NCI-2016-00231 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); 999909106; 09-C-N106 (Other Identifier: National Cancer Institute)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No