Costa Rica HPV Vaccine Trial (CVT)
Long-Term Follow-Up of Participants in the Original CVT
Background and Study Rationale
The original Costa Rica Human Papillomavirus (HPV) Vaccine Trial was a collaboration between investigators in Costa Rica (ACIB-FUNIN) and the National Cancer Institute. CVT was a blinded, randomized, phase III clinical trial of the bivalent HPV 16/18 virus-like particle (VLP) vaccine developed by investigators at NCI and other research institutions, and manufactured by GlaxoSmithKline Biologicals. Its aims were to evaluate vaccine efficacy, immunological correlates of long-term vaccine success and failure, and other factors of immunological and etiological interest. The trial was initiated in June 2004 and enrollment of 7,466 women aged 18–25 years was completed in December 2005.
Eligible participants were consented and randomized to receive three doses of the HPV 16/18 VLP or Havrix (Hepatitis A) vaccine over a period of six months. At entry and throughout follow-up, women were carefully monitored and received state-of-the-art screening for cervical neoplasia. During the blinded phase, women were followed for four years.
CVT Long-Term Follow-Up Study
At the completion of CVT in 2010, the CVT Long Term Follow-Up Study (LTFU) was implemented to extend the follow-up of CVT participants to 10 years, in order to address questions related to duration of protection, long-term safety, prolonged efficacy of fewer than three doses, and behavior of other carcinogenic HPV types in the absence of HPV 16/18 infections. CVT transitioned from the randomized, blinded trial design to an epidemiologic cohort study. Participants in the original control arm were offered the HPV vaccine following the four-year study visit of CVT and were exited from the study in year six. To account for the loss of the ability to document rates of HPV infection and related disease among unvaccinated women, a new control group was enrolled contemporaneously with the four-year CVT study visit, from the same geographic areas and birth cohorts as the original CVT women, and followed via screening (as HPV vaccination of adult women is not included in the national immunization program in Costa Rica). The original HPV arm and the new control group were followed biennially, to compare rates of HPV acquisition, clearance, and disease progression between vaccinated and unvaccinated women.
The CVT study continues in a subset of the HPV-vaccinated women. Women are expected to be followed for a median of 20 years after the initial vaccination to document the durability of single-dose HPV vaccination.
CVT is an important source of data that has generated numerous scientific publications and continues to advance the science of HPV vaccination, natural history, and cervical cancer screening among vaccinated cohorts. In addition to strong evidence for vaccine safety and efficacy, data from the trial demonstrated that three doses of the HPV vaccine may not be necessary, as similar vaccine efficacy against cervical HPV 16/18 infection was observed among women who received two, and even a single dose, after more than 10 years of follow-up. Data from CVT has also demonstrated partial cross-protection against HPV 31, 33 and 45; high efficacy against HPV16/18-associated precancer for more than a decade after initial vaccination, supporting the notion that invasive cervical cancer is preventable; among women approaching screening ages, vaccinated as young adults and with a history of prior intensive screening, HPV-based screening modalities performed better than cytology; negative vaccine efficacy against high-grade cervical precancer caused by non-preventable HPV types, suggesting that unmasking could attenuate long-term reductions in high-grade disease following successful implementation of HPV vaccination programs in screened populations; ~10% HPV vaccine efficacy against carcinogenic HPV types excluding HPV 16, 18, 31, 33, 45; no vaccine efficacy against existing HPV infections; HPV type replacement does not occur among vaccinated individuals within 4 years and is unlikely to occur in vaccinated populations; antibodies generated by HPV infection provide some protection against re-infection; bivalent HPV vaccination does not have an effect in expediting clearance of nontargeted incident infections (pooled data from CVT and PATRICIA trial); strong protection against HPV infections at essentially all non-cervical anatomic sites where HPV causes cancer in women (i.e., anus, vulva, and oral region), and that the level of protection was comparably high to that observed at the cervix among the same women.
For more information, contact Aimée R. Kreimer, Ph.D.
Infections and Immunoepidemiology Branch - Research Areas
- Shing JZ, et al. 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.
- Porras C, Tsang SH, et al. 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.
- Kreimer AR, Sampson JS, et al. Evaluation of Durability of a Single Dose of the Bivalent HPV Vaccine: The CVT Trial. JNCI 2020.
- Tsang SH, Sampson JS, et al. Durability of Cross-Protection by Different Schedules of the Bivalent HPV Vaccine: The CVT Trial. JNCI 2020.
- Herrero R, Wacholder S, Rodriguez AC, et al. Prevention of persistent human papillomavirus infection by an HPV16/18 vaccine: a community-based randomized clinical trial in Guanacaste, Costa Rica. Cancer Discov 2011.
- Herrero R, Hildesheim A, Rodriguez AC, et al. Rationale and design of a community-based double-blind randomized clinical trial of an HPV 16 and 18 vaccine in Guanacaste, Costa Rica. Vaccine 2008.
Requests for CVT Data and Specimens
We encourage collaborations with external investigators. Requests for CVT data will be reviewed for completeness and suitability. If requesting CVT data and specimens, external investigators will be invited to submit a concept and, if it is accepted, they will be partnered with a CVT team member to develop a full proposal. Proposals will require CVT Working Group approval.
To request an application and information packet, please email the CVT coordinator. Please specify if you are requesting data only or data and specimens.