Evidence for single-dose protection by the bivalent HPV vaccine-Review of the Costa Rica HPV vaccine trial and future research studies

Abstract

The Costa Rica Vaccine Trial (CVT), a phase III randomized clinical trial, provided the initial data that one dose of the HPV vaccine could provide durable protection against HPV infection. Although the study design was to administer all participants three doses of HPV or control vaccine, 20% of women did not receive the three-dose regimens, mostly due to involuntary reasons unrelated to vaccination. In 2011, we reported that a single dose of the bivalent HPV vaccine could be as efficacious as three doses of the vaccine using the endpoint of persistent HPV infection accumulated over the first four years of the trial; findings independently confirmed in the GSK-sponsored PATRICIA trial. Antibody levels after one dose, although lower than levels elicited by three doses, were 9-times higher than levels elicited by natural infection. Importantly, levels remained essentially constant over at least seven years, suggesting that the observed protection provided by a single dose might be durable. Much work has been done to assure these non-randomized findings are valid. Yet, the group of recipients who received one dose of the bivalent HPV vaccine in the CVT and PATRICIA trials was small and not randomly selected nor blinded to the number of doses received. The next phase of research is to conduct a formal randomized, controlled trial to evaluate the protection afforded by a single dose of HPV vaccine. Complementary studies are in progress to bridge our findings to other populations, and to further document the long-term durability of antibody response following a single dose.

Keywords: Cervical cancer; HPV; HPV-driven cancers; Human papillomavirus; Prevention; Reduced dose; Vaccine.

Fig. 1

Four-year efficacy against incident HPV16/18 infections, by dose group, in the CVT and PATRICIA trials. Legend. The endpoint assessed was cumulative HPV16 or 18 infections in an analytical cohort of women who were HPV16 and 18 DNA negative at the enrollment visit. VE Vaccine efficacy M-TVC Modified total vaccinated cohort.

Fig. 2

HPV prevalence measured seven years after initial vaccination among women who received 3, 2, 1, and 0- doses in the Costa Rica HPV Vaccine Trial. Legend. The endpoint was HPV16 or 18 infections detected seven years following enrollment among the HPV vaccine groups and the contemporaneous visit among the unvaccinated control group. This was assessed among the total vaccinated cohort and the unvaccinated control group.

Fig. 3

Human Papillomavirus (HPV) type 16 (panel A) and type 18 (panel B) antibody levels up to seven years following initial HPV vaccination, by number of doses received.