Background
Limited data suggest one or two doses of the HPV vaccines confer similar protection to the three-dose regimen. This study aimed to further evaluate the question of reduced-dose efficacy of the HPV-16/18 vaccine.
Methods
Summary-level data from the Costa Rica Vaccine Trial (CVT; NCT00128661) and the PApilloma TRIal against Cancer In young Adults (PATRICIA; NCT001226810), two phase III controlled, randomized, double-blind, clinical trials of the HPV-16/18 AS04-adjuvanted vaccine among young women, were combined in a post-hoc analysis (GSK e-track 202142) to investigate efficacy of fewer doses of the HPV-16/18 vaccine after four years of follow-up. Women were randomly assigned to receive three doses of the HPV-16/18 vaccine or to a control vaccine; yet some received fewer doses. After excluding women with <12-months follow-up or those HPV16/18 DNA-positive at enrollment (for the HPV16/18 endpoint), vaccine efficacy (VE) was calculated against one-time detection of incident HPV infections after three (n=11,110 HPV:11,217control), two (n=611:574), and one (N=292:251) dose(s). The main aim of the study was to ascertain HPV16/18 VE in both full and naïve cohorts, as well as to explore protection conferred against non-vaccine HPV types, by number of doses received.
Findings
VE against incident HPV16/18 infections for three doses was 77·0% (95%CI 74·7 to 79·1%), two doses was 76·0% (95%CI 62·0 to 85·3%), and one dose was 85·7% (95%CI 70·7 to 93·7%). VE against incident HPV31/33/45 infections for three doses was 59·7% (95%CI 56·0 to 63·0%), two doses was 37·7% (95%CI 12·4 to 55·9%), and one dose was 36·6% (95%CI −5·4 to 62·2%). However, two-dose women who received their second dose at six months, but not those receiving it at one month, had efficacy estimates against HPV 31/33/45 similar to the three-dose group (VE 68·1%, 95%CI 27·0 to 87·0%; CVT data only).
Interpretation
Four years following vaccination of women aged 15 to 25 years, one and two dose(s) of the HPV16/18 vaccine appear to protect against cervical HPV16/18 infections, similar to the protection provided by the three-dose schedule. Two doses separated by six months additionally provided limited cross-protection. These data argue for a direct evaluation of one-dose efficacy of the HPV16/18 vaccine.
Funding
The CVT trial was sponsored and funded by the US National Cancer Institute, NCI (contract N01-CP-11005), with funding support from the National Institutes of Health Office of Research on Women’s Health, and done with the support from the Ministry of Health of Costa Rica. Vaccine was provided for CVT by GlaxoSmithKline Biologicals SA, under a Clinical Trials Agreement with the NCI. GlaxoSmithKline Biologicals SA provided support for aspects of the trial associated with regulatory submission needs of the company under US Food and Drug Administration BB-IND 7920. The PATRICIA trial was sponsored by GlaxoSmithKline Biologicals SA.
