Efficacy of Human Papillomavirus Type 16/18 AS04-Adjuvanted Vaccine in Japanese Women Aged 20 to 25 Years: Final Analysis of a Phase 2 Double-Blind, Randomized Controlled Trial

Abstract

Background:Human papillomavirus (HPV) type 16/18 AS04-adjuvanted vaccine was shown to be highly immunogenic and generally well tolerated in the interim analysis of a phase 2 double-blind, randomized controlled multicenter study in Japanese healthy women aged 20 to 25 years. Vaccine efficacy, immunogenicity, and safety are assessed in this study through 24 months after the first vaccination.Methods:Japanese women aged 20 to 25 years were randomly assigned to receive either HPV-16/18 AS04-adjuvanted vaccine (n = 519) or hepatitis A vaccine (n = 521) at 0, 1, and 6 months. Women were assessed for virological, cytological, and histological end points associated with HPV-16/18 and 12 other oncogenic HPV types (types 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68) in cervical specimens and for the vaccine safety and immunogenicity. Antibody concentrations were measured by an enzyme-linked immunosorbent assay. Primary efficacy analysis was performed in the according-to-protocol cohort for efficacy, primary immunogenicity analysis was performed in the according-to-protocol cohort for immunogenicity, and primary safety analysis was done in the total vaccinated cohort.Results:Vaccine efficacy against persistent infections (6 month definition) associated with HPV-16/18 was 100% (95.5% confidence interval, 71.3-100; P < 0.0001). Vaccine efficacy against cervical intraepithelial neoplasia 1+ associated with 14 oncogenic HPV types was 64.9% (95.5% confidence interval, 4.9-89.0; P = 0.02). At 24 months after the first dose of the vaccine, geometric mean antibody titers against HPV-16 and HPV-18 were 1521.5 enzyme-linked immunosorbent assay U/mL and 627.4 enzyme-linked immunosorbent assay U/mL, respectively. The HPV-16/18 AS04-adjuvanted vaccine had a clinically acceptable safety profile.Conclusions:The HPV-16/18 AS04-adjuvanted vaccine showed excellent prophylactic efficacy against 6-month persistent infection with HPV-16/18. The HPV-16/18 AS04-adjuvanted vaccine was generally well tolerated and immunogenic in the study population of healthy Japanese women aged 20 to 25 years.