55. HIGH EFFICACY OF A HPV-16/18 L1 VIRUS-LIKE PARTICLE (VLP) VACCINE ADJUVANTED WITH AS04 AGAINST CIN2+ CAUSED BY HPV-16/18 INFECTION IN A BROAD POPULATION OF YOUNG WOMEN

Abstract

Objectives: Previous studies with the HPV-16/18 L1 VLP AS04 vaccine have shown 100% efficacy against HPV 16/18 associated persistent infection and CIN in women with no previous exposure to oncogenic HPV. This interim analysis of a phase III, randomized, controlled trial assessed vaccine efficacy against HPV 16/18 associated CIN2+ and persistent infection with oncogenic HPV types in a broad population of women. Methods: Healthy women, aged 15-25 years, with d6 sexual partners and no previous colposcopy were eligible and were randomly allocated to 3 doses of HPV or hepatitis A (control) vaccine at 0, 1, 6 months. Serum antibodies for HPV 16/18 were assessed by ELISA. HPV DNA was detected by PCR on cervical cytology and biopsy. Vaccine efficacy was assessed in women who received at least one vaccine dose, had normal or low-grade cytology and were HPV 16/18 sero- and DNA negative at entry. Additional analyses were undertaken to assign causality where multiple HPV types were present. Immunogenicity was evaluated in a subset of women and safety was assessed in the entire vaccinated cohort. Results: 18729 women from Asia Pacific (34%), Europe (34%), North (16.5%) and Latin America (14.9%) were enrolled. 18525 were included in the cohort for vaccine efficacy analyses. Mean age was 20 years and mean follow up 15 months from dose 1. Most HPV 16/18 infections were detected prior to dose 3 in this analysis. Of 23 CIN2+ lesions associated with HPV 16/18, 14 contained multiple oncogenic HPV types: three showed no preceding infection or E4 gene expression for the relevant HPV vaccine type. Vaccine efficacy according to HPV DNA detected in the lesion was 90.4% (95% CI, 53.4-99.3); after additional analyses for causality assignment, efficacy was 100% (95% CI: 74.2-100). Cross-protection against 6-months infection with HPV-45, -31, -52; and broad protection against 12-month persistent non-16/18 oncogenic HPV infection was also demonstrated. Seroconversion was 99.5% after dose 2 and 3. Safety profiles were comparable between groups. Conclusions: In a broad cohort of women, high vaccine efficacy was observed against CIN2+ caused by HPV-16/18.