Efficacy of a quadrivalent HPV (types 6/11/16/18) L1 virus-like particle (VLP) vaccine against vaginal and vulvar pre-cancerous lesions: a combined analysis

Abstract

5011 Background: In the US, 6000 cases of vulvar or vaginal cancer are diagnosed annually. HPV is detected in 75–100% of vulvar cancers in younger women. The most common HPV type detected is HPV 16, followed by HPV 18. These two types also cause a majority of HPV-related vaginal cancers. Treatment to prevent progression to vaginal/vulvar cancer is challenging. Here, we present a combined analysis of 3 randomized, placebo-controlled trials to evaluate the impact of a prophylactic quadrivalent HPV vaccine on the rates of HPV 16- and 18-related vulvar and vaginal neoplasia grade 2/3 (VIN 2/3 and VaIN 2/3). Methods: 18,150 women (16–26 yrs) from the Americas, Europe and Asia were enrolled in 1 of 3 trials. Subjects were randomized to either quadrivalent HPV (Types 6, 11, 16, 18) L1 VLP vaccine or placebo. For all trials, vaccination occurred at day 1, and months 2 and 6. Genital tract specimens were obtained at day 1 and at 6–12 month intervals thereafter for a maximum of 48 months. Colposcopy referral was algorithm-based. Biopsies were HPV-typed. Cytology, histology, and HPV detection were conducted centrally. Analyses were done per protocol (PP) (subjects received 3 doses, had no major protocol violations, were HPV 16 or 18 seronegative at Day 1 and HPV 16 or 18 DNA negative Day 1 through month 7) and modified intention to treat (MITT) (received ≥1 dose and were HPV 16 or 18 negative at Day 1 by serology and DNA). Endpoint counts began after Month 7 and Day 30 in the PP and MITT analyses, respectively. Results: In PP analysis, after an average of 18 months of follow-up, the vaccine was 100% effective (95% CI: 56–100%) in preventing HPV 16- or 18-related VIN 2/3 or VaIN 2/3. There were 10 cases in the placebo group and 0 cases in the vaccine group. In the MITT population, after an average of 2 years of follow-up, there were 24 histologically confirmed cases of HPV 16- or 18-related VIN 2/3 or VaIN 2/3, all in the placebo group (100% efficacy; 95% CI: 83–100%). Conclusions: Quadrivalent HPV VLP vaccine prevented HPV 16 and 18-related vaginal and vulvar high-grade precancerous lesions for at least 2 years post-immunization. This intervention is expected to greatly reduce the risk of vulvar and vaginal cancers. [Table: see text]