High sustained efficacy of a prophylactic quadrivalent human papillomavirus types 6/11/16/18 L1 virus-like particle vaccine through 5 years of follow-up

TLDR

Human papillomavirus causes cervical, vulvar, and vaginal cancers, precancerous dysplasia, and genital warts. This study reports the longest efficacy evaluation to date of a prophylactic quadrivalent HPV 6/11/16/18 L1 virus‑like particle vaccine. In a randomized, placebo‑controlled trial of 552 women aged 16–23, participants received the vaccine at months 0, 2, and 6 and were followed with gynecologic exams, HPV DNA testing, serology, and Pap tests for three years, with a subset of 241 subjects followed for an additional two years. Five years after enrollment, vaccine recipients experienced a 96 % reduction in persistent HPV 6/11/16/18 infection or disease, no cases of precancerous dysplasia or genital warts, and maintained high anti‑HPV antibody titres, demonstrating 100 % efficacy and supporting adolescent and young adult vaccination.

Abstract

Human papillomavirus (HPV) causes cervical, vulvar, and vaginal cancers, precancerous dysplasia, and genital warts. We report data for the longest efficacy evaluation to date of a prophylactic HPV vaccine. In total, 552 women (16-23 years) were enrolled in a randomised, placebo-controlled study of a quadrivalent HPV 6/11/16/18 L1 virus-like-particle vaccine with vaccination at months 0, 2, and 6. At regular intervals through 3 years, subjects underwent gynaecologic examination, cervicovaginal sampling for HPV DNA, serum anti-HPV testing, and Pap testing, with follow-up biopsy as indicated. A subset of 241 subjects underwent two further years of follow-up. At 5 years post enrollment, the combined incidence of HPV 6/11/16/18-related persistent infection or disease was reduced in vaccine-recipients by 96% (two cases vaccine versus 46 placebo). There were no cases of HPV 6/11/16/18-related precancerous cervical dysplasia or genital warts in vaccine recipients, and six cases in placebo recipients (efficacy = 100%; 95% CI:12-100%). Through 5 years, vaccine-induced anti-HPV geometric mean titres remained at or above those following natural infection. In conclusion, a prophylactic quadrivalent HPV vaccine was effective through 5 years for prevention of persistent infection and disease caused by HPV 6/11/16/18. This duration supports vaccination of adolescents and young adults, which is expected to greatly reduce the burden of cervical and genital cancers, precancerous dysplasia, and genital warts.