Author(s): FUTURE III Study Group, Dillner J, Kjaer SK, Wheeler CM, Sigurdsson K,
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Abstract OBJECTIVES: To evaluate the prophylactic efficacy of the human papillomavirus (HPV) quadrivalent vaccine in preventing low grade cervical, vulvar, and vaginal intraepithelial neoplasias and anogenital warts (condyloma acuminata). DESIGN: Data from two international, double blind, placebo controlled, randomised efficacy trials of quadrivalent HPV vaccine (protocol 013 (FUTURE I) and protocol 015 (FUTURE II)). The trials were to be 4 years in length, and the results reported are from final study data of 42 months' follow-up. SETTING: Primary care centres and university or hospital associated health centres in 24 countries and territories around the world. PARTICIPANTS: 17 622 women aged 16-26 years enrolled between December 2001 and May 2003. Major exclusion criteria were lifetime number of sexual partners (>4), history of abnormal cervical smear test results, and pregnancy. INTERVENTION: Three doses of quadrivalent HPV vaccine (for serotypes 6, 11, 16, and 18) or placebo at day 1, month 2, and month 6. MAIN OUTCOME MEASURES: Vaccine efficacy against cervical, vulvar, and vaginal intraepithelial neoplasia grade I and condyloma in a per protocol susceptible population that included subjects who received all three vaccine doses, tested negative for the relevant vaccine HPV types at day 1 and remained negative through month 7, and had no major protocol violations. Intention to treat, generally HPV naive, and unrestricted susceptible populations were also studied. RESULTS: In the per protocol susceptible population, vaccine efficacy against lesions related to the HPV types in the vaccine was 96\% for cervical intraepithelial neoplasia grade I (95\% confidence interval 91\% to 98\%), 100\% for both vulvar and vaginal intraepithelial neoplasia grade I (95\% CIs 74\% to 100\%, 64\% to 100\% respectively), and 99\% for condyloma (96\% to 100\%). Vaccine efficacy against any lesion (regardless of HPV type) in the generally naive population was 30\% (17\% to 41\%), 75\% (22\% to 94\%), and 48\% (10\% to 71\%) for cervical, vulvar, and vaginal intraepithelial neoplasia grade I, respectively, and 83\% (74\% to 89\%) for condyloma. CONCLUSIONS: Quadrivalent HPV vaccine provided sustained protection against low grade lesions attributable to vaccine HPV types (6, 11, 16, and 18) and a substantial reduction in the burden of these diseases through 42 months of follow-up. TRIAL REGISTRATIONS: NCT00092521 and NCT00092534.
This article was published in BMJ
and referenced in Translational Medicine