• FUTURE I/II Study Group, Joakim Dillner, Susanne K Kjaer, Cosette M Wheeler, Kristján Sigurdsson, Ole-Erik Iversen, Mauricio Hernandez-Avila, Gonzalo Perez, Darron R Brown, Laura A Koutsky, Eng Hseon Tay, Patricia García, Kevin A Ault, Suzanne M Garland, Sepp Leodolter, Sven-Eric Olsson, Grace W K Tang, Daron G Ferris, Jorma Paavonen, Matti Lehtinen, Marc Steben, F Xavier Bosch, Elmar A Joura, Slawomir Majewski, Nubia Muñoz, Evan R Myers, Luisa L Villa, Frank J Taddeo, Christine Roberts, Amha Tadesse, Janine T Bryan, Roger Maansson, Shuang Lu, Scott Vuocolo, Teresa M Hesley, Eliav Barr, and Richard Haupt.
• Depatment of Laboratory Medicine, Lund University, Malmö, Sweden. joakim.dillner@med.lu.se
• BMJ. 2010 Jan 1;341:c3493.

ObjectivesTo 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).DesignData 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.SettingPrimary care centres and university or hospital associated health centres in 24 countries and territories around the world.Participants17 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.InterventionThree doses of quadrivalent HPV vaccine (for serotypes 6, 11, 16, and 18) or placebo at day 1, month 2, and month 6.Main Outcome MeasuresVaccine 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.ResultsIn 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.ConclusionsQuadrivalent 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 RegistrationsNCT00092521 and NCT00092534.

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