Four year efficacy of prophylactic human papillomavirus quadrivalent vaccine against low grade cervical, vulvar, and vaginal intraepithelial neoplasia and anogenital warts: randomised controlled trial.

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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.


  • 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
  • And 16 others
  • 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
  • Richard Haupt
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Microbiology in the medical area


  • Vaginal Neoplasms: prevention & control, Uterine Cervical Neoplasms: prevention & control, Urogenital Neoplasms: prevention & control, Papillomavirus Infections: prevention & control, Condylomata Acuminata: prevention & control, Carcinoma in Situ: prevention & control, Cervical Intraepithelial Neoplasia: prevention & control, Vulvar Neoplasms: prevention & control
Original languageEnglish
Article numberc3493
JournalBMJ (Clinical research ed.)
Publication statusPublished - 2010
Publication categoryResearch

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