title: Four year efficacy of prophylactic human papillomavirus quadrivalent vaccine against low grade cervical, vulvar, and vaginal intraepithelial neoplasia and anogenital warts: randomised controlled trial.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  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.
  
  
  METHODS
  Primary care centres and university or hospital associated health centres in 24 countries and territories around the world.
  
  
  METHODS
  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.
  
  
  METHODS
  Three doses of quadrivalent HPV vaccine (for serotypes 6, 11, 16, and 18) or placebo at day 1, month 2, and month 6.
  
  
  METHODS
  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.
  
  
  BACKGROUND
  NCT00092521 and NCT00092534.
authors.affiliation: Depatment of Laboratory Medicine, Lund University, Malmö, Sweden. joakim.dillner@med.lu.se
authors.forename: Joakim
authors.initials: J
authors.lastname: Dillner
authors.forename: Susanne K
authors.initials: SK
authors.lastname: Kjaer
authors.forename: Cosette M
authors.initials: CM
authors.lastname: Wheeler
authors.forename: Kristján
authors.initials: K
authors.lastname: Sigurdsson
authors.forename: Ole-Erik
authors.initials: OE
authors.lastname: Iversen
authors.forename: Mauricio
authors.initials: M
authors.lastname: Hernandez-Avila
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Perez
authors.forename: Darron R
authors.initials: DR
authors.lastname: Brown
authors.forename: Laura A
authors.initials: LA
authors.lastname: Koutsky
authors.forename: Eng Hseon
authors.initials: EH
authors.lastname: Tay
authors.forename: Patricia
authors.initials: P
authors.lastname: García
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Ault
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Garland
authors.forename: Sepp
authors.initials: S
authors.lastname: Leodolter
authors.forename: Sven-Eric
authors.initials: SE
authors.lastname: Olsson
authors.forename: Grace W K
authors.initials: GW
authors.lastname: Tang
authors.forename: Daron G
authors.initials: DG
authors.lastname: Ferris
authors.forename: Jorma
authors.initials: J
authors.lastname: Paavonen
authors.forename: Matti
authors.initials: M
authors.lastname: Lehtinen
authors.forename: Marc
authors.initials: M
authors.lastname: Steben
authors.forename: F Xavier
authors.initials: FX
authors.lastname: Bosch
authors.forename: Elmar A
authors.initials: EA
authors.lastname: Joura
authors.forename: Slawomir
authors.initials: S
authors.lastname: Majewski
authors.forename: Nubia
authors.initials: N
authors.lastname: Muñoz
authors.forename: Evan R
authors.initials: ER
authors.lastname: Myers
authors.forename: Luisa L
authors.initials: LL
authors.lastname: Villa
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Taddeo
authors.forename: Christine
authors.initials: C
authors.lastname: Roberts
authors.forename: Amha
authors.initials: A
authors.lastname: Tadesse
authors.forename: Janine T
authors.initials: JT
authors.lastname: Bryan
authors.forename: Roger
authors.initials: R
authors.lastname: Maansson
authors.forename: Shuang
authors.initials: S
authors.lastname: Lu
authors.forename: Scott
authors.initials: S
authors.lastname: Vuocolo
authors.forename: Teresa M
authors.initials: TM
authors.lastname: Hesley
authors.forename: Eliav
authors.initials: E
authors.lastname: Barr
authors.forename: Richard
authors.initials: R
authors.lastname: Haupt
mesh_terms: D000293:Adolescent; D000328:Adult; D019496:Cancer Vaccines; D002278:Carcinoma in Situ / Q000517:prevention & control*; D003218:Condylomata Acuminata / Q000517:prevention & control; D004311:Double-Blind Method; D005260:Female; D000068857:Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18; D006801:Humans; D030361:Papillomavirus Infections / Q000517:prevention & control*; D053918:Papillomavirus Vaccines; D016896:Treatment Outcome; D014565:Urogenital Neoplasms / Q000517:prevention & control*; D002583:Uterine Cervical Neoplasms / Q000517:prevention & control; D014625:Vaginal Neoplasms / Q000517:prevention & control; D014846:Vulvar Neoplasms / Q000517:prevention & control; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000517:prevention & control*
chemical_list: D019496:Cancer Vaccines; D000068857:Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18; D053918:Papillomavirus Vaccines