title: Efficacy of a quadrivalent prophylactic human papillomavirus (types 6, 11, 16, and 18) L1 virus-like-particle vaccine against high-grade vulval and vaginal lesions: a combined analysis of three randomised clinical trials.
abstract: BACKGROUND
  Vulval and vaginal cancers among younger women are often related to infection with human papillomavirus (HPV). These cancers are preceded by high-grade vulval intraepithelial neoplasia (VIN2-3) and vaginal intraepithelial neoplasia (VaIN2-3). Our aim was to do a combined analysis of three randomised clinical trials to assess the effect of a prophylactic quadrivalent HPV vaccine on the incidence of these diseases.
  
  
  METHODS
  18 174 women (16-26 years) were enrolled and randomised to receive either quadrivalent HPV6/11/16/18 L1 virus-like-particle vaccine or placebo at day 1, and months 2 and 6. Individuals underwent detailed anogenital examination at day 1, 1 month after dose three, and at 6-12-month intervals for up to 48 months. Suspect genital lesions were biopsied and read by a panel of pathologists and vaccine HPV type-specific DNA testing was done. The primary endpoint was the combined incidence of VIN2-3 or VaIN2-3 associated with HPV16 or HPV18. Primary efficacy analyses were done in a per-protocol population.
  
  
  RESULTS
  The mean follow-up time was 3 years. Among women naive to HPV16 or HPV18 through 1 month after dose three (per-protocol population; vaccine n=7811; placebo n=7785), the vaccine was 100% effective (95% CI 72-100) against VIN2-3 or VaIN2-3 associated with HPV16 or HPV18. In the intention-to-treat population (which included 18 174 women who, at day 1, could have been infected with HPV16 or HPV18), vaccine efficacy against VIN2-3 or VaIN2-3 associated with HPV16 or HPV18 was 71% (37-88). The vaccine was 49% (18-69) effective against all VIN2-3 or VaIN2-3, irrespective of whether or not HPV DNA was detected in the lesion. The most common treatment-related adverse event was injection-site pain.
  
  
  CONCLUSIONS
  Prophylactic administration of quadrivalent HPV vaccine was effective in preventing high-grade vulval and vaginal lesions associated with HPV16 or HPV18 infection in women who were naive to these types before vaccination. With time, such vaccination could result in reduced rates of HPV-related vulval and vaginal cancers.
authors.affiliation: Department of Gynecology and Obstetrics, Medical University of Vienna, Vienna, Austria.
authors.forename: Elmar A
authors.initials: EA
authors.lastname: Joura
authors.forename: Sepp
authors.initials: S
authors.lastname: Leodolter
authors.forename: Mauricio
authors.initials: M
authors.lastname: Hernandez-Avila
authors.forename: Cosette M
authors.initials: CM
authors.lastname: Wheeler
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Perez
authors.forename: Laura A
authors.initials: LA
authors.lastname: Koutsky
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Garland
authors.forename: Diane M
authors.initials: DM
authors.lastname: Harper
authors.forename: Grace W K
authors.initials: GW
authors.lastname: Tang
authors.forename: Daron G
authors.initials: DG
authors.lastname: Ferris
authors.forename: Marc
authors.initials: M
authors.lastname: Steben
authors.forename: Ronald W
authors.initials: RW
authors.lastname: Jones
authors.forename: Janine
authors.initials: J
authors.lastname: Bryan
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Taddeo
authors.forename: Oliver M
authors.initials: OM
authors.lastname: Bautista
authors.forename: Mark T
authors.initials: MT
authors.lastname: Esser
authors.forename: Heather L
authors.initials: HL
authors.lastname: Sings
authors.forename: Micki
authors.initials: M
authors.lastname: Nelson
authors.forename: John W
authors.initials: JW
authors.lastname: Boslego
authors.forename: Carlos
authors.initials: C
authors.lastname: Sattler
authors.forename: Eliav
authors.initials: E
authors.lastname: Barr
authors.forename: Jorma
authors.initials: J
authors.lastname: Paavonen
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D006801:Humans; D015337:Multicenter Studies as Topic; D027383:Papillomaviridae / Q000276:immunology*; D030361:Papillomavirus Infections / Q000517:prevention & control*; D053918:Papillomavirus Vaccines; D016032:Randomized Controlled Trials as Topic; D002583:Uterine Cervical Neoplasms / Q000517:prevention & control*; D002578:Uterine Cervical Dysplasia / Q000517:prevention & control*
chemical_list: D053918:Papillomavirus Vaccines