title: The impact of quadrivalent human papillomavirus (HPV; types 6, 11, 16, and 18) L1 virus-like particle vaccine on infection and disease due to oncogenic nonvaccine HPV types in generally HPV-naive women aged 16-26 years.
abstract: BACKGROUND
  Human papillomavirus (HPV)-6/11/16/18 vaccine reduces the risk of HPV-6/11/16/18-related cervical intraepithelial neoplasia (CIN) 1-3 or adenocarcinoma in situ (AIS). Here, its impact on CIN1-3/AIS associated with nonvaccine oncogenic HPV types was evaluated.
  
  
  METHODS
  We enrolled 17,622 women aged 16-26 years. All underwent cervicovaginal sampling and Pap testing at regular intervals for up to 4 years. HPV genotyping was performed for biopsy samples, and histological diagnoses were determined by a pathology panel. Analyses were conducted among subjects who were negative for 14 HPV types on day 1. Prespecified analyses included infection of 6 months' duration and CIN1-3/AIS due to the 2 and 5 most common HPV types in cervical cancer after HPV types 16 and 18, as well as all tested nonvaccine types.
  
  
  RESULTS
  Vaccination reduced the incidence of HPV-31/45 infection by 40.3% (95% confidence interval [CI], 13.9% to 59.0%) and of CIN1-3/AIS by 43.6% (95% CI, 12.9% to 64.1%), respectively. The reduction in HPV-31/33/45/52/58 infection and CIN1-3/AIS was 25.0% (95% CI, 5.0% to 40.9%) and 29.2% (95% CI, 8.3% to 45.5%), respectively. Efficacy for CIN2-3/AIS associated with the 10 nonvaccine HPV types was 32.5% (95% CI, 6.0% to 51.9%). Reductions were most notable for HPV-31.
  
  
  CONCLUSIONS
  HPV-6/11/16/18 vaccine reduced the risk of CIN2-3/AIS associated with nonvaccine types responsible for approximately 20% of cervical cancers. The clinical benefit of cross-protection is not expected to be fully additive to the efficacy already observed against HPV-6/11/16/18-related disease, because women may have >1 CIN lesion, each associated with a different HPV type.
  
  
  BACKGROUND
  ClinicalTrials.gov identifiers: NCT00092521 , NCT00092534 , and NCT00092482.
authors.affiliation: Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA. darfrow@iupui.edu
authors.forename: Darron R
authors.initials: DR
authors.lastname: Brown
authors.forename: Susanne K
authors.initials: SK
authors.lastname: Kjaer
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: 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: Eng Hseon
authors.initials: EH
authors.lastname: Tay
authors.forename: Patricía
authors.initials: P
authors.lastname: Garcia
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: Marc
authors.initials: M
authors.lastname: Steben
authors.forename: F Xavier
authors.initials: FX
authors.lastname: Bosch
authors.forename: Joakim
authors.initials: J
authors.lastname: Dillner
authors.forename: Elmar A
authors.initials: EA
authors.lastname: Joura
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Kurman
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
authors.initials: J
authors.lastname: Bryan
authors.forename: Lisa C
authors.initials: LC
authors.lastname: Lupinacci
authors.forename: Katherine E D
authors.initials: KE
authors.lastname: Giacoletti
authors.forename: Heather L
authors.initials: HL
authors.lastname: Sings
authors.forename: Margaret
authors.initials: M
authors.lastname: James
authors.forename: Teresa M
authors.initials: TM
authors.lastname: Hesley
authors.forename: Eliav
authors.initials: E
authors.lastname: Barr
mesh_terms: D000293:Adolescent; D000328:Adult; D052685:Alphapapillomavirus / Q000145:classification / Q000235:genetics / Q000276:immunology*; D005260:Female; D006801:Humans; D030361:Papillomavirus Infections / Q000517:prevention & control* / Q000821:virology; D053918:Papillomavirus Vaccines; D002583:Uterine Cervical Neoplasms / Q000517:prevention & control / Q000821:virology; D055815:Young Adult
chemical_list: D053918:Papillomavirus Vaccines