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 sexually active women aged 16-26 years.
abstract: BACKGROUND
  We evaluated the impact of a quadrivalent human papillomavirus (HPV) vaccine on infection and cervical disease related to 10 nonvaccine HPV types (31, 33, 35, 39, 45, 51, 52, 56, 58, and 59) associated with >20% of cervical cancers. The population evaluated included HPV-naive women and women with preexisting HPV infection and/or HPV-related disease at enrollment.
  
  
  METHODS
  Phase 3 efficacy studies enrolled 17,622 women aged 16-26 years. Subjects underwent cervicovaginal sampling and Pap testing on day 1 and then at 6-12-month intervals for up to 4 years. HPV typing was performed on samples from enrollment and follow-up visits, including samples obtained for diagnosis or treatment of HPV-related disease. All subjects who received 1 dose and returned for follow-up were included.
  
  
  RESULTS
  Vaccination reduced the rate of HPV-31/33/45/52/58 infection by 17.7% (95% confidence interval [CI], 5.1% to 28.7%) and of cervical intraepithelial neoplasia (CIN) 1-3 or adenocarcinoma in situ (AIS) by 18.8% (95% CI, 7.4% to 28.9%). Vaccination also reduced the rate of HPV-31/58/59-related CIN1-3/AIS by 26.0% (95% CI, 6.7% to 41.4%), 28.1% (95% CI, 5.3% to 45.6%), and 37.6% (95% CI, 6.0% to 59.1%), respectively. Although a modest reduction in HPV-31/33/45/52/58-related CIN2 or worse was observed, the estimated reduction was not statistically significant.
  
  
  CONCLUSIONS
  These cross-protection results complement the vaccine's prophylactic efficacy against disease associated with HPV-6, -11, -16, and -18. Long-term monitoring of vaccinated populations are needed to fully ascertain the population-based impact and public health significance of these findings.
  
  
  BACKGROUND
  ClinicalTrials.gov identifiers: NCT00092521 , NCT00092534 , and NCT00092482.
authors.affiliation: University of New Mexico, Department of Molecular Genetics and Microbiology, Albuquerque, NM 87131, USA. cwheeler@salud.unm.edu
authors.forename: Cosette M
authors.initials: CM
authors.lastname: Wheeler
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
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authors.lastname: Hernandez-Avila
authors.forename: Gonzalo
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authors.lastname: Perez
authors.forename: Darron R
authors.initials: DR
authors.lastname: Brown
authors.forename: Laura A
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authors.lastname: Tay
authors.forename: Patricia
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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
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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
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authors.lastname: Steben
authors.forename: F Xavier
authors.initials: FX
authors.lastname: Bosch
authors.forename: Joakim
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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
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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: Margaret
authors.initials: M
authors.lastname: James
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
mesh_terms: D000230:Adenocarcinoma / Q000517:prevention & control / Q000821:virology; 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; D002578:Uterine Cervical Dysplasia / Q000517:prevention & control / Q000821:virology
chemical_list: D053918:Papillomavirus Vaccines