title: A 9-valent HPV vaccine against infection and intraepithelial neoplasia in women.
abstract: BACKGROUND
  The investigational 9-valent viruslike particle vaccine against human papillomavirus (HPV) includes the HPV types in the quadrivalent HPV (qHPV) vaccine (6, 11, 16, and 18) and five additional oncogenic types (31, 33, 45, 52, and 58). Here we present the results of a study of the efficacy and immunogenicity of the 9vHPV vaccine in women 16 to 26 years of age.
  
  
  METHODS
  We performed a randomized, international, double-blind, phase 2b-3 study of the 9vHPV vaccine in 14,215 women. Participants received the 9vHPV vaccine or the qHPV vaccine in a series of three intramuscular injections on day 1 and at months 2 and 6. Serum was collected for analysis of antibody responses. Swabs of labial, vulvar, perineal, perianal, endocervical, and ectocervical tissue were obtained and used for HPV DNA testing, and liquid-based cytologic testing (Papanicolaou testing) was performed regularly. Tissue obtained by means of biopsy or as part of definitive therapy (including a loop electrosurgical excision procedure and conization) was tested for HPV.
  
  
  RESULTS
  The rate of high-grade cervical, vulvar, or vaginal disease irrespective of HPV type (i.e., disease caused by HPV types included in the 9vHPV vaccine and those not included) in the modified intention-to-treat population (which included participants with and those without prevalent infection or disease) was 14.0 per 1000 person-years in both vaccine groups. The rate of high-grade cervical, vulvar, or vaginal disease related to HPV-31, 33, 45, 52, and 58 in a prespecified per-protocol efficacy population (susceptible population) was 0.1 per 1000 person-years in the 9vHPV group and 1.6 per 1000 person-years in the qHPV group (efficacy of the 9vHPV vaccine, 96.7%; 95% confidence interval, 80.9 to 99.8). Antibody responses to HPV-6, 11, 16, and 18 were noninferior to those generated by the qHPV vaccine. Adverse events related to injection site were more common in the 9vHPV group than in the qHPV group.
  
  
  CONCLUSIONS
  The 9vHPV vaccine prevented infection and disease related to HPV-31, 33, 45, 52, and 58 in a susceptible population and generated an antibody response to HPV-6, 11, 16, and 18 that was noninferior to that generated by the qHPV vaccine. The 9vHPV vaccine did not prevent infection and disease related to HPV types beyond the nine types covered by the vaccine. (Funded by Merck; ClinicalTrials.gov number, NCT00543543).
authors.affiliation: From the Medical University of Vienna, Comprehensive Cancer Center, Vienna (E.A.J.); Moffitt Cancer Center, Tampa, FL (A.R.G.); Department of Clinical Medicine, University of Bergen-Haukeland University Hospital, Bergen, Norway (O.-E.I.); Université Laval, Québec, QC (C.B.), and University of British Columbia, Vancouver (G.S.) - both in Canada; University of Washington, Seattle (C.M.); Coordinating Research Center, Frederiksberg Hospital, University of Copenhagen (J.M.), and Danish Cancer Society Research Center and Department of Gynecology, Rigshospitalet (S.K.K.) - all in Copenhagen; Associação Obras Sociais Irmã Dulce and Oswaldo Cruz Foundation, Brazilian Ministry of Health, Bahia, Brazil (E.D.M.); University of Hong Kong, Hong Kong (Y.N.); Aarhus University Hospital, Department of Obstetrics and Gynecology, Aarhus, Denmark (L.K.P.); Instituto Nacional de Salud Pública, Cuernavaca, Morelos, Mexico (E.L.-P.); Faculty of Tropical Medicine, Mahidol University, Nakhon Pathom, Thailand (P.P.); Investigación Clínica, Medellín, Colombia (J.A.R.); Department of Gynecology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (L.W.); Mackay Memorial Hospital, Taipei, Taiwan (Y.C.Y.); Wolfson Institute of Preventive Medicine, London (J. Cuzick); Royal Women's Hospital, University of Melbourne and Murdoch Childrens Research Institute, Parkville, VIC, Australia (S.M.G.); Division of Gynecologic Oncology, University of Alabama, Birmingham (W.H.); and Merck, Whitehouse Station, NJ (O.M.B., I.S.F.C., J. Chen, R.G., E.M., M.R., S.V., A.L.).
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mesh_terms: D000293:Adolescent; D000328:Adult; D052685:Alphapapillomavirus; D000914:Antibodies, Viral / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D005831:Genital Diseases, Female / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D057194:Intention to Treat Analysis; D030361:Papillomavirus Infections / Q000453:epidemiology / Q000517:prevention & control*; D053918:Papillomavirus Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D002583:Uterine Cervical Neoplasms / Q000517:prevention & control* / Q000821:virology; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000517:prevention & control* / Q000821:virology
chemical_list: D000914:Antibodies, Viral; D053918:Papillomavirus Vaccines