title: Efficacy of a bivalent L1 virus-like particle vaccine in prevention of infection with human papillomavirus types 16 and 18 in young women: a randomised controlled trial.
abstract: BACKGROUND
  Vaccination against the most common oncogenic human papillomavirus (HPV) types, HPV-16 and HPV-18, could prevent development of up to 70% of cervical cancers worldwide. We did a randomised, double-blind, controlled trial to assess the efficacy, safety, and immunogenicity of a bivalent HPV-16/18 L1 virus-like particle vaccine for the prevention of incident and persistent infection with these two virus types, associated cervical cytological abnormalities, and precancerous lesions.
  
  
  METHODS
  We randomised 1113 women between 15-25 years of age to receive three doses of either the vaccine formulated with AS04 adjuvant or placebo on a 0 month, 1 month, and 6 month schedule in North America and Brazil. Women were assessed for HPV infection by cervical cytology and self-obtained cervicovaginal samples for up to 27 months, and for vaccine safety and immunogenicity.
  
  
  RESULTS
  In the according-to-protocol analyses, vaccine efficacy was 91.6% (95% CI 64.5-98.0) against incident infection and 100% against persistent infection (47.0-100) with HPV-16/18. In the intention-to-treat analyses, vaccine efficacy was 95.1% (63.5-99.3) against persistent cervical infection with HPV-16/18 and 92.9% (70.0-98.3) against cytological abnormalities associated with HPV-16/18 infection. The vaccine was generally safe, well tolerated, and highly immunogenic.
  
  
  CONCLUSIONS
  The bivalent HPV vaccine was efficacious in prevention of incident and persistent cervical infections with HPV-16 and HPV-18, and associated cytological abnormalities and lesions. Vaccination against such infections could substantially reduce incidence of cervical cancer.
authors.affiliation: Department of Obstetrics and Gynecology, Norris Cotton Cancer Center, Dartmouth Medical School, Hanover, NH, USA. diane.m.harper@dartmouth.edu
authors.forename: Diane M
authors.initials: DM
authors.lastname: Harper
authors.forename: Eduardo L
authors.initials: EL
authors.lastname: Franco
authors.forename: Cosette
authors.initials: C
authors.lastname: Wheeler
authors.forename: Daron G
authors.initials: DG
authors.lastname: Ferris
authors.forename: David
authors.initials: D
authors.lastname: Jenkins
authors.forename: Anne
authors.initials: A
authors.lastname: Schuind
authors.forename: Toufik
authors.initials: T
authors.lastname: Zahaf
authors.forename: Bruce
authors.initials: B
authors.lastname: Innis
authors.forename: Paulo
authors.initials: P
authors.lastname: Naud
authors.forename: Newton S
authors.initials: NS
authors.lastname: De Carvalho
authors.forename: Cecilia M
authors.initials: CM
authors.lastname: Roteli-Martins
authors.forename: Julio
authors.initials: J
authors.lastname: Teixeira
authors.forename: Mark M
authors.initials: MM
authors.lastname: Blatter
authors.forename: Abner P
authors.initials: AP
authors.lastname: Korn
authors.forename: Wim
authors.initials: W
authors.lastname: Quint
authors.forename: Gary
authors.initials: G
authors.lastname: Dubin
mesh_terms: D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D002213:Capsid / Q000276:immunology; D036022:Capsid Proteins; D002584:Cervix Uteri / Q000821:virology; D004306:Dose-Response Relationship, Immunologic; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007115:Immunization Schedule; D009500:Neutralization Tests; D009856:Oncogene Proteins, Viral / Q000276:immunology*; D027383:Papillomaviridae / Q000276:immunology*; D030361:Papillomavirus Infections / Q000517:prevention & control*; D053918:Papillomavirus Vaccines; D002577:Uterine Cervical Diseases / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000517:prevention & control* / Q000821:virology; D014765:Viral Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D002578:Uterine Cervical Dysplasia / Q000821:virology
chemical_list: D000914:Antibodies, Viral; D036022:Capsid Proteins; C114580:HPV L1 protein, Human papillomavirus; D009856:Oncogene Proteins, Viral; D053918:Papillomavirus Vaccines; D014765:Viral Vaccines