title: Sustained efficacy up to 4.5 years of a bivalent L1 virus-like particle vaccine against human papillomavirus types 16 and 18: follow-up from a randomised control trial.
abstract: BACKGROUND
  Effective vaccination against HPV 16 and HPV 18 to prevent cervical cancer will require a high level of sustained protection against infection and precancerous lesions. Our aim was to assess the long-term efficacy, immunogenicity, and safety of a bivalent HPV-16/18 L1 virus-like particle AS04 vaccine against incident and persistent infection with HPV 16 and HPV 18 and their associated cytological and histological outcomes.
  
  
  METHODS
  We did a follow-up study of our multicentre, double-blind, randomised, placebo-controlled trial reported in 2004. We included women who originally received all three doses of bivalent HPV-16/18 virus-like particle AS04 vaccine (0.5 mL; n=393) or placebo (n=383). We assessed HPV DNA, using cervical samples, and did yearly cervical cytology assessments. We also studied the long-term immunogenicity and safety of the vaccine.
  
  
  RESULTS
  More than 98% seropositivity was maintained for HPV-16/18 antibodies during the extended follow-up phase. We noted significant vaccine efficacy against HPV-16 and HPV-18 endpoints: incident infection, 96.9% (95% CI 81.3-99.9); persistent infection: 6 month definition, 94.3 (63.2-99.9); 12 month definition, 100% (33.6-100). In a combined analysis of the initial efficacy and extended follow-up studies, vaccine efficacy of 100% (42.4-100) against cervical intraepithelial neoplasia (CIN) lesions associated with vaccine types. We noted broad protection against cytohistological outcomes beyond that anticipated for HPV 16/18 and protection against incident infection with HPV 45 and HPV 31. The vaccine has a good long-term safety profile.
  
  
  CONCLUSIONS
  Up to 4.5 years, the HPV-16/18 L1 virus-like particle AS04 vaccine is highly immunogenic and safe, and induces a high degree of protection against HPV-16/18 infection and associated cervical lesions. There is also evidence of cross protection.
authors.affiliation: Department of Obstetrics and Gynecology, Norris Cotton Cancer Center, Dartmouth Medical School, Rubin 880, One Medical Center Drive, Lebanon, NH 03756, 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 M
authors.initials: CM
authors.lastname: Wheeler
authors.forename: Anna-Barbara
authors.initials: AB
authors.lastname: Moscicki
authors.forename: Barbara
authors.initials: B
authors.lastname: Romanowski
authors.forename: Cecilia M
authors.initials: CM
authors.lastname: Roteli-Martins
authors.forename: David
authors.initials: D
authors.lastname: Jenkins
authors.forename: Anne
authors.initials: A
authors.lastname: Schuind
authors.forename: Sue Ann
authors.initials: SA
authors.lastname: Costa Clemens
authors.forename: Gary
authors.initials: G
authors.lastname: Dubin
mesh_terms: D000328:Adult; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015337:Multicenter Studies as Topic; D027383:Papillomaviridae / Q000276:immunology*; D030361:Papillomavirus Infections / Q000150:complications / Q000517:prevention & control*; D053918:Papillomavirus Vaccines; D016032:Randomized Controlled Trials as Topic; D013997:Time Factors; D002583:Uterine Cervical Neoplasms / Q000209:etiology / Q000517:prevention & control; D014765:Viral Vaccines / Q000009:adverse effects / Q000145:classification / Q000276:immunology*; D002578:Uterine Cervical Dysplasia / Q000209:etiology / Q000517:prevention & control
chemical_list: D053918:Papillomavirus Vaccines; D014765:Viral Vaccines