title: Systematic review and meta-analysis of L1-VLP-based human papillomavirus vaccine efficacy against anogenital pre-cancer in women with evidence of prior HPV exposure.
abstract: BACKGROUND
  It is unclear whether L1-VLP-based human papillomavirus (HPV) vaccines are efficacious in reducing the likelihood of anogenital pre-cancer in women with evidence of prior vaccine-type HPV exposure. This study aims to determine whether the combined results of the vaccine trials published to date provide evidence of efficacy compared with control (hepatitis A vaccine/placebo).
  
  
  METHODS
  A systematic review and meta-analysis was conducted. Randomized-controlled trials (RCTs) were identified from MEDLINE, Embase, Web of Science, PubMed, Cochrane Central Register of Controlled Trials and references of identified studies. The bivalent vaccine containing HPV-16 and 18 VLPs from GlaxoSmithKline Biologicals (Rixenstart, Belgium), the quadrivalent vaccine containing HPV-6, 11, 16, and 18 VLPs from Merck & Co., Inc., (Whitehouse Station, NJ USA), and the HPV-16 monovalent vaccine from Merck Research Laboratories (West Point, PA USA) were evaluated.
  
  
  RESULTS
  Three RCT reports and two post-trial cohort studies were eligible, comprising data from 13,482 women who were included in the vaccine studies but had evidence of HPV infection at study entry. Data on efficacy was synthesized using the Mantel-Haenszel weighted fixed-effect approach, or where there was heterogeneity between studies, the DerSimonian and Laird weighted random-effect approach. The mean odds ratio (OR) and 95% confidence interval (CI) for the association between Cervarix, Gardasil and HPV-16 monovalent vaccine and HPV-associated cervical intraepithelial neoplasia grade 3 or worse was 0·90 (95% CI: 0·56, 1·44). For the association between Gardasil and HPV-associated vulval/vaginal intraepithelial neoplasia grades 2-3, the overall OR and 95% CI was 2.25 (95% CI: 0·78, 6.50). Sample size and follow-up were limited.
  
  
  CONCLUSIONS
  There was no evidence that HPV vaccines are effective in preventing vaccine-type HPV associated pre-cancer in women with evidence of prior HPV exposure. Small effects of vaccination however cannot be excluded and a longer-term benefit in preventing re-infection remains possible.
authors.affiliation: Centre for Sexual Health and HIV Research, Research Department of Infection and Population Health, Mortimer Market Centre, University College London, London, United Kingdom.
authors.forename: Ada
authors.initials: A
authors.lastname: Miltz
authors.affiliation: Centre for Sexual Health and HIV Research, Research Department of Infection and Population Health, Mortimer Market Centre, University College London, London, United Kingdom.
authors.forename: Huw
authors.initials: H
authors.lastname: Price
authors.affiliation: Centre for Sexual Health and HIV Research, Research Department of Infection and Population Health, Mortimer Market Centre, University College London, London, United Kingdom.
authors.forename: Maryam
authors.initials: M
authors.lastname: Shahmanesh
authors.affiliation: Centre for Sexual Health and HIV Research, Research Department of Infection and Population Health, Mortimer Market Centre, University College London, London, United Kingdom.
authors.forename: Andrew
authors.initials: A
authors.lastname: Copas
authors.affiliation: Centre for Sexual Health and HIV Research, Research Department of Infection and Population Health, Mortimer Market Centre, University College London, London, United Kingdom.
authors.forename: Richard
authors.initials: R
authors.lastname: Gilson
mesh_terms: D052685:Alphapapillomavirus / Q000276:immunology* / Q000302:isolation & purification; D001005:Anus Neoplasms / Q000517:prevention & control*; D015331:Cohort Studies; D005260:Female; D005833:Genital Neoplasms, Female / Q000517:prevention & control*; D000068857:Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18; D006801:Humans; D053918:Papillomavirus Vaccines / Q000627:therapeutic use*; D011230:Precancerous Conditions / Q000517:prevention & control*; D016032:Randomized Controlled Trials as Topic
chemical_list: D000068857:Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18; D053918:Papillomavirus Vaccines