title: The aetiological role of human papillomavirus in oesophageal squamous cell carcinoma: a meta-analysis.
abstract: BACKGROUND
  The aetiological role of human papillomavirus (HPV) in oesophageal squamous cell carcinoma (OSCC) has been widely researched for more than three decades, with conflicting findings. In the absence of a large, adequately powered single case-control study, a meta-analysis of all available case-control studies is the most rigorous way of identifying any potential association between HPV and OSCC. We present the first global meta-analysis of case-control studies investigating the role of HPV in OSCC.
  
  
  METHODS
  Case-control studies investigating OSCC tissue for presence of HPV DNA were identified. 21 case-control studies analyzing a total of 1223 cases and 1415 controls, met our inclusion criteria. HPV detection rates were tabulated for each study and all studies were assessed for quality. The random effects method was used to pool the odds ratios (OR).
  
  
  RESULTS
  From all OSCC specimens included in this meta-analysis, 35% (426/1223) were positive for HPV DNA. The pooled OR for an HPV-OSCC association was 3.04 (95% CI 2.20 to 4.20). Meta-regression analysis did not find a significant association between OR and any of the quality domains. Influence analysis was non-significant for the effect of individual studies on the pooled estimate. Studies conducted in countries with low to medium OSCC incidence showed a stronger relationship (OR 4.65, 95% CI 2.47 to 8.76) than regions of high OSCC incidence (OR 2.65, 95% CI 1.80 to 3.91).
  
  
  CONCLUSIONS
  Uncertainty around the aetiological role of HPV in OSCC is due largely to the small number and scale of appropriately designed studies. Our meta-analysis of these studies suggests that HPV increases the risk of OSCC three-fold. This study provides the strongest evidence to date of an HPV-OSCC association. The importance of these findings is that prophylactic vaccination could be of public health benefit in prevention of OSCC in countries with high OSCC incidence.
authors.affiliation: School of Public Health and Community Medicine, UNSW Medicine, University of New South Wales, Sydney, Australia. surabhi_liyanage@hotmail.com
authors.forename: Surabhi S
authors.initials: SS
authors.lastname: Liyanage
authors.forename: Bayzidur
authors.initials: B
authors.lastname: Rahman
authors.forename: Iman
authors.initials: I
authors.lastname: Ridda
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Newall
authors.forename: Sepehr N
authors.initials: SN
authors.lastname: Tabrizi
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Garland
authors.forename: Eva
authors.initials: E
authors.lastname: Segelov
authors.forename: Holly
authors.initials: H
authors.lastname: Seale
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Crowe
authors.forename: Aye
authors.initials: A
authors.lastname: Moa
authors.forename: C Raina
authors.initials: CR
authors.lastname: Macintyre
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000209:etiology* / Q000821:virology*; D016022:Case-Control Studies; D004938:Esophageal Neoplasms / Q000209:etiology* / Q000821:virology*; D000077277:Esophageal Squamous Cell Carcinoma; D006801:Humans; D027383:Papillomaviridae / Q000472:pathogenicity*; D030361:Papillomavirus Infections / Q000150:complications* / Q000821:virology*
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