title: The prevalence of viral agents in esophageal adenocarcinoma and Barrett's esophagus: a systematic review.
abstract: OBJECTIVE
  Human papilloma virus (HPV), which may reach the esophagus through orogenital transmission, has been postulated to be associated with esophageal adenocarcinoma (EAC). A systematic review of the literature investigating the prevalence of infectious agents in EAC and Barrett's esophagus (BE) was carried out.
  
  
  METHODS
  Using terms for viruses and EAC, the Medline, Embase, and Web of Science databases were systematically searched for studies published, in any language, until June 2016 that assessed the prevalence of viral agents in EAC or BE. Random-effects meta-analyses of proportions were carried out to calculate the pooled prevalence and 95% confidence intervals (CIs) of infections in EAC and BE.
  
  
  RESULTS
  A total of 30 studies were included. The pooled prevalence of HPV in EAC tumor samples was 13% (n=19 studies, 95% CI: 2-29%) and 26% (n=6 studies, 95% CI: 3-59%) in BE samples. HPV prevalence was higher in EAC tissue than in esophageal tissue from healthy controls (n=5 studies, pooled odds ratio=3.31, 95% CI: 1.15-9.50). The prevalence of Epstein-Barr virus (EBV) in EAC was 6% (n=5, 95% CI: 0-27%). Few studies have assessed other infectious agents. For each of the analyses, considerable between-study variation was observed (I=84-96%); however, sensitivity analyses did not show any major sources of heterogeneity.
  
  
  CONCLUSIONS
  The prevalence of HPV and EBV in EAC is low compared with other viral-associated cancers, but may have been hampered by small sample sizes and detection methods susceptible to fixation processes. Additional research with adequate sample sizes and high-quality detection methods is required.
authors.affiliation: aCancer Epidemiology and Health Services Research Group, Centre for Public Health bNorthern Ireland Biobank, Centre for Cancer Research and Cell Biology, Queens University Belfast cRoyal Victoria Hospital, Belfast Health and Social Care Trust dAntrim Area Hospital Laboratory, Department of Cellular Cytopathology and Molecular Pathology, Northern Health and Social Care Trust, Northern Ireland eInfections and Cancer Biology Group, International Agency for Research on Cancer, World Health Organization, Lyon, France.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Kunzmann
authors.forename: Suzanne
authors.initials: S
authors.lastname: Graham
authors.forename: Charlene M
authors.initials: CM
authors.lastname: McShane
authors.forename: James
authors.initials: J
authors.lastname: Doyle
authors.forename: Massimo
authors.initials: M
authors.lastname: Tommasino
authors.forename: Brian
authors.initials: B
authors.lastname: Johnston
authors.forename: Jackie
authors.initials: J
authors.lastname: Jamison
authors.forename: Jacqueline A
authors.initials: JA
authors.lastname: James
authors.forename: Damian
authors.initials: D
authors.lastname: McManus
authors.forename: Lesley A
authors.initials: LA
authors.lastname: Anderson
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000453:epidemiology / Q000821:virology*; D001471:Barrett Esophagus / Q000175:diagnosis / Q000453:epidemiology / Q000821:virology*; D016009:Chi-Square Distribution; D020031:Epstein-Barr Virus Infections / Q000175:diagnosis / Q000453:epidemiology / Q000821:virology*; D004938:Esophageal Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000821:virology*; D004854:Herpesvirus 4, Human / Q000302:isolation & purification*; D006801:Humans; D016017:Odds Ratio; D027383:Papillomaviridae / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000175:diagnosis / Q000453:epidemiology / Q000821:virology*; D015995:Prevalence; D012307:Risk Factors