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The prevalence of viral agents in esophageal adenocarcinoma and Barrett’s esophagus: a systematic review

Kunzmann, Andrew T.a; Graham, Suzannea; McShane, Charlene M.a; Doyle, Jamesc; Tommasino, Massimoe; Johnston, Brianc; Jamison, Jackied; James, Jacqueline A.b; McManus, Damianc; Anderson, Lesley A.a

European Journal of Gastroenterology & Hepatology: July 2017 - Volume 29 - Issue 7 - p 817–825
doi: 10.1097/MEG.0000000000000868
Original Articles: Gastro-oesophageal Disorders

Background and aims 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 2=84–96%); however, sensitivity analyses did not show any major sources of heterogeneity.

Conclusion 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.

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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

Correspondence to Andrew T. Kunzmann, Institute of Clinical Sciences, Block B, Queens University Belfast, Royal Victoria Hospital, Belfast BT12 6BA, Northern Ireland Tel: +44 28 9097 1640; fax: +44 28 90235900; e-mail:

Received October 6, 2016

Accepted February 8, 2017

Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.