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

Background & Aims: Human papillomavirus (HPV), which may reach the esophagus via orogenital transmission, has been postulated to be associated with esophageal adenocarcinoma. A systematic review of the literature investigating the prevalence of infectious agents in esophageal adenocarcinoma and Barrett's esophagus was undertaken.
Methods: Using terms for viruses and esophageal adenocarcinoma, 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 esophageal adenocarcinoma or Barrett’s esophagus. Random effects meta-analyses of proportions were used to calculate the pooled prevalence and 95% confidence intervals (CI) of infections in esophageal adenocarcinoma and Barrett's esophagus.
Results: A total of 30 studies were included. The pooled prevalence of HPV in esophageal adenocarcinoma tumour samples was 13% (n=19 studies, 95% CI: 2-29%) and 26% (n=6 studies, 95% CI: 3-59%) in Barrett’s esophagus samples. HPV prevalence was higher in esophageal adenocarcinoma 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 esophageal adenocarcinoma 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 (I2=84-96%), however sensitivity analyses did not reveal any major sources of heterogeneity.
Conclusions: The prevalence of HPV and EBV in esophageal adenocarcinoma is low compared to 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 size and high quality detection methods is required.