Associations Between Gastric Cancer Risk and Virus Infection Other Than Epstein-Barr Virus: A Systematic Review and Meta-analysis Based on Epidemiological Studies

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Abstract
INTRODUCTION: Besides Helicobacter pylori and Epstein-Barr virus, other viruses might play potential roles in gastric carcinogenesis. This systematic review and meta-analysis was conducted to compare the prevalence of the viruses between gastric cancer (GC) and any controls. METHODS: Comprehensive literature was searched up to January 25, 2019, and search was updated on April 6, 2020. The studies that compared the prevalence of viruses other than Epstein-Barr virus between GC and healthy or nonmalignant controls were eligible. Stata 12.0 software was used for heterogeneity tests and meta-analyses. Meanwhile, subgroup analysis, sensitivity analysis, and publication bias evaluation were performed where applicable. The power (1–β) was estimated by the PASS 11 software for each individual study. RESULTS: A total of 41 eligible studies were included, concerning 11 kinds of viruses. Prevalence were significantly higher in GC for hepatitis B virus (odds ratio [OR] = 1.39, 95% confidence interval [CI] 1.11–1.75), human cytomegalovirus (OR = 2.25, 95% CI 1.14–4.43), human papillomavirus (HPV) (OR = 1.63, 95% CI 1.05–2.54), and John Cunningham virus (OR = 2.52, 95% CI 1.26–5.04). In subgroup analyses, HPV-16 infection was significantly associated with GC (OR = 2.42, 95% CI 1.00–5.83). DISCUSSION: This study demonstrated that hepatitis B virus, human cytomegalovirus, HPV, and John Cunningham virus were more prevalent in GC. However, the causal relationship between their infection and risk of GC remains inconclusive, and further investigations are required.

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