Meta-analysis Shows That Prevalence of Epstein–Barr Virus-Positive Gastric Cancer Differs Based on Sex and Anatomic Location

Background & Aims

Epstein–Barr virus (EBV) has been causally associated with cancer; some gastric carcinomas have a monoclonal EBV genome in every cancer cell, indicating that they arose from a single infected progenitor cell. However, the proportion of EBV-positive gastric carcinomas is uncertain, and the etiologic significance is unknown.

Methods

We conducted a meta-analysis of 70 studies including 15,952 cases of gastric cancer assessed by in situ hybridization for EBV-encoded small RNA.

Results

The pooled prevalence estimate of EBV positivity was 8.7% (95% confidence interval [CI]: 7.5%–10.0%) overall, with a 2-fold difference by sex: 11.1% (95% CI: 8.7%–14.1%) of gastric cancer cases in males vs 5.2% (95% CI: 3.6%–7.4%) of cases in females. Tumors arising in the gastric cardia (13.6%) or corpus (13.1%) were more than twice as likely to be EBV-positive as those in the antrum (5.2%; P < .01 for both comparisons). EBV prevalence was 4 times higher (35.1%) for tumors in postsurgical gastric stump/remnants. Over 90% of lymphoepithelioma-like carcinomas were EBV positive, but only 15 studies reported any cases of this type; prevalence did not significantly differ between the more common diffuse (7.6%) and intestinal (9.5%) histologies. EBV prevalence was similar in cases from Asia (8.3%), Europe (9.2%), and the Americas (9.9%).

Conclusions

EBV-positive gastric cancers greatly differ from other gastric carcinomas based on sex, anatomic subsite, and surgically disrupted anatomy, indicating that it is a distinct etiologic entity. Epidemiologic studies comparing EBV-positive and -negative gastric cancers are warranted to investigate EBV's role in gastric carcinogenesis.

Abbreviations used in this paper: EBV, Epstein–Barr virus, GC, gastric cancer, EBNAs, EBV nuclear antigens, LMPs, latent membrane proteins