Malignant Salivary Gland Tumors and Epstein-Barr Virus (EBV) Infection: A Systematic Review and Meta-Analysis

Background: Salivary gland tumors are rare head and neck tumors with lymphoepithelial carcinoma (LEC) as a particularly infrequent variant. This study was an evaluation of the incidence of EBV infection in malignant salivary gland tumors with the emphasis on tumor type and geographical area. Methods: Five databases (PubMed, ScienceDirect, Scopus, Web of Science and Cochrane library) were searched for data on the prevalence of EBV in malignant salivary gland tumors. A random-effects meta-analysis was conducted with Comprehensive Meta-Analysis software version 2.0 (CMA 2.0) using the event rate (ER) for estimation of the incidence of EBV in the salivary gland tumor patients. Publication bias was lacking as assessed through funnel plot analysis with the Begg’s and Egger’s tests (P>0.05). Results: Out of 618 studies searched in databases, 19 reported the prevalence of EBV in malignant salivary gland tumors and were included in the present meta-analysis. The pooled ER of all studies was 44% [95%CI=21.5-69.2%] with extreme heterogeneity that for the studies in America was 44.2% [95%CI=4.1-93.6%], in Asia (249 patients) was 70% [95%CI= 33.4-91.6%] and in Europe was 11.8% [95%CI=7.4-85.5%] with extreme heterogeneity for three subgroups. The pooled ER for patients with undifferentiated carcinoma was 86.7% [95%CI=71.5-94.4%] compared with 6.6% [95%CI=2.5-16.5%] for other carcinomas. Conclusions: The incidence of EBV infection in malignant salivary gland tumors in Asia was greater than in Europe and America and the higher presence of EBV infection in LEC cases implies that EBV may be a major factor in its etiology or pathogenesis. Genetic, environmental and other geographic factors may also be involved.