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Relevance of Epstein–Barr virus infection in the oral squamous cell carcinoma: A meta-analysis

Alberto Rodriguez Archilla, Katerina Lopatková


Objectives: The objectives of the study were to assess the main risk factors related to Epstein–Barr virus (EBV) infection on oral squamous cell carcinoma (OSCC) and the influence on its biological behavior. Methodology: A search for articles on EBV infection and mouth neoplasms was performed in the next electronic databases: PubMed (MEDLINE, Cochrane Library), Web of Science, and Spanish Medical Index (IME). From 600 potentially eligible articles, 575 were excluded for several reasons: Articles without full-text availability (201), studies on hairy leukoplakia (256), studies in patients without OSCC (42), studies on malignant salivary gland neoplasms (19), studies in HIV+ or immunocompromised patients (14), and studies with non-usable data (43). Finally, 25 studies were included in this meta-analysis. The statistical software RevMan 5.3 (The Cochrane Collaboration, Oxford, UK) was used to analyze the data. For dichotomous outcomes, the estimates of effects of an intervention were expressed as odds ratio (OR) using the Mantel-Haenszel method with 95% confidence intervals. Results: About 46.3% of oral cancers were infected with EBV. Oral cancer patients had more than triple the risk of being infected with EBV than controls (OR: 3.48, P = 0.01). In contrast, age (>60 years), gender (women), tumor location (tongue-floor of the mouth), tumor differentiation degree (well differentiated), or tumor stage (III and IV) were parameters without significant influence (P > 0.05) in oral cancers infected with EBV. Conclusion: EBV infection may be an important risk factor in oral cancer. Clinical Significance: Specific treatment of EBV infection can improve the biological behavior of oral cancers toward less aggressive tumors.


Epstein–Barr virus infections; herpesvirus 4 human; mouth neoplasms; oral manifestations; prognosis; risk factors

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