Association between Epstein-Barr Virus and Oral Carcinoma: A Systematic Review with Meta-Analysis

The purpose of this meta-analysis is to evaluate the association of Epstein-Barr virus (EBV) with oral squamous cell carcinoma (OSCC). We searched the electronic scientific databases of PubMed and Scopus and included a total of 53 studies that were published from 1990 to 2019. The analysis yielded a 45.37% (95% confidence interval [CI]: 38.90-51.84; p < 0.001) overall pooled prevalence of EBV. Studies that used the applied methods of in situ hybridization, polymerase chain reaction, immunology, or RNA microarray showed the following pooled prevalence: 46.08%, 40.32, 54.97%, and 74.89%, respectively. EBV-infected individuals have a 2.5 higher risk for developing OSCC (odds ratio: 2.57; 95% CI: 1.23% to 5.36%; p < 0.001). The present meta-analysis supports the hypothesis of EBV association with OSCC, pointing to this virus as a risk factor for neoplasia. Our findings also suggest that EBV latent transcripts (latent membrane protein 1, EBV nuclear antigen 1 and 2, and EBV-encoded small RNAs) have an important role in this process. Furthermore, novel advancements could arise from large and standardized studies that are constructed to probe for other latent gene expression, eliminate confounding factors (tobacco, alcohol, and high-risk human papillomavirus infection), and define the relationship between EBV and oral carcinomas.