Assessing the potential association between Epstein-Barr virus and oral squamous cell carcinoma: a systematic review and meta-analysis

Background: This study aims to qualitatively and quantitatively review the association between Epstein-Barr virus (EBV) and oral squamous cell carcinoma (OSCC). Methods: PubMed, Scopus, and Web of Science databases were searched using the keywords "EBV or Epstein Barr virus and Oral cancer or Oral squamous cell carcinoma" for published case-control studies in the English language upto August 2019. Results: The search yielded 985 articles out of which 966 articles were excluded by screening their titles and abstracts as they were irrelevant or duplicates. Based on the full-text assessment of the remaining 19 articles, only 7 satisfied the inclusion criteria and were included in the qualitative analysis, out of which only 4 were compatible to be included in the meta-analysis. The diagnostic modalities used included immunohistochemistry, in situ hybridization and polymerase chain reaction. The diagnostic targets included latent membrane protein (LMP)-1, EBV determined nuclear antigen-1, EBV-encoded small non-polyadenylated RNA-2. The meta-analysis showed that there is an association between the EBV and OSCC. Conclusions: Determining the association of EBV with OSCC is highly tedious due to the contrasting data obtained from individuals' studies which in turn is due to the wide variations in the sensitivity and specificity of the diagnostic modalities used and diagnostic targets selected. Although the meta-analysis revealed an association between EBV and OSCC, the number and the quality of the studies included in the meta-analysis are limited, thus the association requires further validation for any conclusive inference.