Potential Role of Epstein–Barr Virus in Oral Potentially Malignant Disorders and Oral Squamous Cell Carcinoma: A Scoping Review

Though the oral cavity is anatomically proximate to the nasal cavity and acts as a key reservoir of EBV habitation and transmission, it is still unclear whether EBV plays a significant role in oral carcinogenesis. Many studies have detected EBV DNA in tissues and exfoliated cells from OSCC patients. However, very few studies have investigated the expression of functional EBV proteins implicated in its oncogenicity. The most studied are latent membrane protein 1 (LMP-1), a protein associated with the activation of signalling pathways; EBV determined nuclear antigen (EBNA)-1, a protein involved in the regulation of gene expression; and EBV-encoded small non-polyadenylated RNA (EBER)-2. LMP-1 is considered the major oncoprotein, and overexpression of LMP-1 observed in OSCC indicates that this molecule might play a significant role in oral carcinogenesis. Although numerous studies have detected EBV DNA and proteins from OSCC and oral potentially malignant disorders, heterogeneity in methodologies has led to discrepant results, hindering interpretation. Elucidating the exact functions of EBV and its proteins when expressed is vital in establishing the role of viruses in oral oncogenesis. This review summarises the current evidence on the potential role of EBV in oral oncogenesis and discusses the implications as well as recommendations for future research.