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

Abstract

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.

Exploring the link between viruses and cancer in companion animals: a comprehensive and comparative analysis

“…They are double-stranded DNA viruses classified into three different subfamilies, Alfaherpesvirinae , Betaherpesvirinae and Gammaherpevirinae [ 213 ]. In humans, two Gammaharpesvirus are frequently associated with HIV-related neoplasms [ 214 , 215 ], namely Epstein-Barr virus (EBV, Human Herpesvirus 4) and Kaposi’s sarcoma-associated herpesvirus (KSHV, Human Herpesvirus 8). KSHV belongs to the Rhadinovirus genus, it is responsible for epidemic Kaposi’s sarcoma, frequently associated with HIV infection [ 216 , 217 ].…”

Human papillomavirus and Epstein‐Barr virus co‐infection in oral and oropharyngeal squamous cell carcinomas: A systematic review and meta‐analysis

“…EBV is regarded as the major causative agent in nasopharyngeal carcinoma and, although there are numerous reports of detection of the EBV genome in both normal and malignant oral epithelial tissues, the role of EBV in oral oncogenesis remains unclear (Jiang et al., 2012; Kis et al., 2009; Shamaa et al., 2008; Zebardast et al., 2021). As the oral cavity is contiguous with the nasopharynx and is a primary site for transmission and persistence of EBV, a causative link has long seemed likely but remains unproven (Rahman et al., 2022).…”

Betel Quid Chewing and Alcohol Consumption Co- Variate with Detection of Epstein - Barr Virus (EBV) DNA in Oral Squamous Cell Carcinoma Tissues: Preliminary Evidence from a Subset of an Unmatched Case-Control Study

“…Nevertheless, any covariation of EBV with oral risk habits is yet to be established globally as well as in Sri Lanka. In light of these findings, the present study aimed to explore the detection of Epstein-Barr virus (EBV) DNA in oral squamous cell carcinoma tissues of a group of Sri Lankan male patients [6].…”