The role of Epstein-Barr virus in the pathogenesis of NasoPharyngeal Carcinoma

Nasopharyngeal Carcinoma (NPC) is a cancer of the head and neck originating from the epithelial cells of the nasopharynx. It is particularly prevalent in South and Southeast Asia as well as in North Africa, where its aggressive nature and high mortality index underscore the imperative for developing efficient diagnostic and therapeutic strategies. This paper examines the impact of Epstein-Barr Virus (EBV) on NPC development by considering its latent genes—such as LMP1, LMP2, EBNA1, and EBNA2—and the oncogenic pathways they initiate, including NF-κB, JAK/STAT, MAPK, PI3K, and Wnt, which collectively drive cell transformation, proliferation, and immune evasion. In addition, we address the role of EBV in promoting genetic instability through both genetic and epigenetic alterations and highlight emerging evidence on EBV genetic heterogeneity as a factor in disease aggressiveness. We further discuss existing diagnostic approaches based on EBV-specific biomarkers such as VCA-IgA, EBNA1-IgA, and viral DNA detection by PCR, and highlight emerging non-invasive methods that incorporate machine learning and smartphone-based imaging, such as the “Nose-Keeper”, for early detection and personalized risk stratification. Such AI-powered solutions can potentially lower resource barriers and improve early detection outcomes. Additionally, this paper suggests a machine learning–based screening model that integrates clinical, demographic, and serological data to minimize false positives and improve early detection, particularly in resource-limited or non-endemic settings. The paper reviews recent advances in targeted therapies concerning EBV—including immunotherapy, cytolytic virus activation therapy, and gene-targeting strategies—that seek to exploit EBV’s unique role in NPC. Thus, the present study emphasizes the need for further large-scale epidemiological and molecular investigations to refine EBV-based diagnostic and therapeutic approaches, with the ultimate goal of improving patient management and survival in this complex disease.