Epstein–Barr Virus DNA as a Diagnostic and Prognostic Biomarker in Nasopharyngeal Cancer: Insights into EBNA1, BamHI, and BALF5

Nasopharyngeal cancer (NPC) is an Epstein–Barr virus (EBV)-associated malignancy with a particularly strong association in endemic regions. Quantitative EBV DNA has emerged as an important biomarker for NPC diagnosis, risk stratification, treatment-response assessment, and post-treatment surveillance. This review examines the biological and clinical relevance of three EBV genomic targets: EBV nuclear antigen 1 ( EBNA1 ), BamHI- region sequences, including BamHI-W and BARF1 , and BALF5 . EBNA1 is essential for viral genome maintenance during latency and promotes immune evasion and oncogenic signalling. Genes within the BamHI region enhance viral persistence and cellular proliferation, with high copy numbers correlating with advanced disease and poorer outcomes. BALF5 , a lytic-phase DNA polymerase, is implicated in genomic instability and disease progression. Quantitative EBV DNA analysis in plasma, nasopharyngeal brushing, saliva, mouthwash, and tumour tissue demonstrates associations with tumour burden, disease stage, treatment response, and clinical outcomes. Integrating EBV DNA profiling with viral genomic and host multi-omic analyses may improve risk stratification and personalised management. However, variation in specimen types, viral targets, and assay methods warrants further validation before broader clinical application.