Nasopharyngeal carcinoma(NPC)has been a focus of medical research for more than 100 years,with significant interest emerging over the last 58 years following the identification of the link between the disease and Epstein-Barr virus(EBV)infection.NPC possesses several distinctive characteristics among human cancers,nota-bly its well-documented global epidemiology,which reveals localized high-incidence regions primarily in South-east Asia,particularly in the Southern provinces of China near the Pearl river,as well as in Greenland and North Africa.Epidemiological data indicate a marked male predominance,early disease onset,and a nearly 100%preva-lence of latent EBV infection in the tumors.Due to lack of consistent pattern of cancer-related mutations in NPC genomes and excessive DNA-methylation in the tumor cells,NPC can be considered"an epigenetic cancer".De-spite extensive researches,convincing biological explanations for these unique characteristics remain elusive.Re-cently,suggestive evidence has been published that specific local variants of EBV may represent major high risk factors.In spite of tumor and virus specific immunity,it has not been possible to use this for improved treatment.Ongoing studies on the role of the local microflora and tumor microenvironment are essential for a comprehen-sive understanding of host-EBV-tumor interactions.Ultimately,this knowledge aims to enhance diagnosis,dis-ease fractionation,treatment strategies,and potentially prevention of NPC.