Recent advances in the molecular pathogenesis of Epstein–Barr virus–associated nasopharyngeal carcinoma

Epstein-Barr virus (EBV) is a major etiologic factor in nasopharyngeal carcinoma (NPC). Although persistent latent EBV infection has traditionally been viewed as central to NPC carcinogenesis, recent evidence has broadened our understanding of the dynamic interactions between EBV and host cells. Host genetic and epigenetic alterations may precede EBV infection, establishing a cellular environment permissive for viral persistence. Within this permissive context, latent EBV gene products activate oncogenic signaling, with their effects further reinforced by genomic instability and epigenetic reprogramming. This evolving evidence has also challenged the conventional view that EBV in NPC is predominantly restricted to a latent state. Abortive or partial lytic infection may coexist with latency and contribute to malignant phenotypes, while emerging evidence indicates that productive viral replication can occur in a subset of NPC cells and clinical tumors. In parallel, advances in genomic, epigenomic, single-cell, and spatial technologies have uncovered additional mechanisms, including EBNA1-mediated chromosomal instability, EBV-induced three-dimensional chromatin reorganization, and intricate interactions between EBV-infected tumor cells and the immune microenvironment. Collectively, these findings support a dynamic model in which host susceptibility, evolving EBV infection states, and subsequent genomic, epigenomic, and immune remodeling interact to shape NPC development and progression. This review synthesizes recent advances in the molecular pathogenesis of EBV-associated NPC, with particular emphasis on epigenetic reprogramming and the emerging contribution of EBV lytic infection.