Nasopharyngeal carcinoma: epidemiology, risk factors, signaling pathways, clinical features, diagnosis, and management.

Abstract

Nasopharyngeal carcinoma (NPC) is a distinctive epithelial malignancy characterized by marked geographic and ethnic clustering, with the greatest burden concentrated in East and Southeast Asia despite declining age-standardized incidence and mortality rates in many regions. NPC arises from a complex interaction among persistent Epstein-Barr virus (EBV) infection, inherited susceptibility, and environmental exposures. Among these factors, EBV plays a central role in endemic NPC through latent gene products, particularly latent membrane protein 1 (LMP1), latent membrane protein 2A (LMP2A), and Epstein-Barr nuclear antigen 1 (EBNA1), which sustain oncogenic signaling, remodel the tumor microenvironment, and reinforce malignant progression. Clinically, NPC is often diagnosed at a locoregionally advanced stage because of its deep anatomical location and nonspecific early symptoms, making accurate detection, risk stratification, and treatment selection particularly important. Although previous reviews have addressed individual aspects of NPC biology or management, an integrated framework linking epidemiological determinants, viral oncogenesis, host molecular dysregulation, and therapeutic evolution remains needed. This review therefore synthesizes current evidence on NPC epidemiology, risk factors, EBV-associated molecular mechanisms, major signaling pathways and their crosstalk, genetic and epigenetic alterations, clinical features, diagnosis, staging, and management. Particular emphasis is placed on the clinical roles and limitations of plasma EBV DNA, the distinction between established standards and investigational strategies, and emerging molecular and immune-based therapies. By linking mechanistic insights with their clinical and translational implications, this review provides a biologically informed framework for understanding NPC and highlights priorities for biomarker standardization, risk-adapted treatment, and future therapeutic development.