鼻咽癌：流行病学、危险因素、信号通路、临床特征、诊断与治疗

文献信息

中文摘要

鼻咽癌（NPC）是一种独特的恶性上皮性肿瘤，具有显著的地理和种族聚集性，尽管许多地区的年龄标化发病率和死亡率呈下降趋势，但其疾病负担仍主要集中在东亚和东南亚。鼻咽癌的发生源于持续性EB病毒（EBV）感染、遗传易感性和环境暴露之间复杂的相互作用。在这些因素中，EBV通过潜伏基因产物，特别是潜伏膜蛋白1（LMP1）、潜伏膜蛋白2A（LMP2A）和EB病毒核抗原1（EBNA1），在地方性鼻咽癌中发挥核心作用，这些产物维持致癌信号传导、重塑肿瘤微环境并促进恶性进展。临床上，由于鼻咽癌解剖位置深在且早期症状非特异，常于局部区域晚期才被诊断，因此准确的检测、风险分层和治疗选择尤为重要。尽管既往综述已涉及鼻咽癌生物学或治疗的个别方面，但仍需要一个将流行病学决定因素、病毒致癌作用、宿主分子失调和治疗演变联系起来的整合框架。因此，本综述综合了当前关于鼻咽癌流行病学、危险因素、EBV相关分子机制、主要信号通路及其串扰、遗传和表观遗传改变、临床特征、诊断、分期和治疗方面的证据。特别强调了血浆EBV DNA的临床作用与局限性、已确立标准与探索性策略之间的区别，以及新兴的分子和免疫治疗。通过将机制性见解与其临床和转化意义相联系，本综述为理解鼻咽癌提供了一个具有生物学依据的框架，并突出了生物标志物标准化、风险适应性治疗和未来治疗开发方面的优先事项。

英文摘要

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.