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  • Review Article
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Achieving control of nasopharyngeal carcinoma: the role of Epstein–Barr virus-based screening and vaccines

Nature Reviews Clinical Oncology (2025)Cite this article

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Abstract

Nasopharyngeal carcinoma (NPC) is a major disease burden in endemic regions, where Epstein–Barr virus (EBV) infection has a key aetiological role in this malignancy. Both plasma EBV DNA and serum antibodies targeting EBV antigens have been validated independently in large-scale prospective trials as effective biomarkers for early detection of NPC. Plasma EBV DNA analysis by PCR could identify patients with early-stage, asymptomatic NPC. Emergent studies have shown that fragmentomics analysis of plasma EBV DNA can further enhance the specificity of NPC detection at the time of testing and better predict the future risk of NPC. Initial antibody-based NPC screening approaches were based on the detection of immunoglobulin A antibodies targeting EBV viral capsid antigen or Epstein–Barr nuclear antigen 1, which resulted in a subsequent reduction in NPC-specific mortality in a population screening trial. Subsequently, the detection of anti-BNLF2b antibodies alone has been reported to achieve higher sensitivity and specificity relative to the dual antibody approach. Cost-effectiveness analyses support the implementation of NPC screening in endemic regions using either EBV DNA or antibodies. Ongoing research initiatives are focusing on developing prophylactic and therapeutic vaccines as preventive measures against EBV-associated diseases, including NPC. In this Review, we discuss these advances as well as their relevance for the implementation of prevention strategies such as population-wide NPC screening and vaccination in endemic areas of NPC prevalence. We also highlight valuable insights from plasma EBV DNA studies that might facilitate optimization of liquid biopsy-based screening strategies for other types of cancer.

Key points

  • The prevalence of nasopharyngeal carcinoma (NPC) is characterized by marked geographical and ethnic disparities, and is particularly high in southern China and Southeast Asia. NPC is strongly associated with Epstein–Barr virus (EBV) infection, prompting a focus on early detection and prevention, including strategies for screening using EBV-based biomarkers or the development of EBV vaccines, to alleviate the burden of NPC.

  • The quantification of plasma EBV DNA using real-time PCR assays or other sequencing-based methods provides a sensitive and specific biomarker for NPC screening, and evidence suggests that the initial test results can predict future risk of NPC development within the subsequent few years.

  • Quantification of serum antibodies targeting EBV antigens, including EBV viral capsid antigen, Epstein–Barr nuclear antigen 1 (EBNA1) and BNLF2b, has demonstrated promising screening performance, improving early diagnosis of NPC and reducing NPC-specific mortality by 30% in a population screening trial.

  • Further research and the development of risk models based on other EBV-based and human biomarkers, including specific EBV variants and human HLA genotypes, could refine NPC screening and the identification of populations at high risk, thereby enhancing the predictive value and cost-effectiveness of screening programmes.

  • Current efforts in EBV vaccine development focus on administering EBV envelope glycoproteins, such as gp350, gH–gL, gp42 and gB, or EBV proteins expressed in infected NPC cells that promote oncogenic properties, including EBNA1 and latent membrane protein 2. Nanoparticle-based and mRNA-based vaccines have demonstrated promising results in preclinical studies and are being tested in ongoing clinical trials.

  • Plasma EBV DNA-based and serological antibody-based approaches for NPC screening provide numerous insights for the development of blood-based multi-cancer early detection tests, highlighting the importance of longitudinal follow-up, increasing participation in screening programmes and leveraging multimodal-based detection methods.

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Fig. 1: Current approaches and emerging advances for EBV-based screening and prevention of NPC.

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Acknowledgements

W.K.J.L., Y.M., and K.C.A.C. receive research support from the Innovation and Technology Fund under the InnoHK Initiative, a major initiative of the Hong Kong Special Administrative Region Government, and the Research Grants Council of the Hong Kong SAR Government under the NSFC/RGC Joint Research Scheme (N_CUHK495/22).

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Authors and Affiliations

  1. Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China

    W. K. Jacky Lam, Yasine Malki & K. C. Allen Chan

  2. State Key Laboratory of Translational Oncology, Sir Yue Kong Pao Centre for Cancer, Department of Clinical Oncology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China

    Brigette B. Y. Ma & Anthony T. C. Chan

  3. Department of Imaging and Interventional Radiology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China

    Ann D. King

  4. School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China

    Anthony T. C. Chan

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W.K.J.L. holds equity in Illumina. K.C.A.C. holds equity in DRA, Illumina, Insighta and Take2. B.B.Y.M., A.D.K., Y.M. and A.T.C.C. declare no competing interests.

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Lam, W.K.J., Ma, B.B.Y., King, A.D. et al. Achieving control of nasopharyngeal carcinoma: the role of Epstein–Barr virus-based screening and vaccines. Nat Rev Clin Oncol (2025). https://doi.org/10.1038/s41571-025-01079-x

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