Achieving control of nasopharyngeal carcinoma: the role of Epstein-Barr virus-based screening and vaccines.

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.