Population screening for early diagnosis of nasopharyngeal cancer in Singapore: A study protocol

Nasopharyngeal carcinoma (NPC) is characterized by a unique epidemiological distribution in Southeast Asia and is closely linked to Epstein-Barr virus (EBV) infection. Early studies have demonstrated that serum IgA antibodies against EBV antigens and plasma cell-free EBV DNA are useful biomarkers for the early detection of NPC. More recently, high-risk EBV strains for NPC have been identified. We aim to evaluate the effectiveness of a community population based screening programme for early detection of NPC, the performance of EBV biomarkers and the distribution of EBV strains in the Singapore population. Methods We will recruit 20,000 participants aged between 35 and 60 years, of Chinese, Malay, or mixed ethnicity. Participants will undergo EBV -EA IgA serology, plasma EBV DNA testing, and provide saliva samples for EBV strain-typing. High-risk individuals (defined by EBV -EA IgA and/or EBV DNA positivity) will receive a comprehensive head and neck examination including nasoendoscopy, nasopharyngeal biopsy and annual follow up. Low-risk participants will be followed-up with annual phone calls. For participants lost to follow up,Participants will also have their NPC status will be verified through the National Registry of Disease Office. The stage distribution of NPC cases detected through screening will be compared with NPC patients routinely diagnosed in the outpatient clinic. Statistical analysis will evaluate sensitivity, specificity, PPV and NPV of EBV biomarkers. Discussion This study will evaluate the feasibility and accuracy of EBV-based NPC screening in a community setting. By integrating serology, cell-free DNA, and EBV strain types, we aim to improve early detection and guide the development of future risk stratification models. Conclusion This study has the potential to shift NPC diagnosis toward earlier stages and inform sustainable, cost-effective screening strategies for use in endemic populations.