Trends of EBV Serology in Screening of Nasopharyngeal Cancer in a Multiethnic Healthy Singaporean Cohort.

Abstract

Epstein-Barr virus-positive nasopharyngeal carcinoma (EBV-NPC) is highly prevalent in Asia. EBV IgA serologies (targeting viral capsid antigen [VCA] and early antigen [EA]) are commonly used for NPC screening in Singapore. However, the predictive value of longitudinal serologic trends in real-world screening remains unclear. This study evaluated EBV IgA serologic patterns and their relationship with NPC development. We conducted a retrospective cohort study of 1977 asymptomatic individuals screened for NPC between 2008 and 2021 at a tertiary medical center in Singapore. Patients were predominantly Chinese (95%) and aged 12-90 years. Data on EBV IgA serologies (EA-IgA and VCA-IgA), plasma EBV DNA, nasoendoscopy, biopsies, and MRI findings were collected. Primary outcomes included EBV serologic trends (stratified into positive for only one serology type, non-fluctuating positivity, fluctuating positivity, seroconversion or seroreversion) and incidence of NPC during follow-up. Of the 1977 patients, 62% tested positive for either EA-IgA or VCA-IgA. 7.2% showed stable positive titers, 5% had fluctuating titers, 2.4% seroconverted, and 23.5% seroreverted. Six patients (0.3%) developed NPC; all were Chinese, with a mean age of 50. Three had Stage I, one had Stage III, and two had Stage IV disease. Their serologic trajectories varied with no consistent pattern observed. Elevated EBV EA-IgA (2/6) or VCA-IgA (2/6) titers were observed 1-2 years before diagnosis. No consistent EBV serologic pattern preceded NPC diagnosis in this cohort. The low NPC detection rate of 0.3% suggests limited screening utility of EBV serologies in a heterogeneous, intermediate-risk population.