Tan LP, Tan GW, Sivanesan VM, et al. - Given a common issue of late presentation with nasopharyngeal carcinoma (NPC), which is originated from the epithelial cells of nasopharynx, Epstein–Barr virus (EBV)-associated and has the highest incidence and mortality rates in Southeast Asia, researchers examined whether plasma EBV DNA, an established NPC biomarker, could assist in its early detection and could reduce the disease burden. Systematical appraisal of six established and four new biomarkers was done in NPC cases, population controls and hospital controls. The most sensitive plasma biomarker was BamHI-W 76 bp, with 96.7% (29/30), 96.7% (58/60) and 97.4% (226/232) sensitivity to detect Stage I, early stage and all NPC, respectively. Its specificity was 94.2% (113/120) against population controls and 90.4% (113/125) against hospital controls. As per decision tree modeling, an increase in specificity or sensitivity to detect NPC could be achieved by combining BamHI-W 76 bp with VCA IgA or EA IgG. Findings support the utility of EBNA1 99 bp in recognizing NPC patients with poor prognosis in early and advanced stage NPC. Evidence was thus generated in this work for improvement in NPC screening strategies, incorporating considerations of opportunistic screening, joining biomarkers to improve sensitivity or specificity and examining biomarkers from single sampled specimen to avoid logistic problems of resampling.