Nasopharyngeal carcinoma screening using Epstein-Barr virus Cp methylation triage in two population-based screening cohorts.

Nasopharyngeal carcinoma screening in southern China relies on Epstein-Barr virus serology, but its limited positive predictive value leads to excessive referrals. Here we evaluate a triage approach based on nasopharyngeal swab Epstein-Barr virus C promoter methylation quantification (E-CpMQ) among serology high-risk individuals in two population-based screening cohorts (N = 55,682). In the initial screening round (≤18 months) of a single-center cohort (N = 313), E-CpMQ identifies 91.7% of nasopharyngeal carcinoma cases (22/24) with 91.7% specificity (265/289), reducing referrals by 85.3%. Findings are replicated in an independent six-center cohort (N = 345), where E-CpMQ achieves 100% sensitivity (15/15) and 96.1% specificity (317/330), reducing referrals by 91.9%. Compared with nasopharyngeal swab Epstein-Barr virus DNA load triage, E-CpMQ shows equivalent sensitivity but higher specificity, lowering referrals needed to detect one case from 10-14 to approximately 2. Modeling further indicates improved specificity and positive predictive value when integrated into serology-based screening.