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.

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Publication Details

Journal
Nature Communications
Published
2026-04-22
DOI
https://doi.org/10.1038/s41467-026-72285-z
Primary Topic
Head and Neck Cancer Studies
Type
article
Field-Weighted Citation Impact
0.00

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article

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

Zhicong Wu, Dong Ping Rao, J H Ye, Allan Hildesheim et al.
Nature Communications
Head and Neck Cancer Studies
article

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

Zhicong Wu, Dong Ping Rao, J H Ye, Allan Hildesheim, Wen‐Jie Chen, Lin Cao, Z Liu, Ying Sun, Minzhong Tang, Xiaojuan Wen, Wei Ling, S Xie, Ming-Fang Ji, S M Cao, Jun Tao, Yan-Ping Fan, Guang-Cong Yi, Xia Yu, Sui-Ping Huang, Tong Li, Yong-Rui Ling, Hua Chen
article en

Abstract

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.

Nature Communications
Sun Yat-sen University (CN), Guangdong Medical College (CN), Georgetown University (US), Georgetown University Medical Center (US), Xinhui People's Hospital (CN), The First People's Hospital of Shunde (CN), Instituto Costarricense de Investigación y Enseñanza en Nutrición y Salud (CR), Zhongshan People's Hospital (CN), Wuzhou University (CN), Asociación Demográfica Costarricense (CR), National Cancer Institute (US), Guangxi Center for Disease Prevention and Control (CN), Sun Yat-sen University Cancer Center (CN), Jiangmen Central Hospital (CN), Wuzhou Red Cross Hospital (CN), Division of Cancer Epidemiology and Genetics
National Natural Science Foundation of China, Natural Science Foundation of Guangdong Province, National Science and Technology Major Project
Good health and well-being
Openalex Percentile: Top 7%
Head and Neck Cancer Studies
DOIOpen Access PDFOpenAlex
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