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N Engl J Med. 2017 Aug 10;377(6):513-522. doi: 10.1056/NEJMoa1701717.

Analysis of Plasma Epstein-Barr Virus DNA to Screen for Nasopharyngeal Cancer.

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From the Li Ka Shing Institute of Health Sciences (K.C.A.C., W.K.J.L., S.W.I.C., C.M., I.O.L.T., S.Y.M.L., G.C., R.W.K.C., Y.M.D.L.), the Department of Chemical Pathology (K.C.A.C., W.K.J.L., S.W.I.C., C.M., I.O.L.T., S.Y.M.L., G.C., R.W.K.C., Y.M.D.L.), State Key Laboratory of Oncology in South China, Sir Y.K. Pao Centre for Cancer (K.C.A.C., W.K.J.L., S.L.C., S.W.I.C., C.M., I.O.L.T., S.Y.M.L., G.C., E.P.H., B.B.Y.M., R.W.K.C., S.-F.L., A.T.C.C., Y.M.D.L.), Department of Otorhinolaryngology, Head and Neck Surgery (J.K.S.W., W.K.J.L., A.C.H.), Department of Imaging and Interventional Radiology (A.K.), Jockey Club School of Public Health and Primary Care (B.C.Y.Z.), and Department of Clinical Oncology (S.L.C., E.P.H., B.B.Y.M., S.-F.L., A.T.C.C.), Chinese University of Hong Kong, Prince of Wales Hospital - all in Hong Kong.



Circulating cell-free Epstein-Barr virus (EBV) DNA is a biomarker for nasopharyngeal carcinoma. We conducted a prospective study to investigate whether EBV DNA in plasma samples would be useful to screen for early nasopharyngeal carcinoma in asymptomatic persons.


We analyzed EBV DNA in plasma specimens to screen participants who did not have symptoms of nasopharyngeal carcinoma. Participants with initially positive results were retested approximately 4 weeks later, and those with persistently positive EBV DNA in plasma underwent nasal endoscopic examination and magnetic resonance imaging (MRI).


A total of 20,174 participants underwent screening. EBV DNA was detectable in plasma samples obtained from 1112 participants (5.5%), and 309 (1.5% of all participants and 27.8% of those who initially tested positive) had persistently positive results on the repeated sample. Among these 309 participants, 300 underwent endoscopic examination, and 275 underwent both endoscopic examination and MRI; of these participants, 34 had nasopharyngeal carcinoma. A significantly higher proportion of participants with nasopharyngeal carcinoma that was identified by screening had stage I or II disease than in a historical cohort (71% vs. 20%, P<0.001 by the chi-square test) and had superior 3-year progression-free survival (97% vs. 70%; hazard ratio, 0.10; 95% confidence interval, 0.05 to 0.18). Nine participants declined to undergo further testing, and 1 of them presented with advanced nasopharyngeal carcinoma 32 months after enrollment. Nasopharyngeal carcinoma developed in only 1 participant with negative EBV DNA in plasma samples within 1 year after testing. The sensitivity and specificity of EBV DNA in plasma samples in screening for nasopharyngeal carcinoma were 97.1% and 98.6%, respectively.


Analysis of EBV DNA in plasma samples was useful in screening for early asymptomatic nasopharyngeal carcinoma. Nasopharyngeal carcinoma was detected significantly earlier and outcomes were better in participants who were identified by screening than in those in a historical cohort. (Funded by the Kadoorie Charitable Foundation and the Research Grants Council of the Hong Kong government; number, NCT02063399 .).

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