Plasma Epstein-Barr Virus DNA Screening for Nasopharyngeal Cancer

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K.C. Allen Chan, MBBS, PhD, MRCP, FRCPA,


In a Hong Kong study reported in The New England Journal of Medicine, K.C. Allen Chan, MBBS, PhD, MRCP, FRCPA, FHKCPath, FHMAM, of The Chinese University of Hong Kong, Department of Chemical Pathology, and colleagues found that screening for circulating cell-free Epstein-Barr virus (EBV) DNA is useful in detecting nasopharyngeal carcinoma in asymptomatic individuals. 

In the study, 20,174 participants underwent testing for EBV DNA in plasma specimens. Those with initially positive results were retested approximately 4 weeks later, and those with persistently positive results underwent nasal endoscopic examination and magnetic resonance imaging (MRI) for detection of nasopharyngeal cancer. 

Screening Detection Rates 

Overall, EBV DNA was detected in 1,112 participants (5.5%); 309, representing 1.5% of all participants and 27.8% of those with initially positive results, had persistently positive results. Among the 309 persistently positive subjects, 300 underwent endoscopic examination, and 275 underwent both endoscopic examination and MRI; of them, 34 (11.0% of all with persistent positive findings, 11.3% of those undergoing endoscopy, and 12.4% of those undergoing endoscopy and MRI) had nasopharyngeal carcinoma. A significantly higher proportion of participants with nasopharyngeal carcinoma identified by EBV DNA screening had stage I or II disease compared with all patients diagnosed with nasopharyngeal carcinoma in Hong Kong in 2013 (71% vs 20%, P < .001). Those with screen-detected disease in the current study had better 3-year progression-free survival vs a Hong Kong historical cohort of 1,278 age- and sex-matched patients (97% vs 70%; hazard ratio = 0.10; 95% confidence interval = 0.05–0.18). 

Of 9 participants with persistently positive screening results who declined further testing, 1 presented with advanced nasopharyngeal carcinoma 32 months after enrollment. Nasopharyngeal carcinoma was observed in one participant with negative EBV DNA screening within 1 year after testing. Overall, screening had a sensitivity and a specificity for nasopharyngeal carcinoma of 97.1% and 98.6% and positive and negative predictive values of 11.0% and > 99.9%, respectively. 

The investigators concluded: “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.” ■

Chan KCA, et al: N Engl J Med 377:513-522, 2017.