Liquid Biopsy Screening for Nasopharyngeal Carcinoma

Prospective analysis of plasma EBV DNA to screen for nasopharyngeal cancer

In a prospective study, circulating Epstein–Barr virus (EBV) DNA was measured in plasma samples from 20,174 asymptomatic participants in Hong Kong and 34 people of 309 with positive results had nasopharyngeal cancer. Stage distribution and progression-free survival (PFS) were better in these 34 study participants than in a historical cohort. The results are published on 10 August 2017 in The New England Journal of Medicine by researchers from Hong Kong led by Allen Chan.

Circulating cell-free EBV DNA is a biomarker for nasopharyngeal carcinoma explained researchers in a study background. They analyzed EBV DNA in plasma specimens to screen asymptomatic participants in a prospective study for nasopharyngeal carcinoma. The study 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 study 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) with superior 3-year PFS (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 enrolment.

Nasopharyngeal carcinoma developed in only 1 participant with negative EBV DNA in plasma samples within 1 year after testing.

Overall, the sensitivity and specificity of EBV DNA in plasma samples in screening for nasopharyngeal carcinoma were 97.1% and 98.6%, respectively.

The study investigators concluded that analysis of EBV DNA in plasma samples was useful in screening for early asymptomatic nasopharyngeal carcinoma that was detected significantly earlier and outcomes were better in participants who were identified by screening than in those in the historical cohort.

The study ( number NCT02063399) was funded by the Kadoorie Charitable Foundation and the Research Grants Council of the Hong Kong government.


Chan KCA, Woo JKS, King A, et al. Analysis of Plasma Epstein–Barr Virus DNA to Screen for Nasopharyngeal Cancer. N Engl J Med 2017;377:513-522.