EBV DNA positivity may signify asymptomatic nasopharyngeal carcinoma
medwireNews: Patients with plasma samples repeatedly positive for Epstein–Barr virus (EBV) DNA should undergo further screening for nasopharyngeal carcinoma, researchers report.
They found that the presence of EBV DNA in plasma was highly sensitive and specific for nasopharyngeal cancer screening, and that participants with cancers detected by such screening had earlier stage disease and significantly better outcomes than those in a historic cohort.
“This study has shown the potential of analysis of circulating DNA to screen for early nasopharyngeal cancer,” write KC Allen Chan (Chinese University of Hong Kong) and colleagues in The New England Journal of Medicine.
The researchers screened plasma samples from 20,174 ethnically Chinese men aged 40–62 years for EBV DNA, and initially detected the biomarker in 1112 (5.5%) participants.
Of these, 309 (27.8%) had persistently positive results on repeat testing a median 34 days later, and 34 (11.0%) of 300 who underwent further assessment by nasal endoscopic examination and/or magnetic resonance imaging were diagnosed with nasopharyngeal carcinoma.
Chan and team note that 47.1% of the nasopharyngeal carcinomas detected were stage I and 23.5% were stage II, which, when combined, was significantly higher than the 20.0% rate of stage I and II disease reported in a historic cohort of 1278 age- and gender-matched patients from Hong Kong.
The participants with nasopharyngeal carcinoma also had significantly better 3-year progression-free survival than those in the historic cohort, at 97% versus 70%, giving a hazard ratio of 0.10.
The investigators point out that one of the nine patients who declined further testing following repeatedly positive EBV DNA tests presented with advanced nasopharyngeal carcinoma 32 months after enrolment and died 2 months later.
“Had he not declined further assessment, the tumor might have been diagnosed much earlier and a better treatment outcome might have been expected,” they write.
Only one participant who was initially negative for plasma EBV DNA developed nasopharyngeal carcinoma within a year of testing. Chan et al therefore calculated that the sensitivity and negative predictive values of their screening strategy were 97.1% and 100.0%, respectively, while the specificity and positive predictive values were 98.6% and 11.0%, respectively.
They emphasize that a positive predictive value of 11% “is superior to the typical 3% value of existing blood-based tumor markers in a population-screening context.”
The researchers also calculated that to detect one case of nasopharyngeal carcinoma, 593 participants would need to be screened at a cost of US$ 28,600 (€ 24,291).
“Considering the potential decrease in mortality and morbidity, as well as treatment- cost savings associated with the shift in stage distribution, screening for nasopharyngeal carcinoma appears to be a feasible practice in regions with a high incidence of this disease,” they remark.
Chan and co-authors conclude: “Although the current study focused only on men between the ages of 40 and 62 years, this screening protocol should also be applicable to women and persons in other age groups, in whom EBV DNA in plasma is also detected.”
In an accompanying editorial Richard Ambinder, from Johns Hopkins School of Medicine in Baltimore, Maryland, USA describes the findings as “clinically important,” adding that “lives [appear to] have been saved because of this screening.”
He adds: “[I]n the right context, population screening of plasma DNA is a very promising approach to detect early-stage cancer.
“Like cervical cytologic testing or testing for human papillomavirus in the cervix for early detection of cervical cancer, plasma EBV DNA screening may profoundly change the natural history of nasopharyngeal carcinoma,” Ambinder concludes.
By Laura Cowen
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