Plasma EBV DNA analysis may predict future NPC risk

Plasma Epstein-Barr virus (EBV) DNA analysis not only identifies asymptomatic early-stage nasopharyngeal carcinoma (NPC), but also indicates NPC risk in the next 3–5 years, researchers from the Chinese University of Hong Kong (CUHK) have reported.

The researchers recruited 20,174 asymptomatic Chinese men aged 40–62 years for a first round of NPC screening by plasma EBV DNA analysis in 2013–2016. The current study reports results from the second round of screening conducted in 2017–2020 (ie, 3–5 years [median, 43 months] after the first round) among 17,838 participants who had not developed NPC after the first round of screening. [NEJM Evid 2023;doi:10:1056/EVIDoa2200309]

In both rounds of screening, participants with detectable plasma EBV DNA at baseline were retested 4 weeks later. Those with undetectable plasma EBV DNA at the 4-week retest were categorized as transiently positive, while those with persistently positive plasma EBV DNA at the 4-week retest were referred for endoscopy and MRI of the nasopharynx.

In the second round of screening, 423 participants (2.37 percent) had persistently positive plasma EBV DNA. All of them underwent nasal endoscopy, while 382 also underwent MRI. NPC was identified in 24 participants, 16 (67 percent) of whom had stage I/II disease. “None of the NPC patients identified in the second round of screening had stage IV disease,” the researchers noted.

“The proportion of patients with early-stage disease [identified in the second round of screening] was similar to that from the first round of screening [71 percent], but much higher than that [in a historical cohort] of all patients with NPC in Hong Kong in 2013 [20 percent; chi-square test, p<0.001],” they pointed out.

“Notably, detection of EBV DNA in plasma also reflects an increased risk of NPC in the future,” said first author, Professor Allen Chan of the Department of Chemical Pathology, CUHK.

Compared with participants with undetectable plasma EBV DNA in the first round of screening, the relative risk of NPC identification in the second round of screening was 4.4 (95 percent confidence interval [CI], 1.3–15.0) for those with first-round transiently positive results and 16.8 (95 percent CI, 5.7–49.6) for those with first-round persistently positive results.

NPC patients identified in both rounds of screening had higher 3-year progression-free survival rates vs the historical cohort (97 percent [first round] and 100 percent [second round] vs 78.8 percent). At a median follow-up of 33 months after treatment, NPC recurred in none of the 24 patients identified in the second round of screening.

Based on the number of NPC cases identified, the number of individuals to be screened to identify one case was 593 and 713 for the first and second rounds of screening, respectively. “Although we did not conduct a formal cost analysis, we estimate that the cost to detect one NPC case is in the range of USD 25,000–40,000,” the researchers noted. “Further research is required to determine whether the potential decrease in mortality and morbidity, as well as treatment cost savings associated with the shift in stage distribution, would be practical and financially feasible in regions with a high incidence of NPC.” [J Natl Cancer Inst 2021;113:852-862]