EBV DNA Screening Detects Early Asymptomatic Nasopharyngeal Carcinoma

KC Allen Chan, MBBS

Hong Kong researchers were able to detect nasopharyngeal carcinoma significantly earlier by screening for circulating cell-free Epstein-Barr virus (EBV) DNA, according to results recently published in the New England Journal of Medicine.

Investigators discovered stage I disease in 47% of the cohort, nearly 7 times greater than the 5% to 7% observed in historical cohorts. As a result, the 3-year rate of progression-free survival (PFS) among the patients identified by screening was significantly superior (97% vs 70%; hazard ratio, 0.10; 95% CI, 0.05-0.18; P <.001).

Lead investigator KC Allen Chan, MBBS, the Chinese University of Hong Kong, and coauthors wrote that these findings suggest that EBV DNA screening could be a cost-effective way to detect nasopharyngeal carcinoma in asymptomatic populations.

“The costs for each EBV DNA analysis, endoscopic examination, and MRI were $30, $80, and $1000, respectively. On the basis of the results of this study, to detect 1 case, 593 participants would need to be screened at a cost of $28,600,” they wrote. “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.”

Chan et al conducted public health education sessions in Hong Kong from July 2013 to February 2016 to share information about the epidemiologic features and treatment of nasopharyngeal carcinoma. After each session, they invited ethnically Chinese men aged 40 to 62 years to participate in the study. That age group is the most at risk for nasopharyngeal carcinoma, and risk decreases with age.

Participants with a history of cancer or autoimmune conditions and those receiving systemic glucocorticoid or immunosuppressive therapy were excluded in order to minimize the chance of having false-positive results in plasma EBV DNA associated with EBV viral replication in immunocompromised participants.

A total of 20,174 participants from 147 education sessions underwent screening. At enrollment, 1112 participants (5.5%) had detectable EBV DNA in plasma, and received follow-up analysis of EBV DNA in plasma. The median interval between the first and the follow-up tests was 34 days.

Of 309 participants who had persistently positive results, 300 underwent endoscopic examination and 275 also underwent MRI. Twelve participants underwent endoscopic examination instead of MRI.

Thirty-four participants (11.0%) out of 300 were determined to have histologically-proven undifferentiated nasopharyngeal carcinoma. Investigators found that a significantly greater number of these participants had stage I/II disease than those in a historical cohort (71% vs 20%; P <.001).

Only 1 patient out of 19,865 screen-negative persons developed nasopharyngeal carcinoma within 1 year of screening, establishing the sensitivity for the screening strategy at 97.1% and the negative predictive value at 99.995%.

Investigators used the Kaplan-Meier method to compare survival among the participants with nasopharyngeal carcinoma identified by screening versus survival among those identified in a historical cohort. The survival data from the historical cohort were derived from a previous study involving 2687 consecutive patients who received treatment at all public oncology centers in Hong Kong over a period of 5 years. A subgroup of 1278 men aged 40 to 62 years was used for comparison.

Investigators collected a sample containing 20 ml of venous blood from each participant at enrollment, and analyzed EBV DNA in plasma using real-time polymerase-chain-reaction assay targeting the BamHI-W fragment of the EBV genome. The lower detection limit of the assay was 20 EBV genomes per milliliter of plasma. All the samples were analyzed in duplicate. Amplification signals in any replicate were regarded as a positive result, regardless of the level.

In participants with positive results, investigators collected another blood sample approximately 4 weeks later.

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(6):513-522. doi: 10.1056/NEJMoa1701717.