Plasma Epstein–Barr virus DNA useful for nasopharyngeal carcinoma screening

1. Asymptomatic study participants with persistently elevated serum Epstein-Barr virus (EBV) levels were diagnosed with nasopharyngeal carcinoma at rates higher than expected without screening.

2. Patients screened by plasma EBV levels were diagnosed with earlier stage, and therefore more treatable, nasopharyngeal carcinomas than patients presenting with nasopharyngeal carcinoma who were never screened.

Evidence Rating: 2 (Good)

Study Rundown: Analysis of circulating plasma DNA in cancer patients has been typically used to guide treatment options and assess presence of disease. Ideally, plasma DNA analysis could also be used to screen for initial cancer presence and pick-up early stage cases. This study sought to assess plasma EBV as screening for nasopharyngeal carcinoma in Southeast Asia, with goals of assessing ability to detect nasopharyngeal carcinoma in asymptomatic patients and diagnose cases at an early stage.

Asymptomatic males between the ages of 40 and 62 were recruited in Hong Kong to undergo plasma EBV testing to assess for elevation. Participants with persistently elevated EBV levels over 2 tests were determined screen-positive and referred for nasopharyngeal endoscopy and MRI, and biopsy was used to diagnose nasopharyngeal carcinoma. Significantly more participants screened with plasma EBV were diagnosed with nasopharyngeal carcinoma than would be expected without screening, and a significant number of these diagnoses were in stages I and II typically more responsive to treatment. For those diagnosed with nasopharyngeal carcinoma 3-year progression free survival was significantly better than in a comparison group, indicating better outcomes and not likely a finding due to lead-time bias. In terms of number needed to treat (NNT) and cost associated with screening compared to morbidity, mortality, and treatment costs for nasopharyngeal carcinoma, EBV screening may prove to be a feasible in areas with high disease incidence.

Click to read the study, published today in NEJM

Relevant Reading: Development of a real-time quantitative assay for detection of Epstein-Barr virus

In-Depth [prospective cohort]: This study was conducted in Hong Kong between 2013-2016 with the participation of 20 349 men between the ages of 40-62 years. Participants were excluded if they had a prior history of cancer or autoimmune conditions, or were receiving any form of corticosteroid or immunosuppressive treatment. Blood samples were taken and real-time polymerase-chain-reaction (PCR) assessed samples for EBV. Any patient with a positive EBV signal was reevaluated in 4 weeks, and those with two EBV positive samples were deemed screen-positive. Screen-positive patients were referred for nasopharynx evaluation by endoscopy and MRI, and biopsies were taken for diagnosis of nasopharyngeal carcinoma. Of 20 174 eligible men, 5.5% (n = 1112) had EBV detectable at baseline, and 27.8% (n = 309) of those men were screen-positive. Nasopharyngeal carcinoma was detected in 34 men, 11% (34/300) of men undergoing follow-up endoscopy and/or MRI. Stage I or II nasopharyngeal cancer was detected in a higher proportion of patients than in a non-screened comparison cohort (71% vs 20%, p < 0.0001). Progression-free survival was higher in this screened population than a comparison cohort (97% vs. 70%; hazard ratio, 0.10; 95%CI 0.05-0.18; p < 0.001). During follow-up with a median duration of 22 months, 1 patient who was screen-positive who did not undergo further evaluation was diagnosed with advanced stage nasopharyngeal carcinoma, and 2 patients with non-elevated EBV were diagnosed with nasopharyngeal carcinoma. The NNT in this study was 593, at a cost of $28 600. Sensitivity and specificity of EBV DNA screening were 97.1% and 98.6%, respectively.

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