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Background: Although contrast-enhanced magnetic resonance imaging (MRI) detects early-stage nasopharyngeal carcinoma (NPC) not detected by endoscopic-guided biopsy (EGB), a short contrast-free screening MRI would be desirable for NPC screening programs. This study evaluated a screening MRI in a plasma Epstein-Barr virus (EBV)-DNA NPC screening program., Methods: EBV-DNA-screen-positive patients underwent endoscopy, and endoscopy-positive patients underwent EGB. EGB was negative if the biopsy was negative or was not performed. Patients also underwent a screening MRI. Diagnostic performance was based on histologic confirmation of NPC in the initial study or during a follow-up period of at least 2 years., Results: The study prospectively recruited 354 patients for MRI and endoscopy; 40/354 (11.3%) endoscopy-positive patients underwent EGB. Eighteen had NPC (5.1%), and 336 without NPC (94.9%) were followed up for a median of 44.8 months. MRI detected additional NPCs in 3/18 (16.7%) endoscopy-negative and 2/18 (11.1%) EGB-negative patients (stage I/II, n = 4; stage III, n = 1). None of the 24 EGB-negative patients who were MRI-negative had NPC. MRI missed NPC in 2/18 (11.1%), one of which was also endoscopy-negative. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of MRI, endoscopy, and EGB were 88.9%, 91.1%, 34.8%, 99.4%, and 91.0%; 77.8%, 92.3%, 35.0%, 98.7%, and 91.5%; and 66.7%, 92.3%, 31.6%, 98.1%, and 91.0%, respectively., Conclusion: A quick contrast-free screening MRI complements endoscopy in NPC screening programs. In EBV-screen-positive patients, MRI enables early detection of NPC that is endoscopically occult or negative on EGB and increases confidence that NPC has not been missed., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

BACKGROUND: We previously conducted a prospective study to show that nasopharyngeal cancer (NPC) screening with circulating Epstein–Barr virus (EBV) DNA analysis can improve survival. However, the long-term significance of positive results in individuals without cancer was unclear. METHODS: We conducted a second-round screening at a median of 43 months after the initial screening. Participants with detectable plasma EBV DNA were retested in 4 weeks, and those with persistently positive results were investigated with nasal endoscopy and magnetic resonance imaging. RESULTS: Of the 20,174 volunteers who participated in the first-round screening, 17,838 (88.6%) were rescreened. Among them, 423 (2.37%) had persistently detectable plasma EBV DNA. Twenty-four patients were identified as having NPC. A significantly higher proportion of patients had stage I/II cancer than in a historical cohort (67% vs. 20%; chi-square test, P<0.001), and they had superior 3-year progression-free survival (100% vs. 78.8%). Compared with participants with undetectable plasma EBV DNA in the first round of screening, participants with transiently and persistently positive results in the first round were more likely to have a cancer identified in the second round, with relative risks of 4.4 (95% confidence interval, 1.3 to 15.0) and 16.8 (95% confidence interval, 5.7 to 49.6), respectively. CONCLUSIONS: Individuals with detectable plasma EBV DNA but without an immediately identifiable NPC were more likely to have the cancer identified in another round of screening performed 3 to 5 years later. (Funded by Kadoorie Charitable Foundation and others; ClinicalTrials.gov number, NCT02063399.)

A meeting of experts was held in November 2021 to review and discuss available data on performance of Epstein-Barr virus (EBV)-based approaches to screen for early stage nasopharyngeal carcinoma (NPC) and methods for the investigation and management of screen-positive individuals. Serum EBV antibody and plasma EBV DNA testing methods were considered. Both approaches were found to have favorable performance characteristics and to be cost-effective in high-risk populations. In addition to endoscopy, use of magnetic resonance imaging (MRI) to investigate screen-positive individuals was found to increase the sensitivity of NPC detection with minimal impact on cost-effectiveness of the screening program., (© The Author(s) 2023. Published by Oxford University Press.)