review · ecancermedicalscience
Monitoring circulating Epstein-Barr virus DNA during and immediately after radiotherapy provides valuable prognostic insights for patients with locoregionally advanced nasopharyngeal carcinoma. A systematic review evaluating twenty distinct cohorts found that unfavourable viral DNA patterns, including persistent detection, delayed clearance, or rebound after an initial drop, consistently correlated with worse survival outcomes. Patients exhibiting these adverse kinetic patterns experienced significantly higher rates of disease progression and distant metastases, with distant metastasis hazard ratios frequently exceeding two. However, substantial variation across studies regarding assay methods, testing timepoints, and response definitions currently prevents the establishment of standardised clinical decision thresholds. Consequently, while tracking dynamic viral clearance is informative, these measurements cannot yet be used to safely adapt patient treatments outside of formal clinical trials until prospective standardisation occurs.
Nasopharyngeal carcinoma management relies heavily on tracking treatment response to detect treatment failure early. Demonstrating that serial viral DNA changes identify patients at high risk of metastasis offers a potential path toward personalised therapy. However, establishing uniform testing protocols is essential before oncologists can reliably use these molecular markers to tailor radiotherapy or chemotherapy routines in everyday clinical care.
The findings inform the development of clinical diagnostic assays and monitoring protocols for oncology care. Because substantial heterogeneity in testing platforms, sampling intervals, and response criteria currently hinders clinical adoption, the approach remains at an early research stage. Real-world commercialisation will require standardising diagnostic assays and prospectively validating decision thresholds before diagnostic providers can market validated testing kits to guide treatment adaptation.
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Background: Plasma Epstein-Barr virus DNA (EBV-DNA) is an established prognostic biomarker in nasopharyngeal carcinoma (NPC).While baseline EBV-DNA reflects tumour burden, increasing interest has focused on on-treatment EBV-DNA dynamics as a marker of early molecular response (EMR), but heterogeneity in timepoints, EMR definitions and study designs limits clinical translation.Objective: To systematically review and qualitatively synthesise the prognostic significance of plasma EBV-DNA dynamics measured during curative-intent therapy in locoregionally advanced, non-metastatic NPC.Methods: This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 statement.PubMed/ Medical Literature Analysis and Retrieval System Online, Embase, Scopus and Web of Science were searched (January 2004 to December 4, 2025).Eligible studies included prospective and observational designs reporting serial plasma EBV-DNA measurements during treatment and survival outcomes.Owing to heterogeneity in sampling timepoints, EMR constructs and EBV-DNA assays, no quantitative meta-analysis was performed.Risk of bias was assessed using design-appropriate tools.Results: Twenty-one eligible reports, representing 20 analytically distinct study cohorts, met the inclusion criteria.Across treatment strategies and analytical approaches, unfavourable on-treatment EBV-DNA dynamics (persistent detectability, delayed clearance or adverse kinetic patterns) were consistently associated with inferior survival outcomes, particularly distant metastasis-free and event-free survival.In reports providing hazard ratios for distant metastasis-related endpoints, effect sizes were generally greater than 2. EBV-DNA rebound after initial clearance was also associated with unfavourable prognosis, although prospective validation remains required.Conclusion: On-treatment and early post-radiotherapy EBV-DNA dynamics show consistent prognostic associations in locoregionally advanced NPC, but heterogeneous assays, sampling windows and response definitions preclude validated clinical decision thresholds.These measures should not guide treatment adaptation outside clinical trials; prospective standardisation and validation are required.
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DOI: 10.3332/ecancer.2026.2202
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