The appropriate use of circulating EBV-DNA in nasopharyngeal carcinoma: Comprehensive clinical practice guidelines evaluation

Background: In EBV-related nasopharyngeal carcinoma (NPC), quantitative determination of circulating EBV-DNA (cEBV-DNA) can potentially be applied as disease marker. The aim of the study was to investigate if the clinical utility of cEBV-DNA is established in clinical practice guidelines and if recommendations are provided to standardize the quantitative cEBV-DNA determination. Methods: A systematic literature search for NPC guidelines published since 2011 was performed. Information for cEBV-DNA detection method and use in clinical practice was synthesized in consecutive steps of increasing simplification. Results: From 570 titles and abstracts identified by the search, 16 guidelines were included. The selected documents were further clustered as either being based on a systematic literature revision to generate recommendations (4/16) or not (12/16). cEBV-DNA was evaluated in only one guideline based on a systematic revision and in 8 guidelines without systematic revision. Half of available guidelines provide recommendation for its clinical use. Methodological issues on cEBV-DNA determination are discussed by 31% of guidelines, without providing any recommendation on method standardization. Conclusions: Due to its prognostic value, cEBV-DNA is suggested in the pre-treatment work-up and in the follow-up. Guideline producers need to take into more consideration methodological aspects impacting the actual reliability and generalizability of laboratory results.