{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T23:29:32Z","timestamp":1792106972896,"version":"4.4.0"},"reference-count":76,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,2,25]],"date-time":"2019-02-25T00:00:00Z","timestamp":1551052800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004853","name":"Chinese University of Hong Kong","doi-asserted-by":"publisher","award":["VCF2014021"],"award-info":[{"award-number":["VCF2014021"]}],"id":[{"id":"10.13039\/501100004853","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007421","name":"Li Ka Shing Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007421","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2019,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Analysis of circulating tumour DNA (ctDNA), as one type of \u2018liquid biopsy\u2019, has recently attracted great attention. Researchers are exploring many potential applications of liquid biopsy in many different types of cancer. In particular, it is of biological interest and clinical relevance to study the molecular characteristics of ctDNA. For such purposes, plasma Epstein\u2013Barr virus (EBV) DNA from patients with nasopharyngeal carcinoma (NPC) would provide a good model to understand the biological properties and clinical applications of ctDNA in general. The strong association between EBV and NPC in endemic regions has made plasma EBV DNA a robust biomarker for this cancer. There are many clinical utilities of plasma EBV DNA analysis in NPC diagnostics. Its role in prognostication and surveillance of recurrence is well established. Plasma EBV DNA has also been validated for screening NPC in a recent large\u2010scale prospective study. Indeed, plasma EBV DNA could be regarded as an archetypal ctDNA marker. In this review, we discuss the biological properties of plasma EBV DNA from NPC samples and also the clinical applications of plasma EBV DNA analysis in the management of NPC. Of note, the recently reported size analysis of plasma EBV DNA in patients with NPC has highlighted size as an important analytical parameter of ctDNA and demonstrated clinical value in improving the diagnostic performance of an EBV DNA\u2010based NPC screening test. Such insights into ctDNA analysis (including size profiling) may help its full potential in cancer diagnostics for other types of cancer to be realised. \u00a9 2019 The Authors. <jats:italic>The Journal of Pathology<\/jats:italic> published by John Wiley &amp; Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.<\/jats:p>","DOI":"10.1002\/path.5249","type":"journal-article","created":{"date-parts":[[2019,2,4]],"date-time":"2019-02-04T00:08:27Z","timestamp":1549238907000},"page":"641-649","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":72,"title":["Plasma Epstein\u2013Barr virus DNA as an archetypal circulating tumour DNA marker"],"prefix":"10.1002","volume":"247","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8922-5609","authenticated-orcid":false,"given":"Wai Kei Jacky","family":"Lam","sequence":"first","affiliation":[{"name":"Department of Chemical Pathology, The Chinese University of Hong Kong Prince of Wales Hospital  Shatin New Territories, Hong Kong SAR"},{"name":"Li Ka Shing Institute of Health Sciences The Chinese University of Hong Kong  Shatin New Territories, Hong Kong SAR"},{"name":"State Key Laboratory of Translational Oncology, Sir Y.K. Pao Centre for Cancer The Chinese University of Hong Kong, Shatin  New Territories Hong Kong SAR"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwan Chee Allen","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Chemical Pathology, The Chinese University of Hong Kong Prince of Wales Hospital  Shatin New Territories, Hong Kong SAR"},{"name":"Li Ka Shing Institute of Health Sciences The Chinese University of Hong Kong  Shatin New Territories, Hong Kong SAR"},{"name":"State Key Laboratory of Translational Oncology, Sir Y.K. Pao Centre for Cancer The Chinese University of Hong Kong, Shatin  New Territories Hong Kong SAR"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuk Ming Dennis","family":"Lo","sequence":"additional","affiliation":[{"name":"Department of Chemical Pathology, The Chinese University of Hong Kong Prince of Wales Hospital  Shatin New Territories, Hong Kong SAR"},{"name":"Li Ka Shing Institute of Health Sciences The Chinese University of Hong Kong  Shatin New Territories, Hong Kong SAR"},{"name":"State Key Laboratory of Translational Oncology, Sir Y.K. Pao Centre for Cancer The Chinese University of Hong Kong, Shatin  New Territories Hong Kong SAR"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,2,25]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11219"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3003726"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1213261"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3511"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3066"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05610"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12634"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2016.92"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-06-0353"},{"key":"e_1_2_11_11_1","first-page":"1188","article-title":"Quantitative analysis of cell\u2010free Epstein\u2010Barr virus DNA in plasma of patients with nasopharyngeal carcinoma","volume":"59","author":"Lo YMD","year":"1999","journal-title":"Cancer Res"},{"key":"e_1_2_11_12_1","first-page":"6878","article-title":"Molecular prognostication of nasopharyngeal carcinoma by quantitative analysis of circulating Epstein\u2010Barr virus DNA","volume":"60","author":"Lo YMD","year":"2000","journal-title":"Cancer Res"},{"key":"e_1_2_11_13_1","first-page":"5452","article-title":"Quantitative and temporal correlation between circulating cell\u2010free Epstein\u2010Barr virus DNA and tumor recurrence in nasopharyngeal carcinoma","volume":"59","author":"Lo YMD","year":"1999","journal-title":"Cancer Res"},{"key":"e_1_2_11_14_1","first-page":"3431","article-title":"Disparity of sensitivities in detection of radiation\u2010na\u00efve and postirradiation recurrent nasopharyngeal carcinoma of the undifferentiated type by quantitative analysis of circulating Epstein\u2010Barr virus DNA","volume":"9","author":"Leung SF","year":"2003","journal-title":"Clin Cancer Res"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1701717"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa032260"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.20099"},{"key":"e_1_2_11_18_1","first-page":"4059","article-title":"Comparison of Epstein\u2010Barr virus DNA level in plasma, peripheral blood cell and tumor tissue in nasopharyngeal carcinoma","volume":"24","author":"Shao JY","year":"2004","journal-title":"Anticancer Res"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2006.07.012"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcv.2012.05.017"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2000.02344.x"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0215(19990820)84:4<442::AID-IJC20>3.0.CO;2-J"},{"key":"e_1_2_11_23_1","first-page":"1856","article-title":"Circulating Epstein\u2010Barr virus DNA in the serum of patients with gastric carcinoma","volume":"7","author":"Lo YMD","year":"2001","journal-title":"Clin Cancer Res"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc1800433"},{"key":"e_1_2_11_25_1","first-page":"1659","article-title":"DNA fragments in the blood plasma of cancer patients: quantitations and evidence for their origin from apoptotic and necrotic cells","volume":"61","author":"Jahr S","year":"2001","journal-title":"Cancer Res"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1097\/00006676-199807000-00012"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-8981(01)00665-9"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-10-3312"},{"key":"e_1_2_11_29_1","first-page":"2028","article-title":"Molecular characterization of circulating EBV DNA in the plasma of nasopharyngeal carcinoma and lymphoma patients","volume":"63","author":"Chan KCA","year":"2003","journal-title":"Cancer Res"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2000.tb06597.x"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.20520"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2006.05.064"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2005.054783"},{"key":"e_1_2_11_34_1","first-page":"3254","article-title":"Rapid clearance of plasma Epstein\u2010Barr virus DNA after surgical treatment of nasopharyngeal carcinoma","volume":"9","author":"To EWH","year":"2003","journal-title":"Clin Cancer Res"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1086\/302205"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3001720"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1406103111"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2011.169318"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1804184115"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1500076112"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1006162"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-08-1112"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1071-5576(03)00155-2"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.1591"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.1875"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-04-0799"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-0861"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2001.tb03892.x"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/46.8.1078"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.1998.00797.x"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.07.7982"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.31741"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-12-3702"},{"key":"e_1_2_11_54_1","first-page":"2351","article-title":"Kinetics of plasma Epstein\u2010Barr virus DNA during radiation therapy for nasopharyngeal carcinoma","volume":"60","author":"Lo YMD","year":"2000","journal-title":"Cancer Res"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdu117"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2017-019012"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/94.21.1614"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clon.2010.09.001"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2015.3628"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2018.77.7847"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-09-454694"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2016002618"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.4505"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2012.196014"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaf6219"},{"key":"e_1_2_11_66_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40880-017-0256-x"},{"key":"e_1_2_11_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2013.02.006"},{"key":"e_1_2_11_68_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.14137"},{"key":"e_1_2_11_69_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.20129"},{"key":"e_1_2_11_70_1","unstructured":"Hong Kong Cancer Registry.Nasopharyngeal cancer in 2015. Available from:http:\/\/www3.ha.org.hk\/cancereg\/statistics.html."},{"key":"e_1_2_11_71_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2018.36.15_suppl.12021"},{"key":"e_1_2_11_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2017.01.002"},{"key":"e_1_2_11_73_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-018-0021-8"},{"key":"e_1_2_11_74_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3007094"},{"key":"e_1_2_11_75_1","first-page":"1","article-title":"Detection and localization of surgically resectable cancers with a multi\u2010analyte blood test","volume":"3247","author":"Cohen AJD","year":"2018","journal-title":"Science"},{"key":"e_1_2_11_76_1","first-page":"475","article-title":"The biology and clinical utility of EBV monitoring in blood","volume":"391","author":"Kanakry J","year":"2015","journal-title":"Curr Top Microbiol Immunol"},{"key":"e_1_2_11_77_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.28001"}],"container-title":["The Journal of Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpath.5249","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/path.5249","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/path.5249","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/path.5249","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T12:05:49Z","timestamp":1760961949000},"score":1,"resource":{"primary":{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/10.1002\/path.5249"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2,25]]},"references-count":76,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2019,4]]}},"alternative-id":["10.1002\/path.5249"],"URL":"https:\/\/doi.org\/10.1002\/path.5249","archive":["Portico"],"relation":{},"ISSN":["0022-3417","1096-9896"],"issn-type":[{"value":"0022-3417","type":"print"},{"value":"1096-9896","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,2,25]]},"assertion":[{"value":"2018-12-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-01-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-02-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}