{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T22:02:05Z","timestamp":1788386525468,"version":"build-2803163510"},"reference-count":44,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2019,10,8]],"date-time":"2019-10-08T00:00:00Z","timestamp":1570492800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2020,4,15]]},"abstract":"<jats:p>Nasopharyngeal carcinoma (NPC) is originated from the epithelial cells of nasopharynx, Epstein\u2013Barr virus (EBV)\u2010associated and has the highest incidence and mortality rates in Southeast Asia. Late presentation is a common issue and early detection could be the key to reduce the disease burden. Sensitivity of plasma EBV DNA, an established NPC biomarker, for Stage I NPC is controversial. Most newly reported NPC biomarkers have neither been externally validated nor compared to the established ones. This causes difficulty in planning for cost\u2010effective early detection strategies. Our study systematically evaluated six established and four new biomarkers in NPC cases, population controls and hospital controls. We showed that BamHI\u2010W 76\u2009bp remains the most sensitive plasma biomarker, with 96.7% (29\/30), 96.7% (58\/60) and 97.4% (226\/232) sensitivity to detect Stage I, early stage and all NPC, respectively. Its specificity was 94.2% (113\/120) against population controls and 90.4% (113\/125) against hospital controls. Diagnostic accuracy of BamHI\u2010W 121\u2009bp and ebv\u2010miR\u2010BART7\u20103p were validated. Hsa\u2010miR\u201029a\u20103p and hsa\u2010miR\u2010103a\u20103p were not, possibly due to lower number of advanced stage NPC cases included in this subset. Decision tree modeling suggested that combination of BamHI\u2010W 76\u2009bp and VCA IgA or EA IgG may increase the specificity or sensitivity to detect NPC. <jats:italic>EBNA1<\/jats:italic> 99\u2009bp could identify NPC patients with poor prognosis in early and advanced stage NPC. Our findings provided evidence for improvement in NPC screening strategies, covering considerations of opportunistic screening, combining biomarkers to increase sensitivity or specificity and testing biomarkers from single sampled specimen to avoid logistic problems of resampling.<\/jats:p>","DOI":"10.1002\/ijc.32656","type":"journal-article","created":{"date-parts":[[2019,8,30]],"date-time":"2019-08-30T15:43:39Z","timestamp":1567179819000},"page":"2336-2347","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":67,"title":["Systematic comparison of plasma EBV DNA, anti\u2010EBV antibodies and miRNA levels for early detection and prognosis of nasopharyngeal carcinoma"],"prefix":"10.1002","volume":"146","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7934-2462","authenticated-orcid":false,"given":"Lu Ping","family":"Tan","sequence":"first","affiliation":[{"name":"Molecular Pathology Unit, Cancer Research Centre Institute for Medical Research, Ministry of Health Malaysia  Kuala Lumpur Malaysia"},{"name":"Department of Medical Sciences, School of Healthcare and Medical Sciences Sunway University  Selangor Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3872-3485","authenticated-orcid":false,"given":"Geok Wee","family":"Tan","sequence":"additional","affiliation":[{"name":"Molecular Pathology Unit, Cancer Research Centre Institute for Medical Research, Ministry of Health Malaysia  Kuala Lumpur Malaysia"},{"name":"Department of Pathology and Medical Biology University of Groningen, University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3223-9265","authenticated-orcid":false,"given":"Vijaya Mohan","family":"Sivanesan","sequence":"additional","affiliation":[{"name":"Molecular Pathology Unit, Cancer Research Centre Institute for Medical Research, Ministry of Health Malaysia  Kuala Lumpur Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siang Ling","family":"Goh","sequence":"additional","affiliation":[{"name":"Faculty of Science, University of Malaya Institute of Biological Sciences  Kuala Lumpur Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xun Jin","family":"Ng","sequence":"additional","affiliation":[{"name":"Molecular Pathology Unit, Cancer Research Centre Institute for Medical Research, Ministry of Health Malaysia  Kuala Lumpur Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7015-0125","authenticated-orcid":false,"given":"Chun Shen","family":"Lim","sequence":"additional","affiliation":[{"name":"Faculty of Science, University of Malaya Institute of Biological Sciences  Kuala Lumpur Malaysia"},{"name":"Department of Biochemistry School of Biomedical Sciences, University of Otago  Dunedin New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wee Ric","family":"Kim","sequence":"additional","affiliation":[{"name":"Molecular Pathology Unit, Cancer Research Centre Institute for Medical Research, Ministry of Health Malaysia  Kuala Lumpur Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5996-8409","authenticated-orcid":false,"given":"Taznim Begam Binti Mohd","family":"Mohidin","sequence":"additional","affiliation":[{"name":"Faculty of Science, University of Malaya Institute of Biological Sciences  Kuala Lumpur Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nor Soleha","family":"Mohd Dali","sequence":"additional","affiliation":[{"name":"Haematology Unit, Cancer Research Centre Institute for Medical Research, Ministry of Health Malaysia  Kuala Lumpur Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siew Hoon","family":"Ong","sequence":"additional","affiliation":[{"name":"Molecular Pathology Unit, Cancer Research Centre Institute for Medical Research, Ministry of Health Malaysia  Kuala Lumpur Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun Ying","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Sarawak General Hospital, Ministry of Health Malaysia, Jalan Hospital  Kuching Sarawak Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Halimuddin","family":"Sawali","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Queen Elizabeth Hospital, Ministry of Health Malaysia  Kota Kinabalu Sabah Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoke Yeow","family":"Yap","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Kuala Lumpur Hospital, Ministry of Health Malaysia  Kuala Lumpur Malaysia"},{"name":"Department of Surgery, Clinical Campus Faculty of Medicine and Health Sciences University Putra Malaysia at Kuala Lumpur Hospital, Ministry of Health Malaysia  Kuala Lumpur Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faridah","family":"Hassan","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Selayang Hospital, Ministry of Health Malaysia  Batu Caves Selangor Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kin Choo","family":"Pua","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Pulau Pinang Hospital, Ministry of Health Malaysia  Georgetown Pulau Pinang Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng Eng","family":"Koay","sequence":"additional","affiliation":[{"name":"Gleneagles Kuala Lumpur Hospital  Kuala Lumpur Malaysia"},{"name":"Sunway Medical Centre  Bandar Sunway Selangor Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching Ching","family":"Ng","sequence":"additional","affiliation":[{"name":"Faculty of Science, University of Malaya Institute of Biological Sciences  Kuala Lumpur Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8268-5271","authenticated-orcid":false,"given":"Alan Soo\u2010Beng","family":"Khoo","sequence":"additional","affiliation":[{"name":"Molecular Pathology Unit, Cancer Research Centre Institute for Medical Research, Ministry of Health Malaysia  Kuala Lumpur Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the Malaysian Nasopharyngeal Carcinoma Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,10,8]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1158\/1055-9965.482.13.3","article-title":"High incidence of nasopharyngeal carcinoma in native people of Sarawak, Borneo Island","volume":"13","author":"Devi BC","year":"2004","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"e_1_2_9_3_1","first-page":"39","article-title":"Nasopharyngeal carcinoma: epidemiology and dietary factors","volume":"105","author":"Yu MC","year":"1991","journal-title":"IARC Sci Publ"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21492"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.30643"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.20372"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-04-4208"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2015.140"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0215(19980717)77:2<228::AID-IJC11>3.0.CO;2-7"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.7314\/APJCP.2013.14.8.4567"},{"key":"e_1_2_9_11_1","first-page":"1739","article-title":"Prognostic factors in patients with nasopharyngeal carcinoma treated in Hospital Kuala Lumpur","volume":"12","author":"El\u2010Sherbieny E","year":"2011","journal-title":"Asian Pac J Cancer Prev"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.7314\/APJCP.2013.14.11.6513"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-015-0433-1"},{"key":"e_1_2_9_14_1","first-page":"59","article-title":"Nasopharyngeal carcinoma database","volume":"63","author":"Pua KC","year":"2008","journal-title":"Med J Malaysia"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12105-017-0787-0"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2013.12.011"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.26380"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kws404"},{"key":"e_1_2_9_19_1","first-page":"3431","article-title":"Disparity of sensitivities in detection of radiation\u2010naive and postirradiation recurrent nasopharyngeal carcinoma of the undifferentiated type by quantitative analysis of circulating Epstein\u2010Barr virus DNA1,2","volume":"9","author":"Leung SF","year":"2003","journal-title":"Clin Cancer Res"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.29192"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1701717"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1804184115"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trsl.2012.01.015"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-9378-9-38"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.29206"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2013.214213"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.31642"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.17083"},{"key":"e_1_2_9_29_1","first-page":"330","article-title":"Plasma microRNA profiling in nasopharyngeal carcinoma patients reveals miR\u2010548q and miR\u2010483\u20105p as potential biomarkers","volume":"33","author":"Zheng XH","year":"2014","journal-title":"Chin J Cancer"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.25544"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.4161\/cbt.26170"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/1743-422X-10-119"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.31967"},{"key":"e_1_2_9_34_1","volume-title":"Epidemiology of cancer in Sarawak 2001\u20132005","author":"Ooi CH","year":"2009"},{"key":"e_1_2_9_35_1","volume-title":"Sabah cancer registry report 2006\u20132010","author":"Maria S","year":"2015"},{"key":"e_1_2_9_36_1","volume-title":"Malaysian National Cancer Registry Report 2007\u20102011","author":"Azizah AM","year":"2016"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(88)90530-2"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biologicals.2016.04.010"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep09430"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-6866-4_2"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.43.7.3066-3073.2005"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1525-1578(10)60535-1"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000000845"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000005130"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.31856"}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.32656","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ijc.32656","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.32656","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T17:26:15Z","timestamp":1694021175000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.32656"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,8]]},"references-count":44,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2020,4,15]]}},"alternative-id":["10.1002\/ijc.32656"],"URL":"https:\/\/doi.org\/10.1002\/ijc.32656","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"value":"0020-7136","type":"print"},{"value":"1097-0215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,8]]},"assertion":[{"value":"2019-03-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-08-15","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-10-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}