{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T08:35:43Z","timestamp":1773736543333,"version":"3.50.1"},"reference-count":50,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,4,24]],"date-time":"2020-04-24T00:00:00Z","timestamp":1587686400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Cancer Research UK Programme Grant"},{"name":"Integrative Cancer Epidemiology Programme","award":["C18281\/A19169"],"award-info":[{"award-number":["C18281\/A19169"]}]},{"name":"National Institute for Health Research (NIHR) under its Programme Grants for Applied Research Scheme","award":["RP-PG-0707-10034"],"award-info":[{"award-number":["RP-PG-0707-10034"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2020,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Epstein\u2010Barr virus (EBV) causes nasopharyngeal carcinoma (NPC) in endemic regions, where almost every tumor is EBV\u2010positive. In Western populations, NPC is rare, and human papillomavirus infection (HPV) has been suggested as another viral cause. We validated multiplex serology with molecular tumor markers, to define EBV\u2010positive, HPV\u2010positive and EBV\u2010\/HPV\u2010negative NPCs in the United Kingdom, and analyzed survival differences between those groups. Sera from NPC cases (n = 98) and age\u2010 and sex\u2010matched controls (n = 142) from the Head and Neck 5000 clinical cohort study were analyzed. IgA and IgG serum antibodies against 13 EBV antigens were measured and compared with EBER in situ hybridization (EBER\u2010ISH) data of 41 NPC tumors (29 EBER\u2010ISH positive, 12 negative). IgG antibodies to EBV LF2 correctly diagnosed EBV\u2010positive NPCs in 28 of 29 cases, while all EBER\u2010ISH negative NPCs were seronegative to LF2 IgG (specificity = 100%, sensitivity = 97%). HPV early antigen serology was compared to HPV molecular markers (p16 expression, HPV DNA and RNA) available for 41 NPCs (13 positive, 28 negative). Serology matched molecular HPV markers in all but one case (specificity = 100%, sensitivity = 92%). EBV and HPV infections were mutually exclusive. Overall, 67% of the analyzed NPCs were defined as EBV\u2010positive, 18% as HPV\u2010positive and 14% as EBV\/HPV\u2010negative. There was no statistical evidence of a difference in survival between the three groups. These data provide evidence that both, EBV\u2010positive and HPV\u2010positive NPCs are present in a low incidence country, and that EBV and HPV serum antibodies correlate with the viral status of the tumor.<\/jats:p>","DOI":"10.1002\/ijc.33006","type":"journal-article","created":{"date-parts":[[2020,4,12]],"date-time":"2020-04-12T09:53:56Z","timestamp":1586685236000},"page":"461-471","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["<scp>Epstein\u2010Barr<\/scp> virus and human papillomavirus serum antibodies define the viral status of nasopharyngeal carcinoma in a low endemic country"],"prefix":"10.1002","volume":"147","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1432-2767","authenticated-orcid":false,"given":"Julia","family":"Simon","sequence":"first","affiliation":[{"name":"Infections and Cancer Epidemiology, Infection, Inflammation and Cancer Program German Cancer Research Center (DKFZ)  Heidelberg Germany"},{"name":"Faculty of Biosciences Heidelberg University  Heidelberg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lea","family":"Schroeder","sequence":"additional","affiliation":[{"name":"Infections and Cancer Epidemiology, Infection, Inflammation and Cancer Program German Cancer Research Center (DKFZ)  Heidelberg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kate","family":"Ingarfield","sequence":"additional","affiliation":[{"name":"National Institute for Health Research (NIHR), Bristol Biomedical Research Centre University Bristol Hospitals, Bristol NHS Foundation Trust and University of Bristol  Bristol UK"},{"name":"Centre for Trials Research, College of Biomedical and Life Sciences Cardiff University  Cardiff UK"},{"name":"Community Oral Health, University of Glasgow Dental School, College of Medical, Veterinary and Life Sciences University of Glasgow  Glasgow UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Diehl","sequence":"additional","affiliation":[{"name":"Infections and Cancer Epidemiology, Infection, Inflammation and Cancer Program German Cancer Research Center (DKFZ)  Heidelberg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jill","family":"Werner","sequence":"additional","affiliation":[{"name":"Infections and Cancer Epidemiology, Infection, Inflammation and Cancer Program German Cancer Research Center (DKFZ)  Heidelberg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole","family":"Brenner","sequence":"additional","affiliation":[{"name":"Infections and Cancer Epidemiology, Infection, Inflammation and Cancer Program German Cancer Research Center (DKFZ)  Heidelberg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0136-651X","authenticated-orcid":false,"given":"Zhiwei","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics National Cancer Institute  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Pawlita","sequence":"additional","affiliation":[{"name":"Infections and Cancer Epidemiology, Infection, Inflammation and Cancer Program German Cancer Research Center (DKFZ)  Heidelberg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miranda","family":"Pring","sequence":"additional","affiliation":[{"name":"National Institute for Health Research (NIHR), Bristol Biomedical Research Centre University Bristol Hospitals, Bristol NHS Foundation Trust and University of Bristol  Bristol UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Butt","sequence":"additional","affiliation":[{"name":"Infections and Cancer Epidemiology, Infection, Inflammation and Cancer Program German Cancer Research Center (DKFZ)  Heidelberg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andy","family":"Ness","sequence":"additional","affiliation":[{"name":"National Institute for Health Research (NIHR), Bristol Biomedical Research Centre University Bristol Hospitals, Bristol NHS Foundation Trust and University of Bristol  Bristol UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tim","family":"Waterboer","sequence":"additional","affiliation":[{"name":"Infections and Cancer Epidemiology, Infection, Inflammation and Cancer Program German Cancer Research Center (DKFZ)  Heidelberg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,4,24]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.29210"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-06-0353"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.56.6.1699"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.2910280308"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a112470"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19830115)51:2<260::AID-CNCR2820510216>3.0.CO;2-#"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0019100"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa011610"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-17-1929"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1044579X0200086X"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kws479"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-9378-8-30"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.23318"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.21714"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.25450"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa065497"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2012.47.2738"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djv403"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers10070210"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djx005"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.30697"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-14-3323"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2013.11.246"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21492"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-14-973"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/coa.12548"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.5935\/1808-8694.20130075"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/0046-8177(94)90227-5"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.27605"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.44.2.504-512.2006"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.02227-07"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2005.052381"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2005.11.008"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0209379"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.31416"},{"key":"e_1_2_10_37_1","unstructured":"McLennanD NobleM DaviesJ GarrattE. The English Indices of Deprivation 2010. Government DfCaL 2011.https:\/\/www.gov.uk\/government\/statistics\/english-indices-of-deprivation-2010(accessed September 11 2019)."},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/170.1.13"},{"key":"e_1_2_10_39_1","first-page":"289","article-title":"Epstein\u2010Barr virus\u2010specific humoral immune responses in health and disease","volume":"391","author":"Middeldorp JM","year":"2015","journal-title":"Curr Top Microbiol Immunol"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.44.4.1459-1467.2006"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0702332104"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00315-08"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2014.10.030"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canep.2016.03.003"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.23362"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(10)70017-6"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2013.06.207"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-16-0633"},{"key":"e_1_2_10_49_1","first-page":"642","article-title":"The pathogenesis and therapeutics of nasopharyngeal carcinoma","volume":"13","author":"He J\u2010Q","year":"2019","journal-title":"Health Sci J"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/lary.21089"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-08-1175"}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fijc.33006","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.33006","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ijc.33006","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.33006","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T18:43:16Z","timestamp":1700678596000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.33006"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,24]]},"references-count":50,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2020,7,15]]}},"alternative-id":["10.1002\/ijc.33006"],"URL":"https:\/\/doi.org\/10.1002\/ijc.33006","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"value":"0020-7136","type":"print"},{"value":"1097-0215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,24]]},"assertion":[{"value":"2019-11-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-03-24","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-04-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}