{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T17:20:48Z","timestamp":1788542448199,"version":"build-2803163510"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2022,3,24]],"date-time":"2022-03-24T00:00:00Z","timestamp":1648080000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,7,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Epstein\u2013Barr virus (EBV) DNA detection in the nasopharynx is considered a biomarker for nasopharyngeal carcinoma (NPC). We evaluated its performance as a reflex test to triage EBV seropositives within an NPC screening program in China.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>The study population was embedded within an ongoing NPC screening trial and included 1111 participants who screened positive for anti-EBV VCA (antibodies against EBV capsid antigens)\/EBNA1 (EBV nuclear antigen1)-IgA antibodies (of 18\u200a237 screened). Nasopharynx swabs were collected\/tested for EBNA1 gene EBV DNA load. We evaluated performance of EBV DNA in the nasopharynx swab as a reflex test to triage EBV serological high-risk (those referred to endoscopy\/MRI) and medium-risk (those referred to accelerated screening) individuals.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>By the end of 2019, we detected 20 NPC cases from 317 serological high-risk individuals and 4 NPC cases from 794 medium-risk individuals. When used to triage serological high-risk individuals, nasopharynx swab EBV DNA was detected in 19\/20 cases (positivity rate among cases: 95.0%; 95% CI, 75.1%\u201399.9%), with a referral rate of 63.4% (201\/317, 95% CI, 57.8%\u201368.7%) and NPC detection rate among positives of 9.5% (19\/201, 95% CI, 5.8%\u201314.4%). The performance of an algorithm that combined serology with triage of serology high-risk individuals using EBV DNA testing yielded a sensitivity of 72.4% (95% CI, 3.0%-81.4%) and specificity of 97.6% (95% CI, 97.2%-97.9%). When used to triage EBV serological medium-risk individuals, the positivity rate among cases was 75.0% (95% CI, 19.4%-99.4%), with a referral rate of 61.8% (95% CI, 58.4%-65.2%) and NPC detection rate among positives of 0.6% (95% CI, 0.1%-1.8%).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Nasopharynx swab EBV DNA showed promise as a reflex test to triage serology high-risk individuals, reducing referral by ca. 40% with little reduction in sensitivity compared to a serology-only screening program.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/clinchem\/hvac032","type":"journal-article","created":{"date-parts":[[2022,2,17]],"date-time":"2022-02-17T12:08:01Z","timestamp":1645099681000},"page":"953-962","source":"Crossref","is-referenced-by-count":28,"title":["Utility of Epstein\u2013Barr Virus DNA in Nasopharynx Swabs as a Reflex Test to Triage Seropositive Individuals in Nasopharyngeal Carcinoma Screening Programs"],"prefix":"10.1093","volume":"68","author":[{"given":"Geng Hang","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Cancer Prevention, Sun Yat-sen University Cancer Center , Guangzhou , China"},{"name":"Guangdong Provincial Hospital of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine , Guangzhou , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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 , Rockville, MD , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly J","family":"Yu","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics, National Cancer Institute , Rockville, MD , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna E","family":"Coghill","sequence":"additional","affiliation":[{"name":"Cancer Epidemiology Program, Division of Population Sciences, H. Lee Moffitt Cancer Center and Research Institute , Tampa, FL , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao Xia","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cancer Prevention, Sun Yat-sen University Cancer Center , Guangzhou , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shang Hang","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Cancer Prevention, Sun Yat-sen University Cancer Center , Guangzhou , China"},{"name":"State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, and Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-Sen University Cancer Center , Guangzhou , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong Feng","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Cancer Prevention, Sun Yat-sen University Cancer Center , Guangzhou , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi Hong","family":"Huang","sequence":"additional","affiliation":[{"name":"Sihui Cancer Institute , Sihui , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu Qiang","family":"Lu","sequence":"additional","affiliation":[{"name":"Sihui Cancer Institute , Sihui , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Ling","sequence":"additional","affiliation":[{"name":"Sihui Cancer Institute , Sihui , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chu Yang","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Cancer Prevention, Sun Yat-sen University Cancer Center , Guangzhou , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi Jian","family":"Lu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, and Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-Sen University Cancer Center , Guangzhou , China"},{"name":"Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center , Guangzhou , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu Ying","family":"Fan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, and Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-Sen University Cancer Center , Guangzhou , China"},{"name":"Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center , Guangzhou , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin Quan","family":"Tang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, and Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-Sen University Cancer Center , Guangzhou , China"},{"name":"Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center , Guangzhou , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2875-3365","authenticated-orcid":false,"given":"Joshua N","family":"Sampson","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics, National Cancer Institute , Rockville, MD , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, and Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-Sen University Cancer Center , Guangzhou , China"},{"name":"Department of Radiology, Sun Yat-sen University Cancer Center , Guangzhou , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann D","family":"King","sequence":"additional","affiliation":[{"name":"Department of Imaging and Interventional Radiology, The Chinese University of Hong Kong, Hong Kong SAR , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaap M","family":"Middeldorp","sequence":"additional","affiliation":[{"name":"Department of Pathology, Vrije Universiteit Medical Center , Amsterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan","family":"Hildesheim","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics, National Cancer Institute , Rockville, MD , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su Mei","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Cancer Prevention, Sun Yat-sen University Cancer Center , Guangzhou , China"},{"name":"State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, and Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-Sen University Cancer Center , Guangzhou , China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,3,24]]},"reference":[{"key":"2022070317170149600_hvac032-B1","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1056\/NEJM199509143331103","article-title":"Clonal proliferations of cells infected with Epstein\u2013Barr virus in preinvasive lesions related to nasopharyngeal carcinoma","volume":"333","author":"Pathmanathan","year":"1995","journal-title":"N Engl J Med"},{"key":"2022070317170149600_hvac032-B2","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1038\/nrc1452","article-title":"Epstein\u2013Barr virus: 40 years on","volume":"4","author":"Young","year":"2004","journal-title":"Nat Rev 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virus-related serologic antibody tests in nasopharyngeal carcinoma screening: results from the initial phase of a cluster randomized controlled trial in Southern China","volume":"177","author":"Liu","year":"2013","journal-title":"Am J Epidemiol"},{"key":"2022070317170149600_hvac032-B6","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.1093\/annonc\/mdz231","article-title":"Incidence and mortality of nasopharyngeal carcinoma: interim analysis of a cluster randomized controlled screening trial (PRO-NPC-001) in southern China","volume":"30","author":"Ji","year":"2019","journal-title":"Ann Oncol"},{"key":"2022070317170149600_hvac032-B7","doi-asserted-by":"crossref","first-page":"2398","DOI":"10.1002\/ijc.33424","article-title":"Prospective assessment of a nasopharyngeal carcinoma risk score in a population undergoing screening","volume":"148","author":"Chen","year":"2021","journal-title":"Int J 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Oncol"},{"key":"2022070317170149600_hvac032-B11","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1373\/clinchem.2003.022426","article-title":"Improved accuracy of detection of nasopharyngeal carcinoma by combined application of circulating Epstein\u2013Barr virus DNA and anti-Epstein\u2013Barr viral capsid antigen IgA antibody","volume":"50","author":"Leung","year":"2004","journal-title":"Clin Chem"},{"key":"2022070317170149600_hvac032-B12","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1056\/NEJMoa1701717","article-title":"Analysis of plasma Epstein\u2013Barr Virus DNA to screen for nasopharyngeal cancer","volume":"377","author":"Chan","year":"2017","journal-title":"N Engl J Med"},{"key":"2022070317170149600_hvac032-B13","doi-asserted-by":"crossref","first-page":"3209","DOI":"10.1002\/ijc.31642","article-title":"Evaluation of circulating EBV microRNA BART2-5p in facilitating early detection and screening of nasopharyngeal carcinoma","volume":"143","author":"Jiang","year":"2018","journal-title":"Int J Cancer"},{"key":"2022070317170149600_hvac032-B14","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1002\/ijc.21914","article-title":"Noninvasive diagnosis of nasopharyngeal carcinoma: nasopharyngeal brushings reveal high Epstein\u2013Barr virus DNA load and carcinoma-specific viral BARF1 mRNA","volume":"119","author":"Stevens","year":"2006","journal-title":"Int J Cancer"},{"key":"2022070317170149600_hvac032-B15","doi-asserted-by":"crossref","first-page":"2175","DOI":"10.1158\/1078-0432.CCR-12-2897","article-title":"Epstein\u2013Barr virus DNA load in nasopharyngeal brushings and whole blood in nasopharyngeal carcinoma patients before and after treatment","volume":"19","author":"Adham","year":"2013","journal-title":"Clin Cancer Res"},{"key":"2022070317170149600_hvac032-B16","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1111\/cas.12718","article-title":"Quantification of Epstein\u2013Barr virus DNA load in nasopharyngeal brushing samples in the diagnosis of nasopharyngeal carcinoma in southern China","volume":"106","author":"Zheng","year":"2015","journal-title":"Cancer Sci"},{"key":"2022070317170149600_hvac032-B17","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1002\/ijc.30418","article-title":"Epstein\u2013Barr virus mRNA profiles and viral DNA methylation status in nasopharyngeal brushings from nasopharyngeal carcinoma patients reflect tumor origin","volume":"140","author":"Ramayanti","year":"2017","journal-title":"Int J Cancer"},{"key":"2022070317170149600_hvac032-B18","doi-asserted-by":"crossref","first-page":"2689","DOI":"10.1002\/1097-0142(19930415)71:8<2689::AID-CNCR2820710843>3.0.CO;2-H","article-title":"The World Health Organization histological classification of tumours of the upper respiratory tract and ear. A commentary on the second edition","volume":"71","author":"Shanmugaratnam","year":"1993","journal-title":"Cancer"},{"key":"2022070317170149600_hvac032-B19","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-319-40618-3","volume-title":"AJCC cancer staging manual","author":"Amin","year":"2017"},{"key":"2022070317170149600_hvac032-B20","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/S1386-6532(02)00042-2","article-title":"Parallel detection of five human herpes virus DNAs by a set of real-time polymerase chain reactions in a single run","volume":"26","author":"Stocher","year":"2003","journal-title":"J Clin Virol"},{"key":"2022070317170149600_hvac032-B21","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1128\/JCM.39.2.564-569.2001","article-title":"Normalized quantification by real-time PCR of Epstein\u2013Barr virus load in patients at risk for posttransplant lymphoproliferative disorders","volume":"39","author":"Jabs","year":"2001","journal-title":"J Clin 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Epstein\u2013Barr virus DNA enhance population screening of nasopharyngeal carcinoma","volume":"115","author":"Lam","year":"2018","journal-title":"Proc Natl Acad Sci USA"},{"key":"2022070317170149600_hvac032-B28","first-page":"2612","article-title":"Quantitative Epstein\u2013Barr virus DNA analysis and detection of gene promoter hypermethylation in nasopharyngeal (NP) brushing samples from patients with NP carcinoma","volume":"8","author":"Tong","year":"2002","journal-title":"Clin Cancer Res"},{"key":"2022070317170149600_hvac032-B29","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1002\/cncr.28564","article-title":"Evaluation of plasma Epstein\u2013Barr virus DNA load to distinguish nasopharyngeal carcinoma patients from healthy high-risk populations in Southern 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