{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T18:15:53Z","timestamp":1785176153630,"version":"3.55.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T00:00:00Z","timestamp":1742774400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFC2305400"],"award-info":[{"award-number":["2022YFC2305400"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82122050"],"award-info":[{"award-number":["82122050"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82471859"],"award-info":[{"award-number":["82471859"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Specific genetic variations of Epstein-Barr virus (EBV) have been linked to nasopharyngeal (NP) carcinoma (NPC). Because EBV is shed through saliva, saliva samples are commonly used for EBV genotyping in studies of EBV-associated diseases. However, it remains uncertain whether infection with the same EBV strains occurs across different tissues within a host and whether EBV detected in saliva accurately represents the strain in diseased tissues.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted whole-genome sequencing of EBV from paired biopsy tissues, saliva samples, and NP swab samples from 33 patients with newly diagnosed NPC to determine the genetic concordance of EBV strains across different tissue types within the same individual.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Phylogenetic and pairwise genetic distance analysis revealed a high degree of intrahost concordance, indicating infection with the same EBV strains among different samples within the host. Multiple EBV infections were identified in 6% of saliva samples, compared with 3% in tumor tissues. Notably, NPC tumor EBV strains were consistently detected in paired saliva and swab samples. For multiple infections in saliva and NP swab samples, EBV variants of the major strain showed higher genetic concordance with the variants detected in NPC tumors than with variants of the minor strain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our study highlight the genetic consistency of EBV across tumor, NP swab, and saliva samples, supporting the use of saliva as a reliable source for EBV sequencing and genotyping in future epidemiological studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/infdis\/jiaf135","type":"journal-article","created":{"date-parts":[[2025,3,29]],"date-time":"2025-03-29T00:47:33Z","timestamp":1743209253000},"page":"735-744","source":"Crossref","is-referenced-by-count":4,"title":["A Comparative Study of Epstein-Barr Virus Genomes Detected in Tumor, Nasopharyngeal Swab, and Saliva Samples From Patients With Nasopharyngeal Carcinoma"],"prefix":"10.1093","volume":"232","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6543-342X","authenticated-orcid":false,"given":"Jingtong","family":"Liang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center , Guangzhou ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7872-1463","authenticated-orcid":false,"given":"Cheng-Ping","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, National Taiwan University Hospital and National Taiwan University, College of Medicine , Taipei ,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhong","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center , Guangzhou ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7271-6070","authenticated-orcid":false,"given":"Wan-Lun","family":"Hsu","sequence":"additional","affiliation":[{"name":"Data Science Center, College of Medicine, Fu-Jen Catholic University , New Taipei City ,","place":["Taiwan"]},{"name":"Master Program of Big Data in Medical Healthcare Industry, College of Medicine, Fu-Jen Catholic University , New Taipei City ,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3832-6586","authenticated-orcid":false,"given":"Kelly J","family":"Yu","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics, National Cancer Institute , Rockville, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qisheng","family":"Feng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center , Guangzhou ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoping","family":"Ye","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center , Guangzhou ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3360-0382","authenticated-orcid":false,"given":"Tseng-Cheng","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, National Taiwan University Hospital and National Taiwan University, College of Medicine , Taipei ,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0950-0621","authenticated-orcid":false,"given":"Julia","family":"Krushkal","sequence":"additional","affiliation":[{"name":"Biometric Research Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute , Rockville, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0257-2363","authenticated-orcid":false,"given":"Allan","family":"Hildesheim","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics, National Cancer Institute , Rockville, Maryland"},{"name":"Agencia Costarriciense de Investigaciones Biomedicas , San Jose ,","place":["Costa Rica"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7091-4199","authenticated-orcid":false,"given":"Miao","family":"Xu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center , Guangzhou ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiwei","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics, National Cancer Institute , Rockville, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,3,24]]},"reference":[{"key":"2025112408214889300_jiaf135-B1","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1038\/nrc.2016.92","article-title":"Epstein-Barr virus: more than 50 years old and still providing surprises","volume":"16","author":"Young","year":"2016","journal-title":"Nat Rev Cancer"},{"key":"2025112408214889300_jiaf135-B2","doi-asserted-by":"crossref","first-page":"e0169321","DOI":"10.1128\/jvi.01693-21","article-title":"Genomic landscapes of Epstein-Barr virus in pulmonary lymphoepithelioma-like carcinoma","volume":"96","author":"Wu","year":"2022","journal-title":"J Virol"},{"key":"2025112408214889300_jiaf135-B3","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1146\/annurev.pathol.1.110304.100209","article-title":"Spectrum of Epstein-Barr virus\u2013associated diseases","volume":"1","author":"Kutok","year":"2006","journal-title":"Annu Rev Pathol"},{"key":"2025112408214889300_jiaf135-B4","doi-asserted-by":"crossref","DOI":"10.1017\/CBO9780511545313","volume-title":"Human herpesviruses: biology, therapy, and immunoprophylaxis","author":"Arvin","year":"2007"},{"key":"2025112408214889300_jiaf135-B5","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.3389\/fmicb.2016.01602","article-title":"Epstein-Barr virus: diseases linked to infection and transformation","volume":"7","author":"Jha","year":"2016","journal-title":"Front Microbiol"},{"key":"2025112408214889300_jiaf135-B6","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1186\/s40880-015-0018-6","article-title":"Incidence trend of nasopharyngeal carcinoma from 1987 to 2011 in Sihui County, Guangdong Province, South China: an age-period-cohort analysis","volume":"34","author":"Zhang","year":"2015","journal-title":"Chin J Cancer"},{"key":"2025112408214889300_jiaf135-B7","doi-asserted-by":"crossref","first-page":"114","DOI":"10.5732\/cjc.010.10377","article-title":"The prevalence and prevention of nasopharyngeal carcinoma in China","volume":"30","author":"Cao","year":"2011","journal-title":"Chin J Cancer"},{"key":"2025112408214889300_jiaf135-B8","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/S0140-6736(19)30956-0","article-title":"Nasopharyngeal carcinoma","volume":"394","author":"Chen","year":"2019","journal-title":"Lancet"},{"key":"2025112408214889300_jiaf135-B9","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1111\/cas.13954","article-title":"Epstein-Barr virus strain variation and cancer","volume":"110","author":"Kanda","year":"2019","journal-title":"Cancer Sci"},{"key":"2025112408214889300_jiaf135-B10","doi-asserted-by":"crossref","first-page":"10662","DOI":"10.1128\/JVI.01665-14","article-title":"Genomic diversity of Epstein-Barr virus genomes isolated from primary nasopharyngeal carcinoma biopsy samples","volume":"88","author":"Kwok","year":"2014","journal-title":"J Virol"},{"key":"2025112408214889300_jiaf135-B11","doi-asserted-by":"crossref","first-page":"e01132","DOI":"10.1128\/JVI.01132-18","article-title":"Sequence variation of Epstein-Barr virus: viral types, geography, codon usage, and diseases","volume":"92","author":"Correia","year":"2018","journal-title":"J Virol"},{"key":"2025112408214889300_jiaf135-B12","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1093\/clinchem\/hvaa027","article-title":"Sequencing analysis of plasma Epstein-Barr virus DNA reveals nasopharyngeal carcinoma-associated single nucleotide variant profiles","volume":"66","author":"Lam","year":"2020","journal-title":"Clin Chem"},{"key":"2025112408214889300_jiaf135-B13","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1186\/s40880-015-0073-z","article-title":"A single nucleotide polymorphism in the Epstein-Barr virus genome is strongly associated with a high risk of nasopharyngeal carcinoma","volume":"34","author":"Feng","year":"2015","journal-title":"Chin J Cancer"},{"key":"2025112408214889300_jiaf135-B14","doi-asserted-by":"crossref","first-page":"3031","DOI":"10.1002\/ijc.32049","article-title":"High risk Epstein-Barr virus variants characterized by distinct polymorphisms in the EBER locus are strongly associated with nasopharyngeal carcinoma","volume":"144","author":"Hui","year":"2019","journal-title":"Int J Cancer"},{"key":"2025112408214889300_jiaf135-B15","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1038\/s41588-019-0436-5","article-title":"Genome sequencing analysis identifies Epstein\u2013Barr virus subtypes associated with high risk of nasopharyngeal carcinoma","volume":"51","author":"Xu","year":"2019","journal-title":"Nat Genet"},{"key":"2025112408214889300_jiaf135-B16","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1186\/s12943-022-01625-6","article-title":"Multiplex Epstein-Barr virus BALF2 genotyping detects high-risk variants in plasma for population screening of nasopharyngeal carcinoma","volume":"21","author":"Miller","year":"2022","journal-title":"Mol Cancer"},{"key":"2025112408214889300_jiaf135-B17","doi-asserted-by":"crossref","first-page":"5189","DOI":"10.1038\/s41467-021-25402-z","article-title":"A comprehensive risk score for effective risk stratification and screening of nasopharyngeal carcinoma","volume":"12","author":"Zhou","year":"2021","journal-title":"Nat Commun"},{"key":"2025112408214889300_jiaf135-B18","doi-asserted-by":"crossref","first-page":"3652","DOI":"10.1016\/j.cell.2022.08.026","article-title":"Epstein-Barr virus (EBV): biology and clinical disease","volume":"185","author":"Damania","year":"2022","journal-title":"Cell"},{"key":"2025112408214889300_jiaf135-B19","doi-asserted-by":"crossref","first-page":"e1000496","DOI":"10.1371\/journal.ppat.1000496","article-title":"The dynamics of EBV shedding implicate a central role for epithelial cells in amplifying viral output","volume":"5","author":"Hadinoto","year":"2009","journal-title":"PloS Pathog"},{"key":"2025112408214889300_jiaf135-B20","doi-asserted-by":"crossref","first-page":"6546","DOI":"10.1128\/JVI.77.11.6546-6550.2003","article-title":"Multiple Epstein-Barr virus infections in healthy individuals","volume":"77","author":"Walling","year":"2003","journal-title":"J Virol"},{"key":"2025112408214889300_jiaf135-B21","volume-title":"AJCC cancer staging manual. 7th ed","author":"Edge","year":"2010"},{"key":"2025112408214889300_jiaf135-B22","doi-asserted-by":"crossref","first-page":"i884","DOI":"10.1093\/bioinformatics\/bty560","article-title":"fastp: an ultra-fast all-in-one FASTQ preprocessor","volume":"34","author":"Chen","year":"2018","journal-title":"Bioinformatics"},{"key":"2025112408214889300_jiaf135-B23","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1093\/bioinformatics\/btp324","article-title":"Fast and accurate short read alignment with Burrows-Wheeler transform","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"2025112408214889300_jiaf135-B24"},{"key":"2025112408214889300_jiaf135-B25","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1038\/ng.806","article-title":"A framework for variation discovery and genotyping using next-generation DNA sequencing data","volume":"43","author":"DePristo","year":"2011","journal-title":"Nat Genet"},{"key":"2025112408214889300_jiaf135-B26","doi-asserted-by":"crossref","first-page":"80","DOI":"10.4161\/fly.19695","article-title":"A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff: SNPs in the genome of Drosophila melanogaster strain w1118\u202f; iso-2; iso-3","volume":"6","author":"Cingolani","year":"2012","journal-title":"Fly"},{"key":"2025112408214889300_jiaf135-B27","doi-asserted-by":"crossref","first-page":"2470","DOI":"10.1128\/JCM.00330-16","article-title":"Comparison of next-generation sequencing technologies for comprehensive assessment of full-length hepatitis C viral genomes","volume":"54","author":"Thomson","year":"2016","journal-title":"J Clin Microbiol"},{"key":"2025112408214889300_jiaf135-B28","first-page":"W5","article-title":"MAFFT-DASH: integrated protein sequence and structural alignment","volume":"47","author":"Rozewicki","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"2025112408214889300_jiaf135-B29","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s13742-015-0047-8","article-title":"Second-generation PLINK: rising to the challenge of larger and richer datasets","volume":"4","author":"Chang","year":"2015","journal-title":"GigaScience"},{"key":"2025112408214889300_jiaf135-B30","doi-asserted-by":"crossref","first-page":"1530","DOI":"10.1093\/molbev\/msaa015","article-title":"IQ-TREE 2: new models and efficient methods for phylogenetic inference in the genomic era","volume":"37","author":"Minh","year":"2020","journal-title":"Mol Biol Evol"},{"key":"2025112408214889300_jiaf135-B31","doi-asserted-by":"crossref","first-page":"1880","DOI":"10.1016\/j.ajhg.2021.08.005","article-title":"Fast two-stage phasing of large-scale sequence data","volume":"108","author":"Browning","year":"2021","journal-title":"Am J Hum Genet"},{"key":"2025112408214889300_jiaf135-B32","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1186\/s12864-016-3195-z","article-title":"Visualizing tumor evolution with the fishplot package for R","volume":"17","author":"Miller","year":"2016","journal-title":"BMC Genomics"},{"key":"2025112408214889300_jiaf135-B33","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1056\/NEJM199509143331103","article-title":"Clonal proliferations of cells infected with Epstein-Barr virus in preinvasive lesions related to nasopharyngeal carcinoma","volume":"333","author":"Pathmanathan","year":"1995","journal-title":"N Engl J Med"},{"key":"2025112408214889300_jiaf135-B34","doi-asserted-by":"crossref","first-page":"5222","DOI":"10.1128\/JVI.03614-14","article-title":"Genome diversity of Epstein-Barr virus from multiple tumor types and normal infection","volume":"89","author":"Palser","year":"2015","journal-title":"J Virol"},{"key":"2025112408214889300_jiaf135-B35","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1111\/j.1469-1809.1949.tb02451.x","article-title":"The genetical structure of populations","volume":"15","author":"Wright","year":"1951","journal-title":"Ann Eugen"},{"key":"2025112408214889300_jiaf135-B36","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1002\/jmv.21503","article-title":"The dominance of China 1 in the spectrum of Epstein-Barr virus strains from Cantonese patients with nasopharyngeal carcinoma","volume":"81","author":"Li","year":"2009","journal-title":"J Med Virol"},{"key":"2025112408214889300_jiaf135-B37","doi-asserted-by":"crossref","first-page":"1840","DOI":"10.1128\/JVI.77.3.1840-1847.2003","article-title":"Compartmentalization and transmission of multiple Epstein-Barr virus strains in asymptomatic carriers","volume":"77","author":"Sitki-Green","year":"2003","journal-title":"J Virol"},{"key":"2025112408214889300_jiaf135-B38","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1128\/JVI.78.2.868-881.2004","article-title":"Potential selection of LMP1 variants in nasopharyngeal carcinoma","volume":"78","author":"Edwards","year":"2004","journal-title":"J Virol"},{"key":"2025112408214889300_jiaf135-B39","doi-asserted-by":"crossref","first-page":"159","DOI":"10.2739\/kurumemedj.47.159","article-title":"Latent multiple infections by herpes simplex virus type 1","volume":"47","author":"Fujita","year":"2000","journal-title":"Kurume Med J"},{"key":"2025112408214889300_jiaf135-B40","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1007\/s00430-021-00722-5","article-title":"Human cytomegalovirus multiple-strain infections and viral population diversity in haematopoietic stem cell transplant recipients analysed by high-throughput sequencing","volume":"210","author":"Dhingra","year":"2021","journal-title":"Med Microbiol Immunol"},{"key":"2025112408214889300_jiaf135-B41","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/0092-8674(86)90803-2","article-title":"The structure of the termini of the Epstein-Barr virus as a marker of clonal cellular proliferation","volume":"47","author":"Raab-Traub","year":"1986","journal-title":"Cell"},{"key":"2025112408214889300_jiaf135-B42","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1182\/blood.V77.5.1092.1092","article-title":"Epstein-Barr virus infection precedes clonal expansion in Burkitt's and acquired immunodeficiency syndrome-associated lymphoma","volume":"77","author":"Neri","year":"1991","journal-title":"Blood"}],"container-title":["The Journal of Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jid\/advance-article-pdf\/doi\/10.1093\/infdis\/jiaf135\/62573912\/jiaf135.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jid\/article-pdf\/232\/3\/735\/62573912\/jiaf135.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jid\/article-pdf\/232\/3\/735\/62573912\/jiaf135.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T13:22:06Z","timestamp":1763990526000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jid\/article\/232\/3\/735\/8092446"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,24]]},"references-count":42,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,3,24]]},"published-print":{"date-parts":[[2025,9,15]]}},"URL":"https:\/\/doi.org\/10.1093\/infdis\/jiaf135","relation":{},"ISSN":["0022-1899","1537-6613"],"issn-type":[{"value":"0022-1899","type":"print"},{"value":"1537-6613","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,9,15]]},"published":{"date-parts":[[2025,3,24]]}}}