{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T20:06:39Z","timestamp":1777493199823,"version":"3.51.4"},"reference-count":65,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2022,10,24]],"date-time":"2022-10-24T00:00:00Z","timestamp":1666569600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001171","name":"Cancer Institute New South Wales","doi-asserted-by":"publisher","award":["CINSW 2020\/2081"],"award-info":[{"award-number":["CINSW 2020\/2081"]}],"id":[{"id":"10.13039\/501100001171","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Sydney Local Health District Head and Neck Research Fund","award":["CINSW 2020\/2081"],"award-info":[{"award-number":["CINSW 2020\/2081"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Viruses are well known drivers of several human malignancies. A causative factor for oral cavity squamous cell carcinoma (OSCC) in patients with limited exposure to traditional risk factors, including tobacco use, is yet to be identified. Our study aimed to comprehensively evaluate the role of viral drivers in OSCC patients with low cumulative exposure to traditional risk factors. Patients under 50 years of age with OSCC, defined using strict anatomic criteria were selected for WGS. The WGS data was interrogated using viral detection tools (Kraken 2 and BLASTN), together examining &gt;700,000 viruses. The findings were further verified using tissue microarrays of OSCC samples using both immunohistochemistry and RNA in situ hybridisation (ISH). 28 patients underwent WGS and comprehensive viral profiling. One 49-year-old male patient with OSCC of the hard palate demonstrated HPV35 integration. 657 cases of OSCC were then evaluated for the presence of HPV integration through immunohistochemistry for p16 and HPV RNA ISH. HPV integration was seen in 8 (1.2%) patients, all middle-aged men with predominant floor of mouth involvement. In summary, a wide-ranging interrogation of &gt;700,000 viruses using OSCC WGS data showed HPV integration in a minority of male OSCC patients and did not carry any prognostic significance.<\/jats:p>","DOI":"10.3390\/cancers14215213","type":"journal-article","created":{"date-parts":[[2022,10,24]],"date-time":"2022-10-24T11:53:55Z","timestamp":1666612435000},"page":"5213","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Viral Integration Plays a Minor Role in the Development and Prognostication of Oral Squamous Cell Carcinoma"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7435-0834","authenticated-orcid":false,"given":"Laveniya","family":"Satgunaseelan","sequence":"first","affiliation":[{"name":"Department of Tissue Pathology and Diagnostic Oncology, NSW Health Pathology, Royal Prince Alfred Hospital, Sydney, NSW 2050, Australia"},{"name":"Sydney Medical School, Faculty of Medicine and Health Sciences, The University of Sydney, Sydney, NSW 2050, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9234-3243","authenticated-orcid":false,"given":"Dario","family":"Strbenac","sequence":"additional","affiliation":[{"name":"School of Mathematics and Statistics, The University of Sydney, Sydney, NSW 2050, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sahithi","family":"Tadi","sequence":"additional","affiliation":[{"name":"Sydney Head and Neck Cancer Institute, Department of Head and Neck Surgery, Chris O\u2019Brien Lifehouse, Sydney, NSW 2050, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Sydney Head and Neck Cancer Institute, Department of Head and Neck Surgery, Chris O\u2019Brien Lifehouse, Sydney, NSW 2050, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Wykes","sequence":"additional","affiliation":[{"name":"Sydney Medical School, Faculty of Medicine and Health Sciences, The University of Sydney, Sydney, NSW 2050, Australia"},{"name":"Sydney Head and Neck Cancer Institute, Department of Head and Neck Surgery, Chris O\u2019Brien Lifehouse, Sydney, NSW 2050, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carsten E.","family":"Palme","sequence":"additional","affiliation":[{"name":"Sydney Medical School, Faculty of Medicine and Health Sciences, The University of Sydney, Sydney, NSW 2050, Australia"},{"name":"Sydney Head and Neck Cancer Institute, Department of Head and Neck Surgery, Chris O\u2019Brien Lifehouse, Sydney, NSW 2050, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8958-736X","authenticated-orcid":false,"given":"Tsu-Hui (Hubert)","family":"Low","sequence":"additional","affiliation":[{"name":"Sydney Medical School, Faculty of Medicine and Health Sciences, The University of Sydney, Sydney, NSW 2050, Australia"},{"name":"Sydney Head and Neck Cancer Institute, Department of Head and Neck Surgery, Chris O\u2019Brien Lifehouse, Sydney, NSW 2050, Australia"},{"name":"Department of Otolaryngology\u2014Head & Neck Surgery, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW 2109, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean Y. H.","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Mathematics and Statistics, The University of Sydney, Sydney, NSW 2050, Australia"},{"name":"Charles Perkins Centre, The University of Sydney, Sydney, NSW 2050, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1209-772X","authenticated-orcid":false,"given":"Jonathan R.","family":"Clark","sequence":"additional","affiliation":[{"name":"Sydney Medical School, Faculty of Medicine and Health Sciences, The University of Sydney, Sydney, NSW 2050, Australia"},{"name":"Sydney Head and Neck Cancer Institute, Department of Head and Neck Surgery, Chris O\u2019Brien Lifehouse, Sydney, NSW 2050, Australia"},{"name":"Royal Prince Alfred Institute of Academic Surgery, Sydney Local Health District, Sydney, NSW 2050, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruta","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Tissue Pathology and Diagnostic Oncology, NSW Health Pathology, Royal Prince Alfred Hospital, Sydney, NSW 2050, Australia"},{"name":"Sydney Medical School, Faculty of Medicine and Health Sciences, The University of Sydney, Sydney, NSW 2050, Australia"},{"name":"Sydney Head and Neck Cancer Institute, Department of Head and Neck Surgery, Chris O\u2019Brien Lifehouse, Sydney, NSW 2050, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"753366","DOI":"10.3389\/fviro.2021.753366","article-title":"Oncogenic Viruses as Entropic Drivers of Cancer Evolution","volume":"1","author":"Tempera","year":"2021","journal-title":"Front. 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