{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T23:40:56Z","timestamp":1788997256275,"version":"build-2803163510"},"reference-count":105,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2017,8,3]],"date-time":"2017-08-03T00:00:00Z","timestamp":1501718400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute for Dental and Craniofacial Research","award":["R03DE026230-01"],"award-info":[{"award-number":["R03DE026230-01"]}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P30 CA016059"],"award-info":[{"award-number":["P30 CA016059"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Human papillomaviruses (HPV) are detected in 70\u201380% of oropharyngeal cancers in the developed world, the incidence of which has reached epidemic proportions. The current paradigm regarding the status of the viral genome in these cancers is that there are three situations: one where the viral genome remains episomal, one where the viral genome integrates into the host genome and a third where there is a mixture of both integrated and episomal HPV genomes. Our recent work suggests that this third category has been mischaracterized as having integrated HPV genomes; evidence indicates that this category consists of virus\u2013human hybrid episomes. Most of these hybrid episomes are consistent with being maintained by replication from HPV origin. We discuss our evidence to support this new paradigm, how such genomes can arise, and more importantly the implications for the clinical management of HPV positive head and neck cancers following accurate determination of the viral genome status.<\/jats:p>","DOI":"10.3390\/v9080208","type":"journal-article","created":{"date-parts":[[2017,8,3]],"date-time":"2017-08-03T09:47:19Z","timestamp":1501753639000},"page":"208","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":65,"title":["Integration of Human Papillomavirus Genomes in Head and Neck Cancer: Is It Time to Consider a Paradigm Shift?"],"prefix":"10.3390","volume":"9","author":[{"given":"Iain","family":"Morgan","sequence":"first","affiliation":[{"name":"Philips Institute for Oral Health Research, Virginia Commonwealth University (VCU) School of Dentistry, Department of Oral and Craniofacial Molecular Biology, Richmond, VA 23298, USA"},{"name":"VCU Massey Cancer Center, Richmond, VA 23298, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"DiNardo","sequence":"additional","affiliation":[{"name":"VCU Massey Cancer Center, Richmond, VA 23298, USA"},{"name":"VCU Department of Otolaryngology, Richmond, VA 23298, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brad","family":"Windle","sequence":"additional","affiliation":[{"name":"Philips Institute for Oral Health Research, Virginia Commonwealth University (VCU) School of Dentistry, Department of Oral and Craniofacial Molecular Biology, Richmond, VA 23298, USA"},{"name":"VCU Massey Cancer Center, Richmond, VA 23298, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,8,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17684","DOI":"10.18632\/oncotarget.15179","article-title":"Analysis of the Cancer Genome Atlas Sequencing Data Reveals Novel Properties of the Human Papillomavirus 16 Genome in Head and Neck Squamous Cell Carcinoma","volume":"8","author":"Nulton","year":"2017","journal-title":"Oncotarget"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1002\/rmv.488","article-title":"Human Papillomaviruses: Basic Mechanisms of Pathogenesis and Oncogenicity","volume":"16","author":"Hebner","year":"2006","journal-title":"Rev. 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