{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T07:57:20Z","timestamp":1792051040372,"version":"4.4.0"},"reference-count":50,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2004,3,16]],"date-time":"2004-03-16T00:00:00Z","timestamp":1079395200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2004,7,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Human papillomavirus (HPV) is a circular double\u2010stranded DNA virus implicated in at least 90% of cervical and anogenital cancers and has been observed in approximately 20% of squamous cell carcinomas of the head and neck (SCCHN). Transcription of the viral oncogenes <jats:italic>E6<\/jats:italic> and <jats:italic>E7<\/jats:italic> is regulated by expression of the E2 protein. Disruption of the <jats:italic>E2<\/jats:italic> gene sequence due to viral integration results in upregulation of <jats:italic>E6<\/jats:italic> and <jats:italic>E7<\/jats:italic>, which promote tumorigenesis by abrogating p53 and pRb functions. HPV integration sites in cervical and anogenital cancers have been mapped primarily to chromosomal fragile sites and in some cases have been shown to integrate within tumor suppressor genes or other cancer\u2010related genes. To study viral integration sites in SCCHN, we examined an HPV16\u2010infected SCCHN cell line cultured from a tongue\u2010base tumor. HPV fluorescence <jats:italic>in situ<\/jats:italic> hybridization (FISH) revealed multiple integrated viral DNA copies in blocks throughout the genome. Sequential FISH and spectral karyotyping identified integration sites on chromosomes 3, 6, 9q, 13q and t(1;8)(q;?). Restriction site\u2010polymerase chain reaction (RS\u2010PCR) was performed to identify the viral\u2010cellular junctions. Sequence analyses confirmed integration sites at 9q31.1 and 6p21 and revealed a novel junction at 16p12.3. Subsequent chromosome breakage studies suggested that the observed viral\u2010cellular integration sites may have occurred within common fragile sites. Additional studies using RT\u2010PCR for E6<jats:sup>\u2227<\/jats:sup>E7 viral transcripts showed oncoprotein expression from episomal and integrated viral sequences. Our results suggest that viral integration of HPV in SCCHN appears to occur nonrandomly through targeting specific chromosomal sequences prone to breakage. \u00a9 2004 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ijc.20193","type":"journal-article","created":{"date-parts":[[2004,4,13]],"date-time":"2004-04-13T12:23:01Z","timestamp":1081858981000},"page":"701-709","source":"Crossref","is-referenced-by-count":76,"title":["Mapping and analysis of HPV16 integration sites in a head and neck cancer cell line"],"prefix":"10.1002","volume":"110","author":[{"given":"Camille C. 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