biostudies-literatureUnknown20(9)Labarge BHuman papillomavirus (HPV)-positive head and neck cancers, predominantly oropharyngeal squamous cell carcinoma (OPSCC), exhibit epidemiologic, clinical, and molecular characteristics distinct from those OPSCCs lacking HPV. We applied a combination of whole-genome sequencing and optical genome mapping to interrogate the genome structure of HPV-positive OPSCCs. We found that the virus had integrated in the host genome in two thirds of the tumors examined but resided solely extrachromosomally in the other third. Integration of the virus occurred at essentially random sites within the genome. Focal amplification of the virus and the genomic sequences surrounding it often occurred subsequent to integration, with the number of tandem repeats in the chromosome accounting for the increased copy nuMolecular cancer research : MCR1420-1428https://www.ebi.ac.uk/biostudies/studies/S-EPMC9437566biostudies-literatureHuman Papillomavirus Integration Strictly Correlates with Global Genome Instability in Head and Neck Cancer.PMC9437566Hennessy MBroach JRGoldrich DZhang LLabarge BChartrand SGoldenberg DWright SPurnell CfalseHuman Papillomavirus Integration Strictly Correlates with Global Genome Instability in Head and Neck Cancer.Human papillomavirus (HPV)-positive head and neck cancers, predominantly oropharyngeal squamous cell carcinoma (OPSCC), exhibit epidemiologic, clinical, and molecular characteristics distinct from those OPSCCs lacking HPV. We applied a combination of whole-genome sequencing and optical genome mapping to interrogate the genome structure of HPV-positive OPSCCs. We found that the virus had integrated in the host genome in two thirds of the tumors examined but resided solely extrachromosomally in the other third. Integration of the virus occurred at essentially random sites within the genome. Focal amplification of the virus and the genomic sequences surrounding it often occurred subsequent to integration, with the number of tandem repeats in the chromosome accounting for the increased copy nu2022-01-01T00:00:00Z2022 Sep2025-04-04T19:55:56.836Z2025-04-04T19:55:56.836ZS-EPMC94375663565760110.1158/1541-7786.MCR-21-0831