biostudies-literatureUnknown16(1)Sasa NIntegration of human papillomavirus (HPV) into the host genome drives HPV-positive head and neck squamous cell carcinoma (HPV⁺ HNSCC). Whole-genome sequencing of 51 tumors revealed intratumor heterogeneity of HPV integration, with 44% of breakpoints subclonal, and a biased distribution of integration breakpoints across the HPV genome. Four HPV physical states were identified, with at least 49% of tumors progressing without integration. HPV integration was associated with APOBEC-induced broad genomic instability and focal genomic instability, including structural variants at integration sites. HPV⁺ HNSCCs exhibited almost no smoking-induced mutational signatures. Heterozygous loss of ataxia-telangiectasia mutated (ATM) was observed in 67% of tumors, with its downregulaNature communications1052https://www.ebi.ac.uk/biostudies/studies/S-EPMC11770129biostudies-literatureIntratumor heterogeneity of HPV integration in HPV-associated head and neck cancer.PMC11770129Kishikawa TTanaka HSasa NSuzuki MEguchi HInohara HIto RNimura KMizoro YMori MTakenaka YOkada YFukusumi TfalseIntratumor heterogeneity of HPV integration in HPV-associated head and neck cancer.Integration of human papillomavirus (HPV) into the host genome drives HPV-positive head and neck squamous cell carcinoma (HPV⁺ HNSCC). Whole-genome sequencing of 51 tumors revealed intratumor heterogeneity of HPV integration, with 44% of breakpoints subclonal, and a biased distribution of integration breakpoints across the HPV genome. Four HPV physical states were identified, with at least 49% of tumors progressing without integration. HPV integration was associated with APOBEC-induced broad genomic instability and focal genomic instability, including structural variants at integration sites. HPV⁺ HNSCCs exhibited almost no smoking-induced mutational signatures. Heterozygous loss of ataxia-telangiectasia mutated (ATM) was observed in 67% of tumors, with its downregula2025-01-01T00:00:00Z2025 Jan2025-04-04T23:12:08.353Z2025-04-04T23:12:08.353ZS-EPMC117701293986507810.1038/s41467-025-56150-z