Intratumor heterogeneity of HPV integration in HPV-associated head and neck cancer.

ABSTRACT: 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 downregula

SUBMITTER: Sasa N 

PROVIDER: S-EPMC11770129 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature