HPV Oncogenesis Linked to Chromatin State Effects at Viral Integration Sites

Canadian researchers reporting in Genome Biology point to a role for chromatin accessibility, gene expression, and gene splicing changes that occur after human papillomavirus (HPV) integration in the genome in the development of HPV-linked cervical cancer or head and neck cancers. Using RNA sequencing, chromatin immunoprecipitation sequencing, and ATAC-seq profiling on five cell lines that were positive for HPV-16, the team assessed viral integration sites and their consequences, uncovering chromatin state alterations and gene expression shifts stemming from the introduction of a conserved, chromatin accessibility-boosting CTCF transcription factor binding site in HPV in four of the cell lines. The results were backed up by the investigators' subsequent analysis of HPV-positive tumors from the Cancer Genome Atlas, where integrated HPV appeared to turn up the expression of essential genes. "Our results suggest that introduction of a new CTCF binding site due to HPV integration reorganizes chromatin state and upregulates genes essential for tumor viability in some [HPV-positive] tumors," the authors explain. "These findings emphasize a newly recognized role of HPV integration in oncogenesis.