NCM 2022: Analysis of viral and human oncogene expression in human papillomavirus-driven cancer

Human papillomaviruses (HPVs) cause nearly all cervical cancers and expresses two potent oncogenes, E6 and E7. HPV often integrates into the human genome, causing complex local amplification of viral and human DNA. We applied long-read DNA and RNA sequencing to 20 cervical and head-and-neck cancer cell lines to identify HPV integration sites and HPV transcription patterns, as well as host gene mutations. HPV expression and expression of the E6 and E7 genes vary widely between cell lines. We identified host genes disrupted or activated by integration and alterations in DNA methylation due to integrations. HT-3 cells have integrated HPV30, an HPV type not previously associated with cancer. HT-3 cells also have somatic mutations in the TP53 and RB1 tumour suppressor genes and immune evasion genes. Together, these methods show promising potential in accelerating the diagnosis and subclassification of HPV-driven cancers and guiding therapeutic approaches.