Analysis of The Cancer Genome Atlas sequencing data reveals novel properties of the human papillomavirus 16 genome in head and neck squamous cell carcinoma.
Human papillomavirus (HPV) DNA is detected in up to 80% of oropharyngeal carcinomas (OPC) and this HPV positive disease has reached epidemic proportions. To increase our understanding of the disease, we investigated the status of the HPV16 genome in HPV-positive head and neck cancers (HNC). Raw RNA-Seq and Whole Genome Sequence data from The Cancer Genome Atlas HNC samples were analyzed to gain a full understanding of the HPV genome status for these tumors. Several remarkable and novel observations were made following this analysis. Firstly, there are three main HPV genome states in these tumors that are split relatively evenly: An episomal only state, an integrated state, and a state in which the viral genome exists as a hybrid episome with human DNA. Secondly, none of the tumors expressed high levels of E6; E6*I is the dominant variant expressed in all tumors. The most striking conclusion from this study is that around three quarters of HPV16 positive HNC contain episomal versions of the viral genome that are likely replicating in an E1-E2 dependent manner. The clinical and therapeutic implications of these observations are discussed.
['Nulton|Tara J|TJ|', 'Olex|Amy L|AL|', 'Dozmorov|Mikhail|M|', 'Morgan|Iain M|IM|', 'Windle|Brad|B|']
D001271:Atlases as Topic D002294:Carcinoma, Squamous Cell D056915:DNA Copy Number Variations D004279:DNA, Viral D030541:Databases, Genetic D016679:Genome, Viral D006258:Head and Neck Neoplasms D052162:Human papillomavirus 16 D006801:Humans D009856:Oncogene Proteins, Viral D050725:Papillomavirus E7 Proteins D030361:Papillomavirus Infections D012097:Repressor Proteins D000077195:Squamous Cell Carcinoma of Head and Neck
HPV16 head and neck cancer integration TCGA genomic structure