title: Analysis of The Cancer Genome Atlas sequencing data reveals novel properties of the human papillomavirus 16 genome in head and neck squamous cell carcinoma.
abstract: 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.
authors.affiliation: Department of Oral and Craniofacial Molecular Biology, VCU Philips Institute for Oral Health Research, Virginia Commonwealth University School of Dentistry, Richmond, VA, USA.
authors.forename: Tara J
authors.initials: TJ
authors.lastname: Nulton
authors.affiliation: C. Kenneth and Dianne Wright Center for Clinical and Translational Research, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: Amy L
authors.initials: AL
authors.lastname: Olex
authors.affiliation: C. Kenneth and Dianne Wright Center for Clinical and Translational Research, Virginia Commonwealth University, Richmond, VA, USA.|Department of Biostatistics, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: Mikhail
authors.initials: M
authors.lastname: Dozmorov
authors.affiliation: Department of Oral and Craniofacial Molecular Biology, VCU Philips Institute for Oral Health Research, Virginia Commonwealth University School of Dentistry, Richmond, VA, USA.|Massey Cancer Center, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: Iain M
authors.initials: IM
authors.lastname: Morgan
authors.affiliation: Department of Oral and Craniofacial Molecular Biology, VCU Philips Institute for Oral Health Research, Virginia Commonwealth University School of Dentistry, Richmond, VA, USA.|Massey Cancer Center, Virginia Commonwealth University, Richmond, VA, USA.|Department of Internal Medicine, Division of Hematology, Oncology and Palliative Care, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: Brad
authors.initials: B
authors.lastname: Windle
mesh_terms: D001271:Atlases as Topic; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D056915:DNA Copy Number Variations / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics; D030541:Databases, Genetic; D016679:Genome, Viral / Q000235:genetics*; D006258:Head and Neck Neoplasms / Q000235:genetics*; D052162:Human papillomavirus 16 / Q000235:genetics*; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000096:biosynthesis / Q000235:genetics*; D050725:Papillomavirus E7 Proteins / Q000096:biosynthesis; D030361:Papillomavirus Infections / Q000821:virology; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics*; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D004279:DNA, Viral; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16
keywords: HPV16; TCGA; genomic structure; head and neck cancer; integration