title: Identification of biomarkers that distinguish human papillomavirus (HPV)-positive versus HPV-negative head and neck cancers in a mouse model.
abstract: Head and neck squamous cell carcinoma (HNSCC) is a leading cause of cancer mortality worldwide. Recent reports have associated a subset of HNSCC with high-risk human papillomaviruses (HPVs), particularly HPV16, the same subset of HPVs responsible for the majority of cervical and anogenital cancers. In this study we describe a mouse model for HPV-associated HNSCC that employs mice transgenic for the HPV16 oncogenes E6 and E7. In these mice, E6 and E7 induce aberrant epithelial proliferation and, in the presence of a chemical carcinogen, they increase dramatically the animal's susceptibility to HNSCC. The cancers arising in the HPV16-transgenic mice mirror the molecular and histopathological characteristics of human HPV-positive HNSCC that distinguish the latter from human HPV-negative HNSCC, including overexpression of p16 protein and formation of more basaloid cancers. This validated model of HPV-associated HNSCC provides the means to define the contributions of individual HPV oncogenes to HNSCC and to understand the molecular basis for the differing clinical properties of HPV-positive and HPV-negative human HNSCC. From this study, we identify minichromosome maintenance protein 7 (MCM7) and p16 as potentially useful biomarkers for HPV-positive head and neck cancer.
authors.affiliation: McArdle Laboratory for Cancer Research, University of Wisconsin School of Medicine and Public Health, 1400 University Avenue, Madison, WI 53706, USA.
authors.forename: Katerina
authors.initials: K
authors.lastname: Strati
authors.forename: Henry C
authors.initials: HC
authors.lastname: Pitot
authors.forename: Paul F
authors.initials: PF
authors.lastname: Lambert
mesh_terms: D015112:4-Nitroquinoline-1-oxide / Q000378:metabolism; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002273:Carcinogens / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000821:virology*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology; D004947:Esophagus / Q000033:anatomy & histology; D006258:Head and Neck Neoplasms / Q000473:pathology / Q000821:virology*; D052162:Human papillomavirus 16 / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D064168:Minichromosome Maintenance Complex Component 7; D009061:Mouth Mucosa / Q000166:cytology; D009362:Neoplasm Metastasis; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D009856:Oncogene Proteins, Viral / Q000235:genetics; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D002273:Carcinogens; D018797:Cell Cycle Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004268:DNA-Binding Proteins; C068651:E6 protein, Human papillomavirus type 16; D009687:Nuclear Proteins; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; D015112:4-Nitroquinoline-1-oxide; C491086:Mcm7 protein, mouse; D064168:Minichromosome Maintenance Complex Component 7