Identification of Biomarkers That Distinguish Human Papillomavirus (HPV)-Positive versus HPV-Negative Head and Neck Cancers in a Mouse Model

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....

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2006-09, Vol.103 (38), p.14152-14157
Main Authors: Strati, Katerina, Pitot, Henry C., Lambert, Paul F.
Format: Article
Language:English
Subjects:
4-Nitroquinoline-1-oxide - metabolism
Animals
Biological Sciences
Biomarkers, Tumor - metabolism
Cancer
Carcinogens
Carcinogens - metabolism
Carcinoma, Squamous Cell - pathology
Carcinoma, Squamous Cell - virology
Cell Cycle Proteins - genetics
Cell Cycle Proteins - metabolism
Cell Proliferation
Chromosomes
Cyclin-Dependent Kinase Inhibitor p16 - metabolism
Disease Models, Animal
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
Epithelial Cells - cytology
Epithelial Cells - physiology
Esophagus
Esophagus - anatomy & histology
Head
Head and neck neoplasms
Head and Neck Neoplasms - pathology
Head and Neck Neoplasms - virology
Human papillomavirus 16
Human papillomavirus 16 - metabolism
Humans
Mice
Mice, Transgenic
Minichromosome Maintenance Complex Component 7
Mouth Mucosa - cytology
Neoplasm Metastasis
Nuclear Proteins - genetics
Nuclear Proteins - metabolism
Oncogene Proteins, Viral - genetics
Oncogenes
Papillomavirus E7 Proteins
Proteins
Repressor Proteins - genetics
Rodents
Squamous cell carcinoma
Transgenic animals
Tumors
Viruses
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Summary: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 HPV16transgenic 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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0606698103