Identification of biomarkers that distinguish human papillomavirus (HPV)-positive versus HPV-negative head and neck cancers in a mouse model
- McArdle Laboratory for Cancer Research, University of Wisconsin School of Medicine and Public Health, 1400 University Avenue, Madison, WI 53706
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Communicated by William F. Dove, University of Wisconsin, Madison, WI, August 3, 2006 (received for review March 27, 2006)
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.
Footnotes
- *To whom correspondence should be addressed. E-mail: lambert{at}oncology.wisc.edu
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Author contributions: K.S. and P.F.L. designed research; K.S. performed research; K.S., H.C.P., and P.F.L. analyzed data; and K.S. and P.F.L. wrote the paper.
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The authors declare no conflict of interest.
- Abbreviations:
- HNSCC,
- head and neck squamous cell carcinoma;
- HPV,
- human papillomavirus;
- HR-HPV,
- high-risk human papillomavirus;
- K14,
- keratin 14;
- MCM7,
- minichromosome maintenance protein 7;
- 4NQO,
- 4-nitroquinoline 1-oxide.
- © 2006 by The National Academy of Sciences of the USA
