Abstract
Squamous cell carcinoma of the head and neck (HNSCC) is a relatively common human cancer characterized by high morbidity, high mortality, and few therapeutic options outside of surgery, standard cytotoxic chemotherapy, and radiation. Although the most important risk factors are tobacco use and alcohol consumption, the disease is also linked to infection with high-risk types of human papilloma viruses (HPVs). Recent genetic analyses have yielded new insights into the molecular pathogenesis of this disease. Overall, while somatic activating mutations within classical oncogenes including PIK3CA and RAS occur in HNSCC, they are relatively uncommon. Instead genetic data point to a contribution of multiple tumor suppressor pathways, including p53, Rb/INK4/ARF, and Notch, in tumor initiation, progression, and maintenance. The increasingly refined knowledge of HNSCC genetics, combined with ever-more-sophisticated animal models and newer drug targeting strategies, should promote novel therapeutic approaches and improved disease outcomes.
Publication types
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Research Support, N.I.H., Extramural
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Review
MeSH terms
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Alcohol Drinking / adverse effects
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Alcohol Drinking / epidemiology
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Alcohol Drinking / genetics
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Alcohol Drinking / metabolism
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Alphapapillomavirus / genetics
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Alphapapillomavirus / metabolism
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Carcinoma, Squamous Cell / epidemiology
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Carcinoma, Squamous Cell / etiology
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Carcinoma, Squamous Cell / genetics*
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Carcinoma, Squamous Cell / metabolism
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Carcinoma, Squamous Cell / therapy
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Class I Phosphatidylinositol 3-Kinases
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Drug Delivery Systems
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Head and Neck Neoplasms / epidemiology
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Head and Neck Neoplasms / etiology
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Head and Neck Neoplasms / genetics*
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Head and Neck Neoplasms / metabolism
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Head and Neck Neoplasms / therapy
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Humans
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Mutation*
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Papillomavirus Infections / complications
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Papillomavirus Infections / epidemiology
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Papillomavirus Infections / genetics
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Papillomavirus Infections / metabolism
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Phosphatidylinositol 3-Kinases / genetics*
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Phosphatidylinositol 3-Kinases / metabolism
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Tobacco Use Disorder / complications
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Tobacco Use Disorder / epidemiology
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Tobacco Use Disorder / genetics
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Tobacco Use Disorder / metabolism
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Tumor Suppressor Proteins / genetics*
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Tumor Suppressor Proteins / metabolism
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ras Proteins / genetics*
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ras Proteins / metabolism
Substances
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Tumor Suppressor Proteins
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Phosphatidylinositol 3-Kinases
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Class I Phosphatidylinositol 3-Kinases
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PIK3CA protein, human
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ras Proteins