Abstract
Tobacco use and alcohol consumption are the main risk factors associated with head and neck squamous cell carcinoma (SCC) development due to their cytotoxic and mutagenic effects on the exposed epithelia of the upper aerodigestive tract. Epstein-Barr virus (EBV) and high-risk human papillomaviruses (HPVs), both encoding viral oncoproteins able to interfere with cell cycle control, have been recognized as the etiological agents of nasopharynx carcinoma and a fraction of oropharyngeal carcinoma, respectively. Head and neck SCC is a deadly disease and despite innovative treatments represents a major challenge for patients. Recently, a number of genomic studies have highlighted the molecular heterogeneity of head and neck SCC based on methylation profiles, microRNA expression, mutated genes and new druggable pathways which may represent new targets for cancer-tailored therapies. To date, cetuximab is the only FDA-approved anti-epidermal growth factor receptor therapy for the treatment of head and neck SCC. In addition, a number of monoclonal antibodies targeting AKT, mTOR and PI3K pathways are under evaluation. Several therapeutic vaccines against HPV16 and EBV proteins are also under study. The purpose of this article is to review the epidemiology, pathogenesis and molecular features of head and neck SCC, with an emphasis on new therapies.
© 2015 S. Karger AG, Basel.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Alcohol Drinking / adverse effects
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Antibodies, Monoclonal, Humanized / pharmacology*
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Antineoplastic Agents / pharmacology*
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Cancer Vaccines / pharmacology*
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Carcinoma, Squamous Cell* / drug therapy
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Carcinoma, Squamous Cell* / epidemiology
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Carcinoma, Squamous Cell* / etiology
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Cetuximab
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DNA Methylation / drug effects
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Epstein-Barr Virus Infections / complications
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ErbB Receptors / drug effects
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ErbB Receptors / genetics
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ErbB Receptors / metabolism*
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Gene Expression Regulation, Neoplastic / drug effects
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Head and Neck Neoplasms* / drug therapy
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Head and Neck Neoplasms* / epidemiology
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Head and Neck Neoplasms* / etiology
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Human papillomavirus 16 / drug effects
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Humans
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MicroRNAs / metabolism
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Molecular Targeted Therapy / methods*
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Mutation / drug effects
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Oncogene Protein v-akt / drug effects
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Oncogene Protein v-akt / metabolism
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Papillomavirus Infections / complications
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Phosphatidylinositol 3-Kinases / drug effects
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Phosphatidylinositol 3-Kinases / metabolism
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Risk Factors
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Signal Transduction / drug effects
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Smoking / adverse effects
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TOR Serine-Threonine Kinases / drug effects
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TOR Serine-Threonine Kinases / metabolism
Substances
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Antibodies, Monoclonal, Humanized
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Antineoplastic Agents
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Cancer Vaccines
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MicroRNAs
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MTOR protein, human
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EGFR protein, human
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ErbB Receptors
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Oncogene Protein v-akt
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TOR Serine-Threonine Kinases
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Cetuximab