Squamous cell carcinoma is a cancer that arises from particular cells called squamous cells. Squamous cells are found in the outer layer of skin and in the mucous membranes, which are the moist tissues that line body cavities such as the airways and intestines. Head and neck squamous cell carcinoma (HNSCC) develops in the mucous membranes of the mouth, nose, and throat.

HNSCC is classified by its location: it can occur in the mouth (oral cavity), the middle part of the throat near the mouth (oropharynx), the space behind the nose (nasal cavity and paranasal sinuses), the upper part of the throat near the nasal cavity (nasopharynx), the voicebox (larynx), or the lower part of the throat near the larynx (hypopharynx). Depending on the location, the cancer can cause abnormal patches or open sores (ulcers) in the mouth and throat, unusual bleeding or pain in the mouth, sinus congestion that does not clear, sore throat, earache, pain when swallowing or difficulty swallowing, a hoarse voice, difficulty breathing, or enlarged lymph nodes.

HNSCC can spread (metastasize) to other parts of the body, such as the lymph nodes or lungs. If it spreads, the cancer has a worse prognosis and can be fatal. About half of affected individuals survive more than five years after diagnosis.

HNSCC is the seventh most common cancer worldwide. Approximately 600,000 new cases are diagnosed each year, including about 50,000 in the United States. HNSCC occurs most often in men in their 50s or 60s, although the incidence among younger individuals is increasing.

HNSCC is caused by a variety of factors that can alter the DNA in cells. The strongest risk factors for developing this form of cancer are tobacco use (including smoking or using chewing tobacco) and heavy alcohol consumption. In addition, studies have shown that infection with certain strains of human papillomavirus (HPV) is linked to the development of HNSCC. HPV infection accounts for the increasing incidence of HNSCC in younger people.

Researchers have identified mutations in many genes in people with HNSCC; however, it is not yet clear what role most of these mutations play in the development or progression of cancer. The proteins produced from several of the genes associated with HNSCC, including TP53, NOTCH1, and CDKN2A, function as tumor suppressors, which means they normally keep cells from growing and dividing too rapidly or in an uncontrolled way. When tumor suppressors are impaired, cells can grow and divide without control, leading to tumor formation. It is likely that a series of changes in multiple genes is involved in the development and progression of HNSCC.

Genetic Testing Information

• Genetic Testing Registry: Squamous cell carcinoma of the head and neck

Genetic and Rare Diseases Information Center

• Squamous cell carcinoma of the head and neck

Patient Support and Advocacy Resources

• National Organization for Rare Disorders (NORD)

Clinical Trials

• ClinicalTrials.gov

Catalog of Genes and Diseases from OMIM

• SQUAMOUS CELL CARCINOMA, HEAD AND NECK; HNSCC

Scientific Articles on PubMed

• PubMed

• Agrawal N, Frederick MJ, Pickering CR, Bettegowda C, Chang K, Li RJ, Fakhry C, Xie TX, Zhang J, Wang J, Zhang N, El-Naggar AK, Jasser SA, Weinstein JN, Trevino L, Drummond JA, Muzny DM, Wu Y, Wood LD, Hruban RH, Westra WH, Koch WM, Califano JA, Gibbs RA, Sidransky D, Vogelstein B, Velculescu VE, Papadopoulos N, Wheeler DA, Kinzler KW, Myers JN. Exome sequencing of head and neck squamous cell carcinoma reveals inactivating mutations in NOTCH1. Science. 2011 Aug 26;333(6046):1154-7. doi: 10.1126/science.1206923. Epub 2011 Jul 28. Citation on PubMed or Free article on PubMed Central
• Lim AM, Do H, Young RJ, Wong SQ, Angel C, Collins M, Takano EA, Corry J, Wiesenfeld D, Kleid S, Sigston E, Lyons B, Fox SB, Rischin D, Dobrovic A, Solomon B. Differential mechanisms of CDKN2A (p16) alteration in oral tongue squamous cell carcinomas and correlation with patient outcome. Int J Cancer. 2014 Aug 15;135(4):887-95. doi: 10.1002/ijc.28727. Epub 2014 Jan 30. Citation on PubMed
• Mountzios G, Rampias T, Psyrri A. The mutational spectrum of squamous-cell carcinoma of the head and neck: targetable genetic events and clinical impact. Ann Oncol. 2014 Oct;25(10):1889-1900. doi: 10.1093/annonc/mdu143. Epub 2014 Apr 8. Citation on PubMed
• Rothenberg SM, Ellisen LW. The molecular pathogenesis of head and neck squamous cell carcinoma. J Clin Invest. 2012 Jun;122(6):1951-7. doi: 10.1172/jci59889. Citation on PubMed or Free article on PubMed Central
• Stransky N, Egloff AM, Tward AD, Kostic AD, Cibulskis K, Sivachenko A, Kryukov GV, Lawrence MS, Sougnez C, McKenna A, Shefler E, Ramos AH, Stojanov P, Carter SL, Voet D, Cortes ML, Auclair D, Berger MF, Saksena G, Guiducci C, Onofrio RC, Parkin M, Romkes M, Weissfeld JL, Seethala RR, Wang L, Rangel-Escareno C, Fernandez-Lopez JC, Hidalgo-Miranda A, Melendez-Zajgla J, Winckler W, Ardlie K, Gabriel SB, Meyerson M, Lander ES, Getz G, Golub TR, Garraway LA, Grandis JR. The mutational landscape of head and neck squamous cell carcinoma. Science. 2011 Aug 26;333(6046):1157-60. doi: 10.1126/science.1208130. Epub 2011 Jul 28. Citation on PubMed or Free article on PubMed Central