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Head and neck squamous-cell carcinoma

Squamous cell carcinoma of the head and neck with p16 staining in keeping with HPV-associated squamous cell carcinoma. p16 immunostain.

Head and neck cancers are malignant neoplasms that arise in the head and neck region which comprises nasal cavity, paranasal sinuses, oral cavity, salivary glands, pharynx, and larynx. The majority of head and neck cancers histologically belong to squamous cell type and hence they are categorized as Head and Neck Squamous Cell Carcinoma (abbreviated as HNSCC)[Forastiere AA, 2003]. HNSCC are the sixth-most-common cancers worldwide and the third-most-common cancers in developing world. They account for about 5% of all malignancies worldwide (Ferlay J, 2010) and 3% of all malignancies in the United States (Siegel R, 2014).

Risk factors include tobacco consumption (chewing or smoking), alcohol consumption, Epstein-Barr virus (EBV) infection, human papilloma virus (HPV; esp. HPV 16 and 18) infection, betel nut chewing, wood dust exposures, consumption of certain salted fish and others (NCI Factsheet, 2013). EBV infection has been specifically associated with nasopharyngeal cancer. Reverse smoking was considered as a risk factor for oral cancer. Cis-retinoic acid (i.e. supplements of retinoic acid) intake may increase the risk of HNSCC in smokers. Low consumption of fruits and vegetables was associated with higher incidence of HNSCC.

HNSCC classification: Based on the HPV infection status, head and neck cancers are classified into HPV-positive and HPV-negative categories. So far, this is the only available molecular classification. Majority (>50%) of oral cancers are HPV-positive in the U.S. HPV-positive oral cancers are widely prevalent in younger patients and are associated with multiple sexual partners and oral sexual practices. HPV-positive cancers have better prognosis, especially for nonsmokers as compared to HPV-negative cancers.

Staging and grading of HNSCC: HNSCC are classified according to the tumor-node-metastasis (TNM) system of American Joint Committee on cancer. TNM staging system for HNSCC are discussed elsewhere.

Symptoms include lump or sore, sore throat, hoarse of voice, difficulty in swallowing etc (NCI Factsheet, 2013).

Treatment is predominantly based on the stage of the disease. Factors such as patient fitness, baseline swallow, airway functional status, and others are considered before determining the treatment plan. Standard of care for HNSCC includes one or combination of the following: surgery, radiation, chemotherapeutic agents such as cis-platin and 5-Flurouracil. Molecularly targeted therapies were developed since the discovery of role of epidermal growth factor receptor (EGFR) signaling in HNSCC development, progression and prognosis. These targeted therapies include monoclonal antibodies (such as cetuximab, panitumumab etc.) and tyrosine kinase inhibitors (such as erlotinib, gefitinib, etc.). Among these EGFR-targeting agents, only cetuximab has been approved by FDA in 2006 for HNSCC treatment.

Biopsy of a highly differentiated squamous-cell carcinoma of the mouth. Haematoxylin & eosin stain.

Ninety percent (MacMillan, 2015) of cases of head and neck cancer (cancer of the mouth, nasal cavity, nasopharynx, throat and associated structures) are due to squamous cell carcinoma. Symptoms may include a poorly healing mouth ulcer, a hoarse voice or other persistent problems in the area. Treatment is usually with surgery (which may be extensive) and radiotherapy. Risk factors include smoking, alcohol consumption and hematopoietic stem cell transplantation (Elad S, Zadik Y, Zeevi I, et al., 2010, pp. 1243–1244). In addition, recent studies show that about 25% of mouth and 35% of throat cancers are associated with HPV. The five-year disease-free survival rate for HPV-positive cancer is significantly higher when appropriately treated with surgery, radiation and chemotherapy as compared to non-HPV-positive cancer, substantiated by multiple studies including research conducted by Maura Gillison, et al. of Johns Hopkins Sidney Kimmel Cancer Center.


  • Elad S, Zadik Y, Zeevi I, et al. (December 2010). "Oral cancer in patients after hematopoietic stem-cell transplantation: long-term follow-up suggests an increased risk for recurrence". Transplantation. 90 (11): 1243–1244. doi:10.1097/TP.0b013e3181f9caaa. PMID 21119507.
  • "Types of head and neck cancer". MacMillan Cancer Support. 31 July 2015.