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Head and Neck Cancer

General Principles

Head and neck squamous cell cancer (HNSCC) includes carcinoma of the lip, oral cavity, pharynx, nasopharynx, and larynx. It is estimated that nearly 59,000 patients will be diagnosed with HNSCC in the year 2015. Tobacco use and alcohol consumption are associated with increased risk of developing HNSCC. HPV infection is implicated in oropharyngeal squamous cell carcinomas, and the incidence of HPV-associated HNSCC has quadrupled since the 1980s. EBV infection is associated with nasopharyngeal cancers.

  • Field cancerization is an important concept in HNSCC. Given the diffuse nature of mucosal exposure to tobacco smoke, the primary cancer site is often surrounded by areas of premalignant lesions (carcinoma in situ and dysplasia). For this reason, patients with tobacco-associated HNSCC are at increased risk for developing secondary cancers.
  • Leukoplakia and erythroleukoplakia are premalignant lesions of the oral mucosa. Leukoplakia refers to a white mucosal patch that cannot be scraped off, whereas erythroleukoplakia appears red and velvety. Erythroleukoplakias are associated with a higher risk of malignant transformation.


Clinical Presentation

Patients with HNSCC can present with a variety of symptoms depending on the primary tumor site: oral mass, nonhealing ulcers, trismus from invasion of pterygoid muscles, dysphagia, odynophagia, otitis media from eustachian tube blockage, hoarseness, neck mass, weight loss, and cranial nerve palsies. Nasopharyngeal tumors can invade the cavernous sinus and frequently affect the abducens and trigeminal nerves. Salivary gland tumors, which can have nonsquamous pathology, can invade the facial nerve and cause facial nerve–related symptoms.

Diagnostic Testing

  • Comprehensive ear, nose, and throat (ENT) evaluation with fiberoptic endoscopy or mirror exam is required. Particular attention should be paid to assess dentition. Functional evaluation that includes assessment of swallowing, biting, chewing, and speech should be performed.
  • Examination under anesthesia is a critical component of staging. Imaging should include a panorex to evaluate dentition and mandibular bony involvement. A CT of the neck and chest should be obtained to evaluate lymph node involvement and rule out pulmonary metastases, respectively. Whole-body PET can be considered in select patients.
  • p16 positivity on IHC is used as a surrogate for HPV infection and is an independent favorable prognostic factor for survival (N Engl J Med 2010;363:24  [PMID:20530316]).
  • Stage classification: Stage I to II disease does not show lymph node involvement. Stage III tumors are larger (defined as >4 cm for most sites) or have isolated lymph node involvement. Stage IVA/B tumors are locally advanced tumors or show bilateral or bulky cervical lymph node involvement. Stage IVC tumors are associated with distant metastasis.


  • Early stage (I–II): Either surgery or definitive radiation.
  • Locally advanced (stage III–IVA/B): Treatment approaches include:
    • Definitive surgical resection followed by adjuvant radiation with or without chemotherapy
    • Concurrent chemotherapy with radiation
    • Induction chemotherapy followed by concurrent chemotherapy with radiation or radiation alone
  • Metastatic (stage IVC): Palliative chemotherapy.
  • Chemotherapy: Cisplatin is the chemotherapy agent commonly used in combination with radiation for definitive treatment. Induction regimens usually involve a platinum combination with drugs such as 5-fluorouracil (5FU) and a taxane (paclitaxel or docetaxel).
  • Targeted therapy: Cetuximab, a monoclonal antibody against EGFR, can be used in combination with definitive radiation in patients who cannot tolerate traditional chemotherapeutic regimens or in combination with cisplatin and 5FU for the treatment of metastatic disease (N Engl J Med 2008;359:1116  [PMID:18784101]).
  • Surgery: Nodal neck dissection is an important part of surgical management. Radical neck dissection refers to surgical removal of lymph nodes from all five neck stations unilaterally, along with excision of the internal jugular vein, spinal accessory nerve, and sternocleidomastoid. Modified neck dissections spare some of these structures.
  • Organ sparing: Chemoradiation or induction chemotherapy followed by radiation can potentially spare patients from undergoing a total laryngectomy and improve quality of life.
  • Supportive care: Dental evaluation is indicated prior to radiation. Patients undergoing definitive radiation or adjuvant radiation may develop severe mucositis requiring the placement of gastric feeding tube for nutrition. Surgery may lead to loss of speech, swallowing dysfunction, permanent tracheostomy, and disfigurement. Swallowing impairment can lead to aspiration. Radiation can result in severe xerostomia.


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Williams, Dominique, et al., editors. "Head and Neck Cancer." Washington Manual of Medical Therapeutics, 35th ed., Wolters Kluwer Health, 2016. Washington Manual, www.unboundmedicine.com/washingtonmanual/view/Washington-Manual-of-Medical-Therapeutics/602252/all/Head_and_Neck_Cancer.
Head and Neck Cancer. In: Williams D, Ramgopal R, Gdowski M, et al, eds. Washington Manual of Medical Therapeutics. 35th ed. Wolters Kluwer Health; 2016. https://www.unboundmedicine.com/washingtonmanual/view/Washington-Manual-of-Medical-Therapeutics/602252/all/Head_and_Neck_Cancer. Accessed June 15, 2019.
Head and Neck Cancer. (2016). In Williams, D., Ramgopal, R., Gdowski, M., Dretler, A., & Bhat, P. (Eds.), Washington Manual of Medical Therapeutics. Available from https://www.unboundmedicine.com/washingtonmanual/view/Washington-Manual-of-Medical-Therapeutics/602252/all/Head_and_Neck_Cancer
Head and Neck Cancer [Internet]. In: Williams D, Ramgopal R, Gdowski M, Dretler A, Bhat P, editors. Washington Manual of Medical Therapeutics. Wolters Kluwer Health; 2016. [cited 2019 June 15]. Available from: https://www.unboundmedicine.com/washingtonmanual/view/Washington-Manual-of-Medical-Therapeutics/602252/all/Head_and_Neck_Cancer.
* Article titles in AMA citation format should be in sentence-case
TY - ELEC T1 - Head and Neck Cancer ID - 602252 ED - Williams,Dominique, ED - Ramgopal,Rajeev, ED - Gdowski,Mark, ED - Dretler,Alexandra, ED - Bhat,Pavat, BT - Washington Manual of Medical Therapeutics UR - https://www.unboundmedicine.com/washingtonmanual/view/Washington-Manual-of-Medical-Therapeutics/602252/all/Head_and_Neck_Cancer PB - Wolters Kluwer Health ET - 35 DB - Washington Manual DP - Unbound Medicine ER -