Epithelial cancers may arise from the mucosal surfaces of the head and neck including the sinuses, oral cavity, nasopharynx, oropharynx, hypopharynx, and larynx. These tumors are usually squamous cell cancers. Thyroid cancer is discussed in Chap. 173: Thyroid Gland Disorders.

About 51,540 cases (about 3% of adult malignancies) are diagnosed each year and 10,000 people die from the disease. Oral cavity, oropharynx, and larynx are the most frequent sites of primary lesions in the United States; nasopharyngeal primaries are more common in the Far East and Mediterranean countries. Alcohol and tobacco (including smokeless) abuse are risk factors. Human papillomavirus (HPV; usually types 16 and 18) is associated with over half of oropharynx cancers in Western countries and HPV-related cancers have a better prognosis, particularly in nonsmokers.

Nasopharyngeal cancer in the Far East has a distinct histology, nonkeratinizing undifferentiated carcinoma with infiltrating lymphocytes called lymphoepithelioma, and a distinct etiology, Epstein-Barr virus. Squamous cell head and neck cancer may develop from premalignant lesions (erythroplakia, leukoplakia), and the histologic grade affects prognosis. Pts who have survived head and neck cancer commonly develop a second cancer of the head and neck, lung, or esophagus, presumably reflecting the exposure of the upper aerodigestive mucosa to similar carcinogenic stimuli.

Chromosomal deletions and mutations have been found in chromosomes 3p, 9p, 17p, and 13q; mutations in p53 have been reported. Cyclin D1 may be overexpressed. Epidermal growth factor receptor is commonly overexpressed.

Most occur in persons >60 years. Symptoms vary with the primary site. Nasopharynx lesions do not usually cause symptoms until late in the course and then cause unilateral serous otitis media or nasal obstruction or epistaxis. Oral cavity cancers present as nonhealing ulcers, sometimes painful. Oropharyngeal lesions also present late with sore throat or otalgia. Hoarseness may be an early sign of laryngeal cancer. Rare pts present with painless, rock-hard cervical or supraclavicular lymph node enlargement. Staging is based on the size of primary tumor and involvement of lymph nodes. Distant metastases occur in <10% of pts.

Three categories of disease are common: localized, locally or regionally advanced, and recurrent or metastatic. Localized disease occurs in about one-third of pts and is treated with curative intent by surgery or radiation therapy. Radiation therapy is preferred for localized larynx cancer to preserve organ function; surgery is used more commonly for oral cavity lesions. Overall 5-year survival is 60–90%, and most recurrences occur within 2 years. Locally advanced disease is the most common presentation (>50%). Combined-modality therapy using induction chemotherapy, then surgery followed by concomitant chemotherapy and radiation therapy, is most effective. The use of three cycles of cisplatin (75 mg/m² IV day 1) and docetaxel (75 mg/m² IV day 1) plus 5-fluorouracil (5-FU) (750 [mg/m²]/d by 96- to 120-h continuous infusion) before or during radiation therapy is more effective than surgery plus radiation therapy, although mucositis is also more severe; 5-year survival is 34–50%. Cetuximab plus radiation therapy may be more effective than radiation therapy alone but does not improve outcomes when combined with chemoradiotherapy. Head and neck cancer pts are frequently malnourished and often have intercurrent illness. Those who obtain a remission often develop hypothyroidism. Pts with recurrent or metastatic disease (about 10% of pts) are treated palliatively with cisplatin plus 5FU or paclitaxel (200–250 mg/m² with granulocyte colony-stimulating factor support) or with single-agent chemotherapy (a taxane, methotrexate, cisplatin, or carboplatin). Response rates are usually 30–50% and median survival of about 3 months. Use of immune checkpoint inhibitors in salvage therapy has increased median survival to 7.5 months.

The most important intervention is to get the pts to stop smoking. Long-term survival is significantly better in those who stop smoking. Chemopreventive therapy with cis-retinoic acid (3 months of 1.5 [mg/kg]/d followed by 9 months of 0.5 [mg/kg]/d PO) may cause regression of leukoplakia but has no consistent effect on development of cancer and may increase the risk in active smokers.