Head and neck cancers include primary tumors of the oral cavity, oropharynx, nasopharynx, hypopharynx, larynx, paranasal sinuses, thyroid, and salivary glands. Squamous cell carcinoma is the most common form of head and neck cancer and is therefore the focus of this chapter. Thyroid cancer is discussed in MKSAP 18 Endocrinology and Metabolism.
The most important risk factor for head and neck cancer is tobacco use, which includes smoked and smokeless tobacco. Alcohol use is also a known risk factor, and the combination of alcohol and tobacco has been found to synergistically increase risk.
Human papillomavirus (HPV), more likely to be found in men and women with behavioral risk for other sexually transmitted diseases, is a recently recognized and increasingly important cause of head and neck cancer, with most HPV-associated cancers arising in the oropharynx (tonsil and base of tongue most commonly). The prognosis of HPV-associated cancer is significantly better than that for non-HPV-related cancer, but smoking can mitigate this improvement. Treatment of head and neck cancer is not altered based on HPV status, although several ongoing studies are addressing this issue.
Presenting symptoms vary with the location of the cancer, but concerning signs and symptoms that generally should raise suspicion of head and neck cancer include persistent or progressive lymph node enlargement or other neck mass, unilateral hearing loss, unilateral ear pain, nasal obstruction, oral pain, nonhealing oral ulcers, dysphagia, odynophagia, and hoarseness.
Initial evaluation of patients suspected of having head and neck cancer includes history, physical examination, and direct laryngoscopy. Fine-needle aspiration of suspicious lesions will generally establish the diagnosis. Assessment of HPV status using tumor staining for p16, which is overexpressed in HPV-positive cancers, is standard. Although HPV positivity significantly improves prognosis, this finding is not currently used to make treatment decisions.
Once a diagnosis has been established, imaging studies are indicated for accurate assessment of the extent of local disease and evaluation of nodal and distant metastatic disease. MRI is generally superior to CT for anatomic assessment of the primary tumor. PET-CT is useful to identify primary tumors and for evaluating regional lymph nodes, tumor invasion, and distant metastatic disease, although it is not accurate in nodes 5 mm or smaller.
The staging of head and neck cancers is complex, as each subsite uses a different staging system. In general, however, staging of primary tumors is based on both size and extent of invasion into adjacent structures, with higher-stage tumors exhibiting greater degrees of invasiveness. Nodal staging is predicated on the number of nodes involved, size, and presence or absence of bilateral lymphadenopathy. The stage of head and neck cancer, as with many other malignancies, is the single-most important determinant of prognosis. Patients with localized disease have 70% to 90% long-term survival. Given the complexity of head and neck cancer treatment, multimodality tumor board discussion is valuable for determining the proper course of treatment.
Approximately one third of patients present with localized or early-stage head and neck cancer, generally small tumors that have no lymph node metastases. Although surgery is preferred for early-stage oral cancer and radiation for early laryngeal disease, early-stage head and neck cancer can be effectively treated with either surgery or radiation therapy. Treatment decisions weigh the accessibility of the lesion and complications expected with surgical resection, including quality-of-life issues such as appearance and preservation of speech, with the expected morbidity of radiation therapy, including acute mucositis and fatigue, along with more long-lasting alterations in taste, xerostomia, dental disease, and an increased risk of second malignancies. The need for and extent of additional dissection of lymph nodes in the neck is determined by the site and stage of the primary tumor, anatomy of lymphatic drainage, presence or absence of enlarged nodes, and the results of diagnostic imaging.
The need for adjuvant radiation for patients with primary surgical resection is based on tumor pathology and is recommended for patients with one or more high-risk features (Table 46). Combined chemotherapy and radiation can be used for patients felt to be at very high risk for recurrence, most commonly in the setting of extracapsular extension or positive or close margins. Adjuvant chemoradiation is typically given with single-agent cisplatin and concomitant radiation.
For patients with more advanced disease at the time of diagnosis, based on either having an unresectable primary tumor or extensive nodal disease, initial treatment with combined chemotherapy and radiation is recommended. Surgery is reserved for treatment of persistent disease or in the setting of inadequate response to treatment. In patients treated with definitive chemoradiotherapy, systemic therapy can be given with cisplatin, a platinum agent, or with cetuximab, a monoclonal antibody directed against the epidermal growth factor receptor.
Treatment of nasopharyngeal carcinoma differs somewhat from that of other sites. Nasopharyngeal carcinoma is rarely resectable at the time of diagnosis, and therefore surgery plays little role in the treatment of this disease. For very early-stage disease, radiation alone can be used with excellent control rates. However, for all other patients, initial treatment with chemoradiotherapy is used. The role of additional adjuvant chemotherapy in more advanced disease is uncertain.
After treatment of localized disease, a history and physical examination, including direct laryngoscopy, nasopharyngoscopy, or both, to evaluate for local recurrence and second primary cancers should be conducted every 1 to 3 months for the first year after primary treatment, decreasing in frequency thereafter, with annual evaluation at 5 years. Patients treated with radiotherapy that includes the thyroid bed are at risk for hypothyroidism and thyroid carcinoma. Periodic assessment of thyroid function and a physical examination of the thyroid are indicated, although thyroid ultrasonography should not be performed. Similarly, PET-CT or other imaging surveillance following a negative posttreatment scan is not indicated. Imaging should be performed as needed based on signs and symptoms suggestive of recurrent disease. Patients should be offered lung cancer screening if they meet high-risk criteria.
For patients with recurrent head and neck cancer, it is important to decide whether potentially curative therapy is still possible or if treatment instead should be palliative. Cure is most likely in patients whose recurrence is with small localized disease, who have a longer time to recurrence (also termed longer disease-free survival), and who have a site of recurrence in the larynx or nasopharynx. Patients with limited recurrence are treated with surgery and adjuvant therapy as needed. For patients with unresectable local recurrence, treatment with radiation or chemoradiation is appropriate. Reirradiation can be associated with long-term survival, but it is also associated with a potentially significant risk of toxicity including pain, tissue necrosis, infection, and fatal bleeding.
For patients with distant metastatic disease or unresectable persistent local disease not amenable to surgery or radiation, systemic chemotherapy is the mainstay of treatment. The current standard front-line treatment of patients with good performance status is the combination of a platinum agent (cisplatin or carboplatin) with 5-fluorouracil and cetuximab. If progression occurs after front-line therapy, single-agent therapy is indicated, using drugs not previously used. The programmed cell death 1 (PD-1) inhibitors pembrolizumab and nivolumab are FDA approved for treatment following progression after platinum-containing chemotherapy. Patients with distant metastases and unresectable local disease have a poor prognosis, especially if their performance status is declining; treatment decisions should include options for palliative and hospice care.