Head and neck cancers

Incidence

Head and neck cancers are a heterogenous group of malignancies arising in the oral cavity, oropharynx, nasopharynx, larynx, nasal cavity, paranasal sinuses, and salivary glands. Worldwide, head and neck cancer accounts for approximately 380,000 deaths annually. In the United States, head and neck cancers account for 3% of all malignancies; an estimated 63,000 individuals develop head and neck cancer and 13,000 die from it each year. Head and neck cancers of the oral cavity, oropharynx, and larynx are more common in North America and Europe, whereas nasopharyngeal cancer is more common in the Mediterranean and Far East.

Risk factors

Head and neck cancers arise more often in men than in women and in patients of lower socioeconomic status. Smoking is one of the most important risk factors, and risk of head and neck cancer increases with smoking duration and declines with smoking cessation. Alcohol is another independent risk factor and the combination of alcohol use and smoking further increases the risk of head and neck cancer. Viral infections have also been associated with increased risk of head and neck cancer. Epstein-Barr virus has been implicated as the primary etiologic agent in the pathogenesis of nasopharyngeal carcinoma, particularly in South East Asia and other regions where nasopharyngeal cancer is endemic. Finally, human papilloma virus (HPV), the most commonly diagnosed sexually transmitted infection in the United States has been etiologically linked with oropharyngeal squamous cell carcinomas. HPV 16 is the viral subtype detected in most patients. Over 50% of all oropharyngeal cancers are HPV 16 positive. The proportion of HPV-associated head and neck cancer is rising in the United States. HPV positive head and neck cancers have a better prognosis and are as shown in Table 45.1 are clinically distinct from HPV negative cancers.

Diagnosis and staging

The workup of head and neck cancers involves a detailed head and neck physical examination with direct visualization of the primary tumor by fiberoptic flexible laryngopharyngoscopy. An examination under anesthesia may be required to assess the deeper structures or for patients who cannot tolerate an awake examination in the outpatient setting. Subsequently, fine-needle aspiration, core biopsy, or excisional biopsy of a neck node or primary tumor should be performed to obtain a pathologic diagnosis. A contrast-enhanced computed tomography (CT) scan of the head and neck or magnetic resonance image of the head and neck should be obtained to assess the extent of local and regional disease. A CT-positron emission tomography fusion is useful for identifying involved lymph nodes and distant metastases.

The data obtained from these clinical assessments derive the clinical stage of the cancer. The TNM (tumor, node, metastasis) staging system is used and the new American Joint Committee on Cancer 8 classification system incorporates HPV status into staging to better reflect the prognosis of these two groups.

Treatment overview

For many head and neck sites, primary surgery and definitive radiation offer similar rates of local control and cure for localized, early stage disease (stage I–II). Thus, the initial choice of surgery or radiation depends on the surgical accessibility of the tumor, the anticipated functional outcome with resection, and the morbidity associated with surgery versus radiation. After surgical resection of the primary tumor there may be an indication for postoperative radiation or concurrent chemotherapy and radiation (chemoRT) if high-risk pathologic features, such as positive margins, perineural invasion, lymphovascular invasion, and extra nodal extension, are identified in the resected specimen. The finding of multiple positive lymph nodes on elective lymph node dissection at the time of surgery is also an indication for postoperative radiation therapy. For patients receiving primary chemotherapy or chemoRT, neck dissection following systemic treatment is often indicated for lymph node positive disease based on response to chemotherapy.

Intensity modulated radiation therapy (IMRT) is the major modality of radiation used in the treatment of cancers of the head and neck. IMRT allows for modulation of the intensity of radiation such that a higher radiation dose can be delivered to a target (i.e., tumor or involved lymph node region) with a marked reduction in the amount of radiation delivered to surrounding uninvolved tissues. The radiation dose used depends on the size and location of the primary tumor and the neck lymph nodes. For definitive radiation, primary tumors and gross lymphadenopathy are managed with treatment doses greater than or equal to 70 Gy in 2 Gy fractions. Low-risk neck nodal regions are treated with doses at or exceeding 50 Gy. In the postoperative setting doses of radiation from 60 to 66 Gy are required for treatment of microscopic disease. A lower dose of postoperative radiation (e.g., 54 Gy) is currently under investigation for HPV positive disease with equivalent survival statistics.

More advanced stage disease has higher rates of local recurrence and distant metastases and requires combined modality approaches to increase the chance of long-term disease control and cure. Optimal sequencing of therapeutic interventions requires multidisciplinary input and is dictated by the site of the primary tumor, the disease extent, patient comorbid conditions, and patient preferences based on functional preservation and cosmetic outcome. In nonmetastatic disease, cisplatin, given at 100 mg/m ² every 3 weeks in combination with radiation is the current standard of care chemotherapeutic agent for chemoRT for patients (age < 70 and performance status 0-1). ^, In less-fit patients (those with cardiovascular or renal comorbidity, age > 70, or performance status > 1), 40 mg/m ² weekly is used. This weekly regimen has lower renal toxicity and less potential for severe nausea and vomiting. ^, As an alternative, cetuximab, an inhibitor of the epidermal growth factor receptor, can be used for stage III or IV nonmetastatic head and neck cancer. Patients receive this medication as an initial loading dose of 400 mg/m ² followed by weekly 250 mg/m ² in combination with radiation. Another option is the taxotere platinol 5-fluorouracil (TPF) regimen, which involves sequential combined modality therapy with docetaxel (75 mg/m ² ), cisplatin (100 mg/m ² ), and 5-fluorouracil (5-FU, 1000 mg/m ² ) given every 3 weeks for 3 cycles followed by carboplatin (area under the curve [AUC] of 1.5) weekly with daily radiation.

For metastatic disease, recurrent disease, or nonresectable cancers, first-line systemic therapy involves the use of a platinum-based chemotherapy regimen. The combination of platinum agent (cisplatin or carboplatin), 5-FU and cetuximab has been shown to have improved overall survival as compared with platinum and 5-FU alone. An alternative combination of carboplatin and gemcitabine is favored specifically for nasopharyngeal cancers. ^, More recently, the PD-1 inhibitors, nivolumab and pembrolizumab, were approved for use in patients with recurrent head and neck cancer whose disease has progressed after treatment with platinum-containing therapy.

Cardiovascular risk

Patients with head and neck cancer have an increased noncancer mortality with cardiovascular disease comprising a significant portion of noncancer mortality in this population. Importantly, patients with head and neck cancer have a high baseline risk for cardiovascular disease based on common risk factors for malignancy and cardiovascular disease in this population, such as smoking and alcohol use. However, cardiovascular disease risk is increased even in patients without a significant smoking history owing to potential cardiovascular effects of local (e.g., radiation) or systemic head and neck cancer therapies. The cardiovascular risks of head and neck cancer therapies are summarized in Table 45.2 .