Most head and neck cancers occur in patients older than age 50 years. HPV-related malignancies are frequently diagnosed in patients in their 40s, while EBV-related nasopharyngeal cancer can occur in all ages, including teenagers. The manifestations vary according to the stage and primary site of the tumor. Patients with nonspecific signs and symptoms in the head and neck area should be evaluated with a thorough otolaryngologic exam, particularly if symptoms persist longer than 2–4 weeks.
Cancer of the nasopharynx typically does not cause early symptoms. However, on occasion it may cause unilateral serous otitis media due to obstruction of the eustachian tube, unilateral or bilateral nasal obstruction, or epistaxis. Advanced nasopharyngeal carcinoma causes neuropathies of the cranial nerves due to skull base involvement.
Carcinomas of the oral cavity present as nonhealing ulcers, changes in the fit of dentures, or painful lesions. Tumors of the tongue base or oropharynx can cause decreased tongue mobility and alterations in speech. Cancers of the oropharynx or hypopharynx rarely cause early symptoms, but they may cause sore throat and/or otalgia.
Hoarseness may be an early symptom of laryngeal cancer, and persistent hoarseness requires referral to a specialist for indirect laryngoscopy and/or radiographic studies. If a head and neck lesion treated initially with antibiotics does not resolve in a short period, further workup is indicated; to simply continue the antibiotic treatment may be to lose the chance of early diagnosis of a malignancy.
Advanced head and neck cancers in any location can cause severe pain, otalgia, airway obstruction, cranial neuropathies, trismus, odynophagia, dysphagia, decreased tongue mobility, fistulas, skin involvement, and massive cervical lymphadenopathy, which may be unilateral or bilateral. Some patients have enlarged lymph nodes even though no primary lesion can be detected by endoscopy or biopsy; these patients are considered to have carcinoma of unknown primary (Fig. 34-1). If the enlarged nodes are located in the upper neck and the tumor cells are of squamous cell histology, the malignancy probably arose from a mucosal surface in the head or neck. Tumor cells in supraclavicular lymph nodes may also arise from a primary site in the chest or abdomen.
The physical examination should include inspection of all visible mucosal surfaces and palpation of the floor of mouth and tongue and of the neck. In addition to tumors themselves, leukoplakia (a white mucosal patch) or erythroplakia (a red mucosal patch) may be observed; these "premalignant" lesions can represent hyperplasia, dysplasia, or carcinoma in situ and require biopsy. Further examination should be performed by a specialist. Additional staging procedures include CT of the head and neck to identify the extent of the disease. Patients with lymph node involvement should have chest radiography and a bone scan to screen for distant metastases. A positron emission tomographic scan may also be administered and can help to identify or exclude distant metastases. The definitive staging procedure is an endoscopic examination under anesthesia, which may include laryngoscopy, esophagoscopy, and bronchoscopy; during this procedure, multiple biopsy samples are obtained to establish a primary diagnosis, define the extent of primary disease, and identify any additional premalignant lesions or second primaries.
Head and neck tumors are classified according to the TNM (tumor, node, metastasis) system of the American Joint Committee on Cancer. This classification varies according to the specific anatomic subsite (Tables 34-1 and 34-2). Distant metastases are found in <10% of patients at initial diagnosis and are more common in patients with advanced lymph nodal stage; microscopic involvement of the lungs, bones, or liver is more common, particularly in patients with advanced neck lymph node disease. Modern imaging techniques may increase the number of patients with clinically detectable distant metastases in the future.
In patients with lymph node involvement and no visible primary, the diagnosis should be made by lymph node excision. If the results indicate squamous cell carcinoma, a panendoscopy should be performed, with biopsy of all suspicious-appearing areas and directed biopsies of common primary sites, such as the nasopharynx, tonsil, tongue base, and pyriform sinus.
TREATMENT: Head and Neck Cancer
Patients with head and neck cancer can be grossly categorized into three clinical groups: those with localized disease, those with locally or regionally advanced disease, and those with recurrent and/or metastatic disease. Comorbidities associated with tobacco and alcohol abuse can affect treatment outcome and define long-term risks for patients who are cured of their disease.
LOCALIZED DISEASE Nearly one-third of patients have localized disease, that is, T1 or T2 (stage I or stage II) lesions without detectable lymph node involvement or distant metastases. These lesions are treated with curative intent by either surgery or radiation therapy. The choice of modality differs according to anatomic location and institutional expertise. Radiation therapy is often preferred for laryngeal cancer to preserve voice function, and surgery is preferred for small lesions in the oral cavity to avoid the long-term complications of radiation, such as xerostomia and dental decay. Overall 5-year survival is 60–90%. Most recurrences occur within the first 2 years following diagnosis and are usually local.
LOCALLY OR REGIONALLY ADVANCED DISEASE Locally or regionally advanced disease—disease with a large primary tumor and/or lymph node metastases—is the stage of presentation for >50% of patients. Such patients can also be treated with curative intent but not with surgery or radiation therapy alone. Combined modality therapy including surgery, radiation therapy, and chemotherapy is most successful. It can be administered as induction chemotherapy (chemotherapy before surgery and/or radiotherapy) or as concomitant (simultaneous) chemotherapy and radiation therapy. The latter is currently most commonly used and best evidence–supported. In patients with intermediate stage (stage III and early stage IV), concomitant chemoradiotherapy is given postoperatively. It can be administered either as a primary treatment for patients with unresectable disease, to pursue an organ-preserving approach, or in the postoperative setting for intermediate-stage resectable tumors.
Induction chemotherapy In this strategy, patients receive chemotherapy (current standard is a three-drug regimen of docetaxel, cisplatin, and fluorouracil [5-FU]) before surgery and radiation therapy. Most patients who receive three cycles show tumor reduction, and the response is clinically "complete" in up to half. This "sequential" multimodality therapy allows for organ preservation (omission of surgery) in patients with laryngeal and hypopharyngeal cancer, and it has been shown to result in higher cure rates compared with radiotherapy alone.
Concomitant chemoradiotherapy With the concomitant strategy, chemotherapy and radiation therapy are given simultaneously rather than in sequence. Tumor recurrences from head and neck cancer develop most commonly locoregionally (in the head and neck area of the primary and draining lymph nodes). The concomitant approach is aimed at enhancing tumor cell killing by radiation therapy in the presence of chemotherapy (radiation enhancement). Toxicity (especially mucositis, grade 3 or 4 in 70–80%) is increased with concomitant chemoradiotherapy. However, meta-analyses of randomized trials document an improvement in 5-year survival of 8% with concomitant chemotherapy and radiation therapy. Results seem more favorable in recent trials as more active drugs or more intensive radiotherapy schedules are used. The 5-year survival rate is 34–50%. In addition, concomitant chemoradiotherapy produces better laryngectomy-free survival (organ preservation) than radiation therapy alone in patients with advanced larynx cancer. The use of radiation therapy together with cisplatin has also produced improved survival in patients with advanced nasopharyngeal cancer. The outcome of HPV-related cancers seems to be especially favorable following cisplatin-based chemoradiotherapy.
The success of concomitant chemoradiotherapy in patients with unresectable disease has led to the testing of a similar approach in patients with resected intermediate-stage disease as a postoperative therapy. Concomitant chemoradiotherapy produces a significant improvement over postoperative radiation therapy alone for patients whose tumors demonstrate higher risk features, such as extracapsular spread beyond involved lymph nodes, involvement of multiple lymph nodes, or positive margins at the primary site following surgery.
A monoclonal antibody to the EGF-R (cetuximab) increases survival rates when administered during radiotherapy. EGF-R blockade results in radiation sensitization and has milder systemic side effects than traditional chemotherapy agents, although an acneiform skin rash is commonly observed. The integration of cetuximab into current standard chemoradiotherapy regimens is under investigation.
RECURRENT OR METASTATIC DISEASE Ten percent of patients present with metastatic disease, and more than half of patients with locoregionally advanced disease have recurrence, frequently outside the head and neck region. Patients with recurrent and/or metastatic disease are, with few exceptions, treated with palliative intent. Some patients may require local or regional radiation therapy for pain control, but most are given chemotherapy. Response rates to chemotherapy average only 30–50%; the duration of response averages only 3 months, and the median survival time is 6–8 months. Therefore, chemotherapy provides transient symptomatic benefit. Drugs with single-agent activity in this setting include methotrexate, 5-FU, cisplatin, paclitaxel, and docetaxel. Combinations of cisplatin with 5-FU, carboplatin with 5-FU, and cisplatin or carboplatin with paclitaxel or docetaxel are frequently used.
EGF-R–directed therapies, including monoclonal antibodies (e.g., cetuximab) and tyrosine kinase inhibitors (TKIs) of the EGF-R signaling pathway (e.g., erlotinib or gefitinib) have single-agent activity of approximately 10%. Side effects are usually limited to an acneiform rash and diarrhea (for the TKIs). The addition of cetuximab to standard combination chemotherapy with cis- or carboplatin and 5-FU was shown to result in a significant increase in median survival.
COMPLICATIONS Complications from treatment of head and neck cancer are usually correlated to the extent of surgery and exposure of normal tissue structures to radiation. Currently, the extent of surgery has been limited or completely replaced by chemotherapy and radiation therapy as the primary approach. Acute complications of radiation include mucositis and dysphagia. Long-term complications include xerostomia, loss of taste, decreased tongue mobility, second malignancies, dysphagia, and neck fibrosis. The complications of chemotherapy vary with the regimen used but usually include myelosuppression, mucositis, nausea and vomiting, and nephrotoxicity (with cisplatin).
The mucosal side effects of therapy can lead to malnutrition and dehydration. Many centers address issues of dentition before starting treatment, and some place feeding tubes to ensure control of hydration and nutrition intake. About 50% of patients develop hypothyroidism from the treatment; thus, thyroid function should be monitored.