Cancer of the Head and Neck
Summary of Key Points
• In the United States it was estimated that in the year 2012, head and neck cancer would account for 3.2% of all new cancer cases and 2% of all cancer deaths.
• The three major risk factors for head and neck cancer are tobacco, human papillomavirus infection, and alcohol.
• Management of head and neck cancers requires a multidisciplinary approach with effective integration of multiple specialties to achieve the desired goals of cure and functional organ preservation.
• Staging of head and neck cancer should be comprehensive and include a complete physical examination, fiberoptic laryngoscopy, computed tomography and/or magnetic resonance imaging of the head and neck, and a positron emission tomography scan for advanced stage disease to assess nodal involvement and distant metastases.
• The treatment of head and neck cancer is dictated by the primary site.
• Management of paranasal sinus malignancies is primarily surgical, with adjuvant radiation and possibly chemotherapy for advanced lesions. In unresectable and nonoperative cases, definitive radiotherapy should be offered.
• Surgery is generally considered the preferred initial treatment modality for oral cavity lesions. Adjuvant radiotherapy with or without chemotherapy is indicated for patients with high-risk features on surgical pathology. Definitive radiotherapy is reserved for unresectable tumors, nonoperable tumors, and tumors in which surgical resection would result in significant functional impairment.
• Most oropharyngeal cancers in the United States are now due to human papillomavirus and as such have an improved prognosis. Early-stage oropharynx cancers can effectively be treated with surgery or radiation therapy. The standard of care for locally advanced disease is chemoradiation; however, other modes of treatment are under active investigation.
• In persons with larynx cancer, the goal of first-line therapy should be to preserve the function of the larynx, without sacrificing tumor control. Early-stage laryngeal cancer can effectively be treated with either surgery or radiotherapy. In early-stage disease, the anatomic location and extent of disease will dictate if surgery is feasible. The treatment of choice in most locally advanced larynx cancers is concurrent chemotherapy and radiation. Because the Veterans Affairs (VA) larynx study demonstrated poor outcomes for persons with T4a disease, total laryngectomy is also a consideration for these patients.
• Surgical resection is the mainstay of management in salivary gland cancer, whether it arises from the parotid, submandibular, sublingual, or minor salivary glands. Combined therapy is recommended for high-grade malignancies of the salivary gland because postoperative irradiation has been shown to improve local-regional control in patients with positive surgical margins; high-risk features such as advanced stage, high-grade, skin/nerve invasion; and adenoid cystic carcinoma.
• The management of locally recurrent head and neck cancer is technically challenging and should be performed at centers where personnel have experience in treating these patients. Surgery is typically preferred and offered for resectable lesions in the absence of unacceptable functional sequelae. The roles of adjuvant radiotherapy (or reirradiation) and chemotherapy must be determined on a case-by-case basis.
• Metastatic head and neck squamous cell carcinoma carries a poor prognosis with a median survival of months. Systemic therapies are indicated for widespread disease.
1. In the metaanalysis of chemotherapy on head and neck cancer (MACH-NC), the addition of concurrent chemoradiation yielded a significant overall survival benefit of what percentage?
2. What virus is associated with nasopharyngeal carcinoma (NPC) oncogenesis?
3. It is predicted that oropharyngeal cancer incidence will surpass all laryngeal cancer as the most common cancer of the head and neck because of what?
A Increased HPV infectivity rates
B Decreased incidence of smoking, but a higher consumption per user
4. What radiation therapy modality, now considered the standard of care, allows for the conformal delivery of high doses of radiation with sparing, or limiting, of normal tissues?
5. Adenoid cystic carcinomas are almost always associated with what?
1. Answer: B. A metaanalysis from Pignon and colleagues, the MACH-NC evaluated the role of chemotherapy in the treatment of head and neck cancer. The MACH-NC included 31 induction chemotherapy trials for a total of 5311 patients over a median follow-up of 6.1 years. Overall, induction chemotherapy had a nonsignificant absolute survival benefit of 2.4% at 5 years (hazard ratio [HR] 0.96, 95% confidence interval [CI] 0.90-1.02, P = 0.18). Further analysis of 9605 patients who underwent concomitant chemoradiotherapy was derived from 50 randomized trials and confirmed an absolute 5-year survival benefit of 6.5% (HR 0.81; 95% CI 0.78-0.86). The benefit of chemotherapy was due to its effect on deaths related to head and neck cancer (HR 0.78; 95% CI 0.73-0.84) because no benefit was seen for noncancer deaths (HR 0.96; 95% CI 0.82-1.12). Similarly, an absolute benefit of 6.2% was seen in event-free survival (HR 0.79; 95% CI 0.76-0.83). This benefit was largely restricted to patients 70 years of age and younger because there was a statistically significant decreasing effect of chemotherapy on survival with increasing age (P = .003).
2. Answer: C. EBV, one of the seven classified oncoviruses, has been associated with NPC, specifically the nonkeratinizing type. EBV has been demonstrated to be an important biomarker because the presence of serum EBV has a high sensitivity (96%) and specificity (93%) for detecting NPC, circulating EBV-DNA levels have been demonstrated to correlate with tumor burden, and pretreatment EBV-DNA levels were demonstrated to be an independent prognostic variable in NPC, allowing the dichotomization into high-risk (≥4000 copies/ mL) and low-risk (<4000 copies/mL) cohorts. Recent studies have demonstrated that the clearance rate of plasma EBV-DNA during the first month of salvage chemotherapy may predict tumor response and overall survival in patients with metastatic/recurrent NPC; undetectable level after the first cycle indicated significantly better survival.
3. Answer: A. Until recently, smoking and alcohol consumption were the main risk factors for development of oropharyngeal cancer in the United States. Molecular evidence suggests a role for HPV, specifically HPV-16, in the pathogenesis of a subgroup of head and neck squamous cell carcinoma, and the HPV viral oncogenes E6 and E7 are frequently overexpressed in the oropharynx. Interestingly, exposure to HPV had an increased association with oropharyngeal cancer, regardless of tobacco and alcohol use, suggesting two distinct pathways of oncogenesis. Currently, HPV infection is the main etiology and was responsible for 70% of oropharyngeal cancer between 2000-2004, compared with only 16.3% between 1984-1989. The epidemic of HPV-related head and neck malignancies will likely lead to oropharyngeal cancer becoming the most common subsite of disease, surpassing laryngeal carcinoma.
4. Answer: C. IMRT has replaced conventional radiotherapy as the standard of care in the treatment of NPC. IMRT allows the modulation of the radiotherapy beam to achieve additional degrees of radiotherapy beam conformality, allowing a higher dose to be delivered to the tumor while significantly limiting the dose to surrounding normal tissues. Increasing the conformality provides an additional strategy to optimize the therapeutic ratio, separate from the issue of radiotherapy beam precision. Currently, a dose-painting approach is being used in modern IMRT plans, allowing different fraction doses to be simultaneously delivered to tumor volumes and elective nodal regions in a single course of radiotherapy.
5. Answer: C. Adenoid cystic carcinomas account for some 20% of malignant salivary gland tumors. They are frequently located in the minor salivary glands (in 40% to 50% of cases) and less often in the parotid gland (in 20% to 30% of cases). The most common histologic pattern is the classic cribriform type or “Swiss cheese” pattern, characterized by neoplastic cells forming oval or circular spaces or nests. Perineural invasion is almost invariably observed in these tumors, and a diagnosis of adenoid cystic carcinoma without finding perineural invasion should be carefully reconsidered. Adenoid cystic carcinomas are graded into low-, intermediate-, and high-grade tumors based on the amount of solid growth, mitoses, necrosis, and pleomorphism; as with mucoepidermoid carcinoma, the degree of differentiation is correlated with long-term survival.
