Head and Neck Oncology

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[edit] Head and Neck Oncology

Dennis H. Kraus

David G. Pfister

The head and neck contain a variety of tissues and organs. Accordingly, a broad spectrum of malignant lesions can occur in this region. Carcinomas, lymphomas, sarcomas, and melanomas arise in the head and neck; salivary gland, thyroid, ocular, and brain tumors are all technically head and neck malignancies. When nonmelanoma skin cancers are excluded, approximately 80,000 such cancers are diagnosed in the United States each year.

Most often, however, the term head and neck cancer (HNC) refers to squamous cell carcinoma (SCC) arising from the surface epithelium of the upper aerodigestive tract, including the oral cavity, pharynx, larynx, and nasal cavity/paranasal sinuses (Box 183-1). When so defined, approximately 45,000 new cases of HNC are diagnosed each year, or 4% to 5% of all newly diagnosed invasive cancers. SCC or one of its variants is the histologic type in 95% of these cases. HNC comprises a heterogenous group of neoplasms, with important site-specific differences in etiology, clinical presentation, staging, prognosis, treatment, and survival. Unless otherwise specified, HNC refers to cancers of this location and histology. Despite their heterogeneity, certain general principles of management can be identified.

[edit] EPIDEMIOLOGY AND RISK FACTORS

The incidence of HNC has shown a minimal increase over the last 30 years. Patients with HNC are predominantly male (3:1) and have a median age of approximately 60 years. An increasing proportion are women, reflecting increased tobacco use in this population. The oral cavity and the larynx are the two most common primary sites. Marginal improvements in survival have occurred over the last 30 years.

HNC is associated with several etiologic factors, especially tobacco and alcohol use. Inhaled tobacco smoke is probably the most important. It affects most sites, although the association is strongest for laryngeal cancer. The risk increases with the number of cigarettes smoked each day. In individuals who stop smoking, it takes over a decade for their risk of HNC to approach that of a nonsmoker. Other tobacco products besides cigarettes, including cigar, pipe, and smokeless tobacco, are associated with a significant increase in HNC. The popularity of smokeless tobacco in adolescents and young adults has been associated with increases in oral cavity (especially buccal mucosa) and oropharyngeal cancers. Alcohol consumption is a major risk factor for HNC, especially of the oral cavity, oropharynx, and hypopharynx. As with tobacco, the subsequent incidence of cancer is dose related. When tobacco and alcohol are both used by a patient, the two risk factors appear to be synergistic.

Nasopharyngeal cancer is especially prevalent in the Far East, where the incidence is 20 to 25 times higher than in Western countries. The increased risk is diminished but still present in American descendants of Chinese origin. The exact roles played by genetic and environmental factors, however, remain controversial. Epstein-Barr virus (EBV) is a potential etiologic agent. Patients with nasopharyngeal carcinoma have a greater elevation in their EBV viral capsid titers compared with control patients without the disease, and the level of these titers correlates with the tumor burden present. The EBV genome can be demonstrated in nasopharyngeal cancer tissue. Human papillomavirus (HPV) is also an etiologic agent for the development of SCC throughout the upper aerodigestive tract.

[edit] PATHOPHYSIOLOGY

Certain lesions, although not invasive carcinoma, are important to recognize as precursors of SCC. Since a different histologic diagnosis can dramatically affect prognosis and treatment, direct interaction with the pathologist under these circumstances is crucial. Leukoplakia clinically appears as a white patch, which reflects epithelial thickening. It can be distinguished from a candidal infection in that the leukoplakia plaque cannot be removed with direct contact. Leukoplakia most often occurs on the buccal mucosa, dorsal tongue, and alveolar ridges. Most of these lesions are not associated with significant cellular atypia and spontaneously regress in about 25% of patients; longitudinal follow-up of patients with leukoplakia documents a low incidence of malignant transformation (5% to 10%). Erythroplasia, on the other hand, is an ominous mucosal change. Clinically, it appears as a velvety red patch, most often affecting the floor of mouth, ventral tongue, soft palate, and tonsil. This lesion is associated with a high rate of severe dysplasia or in situ/invasive carcinoma at biopsy (80% to 90%). The risk of malignant conversion over time is also significant. As such, erythroplasia always requires biopsy.

Verrucous carcinoma is a low-grade variant of SCC, most often found in the oral cavity and larynx. Clinically it resembles a wart and has an indolent growth pattern. Biopsies of the lesion reveal no invasive cancer. Verrucous carcinoma can be locally aggressive. True verrucous carcinomas rarely develop lymph node metastases.

In the nasopharynx and nasal cavity/paranasal sinuses, the frequency of SCC is slightly less than in other sites (80% to 85%). The incidence of the different types of epidermoid carcinoma of the nasopharynx shows marked geographic variation. Well-differentiated SCC, or World Health Organization (WHO) type I, which is more common in North America, occurs in older patients and is more closely linked to traditional carcinogens of the upper respiratory tract, with less association with EBV. Poorly differentiated carcinomas (WHO types II and III), including those with heavy lymphocytic infiltration (so-called lymphoepithelioma), occur in younger patients, with major endemic areas in Asia and the Mediterranean.

[edit] CLINICAL PRESENTATION AND NATURAL HISTORY

HNC is best described as a local and regional disease. In the majority of patients, symptoms and signs related to the primary tumor or its spread to regional (neck) lymph nodes are the primary manifestations of the disease. Asymptomatic cervical adenopathy may be the presenting complaint. An isolated neck mass in an adult should be considered cancer until proved otherwise. Spread of disease to regional lymphatics generally occurs in a predictable manner. For example, tumors of the oral cavity most often involve the submandibular and upper jugular nodes; tumors of the larynx, hypopharynx, and oropharynx involve the upper and middle jugular nodes; and nasopharynx cancer affects the retropharyngeal, jugulodigastric, and spinal accessory nodes. The frequency of lymph node metastases at presentation is related to the amount of capillary lymphatics draining the primary site. Sites with a rich supply of capillary lymphatics (e.g., nasopharynx, hypopharynx) typically present with enlarged lymph nodes, relative to sites with few lymphatic channels (e.g., glottic larynx, paranasal sinuses). The size of the lesion, its grade, and the depth of tumor invasion are also important in predicting the frequency of lymph node involvement. Large, high-grade, and deeply infiltrating tumors are more likely to have involved lymph nodes.

Tumors most often present as a mass or ulcer. Since much of the mucosal surface is not immediately accessible, symptoms are often ignored, leading to a delay in diagnosis. Symptoms that fail to respond to conservative treatment (antibiotics) in 4 weeks necessitate evaluation by a trained otolaryngologist–head and neck specialist. The symptoms and signs associated with these lesions vary with the primary site and are best understood in the context of the anatomy of the area (Table 183-1).

Table 183-1 Clinical Presentation of Head and Neck Cancer

Distant metastases are uncommon at presentation in HNC, occurring in less than 10% of patients. Ultimately, 20% to 30% of patients manifest distant spread of the disease. Autopsy studies suggest that distant metastases are more frequent but do not manifest clinically because the local and regional aspects of the disease are more prominent. The risk of distant metastases increases with involvement of neck nodes. The most common sites of distant spread are lung, liver, bone, and skin. Hypercalcemia occurs in 3% to 5% of patients and generally reflects recurrent or advanced disease.

Given the central roles tobacco and alcohol abuse play in the development of HNC, other problems stemming from their excessive use are associated with these tumors. An estimated 50% to 60% of patients with HNC show significant signs of malnutrition. Many patients with HNC have comorbid ailments that complicate their management, including alcoholic liver disease and cirrhosis, chronic obstructive pulmonary disease, and vascular disease. Second primary cancers are increasingly appreciated in these patients, arising in other head and neck sites, lung, and esophagus. The terms field defect, field cancerization, and condemned mucosa have been used to describe this phenomenon. The estimated risk is at 3% to 5% each year, although it is much higher in patients who continue to smoke and drink. Ultimately, 10% to 40% of patients develop a second primary cancer.

All smokers and users of smokeless tobacco products should have routine screening examinations of the oral cavity (Fig. 183-1 and Box 183-2).

Figure 183-1 Oral cancer screening form. (From Prout MN et al: J Cancer Educ 7:139, 1992.)

[edit] PATIENT EVALUATION AND STAGING

A careful history documenting symptoms, potential risk factors, and other comorbid medical problems is important. The percentage of total body weight lost in the last 6 months and the patient's performance status, as defined by a well-recognized scale, quantitate disease impact and symptom severity. Physical examination is central to patient evaluation, with a thorough inspection of the head and neck. Palpation of the parotid, submandibular, and thyroid glands is essential. Although the name of specific nodal groups can be used, a leveling system is now applied at many centers and is clinically reproducible (Fig. 183-2). Level I refers to lymph nodes in the submental region and submandibular triangle; levels II, III, and IV refer to the upper, middle, and lower thirds of the internal jugular chain, respectively; and level V refers to nodes in the spinal accessory and transverse cervical chains. Many oral cancers involve the ventral surface of the tongue, and this area is carefully assessed. At certain sites, such as the floor of the mouth and the base of the tongue, visual inspection alone either misses or underestimates the size of a lesion, and palpation or bimanual examination allows a better assessment. The nasopharynx warrants careful scrutiny. Visualization is facilitated by the use of mirrors and rigid and flexible scopes. Flexible scopes are especially useful in patients who continue to have a hyperactive gag reflex after adequate local anesthesia. Vocal cord mobility and facial nerve function are assessed.

Figure 183-2 Level I, lymph nodes in submental region and submandibular triangle; levels II, III, IV, lymph nodes in the upper, middle, and lower thirds of the internal jugular chain; level V, lymph nodes in the spinal accessory and transverse cervical chains.

Medical imaging with computed tomography (CT) and magnetic resonance imaging (MRI) is increasingly used in the evaluation of these patients. A barium swallow may be useful, especially in patients complaining of dysphagia. CT scan has the advantage of lower cost, faster scanning time, and decreased motion artifact. MRI scan has the advantage of better differentiation of soft tissues and may be the preferable study at certain sites (e.g., nasopharynx, base of tongue). Routinely obtaining both studies is unnecessary; they should be ordered by the otolaryngologist–head and neck surgeon only when appropriate.

Because of the low frequency of distant metastases at presentation, an extensive search for distant metastatic disease is not routinely indicated. A chest radiograph is important, as much to document a possible synchronous lung primary or chronic lung disease in this smoking population as to demonstrate metastatic disease. Liver function abnormalities usually reflect alcohol abuse or some other nonmalignant process. Formal imaging of the liver and bones is necessary only if appropriate biochemical abnormalities or symptoms are present. A complete blood count may suggest nutritional deficiency or chronic blood loss. Pulmonary function tests and electrocardiogram (ECG) are incorporated into preoperative assessment and may necessitate additional management.

Endoscopy under anesthesia is especially useful in patients with tumors of the larynx and pharynx. The routine use of so-called triple endoscopy (laryngoscopy, esophagoscopy, bronchoscopy) in the evaluation of these patients is controversial. Proponents emphasize the 5% or higher incidence of synchronous primary cancers that affect prognosis and management. Triple endoscopy is appropriate in two groups: patients at high risk for multiple primaries with clinical evidence of diffuse mucosal abnormalities and patients who have cervical adenopathy without an identifiable primary site.

As with all malignancies, histologic proof is obtained from the primary site. When the primary is occult, histologic confirmation of a suspicious neck node is required. Initially, fine-needle aspiration (FNA) is preferred instead of an open biopsy. FNA is well tolerated and accurate, especially for SCC, with no significant risk of seeding the needle tract. Multiple endoscopies should be performed to exclude an occult primary arising in the nasopharynx, base of tongue, tonsil, or pyriform sinus. If the FNA biopsy is noncontributory, an excisional biopsy is indicated, with the incision part of the usual neck dissection. Preoperative counseling of the patient facilitates rapid neck dissection when malignancy is confirmed on frozen section. When followed over time, 30% of these patients have their primary tumor identified. Interestingly, the patients in whom the primary site is found generally do worse than those in whom it remains occult (30% vs. 60% long-term survival, respectively).

The goal of this evaluation is to stage the cancer appropriately, which helps define prognosis and management and facilitates uniform reporting of treatment results. The staging used for HNC is the tumor-node-metastasis (TNM) system, as determined by the American Joint Committee on Cancer and the International Union Against Cancer (Box 183-3). The T stage depends on the site, size, and extent of invasion at the primary site. Tumors of the oral cavity and oropharynx use the same criteria; other sites are different. The N stage is defined by the number, size, and location relative to the primary lesion of the regional lymph nodes. The M stage refers to the presence or absence of distant metastases. The N (except for the nasopharynx) and M formulations are the same for all primary sites. The respective T, N, and M stages are then combined to create four stages. Stage I is the best prognostic group; stage IV is the worst prognostic group. Clinical staging (excluding information obtained at surgery) is the type most often used, since clinical decisions are typically based on this information.

[edit] MANAGEMENT

Patients with HNC present a challenge on many levels. Ongoing tobacco and alcohol abuse are common, as are other medical comorbidities. The disease and its treatment can cause dysfunction and disfigurement. Optimal treatment and rehabilitation of these patients therefore requires close interdisciplinary cooperation not only among the treating surgical, radiation, and medical oncologists, but also among other health professionals, including dentists and prosthodontists, speech and swallowing therapists, audiologists, nutritionists, occupational and physical therapists, and psychiatrists. Plans for rehabilitating patients should start before treatment.

Control of disease at the primary site and in the neck is the primary goal. Historically, surgery and radiation therapy have been the principal treatment modalities. Chemotherapy's role is best established in the palliative setting but is being actively investigated in combination with surgery and radiation, with important implications for the development of function preserving therapy and the treatment of patients with unresectable disease. In general, treatment is determined by the TNM stage at presentation, although there are site-specific variations (Table 183-2). Management of the primary site and that of the neck are related but also present separate concerns. Treatment plans should consider both survival and quality of life.

Table 183-2 Head and Neck Cancer Treatment by Category and Stage

✢The choice among these options will depend on many factors, including but not limited to disease extent, primary site, a patient's clinical/performance status, and the anticipated outcomes (e.g., disease control, functional, cosmetic) associated with a given approach.

For limited disease (T₁-T₂, N₀-N₁, M₀) single-modality treatment with surgery or radiation is associated with equivalent results (60% to 90% cure rate). The choice of modality depends on a variety of factors, including primary site, patient age and general health, local expertise, functional concerns, and patient preference. Patients with an N₀ stage can have their necks treated electively depending on the risk of occult nodal disease. This estimate is based on T stage, primary site, differentiation of the tumor, evidence of vascular and lymphatic invasion, and depth of invasion of the primary tumor. If the estimated risk of neck failure is greater than 15%, elective neck staging or treatment is advisable. Obviously, the results of treatment with one modality may require the immediate addition of the other. A positive margin after resection or the finding at neck dissection of multiple positive lymph nodes or extracapsular extension necessitates postoperative radiation therapy; a persistent or growing mass after radiation therapy requires resection.

Patients with bulky, advanced resectable disease (T₃-T₄, N₂-N₃, M₀) require treatment with a combination of surgery and radiation, since this approach has improved local and regional disease control compared with unimodality therapy. The expected cure rate in this group is 10% to 60%. Chemotherapy has been studied in combination with standard local and regional treatment to improve tumor control and/or functional outcome. In patients with unresectable disease, radiation therapy alone has been the standard treatment. The integration of chemotherapy with radiation appears to improve response rates and potentially survival.

If a patient has recurrent disease after primary treatment, attempts are made to salvage the patient with surgery and radiation, depending on previous therapy. If a patient previously received definitive radiation therapy, the options of receiving further radiation are limited. Patients undergoing salvage therapy are at higher risk for disease recurrence compared with similarly staged, untreated patients. Patients with recurrent disease that is not amenable to further surgery or radiation and patients with distant metastatic disease (M₁) at presentation or recurrence are treated with palliative chemotherapy.

Five-year survival rates are generally reported for HNC. However, most relapses occur within the first 2 years after treatment. Involved regional lymph nodes reduce the anticipated cure rate within each T stage by approximately 50%. Anticipated survival rates depend on the stage and primary site. For example, hypopharyngeal primaries have a worse prognosis, stage for stage, than laryngeal primaries, even though the structures are immediately adjacent to each other.

The treatment of patients with an occult primary and metastatic SCC in a cervical node depends on the clinical presentation. Patients with an N₁ neck diagnosis can be treated with primary radiation or a neck dissection with equivalent local control. Patients with an N₂ or N₃ neck diagnosis probably require treatment with neck dissection and radiation therapy. Patients with advanced neck disease have a worse prognosis. Elective irradiation of the potential primary mucosal sites should sterilize the low-bulk disease. However, radiation to the mucosal surfaces will increase the morbidity of treatment in the form of xerostomia and potentially complicate subsequent salvage therapy.

[edit] Surgery

Certain advantages are associated with surgical treatment of HNC. The treatment time is shorter, and surgery is limited to those tissues at greatest risk of tumor invasion. The immediate and long-term sequelae of radiation are avoided. Pathologic information found at surgery is useful in predicting prognosis and in planning postoperative treatment with radiation.

An adequate surgical procedure requires margins free from tumor. In more advanced lesions this may necessitate a procedure associated with significant functional or cosmetic morbidity. In patients with laryngeal and pharyngeal tumors a total laryngectomy may be required. Tumors of the oral cavity and oropharynx may require a composite resection, with removal of part of the mandible and en bloc resection of the primary tumor and regional lymph nodes. Patients with extensive oropharyngeal tumors often require total laryngectomy, not to remove the primary tumor but to prevent the sequelae of chronic aspiration. Patients with advanced paranasal sinus tumors may require a radical maxillectomy, which occasionally includes orbital exenteration.

Function-preserving procedures adhere to sound surgical oncologic principles. Supraglottic laryngectomy and hemilaryngectomy are examples that spare laryngeal function. Successful application of these procedures requires both surgical expertise and careful patient selection. The use of a variety of skin and bone grafts can optimize the functional and cosmetic results. A prosthodontist can customize obturators and other prostheses that facilitate speech and swallowing.

Certain features of a tumor indicate that it is unresectable. The distinction between technically unresectable and unresectable for medical reasons is important. Contraindications for resection include massive skull base involvement, prevertebral fascia invasion, carotid artery encasement, and skin infiltration. CT scan and MRI can be helpful in assessing some of these issues.

The traditional radical neck dissection involves removal of the cervical lymphatic tissues, the sternocleidomastoid muscle, the internal jugular vein, and the eleventh cranial nerve. The procedure can be associated with pain, shoulder weakness, and paresthesia. Because of these potential morbidities, a variety of modified and selective procedures that preserve function have evolved. The clinical decision to use one of these modified or selective techniques requires careful patient selection.

[edit] Radiation Therapy

Compared with surgery, radiation is associated with certain advantages. In some instances (e.g., early laryngeal cancer) the functional results are better. When elective therapy to high-risk lymph nodes is indicated, this treatment can easily be incorporated into patient management. This option is especially relevant in patients who are at risk for bilateral neck node involvement. Treatment-related mortality rarely occurs.

The ability of radiation therapy to control local and regional disease as a single modality is inversely related to tumor bulk. The probability of tumor control is dose dependent. Large total doses are required to sterilize SCC. The dose and portals of treatment depend on the primary site and goals of therapy. When single-modality, definitive radiation is used, doses of 6600 to 7000 cGy are necessary. The dose is generally administered over 6 to 7 weeks, with daily fractions of 180 to 200 cGy. These are optimally delivered either by a megavoltage linear accelerator or ⁶⁰Co unit. The dose to the spinal cord must be monitored, since its radiation tolerance is considerably lower.

Radiation therapy can be combined with surgery using preoperative or postoperative dosing. The customary preoperative dose is 5000 cGy; the difficulty of subsequent surgery and the frequency of serious postoperative complications increase when the radiation dose exceeds this level. The postoperative dose to the primary site and neck are influenced by the findings at surgery and range from 5000 to 7000 cGy, depending on factors such as surgical margins and the presence of residual gross disease. Postoperative radiation is currently the usual approach. The local and regional control rate appears to be higher with postoperative treatment, although no survival advantage has been proved. Radiation therapy generally starts 2 to 4 weeks after resection, at which time the wounds are satisfactorily healed.

Adverse effects of radiation in the head and neck can occur both early and late. Mucositis and edema lead to dysphagia, hoarseness, and otitis media. These toxicities are generally managed with conservative measures and resolve with time. Occasionally, temporary placement of a feeding tube, tracheostomy, or myringotomy with pressure-equalizing tubes may be necessary. Fibrosis and induration of irradiated tissues develop to a variable extent. Xerostomia and loss of taste are related to salivary gland dysfunction. Long-term return of function varies, depending in part on dose and portals. The use of certain drugs may ameliorate this toxicity (e.g., amifostine, pilocarpine). Because of the reduction of saliva, dental caries and periodontal disease can be considerable. Dental evaluation before radiation therapy, with extraction of damaged teeth, optimization of oral hygiene, and fluoride treatments, is essential and can prevent longterm complications. Lhermitte's sign, which is characterized by shocklike sensations in the spine, arms, and legs with neck flexion, occurs when the spinal cord is irradiated and is self-limiting. Varying degrees of thyroid dysfunction may develop, and thyroid function tests should be closely monitored in those patients undergoing surgery and radiation to the neck, larynx, or pharynx. Two serious late complications are myelopathy due to overdosing of the cervical spinal cord and osteoradionecrosis of the mandible.

Several techniques aimed at improving the therapeutic index of radiation therapy are under active clinical evaluation and investigation. Radiation implants (brachytherapy) are placed within the tumor bed. The implant can either be permanent (e.g., ¹²⁵I) or temporary via afterloading catheters (e.g., ¹⁹²Ir). These can be used either alone or in combination with external beam treatment. Their use is associated with excellent local control in selected tumors of the oropharynx (base of tongue) and oral cavity. Hyperfractionated radiation (using more than one fraction per day) has yielded encouraging results in patients with advanced tumors. Conformal radiation more precisely delivers treatment to the tumor and facilitates dose escalation.

[edit] Chemotherapy

By itself, chemotherapy is not curative in HNC. A number of chemotherapy agents cause a major shrinkage of tumor in 20% to 40% of HNC patients. Combinations with the drug cisplatin are thought to have the highest response rates. The exact response rate depends on the tumor bulk and previous treatment. Large, previously treated tumors have the lowest response rates.

Historically the prime role of chemotherapy has been in the palliation of patients who have largely exhausted surgical and radiation treatment options or in patients with distant metastatic disease. Under these circumstances the gold standard drug is methotrexate. In general, the treatment is well tolerated, but possible toxicities include mucositis, myelosuppression, hepatotoxicity, nephrotoxicity, and fatigue. Cisplatin is considered to be as active but is associated with more toxicity and greater difficulty of administration. Toxicities include nausea and vomiting, myelosuppression, nephrotoxicity, neurotoxicity, and ototoxity. Other drugs, such as 5-fluorouracil, carboplatin, paclitaxel, and docetaxel, also have activity. Unfortunately, the median duration of response with these agents remains short and the median overall survival poor. In hopes of improving these results, a variety of combination chemotherapy regimens have been compared to treatment with a single agent. These trials have revealed no improvement in survival.

The response rates in patients with previous untreated HNC are higher than in those with recurrent or metastatic disease. Indeed, cisplatin-based combination chemotherapy yields response proportions in the 60% to 90% range, with complete responses in 20% to 60% of patients. Despite these high response rates, induction chemotherapy, adjuvant chemotherapy, or combination therapy integrated with standard surgery and radiation has not improved survival in these patients compared with results from surgery and radiation alone.

The use of chemotherapy in a treatment scheme that does not improve survival may still be useful, if the functional result is superior to that after standard surgery and radiation therapy. Since radiation is most effective when the tumor burden is small, chemotherapy may decrease the tumor bulk before definitive therapy. In one trial, patients with stage III and IV laryngeal cancer received either standard total laryngectomy with postoperative radiation or induction chemotherapy with radiation; total laryngectomy was reserved for patients who had no chemotherapy response or who relapsed. The survival in both treatment groups was equivalent, and more than 60% of surviving patients in the chemotherapy/radiation group had their larynx preserved. Similar data are available for patients with advanced hypopharynx cancer.

The use of chemotherapy concomitantly with radiation has been intensely investigated. The emphasis has been on choosing chemotherapeutic agents that have independent activity in HNC but can also serve as radiation enhancers or sensitizers. Randomized trials suggest this approach yields a higher response rate and improves local control compared with radiation alone. Local mucocutaneous toxicity is generally increased. The potential utility of concomitant chemotherapy and radiation may be a significant part of a functional preservation treatment approach and is often applied to patients with unresectable disease, including advanced nasopharynx cancers, and more recently in patients with advanced oropharynx cancer.

[edit] PREVENTION

Since tobacco and alcohol use are the primary risk factors for HNC, any prevention program must focus on the cessation or modification of these behaviors. Tobacco cessation is most successful when a counseling program is combined with the use of a tapering nicotine patch. Even in patients who stop smoking and consuming alcohol, however, the risk for second malignancy persists for years. Accumulating evidence suggest the retinoids may be important in the prevention of epithelial carcinogenesis, as evaluated in a study of 13-cis retinoic acid (50 to 100 mg/m²/day orally) vs. placebo in patients who were disease free after primary treatment for HNC. No difference was seen in the number or pattern of relapses or the overall survival in the two groups of patients, but the rate of second primary tumors in the treatment group was significantly decreased. Toxicities associated with the 13-cis retinoic acid included skin dryness, cheilitis, hypertriglyceridemia, and conjunctivitis. Approximately 20% of patients did not complete treatment because of toxic effects. Less toxic schedules and less toxic substances (β-carotene, vitamin E) are being investigated.

[edit] SPECIFIC SITES

[edit] Salivary Glands

Cancer of the major and minor salivary glands is uncommon, accounting for about 7% of head and neck malignancies. They arise from the three paired major salivary glands (parotid, submandibular, sublingual) and the approximately 700 minor salivary glands that are distributed throughout the upper aerodigestive tract. There may be an association with previous low-dose radiation exposure, such as that used for acne or lymphoid hypertrophy. An association also may exist between salivary gland tumors and patients with a history of breast cancer, cancer of the male genital tract, HNC, and skin cancer.

A variety of benign and malignant histologic changes occur in the salivary glands. Approximately 80% of all salivary gland tumors arise in the parotid, 10% to 15% in the submandibular gland, and the remainder in the sublingual and minor salivary glands. The odds of a salivary gland neoplasm being malignant are inversely related to the size of the gland. It is estimated that 20% to 30% of parotid, 40% to 60% of submandibular, and the majority of sublingual and minor salivary gland tumors are malignant. The distinction between benign and malignant tumors can be difficult. The parotid is a potential site for regional and distant metastases, particularly for skin cancer arising on the face.

Salivary gland tumors grow by direct extension and infiltration and generally present as a painless swelling. Rapid growth and facial nerve involvement are both associated with a malignant histology and a poor prognosis. The clinical aggressiveness of the tumors varies with size, histology, and grade. The incidence of clinical and subclinical neck node metastases is lower than with HNC. Distant metastases are uncommon. The risk of distant failure is highest for adenoid cystic tumors, the lung being the most common site.

The use of FNA biopsy in the management of salivary neoplasms is controversial. The information does not change therapy in most cases but may be useful in treatment planning for certain patients (e.g., with unresectable tumors). Excisional biopsy should be discouraged, since it only complicates subsequent definitive therapy. CT scan or MRI may provide additional useful information. These modalities distinguish between intrinsic and extrinsic glandular masses, extraglandular extension, and the presence of occult metastatic cervical disease. Sialograms were used more often in the past but have been replaced by these newer technologies.

Surgery is the treatment of choice for salivary gland neoplasms. Enucleation of salivary gland tumors leads to local recurrence, even with benign tumors, and should be avoided. Excision of the superficial or deep lobe of the parotid gland with facial nerve preservation is performed depending on the tumor's location. The entire gland is removed in submandibular and sublingual tumors. Elective neck dissections are generally not performed, although sampling adjacent lymph nodes based on histology and size may have a role. Depending on the location and extent of the parotid tumors, resections may include part of the temporal bone, mandible or zygoma, and the facial nerve. Placement of an immediate nerve graft for facial nerve resection has shown success. Management of the eye, including a moisture chamber at night and the use of artificial preparations for replacement of tears, is mandatory to prevent exposure keratopathy, which can accompany facial paralysis. Postoperative radiation is generally indicated for high-grade, large, deeply invasive tumors with positive or close margins and positive nodes. Doses are similar to those used with HNC. Primary radiation is generally limited to patients with unresectable tumors; neutron beam therapy is under investigation. Chemotherapy has no standard role in the management of salivary gland tumors.

Parotid tumors are associated with better survival than lesions at other sites. Adenoid cystic cancers often have indolent growth, even when distant metastases are present. Ten-year survival statistics are a more accurate estimate of treatment results for many of these tumors because of their long natural histories.

[edit] Thyroid

Cancer of the thyroid accounts for approximately 12,000 new cases per year and 1000 deaths, with an increased incidence in females and whites. Prognosis is improved in women and in patients with disease onset at a younger age. Exposure to radiation therapy places patients at an increased risk for thyroid cancer. Approximately 10% of medullary carcinomas of the thyroid are inherited as an autosomal dominant gene. Medullary thyroid cancer is associated with the multiple endocrine neoplasia (MEN) syndromes.

Thyroid neoplasms represent an array of benign and malignant processes. The most common thyroid mass represents either multinodular goiter or benign follicular adenomas. The well-differentiated thyroid carcinomas—papillary and follicular adenocarcinomas—represent almost 90% of all thyroid malignancies. Papillary adenocarcinoma (50% to 60%) is nearly twice as common as follicular adenocarcinoma (25% to 35%). The high-grade variants include medullary (5%) and undifferentiated/anaplastic (5%) carcinomas.

Thyroid malignancies most often present as a painless thyroid mass. Cervical lymphadenopathy is consistent with lymph node metastases. Unlike HNC, cervical metastases do not adversely affect long-term survival; distant metastases, however, are associated with reduced long-term survival. Hoarseness may represent recurrent laryngeal nerve paralysis. (See Chapter 181 for diagnosis and management.)

[edit] ADDITIONAL READINGS

• M Deiter,et al.: Modern management of cervical scrofula. Head Neck 1989; 11:60.
• JGAM de Visscher, KGH van der Wal, PL de Vogel: The plunging ranula: pathogenesis, diagnosis, and management. J Craniomaxillofac Surg 1989; 17:182.
• WP Dillon, RH Harnsberger: The impact of radiologic imaging on staging of cancer of the head and neck. Semin Oncol 1991; 18:64.
• M Friedman,et al.: Nodal size of metastatic squamous cell carcinoma of the neck. Laryngoscope 1993; 103:854.
• Harrison LB Sessions RB Hong WK Head and neck cancer: a multidisciplinary approach. Philadelphia: Lippincott-Raven; 1999:
• C Jacobs: The internist in the management of head and neck cancer. Ann Intern Med 1990; 113:771.
• ME Johns, MM Goldsmith: Incidence, diagnosis, and classification of salivary gland tumors. Oncology 1989; 3:47.
• ME Johns, MM Goldsmith: Current management of salivary gland tumors. Oncology 1989; 3:85.
• RD Lindberg: Distribution of cervical lymph node metastases from squamous cell carcinoma of the upper respiratory and digestive tracts. Cancer 1972; 29:1446.
• FE Lucente: Impact of the acquired immunodeficiency syndrome epidemic on the practice of laryngology. Ann Otol Rhinol Laryngol 1993; 102 (suppl 161):
• WF McGuirt: Panendoscopy as a screening examination for simultaneous primary tumors in head and neck cancer: a prospective sequential study and review. Laryngoscope 1982; 92:569.
• Mulliken JB, Glowacki J: Hemangioma and vascular malformations in infants and children: a classification based on endothelial characteristics, Plast Reconstr Surg 69:412, 198.
• DG Pfister,et al.: The role of chemotherapy in the curative treatment of head and neck cancer. Surg Oncol Clin N A 1997; 6:749.
• Rice DH Spiro RH Current concepts in head and neck cancer. Atlanta: American Cancer Society; 1989:
• Silverman S Oral cancer. Atlanta: American Cancer Society; 1990:
• IJ Witterick,et al.: Nonpalpable occult and metastatic papillary thyroid carcinoma. Laryngoscope 1993; 103:149.
• WP Work: Hemangiomas of the head and neck. Ann Otol Rhinol Laryngol 1978; 87:633.
• KM Zangwill,et al.: Cat scratch disease in Connecticut: epidemiology, risk factors, and evaluation of a new diagnostic test. N Engl J Med 1993; 329:8.