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National Cancer Institute
Ultima Vez Modificado: 16 de julio del 2012
Cancer of the hypopharynx is uncommon; approximately 2,500 new cases are diagnosed in the United States each year. 1 The peak incidence of this cancer occurs in males and females aged 50 to 60 years. 2 Excessive alcohol and tobacco use are the primary risk factors for hypopharyngeal cancer. 3 4 In the United States, hypopharyngeal cancers are more common in men than in women. 5 In Europe and Asia, high incidences of pharyngeal cancers, namely, oropharyngeal and hypopharyngeal, have been found among men in France, in the counties of Bas-Rhin and Herault; Switzerland, in the section of Vaud; Spain, in the Basque Country region; Slovakia, Slovenia, and India, in the cities of Bombay and Madras. 6 This cancer is extremely rare in children. 7
Upper hypopharyngeal cancers appear to be associated more with heavy drinking and smoking, whereas the lower hypopharyngeal, or postcricoid, cancers are more often associated with nutritional deficiencies. 1 8 Although earlier reports from northern Europe, particularly from Sweden, indicated a link between Plummer-Vinson syndrome, which consisted of sideropenic anemia and epithelial changes of the aerodigestive tract, and other nutritional deficiencies in women, cases of hypopharyngeal cancer among women are currently more likely to be associated with excessive use of alcohol and tobacco, rather than with deficiency diseases. 2 9 10 11
Anatomically, the hypopharynx extends from the plane of the hyoid bone above to the plane of the inferior border of the cricoid cartilage below. The hypopharynx is composed of the following three parts and does not include the larynx:
The lymphatic drainage from the pharynx is into the jugulodigastric, jugulo-omohyoid, upper and middle deep cervical, and retropharyngeal nodes. In the United States and Canada, 65% to 85% of hypopharyngeal carcinomas involve the pyriform sinuses, 10% to 20% involve the posterior pharyngeal wall, and 5% to 15% involve the postcricoid area. 12 Pyriform sinus and postcricoid carcinomas are typically flat plaques with raised edges and superficial ulceration. In contrast, posterior hypopharyngeal wall tumors tend to be exophytic and are often large (i.e., 80% >5 cm) at presentation. 13 Hypopharyngeal carcinomas tend to spread within the mucosa, beneath intact epithelium, and are prone to skip metastasis and to resurface at various locations remote from the primary site. 1 13 Because of this fact and the abundant lymphatic network of the region, a localized hypopharyngeal tumor is the exception. 1
Almost all hypopharyngeal cancers are mucosal squamous cell carcinomas (SCCs). 1 Multiple primary tumors are not uncommon. Approximately 25% of patients in a retrospective study of 150 cases were found to have second primary tumors. 14 Field cancerization may be responsible, in part, for the multiple, synchronous, primary malignant neoplasms that occur in patients with hypopharyngeal cancer. 1 14 15 16 The concept of field cancerization, originally described in 1953, proposes that tumors develop in a multifocal fashion within a field of tissue that has been chronically exposed to carcinogens. 17
Clinically, cancers of the hypopharynx tend to be aggressive and demonstrate a natural history that is characterized by diffuse local spread, early metastasis, and a relatively high rate of distant spread. More than 50% of patients with hypopharyngeal cancer have clinically positive cervical nodes at the time of presentation. In 50% of these individuals, a neck mass is the presenting symptom. 2 18 19 In a retrospective study of 78 cases of hypopharyngeal cancer, other symptoms in addition to a neck mass (25.6%) included dysphagia (46.1%), odynophagia (44.8%), voice change (16.3%), and otalgia (14.2%). 2 A voice change due to pyriform sinus or postcricoid lesions is a late symptom that usually indicates invasion into the larynx or the recurrent laryngeal nerve. 1
In a large, retrospective study of patients with SCC of the larynx and hypopharynx, 87% of patients with pyriform sinus SCC were found to have stage III or stage IV disease; 82% of patients with SCC of the posterior pharyngeal wall were found to have stage III or stage IV disease. 20 As many as 17% of hypopharyngeal SCCs may be associated with distant metastases when clinically diagnosed. 20 This is quite different from the rate of distant metastasis detected at autopsy, which has been reported to be as much as 60%. 21 A relatively high incidence of delayed regional (i.e., 2 or more years after completion of primary therapy) and distant metastatic disease in hypopharyngeal SCC is related to the advanced stage of the disease at diagnosis. Almost 33% of pyriform sinus tumors may be associated with delayed regional metastases. 20
The treatment of hypopharyngeal cancer is controversial, in part because of its low incidence and the inherent difficulty in conducting adequately powered, prospective, randomized clinical studies. 22 Therefore, it is difficult to define the ideal therapy for a specific site or stage of hypopharyngeal cancer. In general, both surgery and radiation therapy are the mainstays of most curative efforts aimed at this cancer. In recent years, chemotherapy has been added to the treatment strategies for selected advanced presentations of hypopharyngeal cancer. 23 In pyriform sinus cancer, neoadjuvant chemotherapy followed by radiation therapy may afford larynx preservation without jeopardizing survival. 24
Chronic pulmonary and hepatic diseases related to the excessive use of tobacco and alcohol are found in patients with hypopharyngeal cancer. Recognition of these comorbidities is essential in the formulation of an appropriate treatment plan. 1 The primary prognostic factors for hypopharyngeal SCC are the following: 1 25 26
In many patients, a poor prognosis is related to poor overall health. 13 The most common cause of failure of treatment of the primary tumor is local and/or regional recurrence. Most treatment failures occur within the first 2 years following definitive therapy. The burden of lymph node metastases may yield information of prognostic value. In a retrospective study, a total volume of metastatic disease of more than 100 cm3 indicated a particularly poor prognosis. 25
In addition to the risk of delayed regional metastases, the risk of developing a second primary tumor in patients with tumors of the upper aerodigestive tract has been estimated to be 4% to 7% per year. 20 26 27 28 Because of these risks, surveillance of patients with hypopharyngeal cancer should be lifelong.
To date, SCC of the hypopharynx has not been associated with any specific chromosomal or genetic abnormalities; 13 however, loss of chromosome 18 was observed in 57% of hypopharyngeal tumors in one study. 29 Several other studies have emphasized the importance of chromosome 11q13 amplification, which may be related to the presence of nodal metastases, greater local aggressiveness, and a higher incidence of tumor recurrence. 30 31 32 33
Almost all hypopharyngeal cancers are epithelial in origin, predominantly squamous cell (i.e., epidermoid) carcinomas (SCCs), and may be preceded by various precancerous lesions. 1 2 Rare types of hypopharyngeal carcinomas include the following:
The term, leukoplakia, should be used only as a clinically descriptive term meaning that the observer sees a white patch that does not rub off, the significance of which depends on the histologic findings. 10 Based on this description, leukoplakia can range from hyperkeratosis to an actual early invasive carcinoma or may represent only a fungal infection, lichen planus, or other benign oral disease.
The staging systems are all clinical staging and are based on the best possible estimate of the extent of disease before treatment. The assessment of the primary tumor is based on inspection and palpation, when possible, and by both indirect mirror examination and direct endoscopy. The tumor must be confirmed histologically, and any other pathologic data obtained from a biopsy may be included. Additional radiographic studies may be included. As an adjunct to clinical examination, computed tomography and/or magnetic resonance imaging are needed for an accurate staging of laryngeal and hypopharyngeal carcinomas because both cross-sectional imaging modalities are known to reliably evaluate deep tumor infiltration. 1 2 3 The appropriate nodal drainage areas are examined by careful palpation. If a patient relapses, complete restaging must be done to select the appropriate additional therapy.
The American Joint Committee on Cancer has designated staging by TNM classification to define hypopharyngeal cancer. 4
|TX||Primary tumor cannot be assessed.|
|T0||No evidence of primary tumor.|
|Tis||Carcinoma in situ.|
|T1||Tumor limited to 1 subsite of hypopharynx and/or 2 cm in greatest dimension.|
|T2||Tumor invades >1 subsite of hypopharynx or an adjacent site, or measures >2 cm but not >4 cm in greatest dimension without fixation of hemilarynx.|
|T3||Tumor >4 cm in greatest dimension or with fixation of hemilarynx or extension to esophagus.|
|T4a||Moderately advanced local disease.|
|Tumor invades thyroid/cricoid cartilage, hyoid bone, thyroid gland, or central compartment soft tissue.b|
|T4b||Very advanced local disease.|
|Tumor invades prevertebral fascia, encases carotid artery, or involves mediastinal structures.|
|Oropharynx and Hypopharynx|
|NX||Regional lymph nodes cannot be assessed.|
|N0||No regional lymph node metastasis.|
|N1||Metastasis in a single ipsilateral lymph node, 3 cm in greatest dimension.|
|N2||Metastases in a single ipsilateral lymph node, >3 cm but 6 cm in greatest dimension, or in multiple ipsilateral lymph nodes, none >6 cm in greatest dimension, or in bilateral or contralateral lymph nodes, none >6 cm in greatest dimension.|
|N2a||Metastasis in a single ipsilateral lymph node >3 cm but 6 cm in greatest dimension.|
|N2b||Metastases in multiple ipsilateral lymph nodes, none >6 cm in greatest dimension.|
|N2c||Metastases in bilateral or contralateral lymph nodes, none >6 cm in greatest dimension.|
|N3||Metastasis in a lymph node >6 cm in greatest dimension.|
|M0||No distant metastasis.|
|IVC||Any T||Any N||M1|
Hypopharyngeal cancer usually does not give rise to symptoms until late in the course of the disease. Because of this and the high incidence of early metastasis, survival rates for carcinoma of the hypopharynx are perhaps the lowest of all cancer sites in the head and neck.
No single therapeutic regimen offers a clear-cut superior survival advantage over other regimens. Although the literature highlights various therapeutic options, few reports present any valid comparative studies. The ultimate therapeutic choice will depend on a careful review of each individual case, paying attention to the staging of the neoplasm, the general physical condition of the patient, the emotional status of the patient, the experience of the treating team, and the available treatment facilities. 1 2
Except for very early stage (T1) cancers of this region, treatment has primarily been surgery, usually followed with postoperative radiation therapy (PORT). Some early stage (T1 and T2), low-volume, exophytic pyriform sinus carcinomas have been successfully treated with radiation alone. 3 4 5 Single-modality therapy of advanced-stage hypopharyngeal cancer, with either surgery or radiation therapy, has resulted in consistently poor survival. 6 7 8 Combined-modality treatment should be considered for patients who present with stage III or stage IV disease. 4 6 9 10 When used in conjunction with surgery, radiation therapy is typically administered postoperatively. Alternative strategies using neoadjuvant chemotherapy and radiation therapy may increase the chance for local control in selected advanced presentations to a level approaching that of resection and PORT. 4 In addition, combined chemotherapy and radiation therapy may offer better tumor control with organ preservation than does radiation therapy alone. 11 12 13 Patients with stage III and advanced resectable stage IV cancer should be considered for a larynx preservation approach including neoadjuvant chemotherapy and radiation therapy. 14 15 16
A review of published clinical results of radical radiation therapy for head and neck cancer suggests a significant loss of local control when the administration of radiation therapy was prolonged; therefore, lengthening of standard treatment schedules should be avoided whenever possible. 17 18 Chronic pulmonary and hepatic diseases related to excessive tobacco and alcohol use are common in patients with head and neck cancer; recognition of these comorbidities is essential to the formulation of an appropriate treatment plan. 6 Patients who smoke during radiation therapy appear to have lower response rates and shorter survival durations than those who do not; 19 consequently, patients should be counseled to stop smoking before beginning radiation therapy. Accumulating evidence has demonstrated a high incidence (i.e., >30%40%) of hypothyroidism in patients who have received external-beam radiation therapy to the entire thyroid gland or to the pituitary gland. Thyroid function testing of patients should be considered prior to therapy and as part of posttreatment follow-up. 20 21
Except for the very early T1 cancers of this region, treatment has been primarily surgery, usually followed with postoperative radiation therapy. Because these tumors are clinically silent until they reach advanced stages, it is very unusual to diagnose them at the T1 N0 stage. In most available retrospective reviews, T1 N0 cases represent only 1% to 2% of all patients seen. In the case of exophytic T1 N0 lesions, radiation therapy alone may be considered for treatment. 1 2
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage I hypopharyngeal cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
Treatment has been primarily surgery, which is usually followed with postoperative radiation therapy (PORT). Because these tumors are clinically silent until they reach advanced stages, it is very unusual to diagnose these tumors at the T2 N0 stage.
Most neoadjuvant chemotherapy clinical trials have included stage II hypopharyngeal carcinoma patients for the trials because of the low survival rates for this group of patients. 5
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage II hypopharyngeal cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
The management of this group of patients is complex and requires multidisciplinary input to establish the optimal treatment regimen. New surgical techniques and reconstructions using the gastric pull-up operation or free jejunal transfers have greatly reduced the morbidity associated with resection of these tumors and have almost eliminated the need for multistage reconstructions. This has greatly aided the combined treatment regimens because these patients have a high likelihood of beginning postoperative radiation therapy (PORT) within 3 to 4 weeks following resection.
Details of surgical procedures and their modifications of radiation fields or dosage schedules are not specifically designated here because of legitimate variations in techniques that, according to various retrospective data, give similar survival results in different treatment centers. This group of patients should be managed by surgeons and radiation oncologists who are skilled in the multiple procedures and techniques available and who are actively and frequently involved in the care of these patients.
To review treatment options for stage III unresectable hypopharyngeal cancer, see Stage IV Hypopharyngeal Cancer, Unresectable.
Treatment options under clinical evaluation:
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