Cancer of the hypopharynx is uncommon; approximately 2500 new cases are diagnosed in the United States each year.[1] The peak incidence of this cancer occurs at 59 to 60 years of age.[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 (both oropharyngeal and hypopharyngeal) have been found among men in France (Bas-Rhin and Herault), Switzerland (Vaud), Spain (Basque Country), Slovakia, Slovenia, and India (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 (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.[2,9-11]

Anatomically, the hypopharynx extends from the plane of the hyoid bone above to the plane of the inferior border of the cricoid cartilage below. It is composed of 3 parts, the pyriform sinus, the postcricoid area, and the posterior pharyngeal wall, 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 (80% >5 cm) at presentation.[13] Hypopharyngeal carcinomas tend to spread within the mucosa, beneath intact epithelium, and are prone to “skip” metastasis, resurfacing 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.[1,14-16] 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. Over 50% of patients with hypopharyngeal cancer have clinically positive cervical nodes at the time of presentation. In one half 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 IV disease; 82% of patients with SCC of the posterior pharyngeal wall were found to have stage III or IV disease.[20] Up to 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, reported to be as high as 60%.[21] A relatively high incidence of delayed regional (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 one third 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 radiotherapy 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 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 stage, age, and performance status.[1,25,26] Presentation at a late stage, multisite involvement within the hypopharynx, unrestricted soft tissue tumor growth, an extensive regional lymphatic network allowing development of metastases, and restricted surgical options for complete resection, contribute to an overall poor prognosis. In many patients, the 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 greater 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.[20,26-28] 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 1 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.[30-33]

References

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3. Blot WJ, McLaughlin JK, Winn DM, et al.: Smoking and drinking in relation to oral and pharyngeal cancer. Cancer Res 48 (11): 3282-7, 1988.  [PUBMED Abstract]
   
   
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