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. 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. In pyriform sinus cancer, neoadjuvant chemotherapy followed by radiation therapy may afford larynx preservation without jeopardizing survival.
Prognosis and Survival
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. The primary prognostic factors for hypopharyngeal SCC are the following:[1,25,26]
- Performance status.
Factors that contribute to an overall poor prognosis with hypopharyngeal SCC include the following:
- Presentation at a late stage.
- Multisite involvement within the hypopharynx.
- Unrestricted soft-tissue tumor growth.
- An extensive regional lymphatic network allowing development of metastases.
- Restricted surgical options for complete resection.
In many patients, a poor prognosis is related to poor overall health. 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.
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; however, loss of chromosome 18 was observed in 57% of hypopharyngeal tumors in one study. 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]
- Mendenhall WM, Werning JW, Pfister DG: Treatment of head and neck cancer. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 729-80.
- Uzcudun AE, Bravo Fernández P, Sánchez JJ, et al.: Clinical features of pharyngeal cancer: a retrospective study of 258 consecutive patients. J Laryngol Otol 115 (2): 112-8, 2001.
- 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.
- Day GL, Blot WJ, Shore RE, et al.: Second cancers following oral and pharyngeal cancers: role of tobacco and alcohol. J Natl Cancer Inst 86 (2): 131-7, 1994.
- Canto MT, Devesa SS: Oral cavity and pharynx cancer incidence rates in the United States, 1975-1998. Oral Oncol 38 (6): 610-7, 2002.
- Franceschi S, Bidoli E, Herrero R, et al.: Comparison of cancers of the oral cavity and pharynx worldwide: etiological clues. Oral Oncol 36 (1): 106-15, 2000.
- Siddiqui F, Sarin R, Agarwal JP, et al.: Squamous carcinoma of the larynx and hypopharynx in children: a distinct clinical entity? Med Pediatr Oncol 40 (5): 322-4, 2003.
- WYNDER EL, HULTBERG S, JACOBSSON F, et al.: Environmental factors in cancer of the upper alimentary tract; a Swedish study with special reference to Plummer-Vinson (Paterson-Kelly) syndrome. Cancer 10 (3): 470-87, 1957 May-Jun.
- Ahlbom HE: Simple achlorhydric anaemia, Plummer-Vinson syndrome, and carcinoma of the mouth, pharynx, and oesophagus in women: observations at Radiumhemmet, Stockholm. Br Med J 2 (3945): 331-3, 1936.
- Larsson LG, Sandström A, Westling P: Relationship of Plummer-Vinson disease to cancer of the upper alimentary tract in Sweden. Cancer Res 35 (11 Pt. 2): 3308-16, 1975.
- Amos A: Women and smoking. Br Med Bull 52 (1): 74-89, 1996.
- Barnes L, Johnson JT: Pathologic and clinical considerations in the evaluation of major head and neck specimens resected for cancer. Part I. Pathol Annu 21 Pt 1: 173-250, 1986.
- Helliwell TR: acp Best Practice No 169. Evidence based pathology: squamous carcinoma of the hypopharynx. J Clin Pathol 56 (2): 81-5, 2003.
- Raghavan U, Quraishi S, Bradley PJ: Multiple primary tumors in patients diagnosed with hypopharyngeal cancer. Otolaryngol Head Neck Surg 128 (3): 419-25, 2003.
- Tabor MP, Brakenhoff RH, van Houten VM, et al.: Persistence of genetically altered fields in head and neck cancer patients: biological and clinical implications. Clin Cancer Res 7 (6): 1523-32, 2001.
- Braakhuis BJ, Tabor MP, Kummer JA, et al.: A genetic explanation of Slaughter's concept of field cancerization: evidence and clinical implications. Cancer Res 63 (8): 1727-30, 2003.
- Slaughter DP, Southwick HW, Smejkal W: Field cancerization in oral stratified squamous epithelium: clinical implications of multicentric origin. Cancer 6 (5): 963-8, 1953.
- Horwitz SD, Caldarelli DD, Hendrickson FR: Treatment of carcinoma of the hypopharynx. Head Neck Surg 2 (2): 107-11, 1979 Nov-Dec.
- Keane TJ: Carcinoma of the hypopharynx. J Otolaryngol 11 (4): 227-31, 1982.
- Spector JG, Sessions DG, Haughey BH, et al.: Delayed regional metastases, distant metastases, and second primary malignancies in squamous cell carcinomas of the larynx and hypopharynx. Laryngoscope 111 (6): 1079-87, 2001.
- Kotwall C, Sako K, Razack MS, et al.: Metastatic patterns in squamous cell cancer of the head and neck. Am J Surg 154 (4): 439-42, 1987.
- Godballe C, Jørgensen K, Hansen O, et al.: Hypopharyngeal cancer: results of treatment based on radiation therapy and salvage surgery. Laryngoscope 112 (5): 834-8, 2002.
- Hinerman RW, Amdur RJ, Mendenhall WM, et al.: Hypopharyngeal carcinoma. Curr Treat Options Oncol 3 (1): 41-9, 2002.
- Lefebvre JL, Chevalier D, Luboinski B, et al.: Larynx preservation in pyriform sinus cancer: preliminary results of a European Organization for Research and Treatment of Cancer phase III trial. EORTC Head and Neck Cancer Cooperative Group. J Natl Cancer Inst 88 (13): 890-9, 1996.
- Jakobsen J, Hansen O, Jørgensen KE, et al.: Lymph node metastases from laryngeal and pharyngeal carcinomas--calculation of burden of metastasis and its impact on prognosis. Acta Oncol 37 (5): 489-93, 1998.
- Khuri FR, Lippman SM, Spitz MR, et al.: Molecular epidemiology and retinoid chemoprevention of head and neck cancer. J Natl Cancer Inst 89 (3): 199-211, 1997.
- Pfister DG, Shaha AR, Harrison LB: The role of chemotherapy in the curative treatment of head and neck cancer. Surg Oncol Clin N Am 6 (4): 749-68, 1997.
- León X, Quer M, Diez S, et al.: Second neoplasm in patients with head and neck cancer. Head Neck 21 (3): 204-10, 1999.
- Poetsch M, Kleist B, Lorenz G, et al.: Different numerical chromosomal aberrations detected by FISH in oropharyngeal, hypopharyngeal and laryngeal squamous cell carcinoma. Histopathology 34 (3): 234-40, 1999.
- Meredith SD, Levine PA, Burns JA, et al.: Chromosome 11q13 amplification in head and neck squamous cell carcinoma. Association with poor prognosis. Arch Otolaryngol Head Neck Surg 121 (7): 790-4, 1995.
- Muller D, Millon R, Velten M, et al.: Amplification of 11q13 DNA markers in head and neck squamous cell carcinomas: correlation with clinical outcome. Eur J Cancer 33 (13): 2203-10, 1997.
- Rodrigo JP, García LA, Ramos S, et al.: EMS1 gene amplification correlates with poor prognosis in squamous cell carcinomas of the head and neck. Clin Cancer Res 6 (8): 3177-82, 2000.
- Rodrigo JP, González MV, Lazo PS, et al.: Genetic alterations in squamous cell carcinomas of the hypopharynx with correlations to clinicopathological features. Oral Oncol 38 (4): 357-63, 2002.