Head and Neck Malignancies

Introduction

Head and neck malignancies account for only about 5-7% of all new cancer cases in the US, occurring more than twice as often in men as in women. Mortality rates have been declining steadily since the 1980's, with a ten-year survival rate in 1999 of 46%. Notably, the prevalence of these cancers is highest amongst populations with habitual tobacco and excessive alcohol use. The broad category of head and neck cancers can be further subdivided according to the primary tumor site, reflecting the complex anatomy of the head and neck region. These sites include the nasal fossa and paranasal sinuses, skull base, nasopharynx, oral cavity, oropharynx, salivary gland, larynx and the neck.

Epidemiology and Etiology

• Incidence of 40,000 new cases in the US each year, with the highest overall incidence rate in black males. Mortality rate of 12,000 US deaths annually.
• Etiology is linked to tobacco use for all tumor sites, as every form of tobacco is known to result in dysplastic and carcinogenic injuries. Alcohol is thought to play a synergistic role with tobacco, though its use alone is not clearly linked to cellular damage and malignancy.
• Hereditary factors are not clearly identified.
• Risk factors include heavy smoking and drinking, which both have a linear dose-risk effect where duration is more important than intensity; EBV infection in cancer of the nasopharynx; vitamin deficiencies and malnutrition; poor orodental hygiene; chronic inflammation in laryngeal cancer; sun exposure in carcinoma of the lip [1].

Screening Recommendations

• Annual physical exam and routine dental care may be most appropriate screening guidelines available for detecting early head and neck malignancies [2].

Clinical Presentation

• History: Generally present with weight loss and persistent lump or mass from advanced disease, but symptoms also vary based on anatomic site involved
  • Oral cavity= gingival swelling, pain, bleeding, loosening teeth
  • Nose and paranasal sinuses = unilateral obstruction, epistaxis
  • Nasopharynx = pain, otologic changes, nasal obstruction
  • Oropharynx = dull ache, dysphagia, referred otalgia, trismus
  • Laryngeal area = voice changes, dysphagia, odynophagia, dyspnea
  • Salivary gland = unilateral symptoms, impaired jaw mobility
• Physical exam: Usually palpable or visible lump/mass; can also include associated cranial nerve defects, gingival hyperplasia, nonhealing ulcerative or exophytic oral lesions, erythroplakia, stridor from large glottic tumors
• Lab studies: Not very valuable in diagnosis
• Radiologic studies: Plain x-ray films, CT, MRI best for demarcating depth of tumor invasion and distinguishing malignant change from inflammation, angiography depending on tumor location, upper GI series
• Diagnostic studies: Flexible fiberoptic nasopharyngoscopy with biopsies, direct laryngoscopy with esophagoscopy, videostroboscopy for laryngeal tumors

Natural Course and Pathology

• Staging follows the American Joint Committee on Cancer criteria and is uniform for tumors of all head and neck primary sites, except for the nasopharynx.
• Prognosis for cure worsens as depth of tumor invasion increases and degree of cellular differentiation decreases [3]. Nutritional status and over-expression or mutation of the p53 gene may also play a role.
• Histologic grade is extremely important predictor of long-term outcome. Cell type in majority of cases is squamous cell carcinoma, which is further categorized as either macroscopic if changes are observed pathologically, or microscopic if magnification is required. Adenocarcinomas of salivary gland origin also possible and include mucoepidermoid and adenoid cystic subtypes.

Treatment

Early stage disease

• Surgery alone is often the standard of care for early stage disease.
• Radiation therapy alone is also acceptable for stage I and II malignancies, although squamous cells are only moderately radiosensitive.
  • In patients with N0 or N1 supraglottic carcinoma, local control was achieved in up to 86% of cases, but with relapse rates as high as 79% [4].
  • Advantages over surgery usually include improved function and cosmesis.
  • Brachytherapy and interstitial implants are sometimes used for tumors involving tongue, lip, floor of mouth, skin and buccal mucosa.

Late stage disease

• Surgery is part of a combination approach, either before or after other modalities.
  • Radical or modified neck dissection if there is cervical lymph node spread.
  • Reconstructive procedures are very important adjunct to tumor resection.
• Radiation therapy plays role in large, unresectable tumors for palliation and preservation of speech and swallowing functions [5].
• Chemotherapy combination regimens have not yet demonstrated better tumor control or survival when used alone. However, many late stage disease patients are at risk of occult metastases and/or recurrence, thus chemotherapy plays a role.
  • Induction chemotherapy for recurrent or metastatic disease found to decrease rate of distant metastases, as compared to patients who did not receive chemotherapy [6].
  • Neoadjuvant regimens including cisplatin and 5-FU found to have excellent tumor response, with lower rate of distant metastases compared to untreated. Survival, however, is unchanged compared to those treated with conventional surgery and radiation [7].
  • Chemoradiation for stage II or III to synergistically improve tumor response, but at cost of significant toxicities [8].

References

1. Decker JL, Goldstein JC: Risk factors in head and neck cancer. New England Journal of Medicine 306(19): 1151-1155, 1982.

2. Mashberg A, Barsa P: Screening for oral and oropharyngeal squamous carcinomas. Ca-A Cancer Journal for Clinicians 34(5):262-268, 1984.

3. Yilmaz T, Hosal AS, Gedikoglu G, et al.: Prognostic significance of depth of invasion in cancer of the larynx. Laryngoscope 108(5):764-768, 1998.

4. Nafoor BM, Spiro IJ, Wang CC, et al: Results of accelerated radiotherapy for supraglottic carcinoma. Head Neck 20:379-384, 1998.

5. Strohl RA: The etiology and management of acute and late sequelae of radiation therapy in persons with head and neck cancers. Otolaryngol Head Neck Nurs 13(4):23-27, 1995.

6. The Department of Veterans Affairs Laryngeal Cancer Study Group: Induction chemotherapy plus radiation compared with surgery and radiation in patients with advanced laryngeal cancer. N Engl J Med 324:1685-1690, 1991.

7. Jacobs C, Makuch R: Efficacy of adjuvant chemotherapy for patients with respectable head and neck cancer. J Clin Oncol 8:838-847, 1990.

8. Brizel DM, Albers ME, Fisher SR, et al: Hyperfractionated irradiation with or without concurrent chemotherapy for locally advanced head and neck cancer. N Engl J Med 338:1798-1803, 1998.