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 [1-2]. Mortality rates have been steadily declined by approximately 44% since 1975, with a ten-year survival rate of 46% in 1999. Notably, while the prevalence of HPV-positive cancers has been increasing, the proportion of these cancers with habitual tobacco use and excessive alcohol consumption has been decreasing [2]. The broad category of head and neck cancers can be further subdivided based on 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 neck.

Epidemiology and Etiology

• The incidence is approximately 54,000 new cases in the U.S. each year, with the highest overall incidence rate in white males. The annual mortality rate is approximately 11,000 deaths in the U.S.
• Historically, the etiology of head and neck cancers has been strongly associated with tobacco use across all tumor sites, as all forms of tobacco are known to cause dysplastic and carcinogenic injuries. Alcohol is believed to play a synergistic role with tobacco, though its use alone has not been clearly linked to cellular damage or malignancy. However, HPV-positive cases now outnumber those related to tobacco and alcohol exposure.
• Hereditary factors have not been clearly identified.
• Risk factors include heavy smoking and drinking, which both have a linear dose-risk effect where duration is more important than intensity; HPV infection; EBV infection in cancer of the nasopharynx; vitamin deficiencies and malnutrition; poor dental hygiene; chronic inflammation in laryngeal cancer; sun exposure in carcinoma of the lip. 
  • HPV vaccination has been shown to effectively reduce HPV positive head and neck cancers [3,4].

Screening Recommendations

• An annual physical examination and routine dental care are likely the most appropriate screening guidelines for detecting early head and neck malignancies [5].  

Clinical Presentation

• History: Generally present with weight loss and persistent painless 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. HPV-circulating tumor DNA can be useful for disease surveillance [6].
• Radiologic studies: CT and MRI of the head and neck are ideal for demarcating depth of tumor invasion and distinguishing malignant change from inflammation. Additionally, angiography or upper GI series may be performed depending on tumor location.  
• 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 primary tumors of all head and neck regions, except for the nasopharynx and HPV-positive cancers of the oropharynx.
• Prognosis depends on the disease site and patient characteristics. In general, positive surgical margins and lymph nodes with cancer extending outside the capsule (known as extranodal extension, or ENE) are poor prognostic indicators. Patients with oropharyngeal cancer generally have a better prognosis if the tumor is p16+ and there is little to no smoking history [7].
• Histology in the majority of cases is squamous cell carcinoma, which is further categorized as either macroscopic if changes are observable without magnification, or microscopic if magnification is required. Adenocarcinomas of salivary gland origin are also possible and include mucoepidermoid subtypes.

Treatment

Early-stage disease

• Surgery alone with selective or comprehensive neck dissection, is often preferred for early-stage cancers of the oropharynx, oral cavity,  and hypopharynx.
  • Transoral robotic surgery (TORS) has significantly reduced much of the morbidity previously associated with oropharyngeal cancer resection. A phase II trial comparing TORS with radiation therapy found no clinically meaningful difference in swallowing outcomes. Both options are often presented to the patient if TORS is available [8].
  • Radiation therapy, with or without chemotherapy, may be recommended after surgery if high-risk features (such as lymph node involvement, nerve involvement or positive surgical margins) are present on pathology. 
• Radiation therapy alone is also an option for early-stage tumors of the oropharynx. It is the preferred treatment for early-stage tumors of the vocal cords and nasopharynx.  
  • Brachytherapy and interstitial implants are sometimes used for tumors involving tongue, lip, floor of mouth, skin, and buccal mucosa.
  • HPV-positive cancers have been found to be more radiosensitive than HPV-negative tumors [9].

Late-stage disease

• Radiation therapy plays a key role in the treatment of large, unresectable tumors with the goal of preserving speech and swallowing function, or for palliation [10].
• In patients with larger tumors, a combination of chemotherapy and radiation is often recommended, though this increases patient toxicities [8]. Chemotherapy alone is not recommended unless used in the induction setting in specific scenarios, such as reducing tumor burden.
  • In patients with advanced cancer of the nasopharynx, patients may receive induction chemotherapy followed by concurrent chemoradiation.
• Surgery may still be recommended in certain disease sites, such as the oropharynx or oral cavity.