Description

Diverse group of malignancies; many histologic types. The vast majority (~90%) of head and neck cancers are squamous cell carcinomas (HNSCC—the focus of this review).

• Characterized by region: pharynx, larynx, oral cavity, salivary glands, nasal cavity, and sinuses

Epidemiology

• More common in males than females. Incidence increases with age, median age = 60s.
• Strongly associated with tobacco, alcohol, and viral infections (human papillomavirus [HPV] 16 and Epstein-Barr virus [EBV])
  • HPV-positive cancers occur in younger patients, ages 40 to 50 years, with male predominance.

Incidence
600,000 new cases and 300,000 deaths yearly worldwide; estimated 60,000 new cases in the United States; sixth most common cancer

• Incidence of HPV-positive tumors is increasing, and HPV-negative tumor incidence is decreasing.

Prevalence
~275,000 people in the United States with oropharyngeal cancer

• Prevalence of HPV in HNSCC is ~20%. Roughly 40% oropharyngeal sites are HPV positive.

Etiology and Pathophysiology

• Tobacco, alcohol, and HPV and EBV are known causative agents. EBV is associated with nasopharyngeal cancer; HPV is associated with oropharyngeal cancer.
• HPV-positive and HPV-negative tumors are distinct entities.
  • HPV-positive tumors have fewer mutations than HPV-negative tumors.
  • HPV-positive tumors may exhibit inactivation of p53 and Rb tumor suppressor proteins by viral oncoproteins E6 and E7, respectively.
  • HPV-positive tumors have a higher incidence in activating mutations in PIK3CA than do HPV-negative tumors.
  • TP53 mutation is common in HPV-negative tumors and is an early event in disease progression.

Genetics
Positive family history confers twice the risk of HNSCC. This may be due to polymorphisms in genes encoding for enzymes metabolizing tobacco and alcohol.

Risk Factors

Distinct risk factors exist for HPV-positive and HPV-negative HNSCC.

• Dose-dependent relationship between smoking and HNSCC. Alcohol is an additional risk factor.
• HPV-positive HNSCC is linked to oral sex, high number of lifetime sexual partners (oral and genital), and other sexual risk factors.
• Other risk factors include occupational exposures (nickel, woodworking, textiles), poor dental hygiene, use of mouthwash, betel quid, preserved/salted foods in childhood, and low-fiber diet.

General Prevention

• Avoid tobacco and alcohol.
• Safe sexual behaviors
• HPV vaccination may prevent some HPV HNSCC.
• No effective screening available

Commonly Associated Conditions

• Other primary malignancies are common, especially among smokers.
• Medical comorbidities that occur with chronic alcohol and tobacco abuse may be present.
• Malnutrition