Human Papillomavirus

HPV stands for Human Papillomavirus

• It is a DNA virus with multiple subtypes.
• High-risk types, especially HPV-16 and HPV-18, are oncogenic and associated with cancers such as:
  • Oropharyngeal squamous cell carcinoma (tonsil, base of tongue)
  • Cervical cancer
  • Anal, penile, and vulvar cancers
• Low-risk types (e.g., HPV-6, HPV-11) typically cause benign warts.

In head and neck cancer, HPV-16 is the predominant high-risk subtype driving tumor development.

HPV in Head & Neck Cancer

1. Epidemiology

• HPV-positive HNC is increasing, especially in oropharyngeal squamous cell carcinoma (OPSCC) (tonsil, base of tongue).
• Most common type: HPV-16 (~90% of cases).
• Typically affects younger patients with less smoking history.

2. Pathophysiology

• HPV oncoproteins E6 and E7 inactivate p53 and Rb, leading to uncontrolled cell proliferation.
• Results in distinct molecular and clinical profile compared to HPV-negative HNC.

3. Clinical Features

• Tumors often present as tonsillar or base of tongue masses.
• Cervical lymphadenopathy is common at presentation.
• Patients are generally non-smokers or light smokers, younger, and healthier than HPV-negative patients.

4. Prognostic Significance

• HPV-positive OPSCC has significantly better prognosis than HPV-negative disease.
• Better response to chemoradiation, lower recurrence, higher survival.

5. Diagnosis

• p16 immunohistochemistry (IHC) is used as a surrogate marker for HPV positivity.
• HPV DNA or RNA testing can confirm.
• HPV testing is standard for oropharyngeal cancers, not routine for oral cavity, larynx, or hypopharynx.

6. Implications for Therapy

• HPV-positive tumors may allow for treatment de-escalation in clinical trials due to favorable prognosis.
• Standard therapy still includes surgery, radiation, and/or chemoradiation, but trials are ongoing for reduced intensity regimens.

7. Risk Factors

• Sexual behavior: oral sex, multiple partners
• Less associated with tobacco/alcohol than HPV-negative HNC

8. Summary Table