Human Papillomavirus (HPV)

Epidemiology and Etiology:

• Nonenveloped DNA virus (papovavirus family)
• In benign neoplasms:
• HPV genome is maintained in an episomal (non-integrated) form
• E6 viral protein binds to p53 with weak affinity, and does not induce its degradation
• E7 viral protein binds only weakly to RB
• In malignant neoplasms (HPV types 16,18):
• HPV DNA is integrated into the host cell genome
• Site of viral integration is random, but clonal
• Process of integration interrupts the E1/E2 open reading frame of the viral genome
• Loss of E2 expression
• Consequent overexpression of E6 and E7 proteins
• E6 and E7 act to immortalize and transform cells
1. E6 binds to p53, inducing its degradation
2. E7 binds to RB, inducing its degradation
1. E7 also can interfere with p53 transcriptional activity
2. E7 can also inactivate p21
• Additional somatic mutations are likely necessary for malignant transformation
• People with p53 with an arginine at amino acid 72 (polymorphic site) may increase risk of developing cervical cancer (more easily degraded by E6)

Common sites:

Gross features:

Histologic features:

Immunophenotype:

Marker:

Sensitivity:

Specificity:

Molecular features:

Other features:

• Complications:
• Benign neoplasms:
• Squamous papilloma (wart) (HPV types 1,2,4,7)
• Low malignant potential:
• Squamous papilloma (wart) (HPV types 6,11)
• Malignant neoplasms:
• Squamous cell carcinoma (HPV types 16, 18, 31, 33, 35, 51)
• cervix, anogenital, oral, laryngeal

References:

· Kumar V, Fausto N, Abbas A. Robbins & Cotran Pathologic Basis of Disease, Seventh Edition. 7th ed. Saunders; 2004:1552.