Types

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• Low-risk HPV types 6 and 11
  • Anogenital warts (condylomata acuminata)
• High-risk HPV types 16, 18, 31, and 33
  • Cervical cancer (responsible for 70% of cases)
  • High risk of anogenital, oral, and oropharyngeal squamous cell carcinoma
• HPV types 1, 2, and 4: cause skin warts, such as common warts (verruca vulgaris) and plantar warts (myrmecias)

Pathophysiology

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• HPV expresses the following oncoproteins
  • E6 → inhibition of p53 protein → inhibition of the intrinsic apoptotic pathway and inhibition of p21 protein
  • E7
    • Inhibition of retinoblastoma protein (pRb) → increased activity of E2F-family of transcription factors
    • Inhibits p21 and p27 (CDK inhibitors) → increased activity of cyclin-dependent kinase

Mnemonic

6 comes before 7 and P comes before R: E6 inhibits P53 and E7 inhibits pRb

Pathology

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• HPV infect stratum basale, where epithelial cells are replicating
• Epidermal hyperplasia and hyperkeratosis
• Koilocytes
  • Pathognomonic of an infection with HPV
  • Dysplastic squamous cells characterized by well-defined, clear, balloon-like, perinuclear halo and hyperchromasia

Nonanogenital manifestations

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Common warts (verruca vulgaris)

• Pathogen: particularly low-risk HPV types 2 and 4
• Clinical features
  • Lesions are plaques or papules
    • Skin-colored or whitish
    • Usually firm, often with a rough and scaly surface
    • Sometimes have a cauliflower-like appearance

Anogenital warts (Condylomata acuminata)

• Pathogen: HPV types that infect the mucosal epithelium (e.g., HPV types 6 and 11)
• Clinical features
  • Flat, papular, or pedunculated exophytic, cauliflower-like lesions
  • Located on any part of the anogenital mucosa (e.g., glans penis, vagina, cervix, anal canal) and/or perineal skin
  • Typically asymptomatic; occasionally cause pruritus or pain

Treatment

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• Imiquimod
  • Local treatment
  • Mechanism of action: toll-like receptor 7 agonist → activates immune cells (i.e., macrophages, monocytes, dendritic cells)
  • Indication: actinic keratoses, superficial basal cell carcinomas, herpes simplex infections, and anogenital warts
  • Adverse effects: burning pain at application site, dermal rash, pruritus