Human papillomavirus infection

Types

Low-risk HPV types 6 and 11
- Anogenital warts (condylomata acuminata)
- Primarily transmitted through sexual contact
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
- Primarily transmitted through sexual contact
HPV types 1, 2, and 4: cause skin warts, such as common warts (verruca vulgaris) and plantar warts (myrmecias)
- Primarily transmitted through non-sexual skin-to-skin contact or contact with contaminated surfaces

Immunodeficiency (e.g., due to HIV infection, chemotherapy)
Additional risk factors for genital/mucosal HPV infections include:
- Unprotected sex
- Higher number of lifetime sexual partners
- Early age at first sexual activity
- Lack of circumcision in male individuals

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

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

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

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
If transmit to children during birth: Laryngeal papillomatosis

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