Human papillomavirus

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HPV Virology - The Naked Truth

  • Family: Papillomaviridae
  • Structure: Non-enveloped ("naked") icosahedral capsid, making it environmentally stable.
  • Genome: Circular, double-stranded DNA.
  • Subtypes & Risk:
    • High-Risk (Oncogenic): 16, 18, 31, 33. Associated with cervical, penile, and oropharyngeal cancers.
    • Low-Risk (Non-oncogenic): 6, 11. Associated with condylomata acuminata (genital warts).

HPV virion structure with DNA, histone, and capsid protein

⭐ The viral genome is episomal (circular DNA) in benign lesions but often integrates into the host genome in malignant cancers.

Pathogenesis - Hijacking the Cell

  • Infects basal keratinocytes of squamous epithelium, requiring a break in the skin or mucosa.
  • Viral oncoproteins E6 & E7 are the primary drivers of oncogenesis.
    • E6 → promotes degradation of the p53 tumor suppressor.
    • E7 → promotes degradation of the Rb (Retinoblastoma) tumor suppressor.
  • Histological hallmark: Koilocytes (enlarged keratinocytes with a clear perinuclear halo and a wrinkled, hyperchromatic nucleus).

Koilocytes in cervical smear (HPV infection)

⭐ In high-risk HPV types (e.g., 16, 18), the viral DNA integrates into the host genome, leading to constitutive expression of E6 and E7. In low-risk types, it typically remains episomal.

Clinical Syndromes - Warts and Worse

  • Low-risk HPV (Types 6, 11): Primarily associated with benign lesions.

    • Condylomata acuminata: Anogenital warts, often appearing as soft, cauliflower-like growths.
    • Recurrent Respiratory Papillomatosis: Benign tumors in the respiratory tract, most commonly the larynx.
  • High-risk HPV (Types 16, 18): Strong association with malignancy.

    • Causes squamous cell carcinoma of the cervix, anus, penis, vulva, vagina, and oropharynx.
    • Integration into the host genome and expression of oncoproteins E6 (inhibits p53) and E7 (inhibits pRb) drive carcinogenesis.

⭐ While HPV 16 is the most oncogenic type, coinfection with HPV 18 significantly increases the risk for rapid progression to cervical cancer.

Koilocytes in Pap smear, indicative of HPV infection

Screening & Prevention - Guarding the Gates

  • Screening Workflow:
  • Diagnostic Tests:
    • Pap Smear: Detects koilocytes (perinuclear halos), a sign of HPV infection and dysplasia.
    • HPV DNA/RNA Testing: Identifies high-risk viral types (e.g., 16, 18).
    • Biopsy: Definitive diagnosis of Cervical Intraepithelial Neoplasia (CIN).

Koilocytes on Pap smear, indicative of HPV infection

  • Prevention:
    • Gardasil 9 Vaccine: Protects against HPV types 6, 11 (genital warts) and 16, 18, 31, 33, 45, 52, 58 (oncogenic).
    • Recommended for ages 9-26; catch-up vaccination possible up to age 45.

Exam Favorite: Most HPV infections (>90%) are transient and resolve spontaneously within 2 years without causing disease.

High‑Yield Points - ⚡ Biggest Takeaways

  • Human Papillomavirus (HPV) is a non-enveloped, dsDNA virus transmitted via direct contact.
  • High-risk types (16, 18) are the primary cause of cervical, anal, and oropharyngeal cancers.
  • Low-risk types (6, 11) cause condylomata acuminata (anogenital warts).
  • Oncogenesis is driven by viral oncoproteins E6 (inhibits p53) and E7 (inhibits Rb).
  • Koilocytes on a Pap smear are the classic cytopathic finding.
  • Prevention is highly effective with the HPV vaccine (Gardasil 9).

Practice Questions: Human papillomavirus

Test your understanding with these related questions

A 56-year-old woman makes an appointment with her physician to discuss the results of her cervical cancer screening. She has been menopausal for 2 years and does not take hormone replacement therapy. Her previous Pap smear showed low-grade squamous intraepithelial lesion (LSIL); no HPV testing was performed. Her gynecologic examination is unremarkable. The results of her current Pap smear is as follows: Specimen adequacy satisfactory for evaluation Interpretation low-grade squamous intraepithelial lesion Notes atrophic pattern Which option is the next best step in the management of this patient?

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Flashcards: Human papillomavirus

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What is the cancer risk associated with HPV31?_____

TAP TO REVEAL ANSWER

What is the cancer risk associated with HPV31?_____

High

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