Human papilloma virus

• Human papillomavirus


  A DNA virus from the Papillomaviridae family that causes infections

  
• Many HPV infections cause no symptoms and 90% resolve spontaneously within two years
• In some cases, HPV infection persists and results in either warts or precancerous lesions
• Nearly all cervical cancer is due to HPV, and two strains HPV16 and HPV18 account for 70% of all cases
• An individual can become infected with more than one type of HPV, and the disease is only known to affect humans
• Risk factors for persistent HPV infection


  • Early age of first sexual intercourse
  • Multiple sexual partners
  • Smoking
  • Poor immune function
• Transmission of HPV


  • Typically spread by direct skin to skin contact
  • Can spread from mother to baby during pregnancy
  • Types that cause warts may spread via surfaces
  • Not killed by common hand sanitizers and disinfectants, increasing possibility of transfer via fomites
• HPV types


  • HPV 5 can establish persistent infections without symptoms
  • HPV 1 and 2 can cause common warts
  • HPV 6 and 11 can cause genital warts and laryngeal papillomatosis
  • About 12 "high-risk" types including 16, 18, 31, 45 linked to cancer

  
• Skin infection with HPV is very widespread and can cause noncancerous skin growths called warts
• Skin warts are most common in childhood and typically appear and regress spontaneously over the course of weeks to months. Recurring skin warts are common

  
• All HPVs are believed to be capable of establishing long-term "latent" infections in small numbers of stem cells present in the skin

  
• Papillomaviruses


  • Non-enveloped virus with double stranded circular DNA and icosahedral nucleocapsid
  • Small, 52-55 nm in diameter
  • 72 pentamers of L1 gene
  • Genome composed of six early genes (E1, E2, E4, E5, E6, E7) and two late genes (L1 major and L2 minor)

  
• HPV pathogenesis


  1. Infection limited to basal cells of stratified epithelium

  2. Virus infects through microabrasions or epithelial trauma exposing basement membrane

  3. Infectious process is slow, taking 12-24 hours for transcription initiation

  4. Viral particles released as result of degeneration of desquamating cells

  5. Viral genome transported to nucleus and establishes at 10-200 copies per cell

  6. Transcriptional cascade as host keratinocyte divides and differentiates

  
• Immune system fails to control HPV

  Infection with high-risk HPV types can favor cancer development
• HPV is believed to cause cancer by integrating its genome into nuclear DNA, and some early genes like E6 and E7 act as oncogenes promoting tumor growth and malignant transformation
• Nearly all cases of cervical cancer are associated with HPV infection, with HPV16 and HPV18 present in 70% of cases

  
• Natural history of HPV and disease progress

  1. Initial HPV infection

  2. Cleared HPV infection

  3. CIN I

  4. Persistent infection CIN II/III

  5. Cancer (up to 20 years)

  
• HPV genome integration can promote carcinogenesis by causing genomic instability and alterations in DNA copy number

  
• Diagnosis methods


  • Clinical diagnosis
  • Biopsy showing koilocytes
  • DNA hybridization tests
  • Polymerase chain reaction
• Treatments


  • For genital warts: alpha interferon
  • For skin warts: liquid nitrogen, for plantar warts: surgical removal
  • For severe HPV infection: Cidofovir
• HPV vaccine


  • Made from proteins of virus outer coat, inactivated vaccine, highly immunogenic
  • Over 99% effective at preventing pre-cancerous lesions associated with HPV 16 and 18
  • May boost immunity and prevent re-infection or reduce recurrences
  • Requires a course of 3 injections