Human Papillomavirus

Aka: Human Papillomavirus, HPV, Papillomavirus Infection

1. See Also
   1. Common Wart
   2. Genital Wart
2. Epidemiology
   1. Women have been primary initial target for cervical Cancer Prevention
      1. High risk HPV Prevalence in U.S. females ages 15 to 19 years old: 20-25%
   2. Men have been added in U.S. as of 2012 for HPV-related Cancer Prevention
      1. Annual number of new cases of HPV-related cancers in american men: 9810
      2. HPV-related cancers in males include oral cavity, oropharynx, Larynx, anal cancer, penis
3. Types: High Risk
   1. HPV 16 (causes 50% of all Cervical Cancers, usually squamous cell cancers)
   2. HPV 18 (causes 20% of all Cervical Cancers, usually adenocarcinoma)
4. Types: Low Risk (responsible for 95% of Genital Warts)
   1. HPV 6
   2. HPV 11
5. Pathophysiology
   1. Group of over 100 DNA viruses that infect epithelial cells
   2. Transmission of HPV from Genital Warts
      1. HPV is very contagious due to high viral loads
      2. Transmission rate: 65%
      3. Incubation period duration following exposure: 3 weeks to 8 months
      4. Oral transmission occurs at a lower rate
      5. Perinatal transmission is rare
   3. Course
      1. Spontaneous clearance of high risk or low risk HPV within 2 years for 90% of patients
      2. Genital Warts clear on average within 6 months with treatment
      3. Progression to cancer is a small percentage of overall HPV cases and typically develops over years to decades
   4. Cancer development
      1. HPV invades human cells
      2. HPV DNA integrates into host cell
      3. Viral oncoproteins (E6 and E7) are expressed
      4. Oncoproteins bind and block tumor suppression genes (TP53, RB1)
6. Associated Conditions: Genital infections
   1. Caused by ~40 HPV types
   2. Transient HPV infection without lesions
      1. HPV is the most common STD in women
      2. Lifetime Prevalence in sexually active women: 80%
      3. HPV infection peaks at age 20 (and again post-Menopause in some patients)
   3. Genital Warts (Condyloma acuminata)
      1. Lifetime Prevalence (U.S.): 1%
   4. Cervical Cancer (caused by ~15 High Risk HPV types)
      1. HPV infection precedes Cervical Cancer diagnosis by 10-20 years
      2. Typically diagnosed after age 40
         1. HPV screening for ages 30-40 has highest yield
   5. Perianal warts
      1. Local spread from genitalia or
      2. Receptive anal intercourse
   6. Genital cancers that occur less commonly
      1. Vaginal cancer
      2. Vulvar Cancer
      3. Anal cancer
      4. Penile Cancer (uncircumsized men)
   7. Other lesions associated with HPV infection
      1. Oral squamous cell cancer
      2. Respiratory papillomatosis
7. Associated Conditions: Non-genital
   1. Common Wart
   2. Plantar Wart
   3. Respiratory papillomatosis
8. Labs: HPV DNA testing by PCR
   1. Hybrid Capture II (Thirteen high risk HPV types)
   2. Cervista (HPV 16, 18)
   3. Cervista (HPV 14)
9. Protocol: Cervical HPV testing
   1. HPV testing above has 90% sensitivity at Cervix
   2. Perform HPV DNA testing with Pap Smear at age 30 and if negative repeat in 3 years
10. Prevention
    1. HPV Vaccines
       1. Quadrivalent Vaccine
          1. Gardasil (HPV types 6, 11, 16, 18)
       2. Bivalent Vaccine
          1. Cervarix (HPV types 16, 18)
    2. Condoms
       1. Efficacy is 70% in HPV transmission prevention
    3. Tobacco Cessation
       1. Tobacco use is associated with Genital Wart development and persistent HPV infection
    4. Circumcision (routine at birth)
       1. Lower risk of HPV infection
11. References
    1. Juckett (2010) Am Fam Physician 82(10): 1209-14
    2. Koshiol (2008) Am J Epidemiol 168(2): 123-37
    3. Schiffman (2007) Lancet 370(9590): 890-907