Human Papillomavirus

Aka: Human Papillomavirus, HPV, Papillomavirus Infection, HPV Genotype, HPV Test

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II. Epidemiology

  1. Prevalence: Estimated 79 million in U.S. are HPV infected (2013)
    1. HPV Lifetime Prevalence in those with at least one sexual partner: 85% in women, 91% in men
    2. Peak HPV Prevalence: 20-25 years in women, 25 to 35 years in men
  2. Incidence: 14 million new infections U.S. per year (2013)
  3. 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%
  4. 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

III. Risk Factors

  1. Anogenital HPV Infection
    1. Early sexual contact (younger age of onset)
    2. Multiple sexual partners
    3. Other Sexually Transmitted Infections
    4. HIV Infection
    5. Immunocompromised State
    6. No barrier protection during sex
  2. Persistent HPV infection (risk for progression)
    1. Alcohol use (oral and Genital HPV)
    2. Tobacco Abuse (oral and Genital HPV)

IV. Types: High Risk for Anogenital Neoplasia and Cancer

  1. HPV 16 (causes 50% of all Cervical Cancers, usually squamous cell cancers)
  2. HPV 18 (causes 20% of all Cervical Cancers, usually adenocarcinoma)
  3. HPV 31 (causes 4% of all Cervical Cancers)
  4. Other higher risk HPV types
    1. HPV 33, 35, 39, 45
    2. HPV 51, 52, 56, 58, 59, 66, 68

V. Types: Low Risk HPV

  1. Cutaneous Warts (Common Warts)
    1. HPV 1
    2. HPV 2
    3. HPV 4
  2. Palmoplantar Warts
    1. HPV 1
    2. HPV 2
    3. HPV 27
    4. HPV 57
  3. Mucosal Warts (responsible for 95% of Genital Warts)
    1. HPV 6
    2. HPV 11

VI. Pathophysiology

  1. Group of over 200 DNA viruses that infect epithelial cells (skin and mucosa)
  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
    6. Nearly one third of Genital Warts contain both High risk and low risk HPV types
  3. Course
    1. Spontaneous clearance of high risk or low risk HPV within 2 years for 90% of patients
    2. Genital Warts clear spontaneously in up to 30% of cases within 4 months
    3. Genital Warts clear on average within 6 months with treatment (80% effective)
    4. 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)

VII. 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. Perianal warts
    1. Local spread from genitalia or
    2. Receptive anal intercourse
  5. Cervical Cancer
    1. Caused by ~15 High Risk HPV types (see above)
    2. HPV positive in 90% (HPV 16 or 18 in 90%)
    3. CIN 1-2 typically regress spontaneously, but persistence >1-2 years are more likely to progress to CIN3
    4. CIN3 progresses to invasive Cervical Cancer in 12 to 30% of cases
    5. HPV infection precedes Cervical Cancer diagnosis by 10-20 years
    6. Typically diagnosed after age 40
      1. HPV screening for ages 30-40 has highest yield
  6. Genital cancers that occur less commonly
    1. Vaginal cancer
    2. Vulvar Cancer
    3. Anal cancer
      1. HPV positive in 90% (HPV 16 or 18 in 86%)
    4. Penile Cancer (uncircumsized men)
      1. HPV positive in 60% (HPV 16 or 18 in 75%)
  7. Other lesions associated with HPV infection
    1. Oral squamous cell cancer
      1. HPV positive in 70% (HPV 16 or 18 in >80%)
      2. HPV positive lesions present at younger age than HPV negative lesions
      3. With treatment, HPV positive lesions have higher survival rates than HPV negative lesions
    2. Respiratory papillomatosis (perinatal transmission)

VIII. Associated Conditions: Non-genital

  1. Common Wart
  2. Plantar Wart
  3. Respiratory papillomatosis (perinatal transmission)

IX. Labs: HPV DNA testing by PCR

  1. Aptiva HPV - RNA (14 high risk HPV types)
    1. Test Sensitivity: 97.6%
    2. Test Specificity: 90.2%
  2. Cervista HPV HR - DNA (14 high risk HPV types)
    1. Lower Test Sensitivity (89%) than other tests
    2. Test Specificity: 91%
    3. Gives only positive or negative result (without type specific info)
  3. Cobas HPV - DNA (HPV 14 high risk HPV types)
    1. Test Sensitivity: 97.3%
    2. Test Specificity: 84.5%
  4. Hybrid Capture II (13 high risk HPV types)
    1. Test Sensitivity: 97.5%
    2. Test Specificity: 84.3%

X. 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 5 years

XI. Prevention

  1. HPV Vaccines
    1. See Human Papilloma Virus Vaccine (Gardasil-9)
    2. Most effective when administered before the onset of sexual activity
    3. FDA approved for ages 9 to 45 years old
    4. Part of Primary Series in U.S. for both genders at age 11-12 years old
  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 in the U.S.)
    1. Lower risk of HPV infection

XII. References

  1. Juckett (2010) Am Fam Physician 82(10): 1209-14 [PubMed]
  2. Koshiol (2008) Am J Epidemiol 168(2): 123-37 [PubMed]
  3. Schiffman (2007) Lancet 370(9590): 890-907 [PubMed]
  4. Quinlan (2021) Am Fam Physician 104(2):152-9 [PubMed]

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