Human Papillomavirus (HPV) Infection

Background

• Human papillomaviruses are small, nonenveloped, double-stranded DNA viruses.
• > 200 HPV types have been identified and are classified based on the genetic sequence of the L1 major structural protein, tissue tropism, and oncogenic risk in humans.
  • Most HPV types (approximately 80) infect the cutaneous epithelium (nonmucosal) and cause skin warts on the hands and feet.
  • About 40 types infect the mucosal epithelium, including > 12 high-risk (oncogenic) types.
• Infection occurs in both men and women, with the highest prevalence in women aged 20-25 years.
• Risk factors for sexually transmitted HPV infection include:
  • being sexually active
  • increased number of different sexual partners
  • young age at sexual initiation
  • being uncircumcised (for both the male and his female partner)
  • decreased condom use
  • history of other sexually transmitted infections
• Risk factors for plantar warts include:
  • close contact with an affected person (such as family member, classmate, or teammate), including sharing unwashed shoes, socks, equipment, and other personal items
  • use of communal shower or locker room without protective footwear
  • pedicure with improperly sanitized tools or using tools on other areas of skin after wart contact
  • not changing socks daily or wearing poorly ventilated footwear and athletic clothing
• HPV is the most common sexually transmitted infection, with an estimated 79 million people infected in the United States.
• Cutaneous infection is transmitted by contact with viral particles, either through direct contact with existing wart or fomites.
• Infection is usually self-limited and asymptomatic, but when present, clinical manifestations include:
  • common, flat, anogenital, periungual, and plantar warts
  • malignancies including cervical, vaginal, vulvar, anal, penile, and oropharyngeal cancers
  • recurrent respiratory papillomatosis
  • skin lesions in patients with epidermodysplasia verruciformis, which may progress to cutaneous squamous cell carcinoma
  • cutaneous and anogenital warts in patients with warts, hypogammaglobulinemia, recurrent infections, and myelokathexis (WHIM) syndrome, a very rare autosomal dominant primary immunodeficiency disorder
• Cervical or anogenital HPV infection may increase risk of HIV acquisition.

Evaluation

• A diagnosis of warts is typically made clinically and may be confirmed by biopsy in certain circumstances, such as
  • suspicion of squamous cell carcinoma or Bowen disease, especially in adults
  • immunocompromised patients
  • lesions unresponsive to or worsening with standard therapy
  • lesions which are atypical, have sudden growth or increased pigmentation, indurated, fixed, bleeding, or ulcerated
• Further visualization of genital warts may require colposcopy, proctoscopy, meatoscopy, or urethroscopy.
• Recurrent respiratory papillomatosis is often difficult to diagnose due to nonspecific symptoms, and testing may include imaging, laryngoscopy or bronchoscopy, and biopsy of lesions.
• HPV DNA testing for high-risk (oncogenic) types is recommended as part of routine cervical cancer screening, but specific recommendations vary by professional organization
• In patients with oropharyngeal cancer, HPV testing using p16 immunohistochemistry to determine tumor status is recommended to guide management.
• Testing of other clinical samples (anal, oral, vaginal, penile) is commonly used for epidemiologic surveillance.

Management

• 70%-90% of HPV infections are asymptomatic and resolve spontaneously within 1-2 years.
• There is no specific antiviral treatment against HPV.
• When required, the management strategy is based on the specific clinical manifestation of infection such as warts, precancerous lesions, or malignancies.
• For sexually transmitted HPV infection, abstinence is the only way to prevent transmission. Strategies to reduce risk of infection include consistent and correct use of physical barriers, such as condoms, during sexual activity and limiting the number of different sexual partners.
• Practices to reduce risk of exposure and prevent verruca vulgaris (common warts) and plantar warts include washing hands frequently and covering areas of abraded skin; wearing foot gear in areas of communal locker rooms, swimming pools, and showers; and discouraging sharing of towels, shoes, or socks.
• Immunization
  • The World Health Organization (WHO) recommends vaccination of females aged 9-14 years before the onset of sexual activity. Vaccination of other populations, including females ≥ 15 years old and males, should only occur when feasible, affordable, and not diverting resources away from primary target population.
  • The Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices recommends routine HPV vaccination of males and females at age 11-12 years (minimum age 9 years).
    • Dosing schedule is based on age at first dose.
      • If aged 9-14 years at first dose, give second dose 6-12 months after first dose.
      • If ≥ 15 years old at first dose, give second dose 1-2 months after first, and give third dose 6 months after first (minimum intervals 12 weeks between second and third dose; 5 months between first and third doses).
    • For all adults ≤ 26 years old, vaccination is recommended if any or all doses were not received when younger. For adults aged 27-45 years, the decision to vaccinate should be based on shared clinical decision making.