Human Papilloma Virus

Snapshot

  • A 38-year-old male presents to the clinic with a history of soft, raised flesh-colored growths on his glans penis, prepuce, and penile shaft. He is sexually active with multiple partners and uses condoms infrequently. Excisional biopsy was carried out.

Introduction

  • Classification
    • Virus
      • non-enveloped, circular double-stranded DNA virus
  • Epidemiology
    • only infect humans  
      • most common sexually transmitted infection (STI)
      • among adults ages 18-59 in the U.S.A., prevalence of 45% for men and 40% for women
    • risk factors
      • multiple sex partners
      • individuals with new sex partners
  • Pathogenesis
    • transmission
      • from one epithelial surface to another
      • sexual activity
      • close skin-to-skin contact
    • multiple serotypes (> 75) and serotype determines disease
    • viral oncogenes in high-risk HPV infections (HPV types 16, 18, 31, and 33)  
      • E6 degrades tumor suppressor p53 protein
      • E7 binds to Rb protein and disrupts interaction between Rb and E2F
        • allows for replication and cellular division
  • Associated conditions:
    • cutaneous warts (HPV types 1 and 2)
    • condyloma acuminata/anogenital warts (HPV types 6 and 11) 
    • laryngeal papillomatosis (HPV types 6 and 11)
    • precancerous and cancerous genitourinary/oropharyngeal lesions (HPV types 16, 18, 31, 33)
      • cervical cancer
      • head and neck cancer 
      • anal cancer
      • penile cancer
    • HIV infections promotes persistence of HPV infection and may promote HPV-associated oncogenesis
  • Prevention
    • vaccinations
      • Gardasil 9 in the USA
        • targets HPV types 1, 6, 16, 18, 31, 33, 45, 52, and 58
      • females age 9-26; males age 9-21
  • Prognosis
  • depends on clinical presentation and conditions

Presentation

  • Symptoms
    • most cases will present asymptomatically and will self-resolve
    • cutaneous warts/common hand warts 
    • condyloma acuminata (anogenital warts) 
    • laryngeal papillomatosis 
      • hoarseness, shortness of breath, and chronic cough 
      • dysphagia, pneumonia, and recurrent upper respiratory infections
    • oropharyngeal neoplasms/cancer
      • typically in young patients
    • genitourinary neoplasms/cancer
      • abnormal bleeding
      • discomfort during sexual intercourse
      • abnormal discharge  
  • Physical exam
    • cutaneous warts/common hand warts 
      • rough, raised bumps on hands, fingers, and soles of feet
    • condyloma acuminata 
      • often cauliflower-shaped
    • oropharyngeal neoplasms/cancer
      • lesions occurs mainly at base of tongue and tonsils
      • ulcer, sores, swelling, and painful lesions
    • genitourinary neoplasms/cancer
      • cervical cancer
        • pelvic exam and colposcopy may demonstrate abnormal cells
      • anal cancer
        • digital rectal exam and anoscopy may demonstrate lesions
      • penile cancer
  • abnormal growths or lesions

Studies

  • Labs
    • gold standard is in situ hybridization or PCR to detect HPV DNA
      • HPV-16 viral load
  • Indirect laryngoscopy
    • allows for direct visualization of lesions at the larynx
  • Histopathology
    • koilocytic cells on biopsy or Pap smear  
  • Screening
  • Pap smear for women beginning at age 21

Differential

  • Condyloma lata of secondary syphilis
    • differentiating factor
      • condyloma lata are more flat-topped
  • Molluscum contagiosum
    • differentiating factor
      • have central dimpling and often in immunocompromised individuals
  • Genital herpes
    • differentiating factor
  • painful ulcerating lesions

Treatment

  • Most HPV infections are cleared by the body’s immune system
  • Common warts
    • often resolve without treatment
    • use of OTC salicylic acid and other prescription medications
    • surgical procedures such as cryotherapy, electrocautery, and laser therapy
  • Laryngeal papillomatosis 
    • surgical removal, though high recurrance rate 
    • adjuvant non-surgical treatments
      • antiviral (e.g., cidofovir)
      • interferon 
      • photodynamic therapy
  • Cancer
    • chemotherapy
    • immunotherapy
  • surgical resection +/- radiation therapy

Complications

  • Cervical cancer 
  • Anal cancer 
  • Head and neck cancer 
  • Penile cancer