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Human papillomavirus infection

Last updated: November 13, 2020

Summary

The human papilloma virus (HPV) causes infections of the skin and mucous membranes. The locations and specific manifestations of infection depend on the type of virus and its mode of transmission. Many HPV strains are already spread during infancy and childhood through direct skin-to-skin contact and may remain dormant inside the cell, while others (especially HPV-1, HPV-2, and HPV-4) can cause common warts (verruca vulgaris). Other strains are sexually transmitted (especially in young adults) and can be further divided into low-risk and high-risk HPV types. Low-risk types (especially HPV-6 and HPV-11) can cause benign anogenital warts (condylomata acuminata) and papillomatous nodules in other genital (e.g., squamous intraepithelial lesions of the cervix) or non-genital (e.g., oral warts, respiratory papillomatosis) mucosal areas. Infection with oncogenic high-risk HPV types (especially HPV-16 and HPV-18) may lead to malignant disease. These high-risk strains account for more than 70% of cervical cancers and can also cause genital, oral, and oropharyngeal squamous cell cancers. Risk factors for infection include skin damage, immunocompromise, early first sexual intercourse, and frequent change of sexual partners. Most HPV infections are asymptomatic and self-limiting, although pruritus, tenderness, and bleeding may occur. Diagnosis is often based on the physical exam alone, but can be confirmed with diagnostic tests (e.g., PCR), particularly in asymptomatic HPV infections of the cervix. Treatment of condylomas includes the use of local ointments, cryotherapy, and electrocoagulation. However, surveillance is important since recurrence rates are high and malignant transformation is possible. Prevention includes education about safe sexual practices and the proper use of condoms, as well as vaccination of all persons 9–26 years of age.

Etiology

Human papillomavirus [1]

Route of transmission

  • Transmission occurs between two epithelial surfaces.
    • Close personal contact: cutaneous warts
    • Sexual contact: anogenital lesions

Risk factors [3]

Pathogenesis

6 comes before 7 and P comes before R: E6 inhibits P53 and E7 inhibits pRb

Anogenital manifestations

Epidemiology

Genital intraepithelial neoplasms

Condylomata acuminata (anogenital warts)

Flat condylomata

  • Pathogen: : particularly HPV types 3 and 10
  • Clinical features: flat, white-brown, slightly elevated, scattered plaques in the anogenital region
  • Differential diagnosis: condylomata lata (usually flat, smooth, and moist) in syphilis
  • Treatment
    • Curettage or laser surgery
    • Regular checks are necessary because of the high risk of malignancy

Bowenoid papulosis

  • Description: : transitional stage between a genital wart and Bowen disease (a squamous cell carcinoma in situ)
  • Pathogen: : most commonly HPV-16
  • Clinical features: multiple, flat, red-brown pigmented papules on the external genitalia (particularly the penile shaft, glans, foreskin, vulva, and perianal region)
  • Treatment
    • Re-examination every 3–6 months (lesions often regress spontaneously)
    • If persistent: local destructive therapy (see “Treatment” of “Condylomata acuminata“ above) followed by surveillance (annual examinations), since lesions may recur
  • Prognosis: malignant transformation occurs in 2.6% of cases. [6]

Giant condylomata (Buschke-Löwenstein tumor)

Nonanogenital manifestations

Epidemiology

Common warts (verruca vulgaris)

  • Pathogen: : particularly low-risk HPV types 2 and 4
  • Clinical features
    • Lesions are plaques or papules
      • Skin-colored or whitish
      • Usually firm, often with a rough and scaly surface
      • Sometimes have a cauliflower-like appearance
      • Located on the elbows, knees, fingers, and/or palms
    • Often asymptomatic but may cause tenderness (depending on the location) and pruritus → scratching → bleeding
  • Treatment

Plantar warts (verruca plantaris)

  • Pathogen: particularly HPV types 1
  • Clinical features
    • Rough, hyperkeratotic lesions on the sole of the foot
    • Often grow inwardly and cause pain while walking

Flat warts (verruca plana)

  • Pathogen: particularly HPV types3 and 10
  • Clinical features
    • Multiple small, flat patches or plaques
    • Localized on the face, hands, and shins

Nonanogenital mucosal manifestations

HPV types that cause mucosal manifestations in the genital area may also lead to nonanogenital mucosal manifestations, such as:

Pathology

Differential diagnoses

The differential diagnoses listed here are not exhaustive.

Treatment

  • There is no treatment for the infection itself.
  • In most cases the infection clears up without any treatment
  • Several factors guide the choice of the treatment of anogenital warts, including wart characteristics (i.e., size, number, and anatomic site), patient preference, and potential adverse effects.
  • Treatment options of HPV–related anogenital warts are:
    • Routine clinical monitoring
    • Local treatment with one of the following:
      • Podophyllotoxin
      • Imiquimod
      • Trichloroacetic acid
    • Cryotherapy
    • Surgical removal (e.g., tangential scissor, shave excision, curettage, laser, electrosurgery)
  • Evidence of malignancy should always be excluded on HPV–related cervical lesions via cytological and histological monitoring.
  • For treatment options of HPV–related cervical lesions, see “Treatment” in “Cervical cancer.”

Reference:[8]

Prognosis

  • High rate of recurrence
  • Infection with high-risk types may transition to precancerous or malignant lesions after several years. [3]

Prevention

  • Education about possible risk factors and effective preventive measures, such as: [3]
    • HPV vaccination [9]
      • Recommended to all persons aged 9–26 years (routinely performed at 11–12 years of age because vaccination is most effective before exposure to HPV through sexual activity).
      • Recommended for some adults aged 27–45 years based on a discussion of benefits and risks between the patient and the clinician (e.g., in order to complete the HPV vaccine series).
      • Not licensed for use in adults aged > 45 years.
      • See “Prevention” in “Cervical cancer.”
    • Use of condoms: Condoms decrease the risk of infection but do not provide full protection, as uncovered areas may still be infected. [3]

Special patient groups

Pregnancy [1]

References

  1. HPV and Men - Fact Sheet. https://www.cdc.gov/std/hpv/stdfact-hpv-and-men.htm. Updated: November 4, 2016. Accessed: January 3, 2017.
  2. Moscicki AB. Human papillomavirus disease and vaccines in adolescents.. Adolescent medicine: state of the art reviews. 2010; 21 (2): p.347-63, x-xi.
  3. Human Papillomavirus. https://www.cdc.gov/vaccines/pubs/pinkbook/hpv.html. Updated: August 5, 2015. Accessed: January 3, 2017.
  4. Other Sexually Transmitted Diseases. https://www.cdc.gov/std/stats14/other.htm#hpv. Updated: November 17, 2015. Accessed: January 3, 2017.
  5. Singhal RR, Patel TM, Pariath KA, Vora RV. Premalignant male genital dermatoses.. Indian journal of sexually transmitted diseases and AIDS. undefined; 40 (2): p.97-104. doi: 10.4103/ijstd.IJSTD_106_17 . | Open in Read by QxMD
  6. Fox PA, Tung MY. Human papillomavirus: burden of illness and treatment cost considerations.. Am J Clin Dermatol. 2005; 6 (6): p.365-81. doi: 10.2165/00128071-200506060-00004 . | Open in Read by QxMD
  7. Human papillomavirus (HPV) and cervical cancer. http://www.who.int/mediacentre/factsheets/fs380/en/. Updated: June 1, 2016. Accessed: January 2, 2017.
  8. Sexually Transmitted Diseases Treatment Guidelines 2015. https://www.cdc.gov/std/tg2015/default.htm. . Accessed: January 6, 2020.
  9. Meites E, Szilagyi PG, Chesson HW, Unger ER, Romero JR, Markowitz LE. Human Papillomavirus Vaccination for Adults: Updated Recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep. 2019; 68 (32): p.698-702. doi: 10.15585/mmwr.mm6832a3 . | Open in Read by QxMD