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Genital Warts

(Condylomata Acuminata; Venereal Warts; Anogenital Warts)

by J. Allen McCutchan, MD, MSc

Genital warts are lesions of the skin or mucous membranes of the genitals caused by certain types of human papillomavirus (HPV). Some types of HPV cause flat warts in the cervical canal or anus; infection with certain HPV types can lead to cancer. Diagnosis of external warts is based on their clinical appearance. Multiple treatments exist, but few are highly effective unless applied repeatedly over weeks to months. Genital warts may resolve without treatment in immunocompetent patients but may persist and spread widely in patients with decreased cell-mediated immunity (eg, due to pregnancy or HIV infection).

In the US, an estimated 1.4 million people have genital warts at any given time. In the United States, there are about 6 million new cases of genital HPV infection each year. By age 50, about 80% of women have been infected at least once.

Most HPV infections clear spontaneously within 1 to 2 yr, but some persist.

Etiology

There are > 100 known types of HPV. Some cause common skin warts (see Warts). Some infect primarily the skin and mucosa of the anogenital region.

Important manifestations of anogenital HPV include

  • Genital warts (condyloma acuminatum)

  • Intraepithelial neoplasia and carcinoma of the cervix, anus, or penis

  • Bladder and oral cancers

  • Bowenoid papulosis

Condylomata acuminata are benign anogenital warts most often caused by HPV types 6 and 11. Low- and high-grade intraepithelial neoplasia and carcinoma may be caused by HPV. Virtually all cervical cancer is caused by HPV; about 70% is caused by types 16 and 18, and many of the rest result from types 31, 33, 35, and 39. HPV types that affect mainly the anogenital area can be transmitted to the oropharynx by orogenital contact; type 16 appears responsible for many cases of oropharyngeal cancer. HPV types 16 and 18 can also cause cancer in other areas, including the vulva, vagina, and penis.

HPV is transmitted from lesions during skin-to-skin contact. The types that affect the anogenital region are usually transmitted sexually by penetrative vaginal or anal intercourse, but digital, oral, and nonpenetrative genital contact may be involved.

Genital warts are more common among immunocompromised patients. Growth rates vary, but pregnancy, immunosuppression, or maceration of the skin may accelerate the growth and spread of warts.

Symptoms and Signs

Warts appear after an incubation period of 1 to 6 mo. Visible anogenital warts are usually soft, moist, minute pink or gray polyps (raised lesions) that enlarge, may become pedunculated, have rough surfaces, and may occur in clusters. They are usually asymptomatic, but some patients have itching, burning, or discomfort.

In men, warts occur most commonly under the foreskin, on the coronal sulcus, within the urethral meatus, and on the penile shaft. They may occur around the anus and in the rectum, especially in homosexual men. In women, warts occur most commonly on the vulva, vaginal wall, cervix, and perineum; the urethra and anal region may be affected. HPV types 16 and 18 usually cause flat endocervical or anal warts that are difficult to see and diagnose clinically.

Diagnosis

  • Clinical evaluation, sometimes including colposcopy, anoscopy, or both

Genital warts are usually diagnosed clinically. Their appearance usually differentiates them from condyloma lata of secondary syphilis (which are flat-topped) and from carcinomas. However, serologic tests for syphilis (STS) should be done initially and after 3 mo. Biopsies of atypical, bleeding, ulcerated, or persistent warts may be necessary to exclude carcinoma.

Endocervical and anal warts can be visualized only by colposcopy and anoscopy. Applying a 3 to 5% solution of acetic acid for a few minutes before colposcopy causes warts to whiten and enhances visualization and detection of small warts.

Nucleic acid amplification tests (NAAT) for HPV DNA confirm the diagnosis and allow typing of HPV, but their role in HPV management, including cervical cancer screening, is not yet clear.

Treatment

  • Mechanical removal (eg, by cryotherapy, electrocauterization, laser, or surgical excision)

  • Topical treatment (eg, with antimitotics, caustics, or interferon inducers)

No treatment of anogenital warts is completely satisfactory, and relapses are frequent and require retreatment. In immunocompetent people, genital warts may resolve without treatment. In immunocompromised patients, warts may be less responsive to treatment.

Genital warts may be removed by cryotherapy, electrocauterization, laser, or surgical excision; a local or general anesthetic is used depending on the size and number to be removed. Removal with a resectoscope may be the most effective treatment; a general anesthetic is used.

Topical antimitotics (eg, podophyllotoxin, podophyllin, 5-fluorouracil), caustics (eg, trichloroacetic acid), interferon inducers (eg, imiquimod), and sinecatechins (a newer botanical product with an unknown mechanism) are widely used but usually require multiple applications over weeks to months and are frequently ineffective. Before topical treatments are applied, surrounding tissue should be protected with petroleum jelly. Patients should be warned that after treatment, the area may be painful.

Interferon alfa (eg, interferon alfa-2b, interferon alfa-n3), intralesionally or IM, has cleared intractable lesions on the skin and genitals, but optimal administration and long-term effects are unclear. Also, in some patients with bowenoid papulosis of the genitals (caused by type 16 HPV), lesions initially disappeared after treatment with interferon alfa but reappeared as invasive cancers.

For intraurethral lesions, thiotepa (an alkylating drug), instilled in the urethra, is effective. In men, 5-fluorouracil applied bid to tid is highly effective for urethral lesions, but rarely, it causes swelling, leading to urethral obstruction. Endocervical lesions should not be treated until Papanicolaou (Pap) test results rule out other cervical abnormalities (eg, dysplasia, cancer) that may dictate additional treatment.

By removing the moist underside of the prepuce, circumcision may prevent recurrences in uncircumcised men.

Sex partners of women with endocervical warts and of patients with bowenoid papulosis should be counseled and screened regularly for HPV-related lesions. A similar approach can be used for HPV in the rectum.

Current sex partners of people with genital warts should be examined and, if infected, treated.

Prevention

A quadrivalent vaccine that protects against the 2 types of HPV (types 6 and 11) that cause > 90% of visible genital warts is available. This vaccine also protects against the 2 types of HPV (types 16 and 18) that cause most cervical cancers. A bivalent vaccine that protects against types 16 and 18 is also available.

The HPV vaccine (quadrivalent or bivalent—see Recommended Immunization Schedule for Ages 7–18 yr) is recommended for girls and women aged 9 to 26 yr for prevention of initial infection. Three doses are given, preferably at age 11 to 12 yr. The vaccine should be administered before onset of sexual activity, but girls and women who are sexually active should still be vaccinated.

Only the quadrivalent vaccine is recommended for males. Three doses of the vaccine are recommended for boys at age 11 to 12; boys aged 13 to 21 who have not completed the 3-dose series should also be given the vaccine. The vaccine is also recommended for men up to age 26 who have sex with men or whose immune system is compromised; it may be given to men aged 22 to 26 if they have not completed the 3-dose series.

Because of the location of these warts, condoms may not fully protect against infection.

Key Points

  • Genital warts are caused by a few types of human papillomavirus (HPV).

  • HPV types 16 and 18 cause about 70% of cervical cancers and can cause cancer in other areas, including the vulva, vagina, penis, and oropharynx.

  • Diagnose warts by inspection; HPV testing is available, but its role in HPV management is unclear.

  • Remove warts mechanically or using various topical treatments.

  • HPV vaccination is recommended for children and young adults of both sexes.

Resources In This Article

Drugs Mentioned In This Article

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  • ALDARA
  • CARAC

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