Genital Warts

Treatment of genital warts should be guided by the preference of the patient, the available resources, and the experience of the health-care provider. No definitive evidence suggests that any of the available treatments are superior to any other and no single treatment is ideal for all patients or all warts. The use of locally developed and monitored treatment algorithms has been associated with improved clinical outcomes and should be encouraged. Because of uncertainty regarding the effect of treatment on future transmission of HPV and the possibility of spontaneous resolution, an acceptable alternative for some persons is to forego treatment and wait for spontaneous resolution.

The majority of patients have <10 genital warts, with a total wart area of 0.5–1.0 cm2. These warts respond to various treatment modalities. Factors that might influence selection of treatment include wart size, wart number, anatomic site of wart, wart morphology, patient preference, cost of treatment, convenience, adverse effects, and provider experience. Factors that might affect response to therapy include the presence of immunosuppression and compliance with therapy. The majority of patients require a course of therapy rather than a single treatment. In general, warts located on moist surfaces or in intertriginous areas respond better to topical treatment than do warts on drier surfaces.

The treatment modality should be changed if a patient has not improved substantially. The majority of genital warts respond within 3 months of therapy. The response to treatment and its side effects should be evaluated throughout the course of therapy.

Complications occur rarely if treatments for warts are employed properly. Patients should be warned that persistent hypopigmentation or hyperpigmentation occurs commonly with ablative modalities. Depressed or hypertrophic scars are uncommon but can occur, especially if the patient has had insufficient time to heal between treatments. Rarely, treatment can result in disabling chronic pain syndromes (e.g., vulvodynia or analdynia, and hyperesthesia of the treatment site) or, in the case of rectal warts, painful defecation or fistulas. A limited number of case reports of severe systemic effects from podophyllin resin and interferon have been documented.

Treatment regimens are classified into patient-applied and provider-applied modalities. Patient-applied modalities are preferred by some patients because they can be administered in the privacy of the patient’s home. To use patient-applied modalities effectively, compliance with the treatment regimen is important along with the ability to identify and reach all genital warts.

Recommended Regimens for External Genital Warts

Patient-Applied:

Podofilox 0.5% solution or gel. Patients should apply podofilox solution with a cotton swab, or podofilox gel with a finger, to visible genital warts twice a day for 3 days, followed by 4 days of no therapy. This cycle may be repeated, as necessary, for up to four cycles. The total wart area treated should not exceed 10 cm2, and the total volume of podofilox should be limited to 0.5 mL per day. If possible, the health-care provider should apply the initial treatment to demonstrate the proper application technique and identify which warts should be treated. The safety of podofilox during pregnancy has not been established.
OR
Imiquimod 5% cream. Patients should apply imiquimod cream once daily at bedtime, three times a week for up to 16 weeks. The treatment area should be washed with soap and water 6–10 hours after the application. The safety of imiquimod during pregnancy has not been established.

Provider-Administered:

Cryotherapy with liquid nitrogen or cryoprobe. Repeat applications every 1–2 weeks.
OR
Podophyllin resin 10%–25% in a compound tincture of benzoin. A small amount should be applied to each wart and allowed to air dry. The treatment can be repeated weekly, if necessary. To avoid the possibility of complications associated with systemic absorption and toxicity, two important guidelines should be followed: 1) application should be limited to <0.5 mL of podo-phyllin or an area of <10 cm2 of warts per session, and 2) no open lesions or wounds should exist in the area to which treatment is administered. Some specialists suggest that the preparation should be thoroughly washed off 1–4 hours after application to reduce local irritation. The safety of podophyllin during pregnancy has not been established.
OR
Trichloroacetic acid (TCA) or Bichloroacetic acid (BCA) 80%–90%. A small amount should be applied only to the warts and allowed to dry, at which time a white “frosting” develops. If an excess amount of acid is applied, the treated area should be powdered with talc, sodium bicarbonate (i.e., baking soda), or liquid soap preparations to remove unreacted acid. This treatment can be repeated weekly, if necessary.
OR
Surgical removal either by tangential scissor excision, tangential shave excision, curettage, or electrosurgery

Alternative Regimens

Intralesional interferon
OR
Laser surgery

Podofilox 0.5% solution or gel, an antimitotic drug that destroys warts, is relatively inexpensive, easy to use, safe, and self-applied by patients. The majority of patients experience mild-to-moderate pain or local irritation after treatment. Imiquimod is a topically active immune enhancer that stimulates production of interferon and other cytokines. Local inflammatory reactions are common with the use of imiquimod; these reactions include redness and irritation and are usually mild to moderate. Traditionally, follow-up visits are not required for patients using self-administered therapy. However, follow-up might be useful several weeks into therapy to determine the appropriateness of medication use and the response to treatment.

Cryotherapy destroys warts by thermal-induced cytolysis. Health-care providers must be trained on the proper use of this therapy because over- and undertreatment might result in complications or low efficacy. Pain after application of the liquid nitrogen, followed by necrosis and sometimes blistering, is common. Local anesthesia (topical or injected) might facilitate therapy if warts are present in many areas or if the area of warts is large.

Podophyllin resin, which contains several compounds, including antimitotic podophyllin lignans, is another treatment option. The resin is most frequently compounded at 10%–25% in a tincture of benzoin. However, podophyllin resin preparations differ in the concentration of active components and contaminants. The shelf life and stability of podophyllin preparations are unknown. A thin layer of podophyllin resin must be applied to the warts and allowed to air dry before the treated area comes into contact with clothing; overapplication or failure to air dry can result in local irritation caused by spread of the compound to adjacent areas.

Both TCA and BCA are caustic agents that destroy warts by chemical coagulation of proteins. Although these preparations are widely used, they have not been investigated thoroughly. TCA solutions have a low viscosity comparable with that of water and can spread rapidly if applied excessively; therefore, they can damage adjacent tissues. Both TCA and BCA should be applied sparingly and allowed to dry before the patient sits or stands. If pain is intense, the acid can be neutralized with soap or sodium bicarbonate.

Surgical therapy has the advantage of usually eliminating warts at a single visit. However, such therapy requires substantial clinical training, additional equipment, and a longer office visit. After local anesthesia is applied, the visible genital warts can be physically destroyed by electrocautery, in which case no additional hemostasis is required. Care must be taken to control the depth of electrocautery to prevent scarring. Alternatively, the warts can be removed either by tangential excision with a pair of fine scissors or a scalpel or by curettage. Because the majority of warts are exophytic, this procedure can be accomplished with a resulting wound that only extends into the upper dermis. Hemostasis can be achieved with an electrocautery unit or a chemical styptic (e.g., an aluminum chloride solution). Suturing is neither required nor indicated in the majority of cases if surgical removal is performed properly. Surgical therapy is most beneficial for patients who have a large number or area of genital warts. Carbon dioxide laser and surgery might be useful in the management of extensive warts or intraurethral warts, particularly for those patients who have not responded to other treatments.

Interferons, both natural or recombinant, have been used for the treatment of genital warts. They have been administered systemically (i.e., subcutaneously at a distant site or IM) and intralesionally (i.e., injected into the warts). Systemic interferon is not effective. The efficacy and recurrence rates of intralesional interferon are comparable to other treatment modalities. Administration of intralesional interferon is associated with stinging, burning, and pain at the injection site. Interferon is probably effective because of its antiviral and/or immunostimulating effects. Interferon therapy is not recommended as a primary modality because of inconvenient routes of administration, frequent office visits, and the association between its use and a high frequency of systemic adverse effects.

Because of the shortcomings associated with all available treatments, some clinics employ combination therapy (i.e., the simultaneous use of two or more modalities on the same wart at the same time). No data support the use of more than one therapy at a time to improve efficacy of treatment, and some specialists believe that combining modalities might increase complications.

Recommended Regimens for Cervical Warts

For women who have exophytic cervical warts, high-grade SIL must be excluded before treatment is initiated. Management of exophytic cervical warts should include consultation with a specialist.

Recommended Regimens for Vaginal Warts

Cryotherapy with liquid nitrogen. The use of a cryo-probe in the vagina is not recommended because of the risk for vaginal perforation and fistula formation.
OR
TCA or BCA 80%–90% applied to warts. A small amount should be applied only to warts and allowed to dry, at which time a white “frosting” develops. If an excess amount of acid is applied, the treated area should be powdered with talc, sodium bicarbonate, or liquid soap preparations to remove unreacted acid. This treatment can be repeated weekly, if necessary.

Recommended Regimens for Urethral Meatus Warts

Cryotherapy with liquid nitrogen
OR
Podophyllin 10%–25% in compound tincture of benzoin. The treatment area must be dry before contact with normal mucosa. This treatment can be repeated weekly, if necessary. The safety of podophyllin during pregnancy has not been established.

Although data evaluating the use of podofilox and imiquimod for the treatment of distal meatal warts are limited, some specialists recommend their use in some patients.

Recommended Regimens for Anal Warts

Cryotherapy with liquid nitrogen
OR
TCA or BCA 80%–90% applied to warts. A small amount should be applied only to warts and allowed to dry, at which time a white “frosting” develops. If an excess amount of acid is applied, the treated area should be powdered with talc, sodium bicarbonate, or liquid soap preparations to remove unreacted acid. This treatment can be repeated weekly, if necessary.
OR
Surgical removal

Warts on the rectal mucosa should be managed in consultation with a specialist. Many persons with warts on the anal mucosa also have warts on the rectal mucosa, so persons with anal warts can benefit from an inspection of the rectal mucosa by digital examination or anoscopy.

Genital HPV Infection

Education and counseling are vital aspects of managing patients with genital warts.

• Genital HPV infection is common among sexually active adults. The majority of sexually active adults will have it at some point in their lives, although the majority of them will never know because the infection usually has no symptoms and clears on its own.

• Genital HPV infection is usually sexually transmitted. The incubation period (i.e., the interval between initial exposure and established infection or disease) is variable, and determining the timing and source of infection is frequently difficult. Within ongoing sexual relationships, sex partners usually are infected by the time of the patient’s diagnosis, although they might have no symptoms or signs of infection.

• No recommended uses of the HPV test to diagnose HPV infection in sex partners have been established. HPV infection is commonly transmitted to partners but usually goes away on its own.

Genital Warts

• Genital warts are caused by specific types of HPV infection. The types that cause genital warts are different from the types that cause cervical and other anogenital cancers.

• Persons can possibly have infection with the types of HPV that cause genital warts but never develop symptoms. Why some persons with genital HPV infection develop warts and others do not is unclear. Immunity probably plays a key role.

• The natural history of genital warts is usually benign, but recurrence of genital warts within the first several months after treatment is common. Treatment for genital warts can reduce HPV infection, but whether the treatment results in a reduction in risk for transmission of HPV to sex partners is unclear. The duration of infectivity after wart treatment is unknown.

• Condoms might reduce the risk for HPV-associated diseases (e.g., genital warts and cervical cancer). Consistent condom use also may reduce the risk for genital HPV (18). HPV infection can occur in areas that are not covered or protected by a condom (e.g., scrotum, vulva, or perianus).

• The presence of genital warts is not an indication for HPV testing, a change in the frequency of Pap tests, or cervical colposcopy.

• HPV testing is not indicated for partners of persons with genital warts.

Examination of sex partners is not necessary for the management of genital warts because no data indicate that reinfection plays a role in recurrences. In addition, providing treatment for genital warts solely for the purpose of preventing future transmission cannot be recommended because the value of treatment in reducing infectivity is unknown. However, sex partners of patients who have genital warts might benefit from counseling and examination to assess the presence of genital warts and other STDs.

The counseling of sex partners provides an opportunity for these partners to

• learn that HPV infection is common and probably shared between partners,
• receive STD evaluation and screening and Pap screening if they are female.

Female sex partners of patients who have genital warts should be reminded that cytologic screening for cervical cancer is recommended for all sexually active women.