Patient-Applied:
Imiquimod 3.75% or 5% cream†
ORPodofilox 0.5% solution or gel
ORSinecatechins 15% ointment†
Provider–Administered:
Cryotherapy with liquid nitrogen or cryoprobe
ORSurgical removal either by tangential scissor excision, tangential shave excision, curettage, laser, or electrosurgery
ORTrichloroacetic acid (TCA) or bichloroacetic acid (BCA) 80%–90% solution
*Many persons with external anal warts also have intra-anal warts. Thus, persons with external anal warts might benefit from an inspection of the anal canal by digital examination, standard anoscopy, or high-resolution anoscopy.
†Might weaken condoms and vaginal diaphragms.
Imiquimod is a patient-applied, topically active immune enhancer that stimulates production of interferon and other cytokines. Imiquimod 5% cream should be applied once at bedtime, three times a week for up to 16 weeks (768). Similarly, imiquimod 3.75% cream should be applied once at bedtime, but is applied every night (769). With either formulation, the treatment area should be washed with soap and water 6–10 hours after the application. Local inflammatory reactions, including redness, irritation, induration, ulceration/erosions, and vesicles might occur with the use of imiquimod, and hypopigmentation has also been described (770). A small number of case reports demonstrate an association between treatment with imiquimod cream and worsened inflammatory or autoimmune skin diseases (e.g., psoriasis, vitiligo, and lichenoid dermatoses) (771-773). Data from studies of human subjects are limited regarding use of imiquimod in pregnancy, but animal data suggest that this therapy poses low risk (317).
Podofilox (podophyllotoxin) is a patient-applied antimitotic drug that causes wart necrosis. Podofilox solution (using a cotton swab) or podofilox gel (using a finger) should be applied to anogenital warts twice a day for 3 days, followed by 4 days of no therapy. This cycle can 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 proper application technique and identify which warts should be treated. Mild to moderate pain or local irritation might develop after treatment. Podofilox is contraindicated in pregnancy (317).
Sinecatechins is a patient-applied, green-tea extract with an active product (catechins). Sinecatechins 15% ointment should be applied three times daily (0.5 cm strand of ointment to each wart) using a finger to ensure coverage with a thin layer of ointment until complete clearance of warts is achieved. This product should not be continued for longer than 16 weeks (774-776). The medication should not be washed off after use. Genital, anal, and oral sexual contact should be avoided while the ointment is on the skin. The most common side effects of sinecatechins are erythema, pruritus/burning, pain, ulceration, edema, induration, and vesicular rash. The medication is not recommended for persons with HIV infection, other immunocompromised conditions, or with genital herpes because the safety and efficacy of therapy has not been evaluated. The safety of sinecatechins during pregnancy is unknown.
Cryotherapy is a provider-applied therapy that destroys warts by thermal-induced cytolysis. Health-care providers must be trained on the proper use of this therapy because over- and under-treatment can result in complications or low efficacy. Pain during and 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.
Surgical therapy has the advantage of eliminating most warts at a single visit, although recurrence can occur. Surgical removal requires substantial clinical training, additional equipment, and sometimes a longer office visit. After local anesthesia is applied, anogenital 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, by carbon dioxide (CO2) laser, or by curettage. Because most 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, in cases of very minor bleeding, a chemical styptic (e.g., an aluminum chloride solution). Suturing is neither required nor indicated in most cases. In patients with large or extensive warts, surgical therapy, including CO2 laser, might be most beneficial; such therapy might also be useful for intraurethral warts, particularly for those persons who have not responded to other treatments. Treatment of anogenital and oral warts should be performed in an appropriately ventilated room using standard precautions (http://www.cdc.gov/hicpac/pdf/isolation/Isolation2007.pdf#page=2) and local exhaust ventilation (e.g., a smoke evacuator) (777) (http://www.cdc.gov/niosh/docs/hazardcontrol/hc11.html).
Trichloroacetic acid (TCA) and bichloroacetic acid (BCA) are provider-applied caustic agents that destroy warts by chemical coagulation of proteins. Although these preparations are widely used, they have not been investigated thoroughly. TCA solution has a low viscosity comparable with that of water and can spread rapidly and damage adjacent tissues if applied excessively. A small amount should be applied only to the warts and allowed to dry (i.e., develop white frost on tissue) before the patient sits or stands. If pain is intense or an excess amount of acid is applied, the area can be covered with sodium bicarbonate (i.e., baking soda), washed with liquid soap preparations, or be powdered with talc to neutralize the acid or remove unreacted acid. TCA/BCA treatment can be repeated weekly if necessary.
Alternative Regimens for External Genital Warts
Less data are available regarding the efficacy of alternative regimens for treating anogenital warts, which include podophyllin resin, intralesional interferon, photodynamic therapy, and topical cidofovir. Further, alternative regimens might be associated with more side effects. Podopyllin resin is no longer a recommended regimen because of the number of safer regimens available, and severe systemic toxicity has been reported when podophyllin resin was applied to large areas of friable tissue and was not washed off within 4 hours (778-780). Podophyllin resin 10%–25% in a compound tincture of benzoin might be considered for provider-administered treatment under conditions of strict adherence to recommendations. Podophyllin should be applied to each wart and then allowed to air-dry before the treated area comes into contact with clothing. Over-application or failure to air-dry can result in local irritation caused by spread of the compound to adjacent areas and possible systemic toxicity. The treatment can be repeated weekly, if necessary. To avoid the possibility of complications associated with systemic absorption and toxicity, 1) application should be limited to <0 .5="" 1="" 2="" 3="" active="" administered="" after="" an="" and="" any="" application.="" are="" area="" be="" been="" cm2="" components="" concentration="" contain="" contaminants.="" differ="" during="" established.="" font="" friable="" has="" hours="" in="" is="" lesions="" ml="" not="" of="" off="" open="" or="" per="" podophyllin="" pregnancy="" preparation="" preparations="" resin="" safety="" session="" shelf-life="" should="" stability="" the="" thoroughly="" tissue="" to="" treatment="" unknown.="" warts="" washed="" which="" wounds="">
