genital wart therapy

Treatment options for genital warts include therapies that are patient applied and those that are clinician administered, based on the size and location of lesions.
Some patients elect to forgo treatment, because many lesions regress spontaneously. However, many patients have recurrent disease within 3–6 months after treatment,
particularly those who are infected with HIV. The goals in treatment of external genital warts are to provide symptomatic relief or cosmesis, or to alleviate anxiety. The type of treatment chosen depends on the size and location of the lesion, and the reasons for treatment.
Other factors that may influence treatment choices include patient preference, cost, adverse effects of treatment, and provider experience.

As noted below, some treatment options are contraindicated in pregnancy, and this needs to be considered. In general, smaller lesions are easier to treat than larger ones. Warts that are smaller than 1 cm2 at the base are more likely to be successfully treated by topical therapy alone. In contrast, diffuse and large lesions may require surgical intervention.
outlines a treatment algorithm for genital warts. We sometimes choose not to treat large, circumferential perianal genital warts if they are not symptomatic. The reason for this is that multiple staged procedures are usually needed for complete treatment, surgery is
painful, and lesions are often recurrent. We would only recommend surgery in these cases to remove foci of disease that are causing symptoms, or if the goal is to rule
out invasive cancer.

Warts that are located on dry surfaces, are chronic (duration >1 year), or are multiple (>10) are more difficult to treat. Many patients require multiple treatments before successful removal of genital warts, and warts may recur after several months. There is no evidence
that one therapeutic modality is superior to another, and the agent chosen may depend on local availability or experience of the clinician in using a particular treatment modality. The impact of treatment on the transmission of genital warts is unknown.

A. PATIENT-APPLIED THERAPIES

Imiquimod 5% cream (Aldara) is a topical immune response modifier that induces cytokines locally without a direct antiviral effect. Patients apply 5% cream once daily
before bedtime, three times a week for up to 16 weeks. Six to ten hours following the application, the affected area should be washed off with soap and water. Unlike podophyllotoxin (discussed below), there is no limit to the surface area that can be treated.

The major adverse effect is mild to moderate local erythema. The safety of imiquimod in pregnancy has not been established, and it should not be used by pregnant women (category C).
Podofilox 0.5% solution or gel (Condylox Gel) works by arresting the cell cycle in metaphase, leading to cell death. Patients can apply the gel with a finger, or the
solution with a cotton swab to palpable warts. Podofilox is used twice daily for 3 days, followed by no therapy for 4 days. Up to four cycles may be performed. A maximum
surface area of 10 cm2 is recommended, and the total daily volume of podofilox should not exceed 0.5 mL.

Adverse effects include mild skin irritation, but local ulceration and pain can occur depending on the duration of use. Safety in pregnancy has not been established
(category C).

B. PROVIDER-APPLIED THERAPIES

Cryotherapy can be performed in the office using liquid nitrogen spray, a liquid nitrogen–soaked swab, or a cryoprobe cooled with nitrous oxide. The freeze-thaw cycle produces cell lysis and destruction of the wart. The freeze margin should extend 2–3 mm beyond the margins of
the wart. Cryotherapy can be repeated every 3 weeks.
Adverse effects include some pain during and for a variable time after the procedure. Swelling and erythema may also occur. This treatment modality is safe for use during pregnancy.
Podophyllin resin 25% in tincture of benzoin (Podocon-25; Paddock Laboratories, Minneapolis, MN) is similar to podofilox except that it is provider applied. The liquid is applied to the affected area, allowed to dry, and washed off after 6 hours. Total volume should not
exceed 0.5 mL per session. Therapy may be repeated in 1 week. Adverse effects include skin irritation, ulceration, and pain, depending on how much solution is applied.
Rarely, polyneuritis, paresthesias, leucopenia, and thrombocytopenia may occur. Safety in pregnancy has not been established (category C).

Trichloroacetic acid (TCA), 80%, destroys affected tissue by protein coagulation. Typically, a small quantity of TCA is applied to the lesion until it appears white or
frosted; the acid is then allowed to dry. Care should be taken to ensure that TCA does not run off the lesion to cover areas of normal skin. To provide greater control,
we soak the stick end of a cotton swab in a small amount of TCA and apply it by touching the stick end to the lesion. Temporary burning may occur at the time of application to the wart. If too much TCA is applied, or if surrounding tissue is inadvertently treated—resulting
in substantial pain—talc, liquid soap, or sodium bicarbonate can be used to neutralize the acid. A barrier of petroleum jelly could also be used to protect areas adjacent
to the wart undergoing treatment. As with cryotherapy multiple treatment applications are often necessary. TCA is safe for use during pregnancy.

C. SURGICAL OPTIONS
Use of an infrared coagulator (Redfield Corporation, Rochelle Park, NJ) is an FDA-approved option for the treatment of genital warts. The infrared coagulator uses
light technology to generate intense heat at the tip of the device, producing coagulative necrosis without a smoke plume. This procedure can be performed in the office using local anesthesia only. The infrared coagulator is particularly useful for larger lesions that would have normally required intraoperative fulguration or laser surgery.
Laser surgery is an option for extensive genital warts, particularly those that have been refractory to other treatment modalities. Trained operators focus the laser
on affected tissue. Laser energy is converted into heat, vaporizing the genital wart. The maximum recommended depth of tissue destruction is 1 mm. Adverse effects include pain and scarring, and operators may develop warts by dispersion of virions during the procedure.

This procedure is performed in the operating room under anesthesia and is one of the most expensive treatment options for genital warts. It can also be done in the office.
Scissor excision and other excisional procedures are considered first-line therapy by some providers for large warts causing obstructive symptoms. After local anesthesia,
the wart is usually excised down to normal tissue or mucosa (using fine scissors or a scalpel), and the roots of the lesion are destroyed by electrocautery, with no
further hemostasis required. Suturing is rarely needed.

Complications include strictures and scarring, particularly if subcutaneous tissue or submucosal fat is inadvertently cauterized.

D.OTHER TREATMENT OPTIONS

5-Fluorouracil (5-FU) can be used as a gel with epinephrine and injected intralesionally for the treatment of genital warts. 5-FU acts by blocking the methylation of
deoxyuridylic acid, arresting DNA synthesis and causing cell death. Adverse effects—pain and ulceration, with dysuria if used in the urethra—limit the use of this drug.
5-FU is not recommended during pregnancy (category D). Cidofovir disrupts viral chain elongation by competitively inhibiting the incorporation of deoxycytidine
triphosphate (dCTP) into viral DNA. Applied topically as a 1% gel, cidofovir has been demonstrated to be effective in a randomized controlled trial of the treatment of
genital warts. This therapy is still experimental.

Interferon alfa can be given systemically, topically (not generally effective), or, as is more often the case,intralesionally. Intralesional interferon is not FDAcleared for the treatment of genital warts although it is used widely.