Current Update on the Treatment of Genital Warts

Valerie R Yanofsky; Rita V Linkner; David Pompei; Gary Goldenberg

Disclosures

Expert Rev Dermatol. 2013;8(3):321-332. 

In This Article

Therapies Not Generally Recommended

Several therapies that were commonly used in the past are now no longer recommended in the primary care setting based on both low efficacy and high risk of toxicity. These include podophyllin, 5-fluorouracil (5-FU) and interferon therapy.[67]

Podophyllin 25% Solution

Podophyllin was the first topical agent approved for genital warts. Despite podophyllin containing the same active ingredient as podophyllotoxin, efficacy is limited, with clearance ranging from 20 to 50% at 3-month follow-up, and an inability to induce a lasting remission.[68] When used as monotherapy, it is generally considered less effective than podophyllotoxin, cryotherapy or electrosurgery.[39,61] Furthermore, podophyllin is commonly associated with adverse skin reactions such as burning, redness, pain, itching, and swelling. This may be, in part, due to a lack of standardized drug preparation, which leads to significant variations between samples in the concentration of active ingredient. Application of the drug to the cervix or vaginal epithelium is contraindicated due to the high risk of chemical burns. Podophyllin has also been shown to enter the systemic circulation, and in rare circumstances has been linked to the development of enteritis, bone marrow suppression, abdominal pain and neurological compromise.[69]

5-FU 1% & 5% Cream or Solution

5-FU is a pyrimidine antimetabolite that interferes with DNA synthesis by blocking the methylation of deoxyruidylic acid, resulting in impaired mitosis and cell death. It is one of the oldest chemotherapeutic agents currently available, and has been effectively used in the treatment of cancer for over 40 years. More recently, 5-FU prepared as a cream or solution of 1–5% has been used experimentally for the treatment of EGW, and has been associated with highly variable response rates. Clearance rates are generally found to be comparable with those seen with imiquimod 5%; however, 5-FU is associated with higher rates of recurrence and a significantly more severe side-effect profile.[3,70] Although it is not officially approved by the FDA for the treatment of genital warts, topical 5-FU is still seen as a favorable option for urethral condylomata.[71–73]

Interferon Therapy

Interferons are cytokines released by cells of the immune system in response to the presence of invading pathogens. They are thought to both inhibit viral replication within a host cell and stimulate a more robust immune response. Interferon therapy can be administered both systemically via oral or intramuscular injection, as well as locally via direct intralesional injections. The dose and duration of treatment typically depends on the mode of administration, with anywhere between 1 and 3 million units being used daily or every other day, for a duration of 3 weeks.

To date, interferon therapy has been used predominantly for the treatment of cancers such as malignant melanoma. Recent evidence suggests, however, that it may be a useful therapy for EGW, either independently or as an adjuvant to surgical treatment.[74,75] A meta-analysis of 12 randomized clinical trials showed that, when compared with placebo, intralesional interferon injections resulted in significantly higher rates of complete wart clearance (p < 0.00001). In contrast, systemically used interferon therapy showed no such benefit (p > 0.05).[74,76]

Since interferon therapy is known to directly inhibit viral replication, as well as provide an immune-boosting effect, it is more likely to target all virally infected cells, including those that may be subclinical and difficult to detect. Ultimately, this may lead to lower recurrence rates and better long-term efficacy, especially when used in combination with other treatments. However, the benefit of interferon therapy as an adjunct to surgical treatment remains unclear, with several studies showing significant advantages relative to placebo, while others still showing no such effect.[75,77]

Side effects are more common with systemic injections, and include influenza-like symptoms such as headaches, nausea, vomiting, fatigue and myalgia. For their part, intralesional injections are typically quite painful, and often require the use of local anesthesia.[43]

Although interferon therapy seems like a promising treatment option, further comprehensive research is needed in order to more accurately evaluate its effectiveness.[74] Additionally, each interferon injection is extremely costly, and it therefore only considered as a last-resort therapy, reserved for severe cases, which are unresponsive to other forms of treatment.[74]

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