Intralesional Immunotherapy for Genital Warts

Intralesional immunotherapy employing skin test (recall) antigens derived from mumps, Candida, and Trichophyton is an effective and safe treatment for verruca vulgaris and verruca plana.^{1 - 2} In adults, we have shown individual treated wart response rates of 60% to 74% (saline control, 22%) and complete clearing of uninjected anatomically distinct and distant warts in 49% to 71% (saline control, 16%). In children with treatment-resistant warts (2 modalities), complete response rates were 47% and 34%, respectively.³

Genital warts cause significant morbidity and discomfort. In addition to traditional destructive modalities, genital warts have been successfully treated by imiquimod, a biologic response modifier capable of increasing, among other cytokines, tissue levels of interferon-α.⁴ Eradication of all baseline warts is reported in roughly 50% of subjects treated with 5% imiquimod cream. Differences in response rates between women (77%) and men (40%) have been reported.⁵ Intralesional injection of interferon alfa is also approved for the treatment of genital warts, with response rates of 47% to 62% reported.⁶

Herein, we report retrospective uncontrolled data pertaining to the results of intralesional immunotherapy for genital warts in 21 subjects who received either a single antigen or combined antigens.

We reviewed medical charts retrospectively to identify patients treated for genital warts using intralesional immunotherapy in the Department of Dermatology at the University of Arkansas for Medical Sciences, Little Rock, during the 12-month period ending June 2004. Twenty-one patients were identified. For subjects treated according to study protocols, the protocol had received approval from the institutional investigation review boards of the University of Arkansas for Medical Sciences and the Central Arkansas Veterans Healthcare System, Little Rock.

The diagnosis of genital warts was made by clinical examination (S.M.J. or T.D.H.). Treatment and assessments were performed as described previously.^{1 - 2} Briefly, 1 lesion was selected for treatment and was directly injected with mumps (Connaught, Swiftwater, Pa), Candida (Bayer, Spokane, Wash) or Trichophyton (Alk-Abello, Round Rock, Tex) skin test antigen alone (0.3 mL); the combination of mumps, Candida, and Trichophyton skin test antigens (0.1 mL each); the combination of Candida and Trichophyton skin test antigens (0.1 mL each). Mumps antigen preparation is no longer commercially available. Injections were performed at 3-week intervals until warts cleared, a judgment was made that the maximum benefit had been reached, or the patient no longer wanted treatment. Measurements of involved surface area were made at baseline examination. Assessments of response at the injection site as well as of untreated distant lesions were made at each subsequent visit. Response was judged based on reduction of surface area involvement expressed as a percentage of the pretreatment measurement.

Data for the 21 patients are given in the Table. Sixteen patients were treated as part of a study protocol (as yet unpublished), including subjects with verruca vulgaris and condyloma in which 1 arm included co-injection of interferon alfa-2b (3 subjects), and 5 patients were treated in our clinic, off protocol. Fifteen patients were referred to our clinic because of previous treatment failure. Five patients failed to follow up, and 6 patients chose not to continue treatment with intralesional immunotherapy, leaving 10 patients judged to have completed the course of therapy. Adverse reactions, consisting of local erythema and edema, were noted in 3 subjects. All signs and symptoms were transient, lasting less than 24 hours.

Of the 10 patients who completed the course of therapy, 5 experienced complete resolution of warts by the time of the last visit, including distant response of untreated lesions in 4. The fifth patient had a single wart. Of the 10 patients, 5 (50%) experienced 75% to 95% clearing of treated and untreated warts. Based strictly on intent-to-treat analysis, 5 subjects (24%) enrolled in the study experienced 100% resolution, 5 (24%) experienced 75% to 95% clearing of warts, and the remaining 11 (52%) experienced less than 50% clearing of treated and untreated warts.

Current treatment options for patients with genital warts include cryotherapy; application of podophyllum, bichloroacetic, and trichloroacetic acid, cidofovir, interferon, or imiquimod cream; or laser and surgical ablation. Intralesional injection of skin recall antigens is effective in patients with genital warts. Of all 21 patients, 10 (48%) experienced 75% to 100% clearing of warts, and 5 (24%) were noted to have resolution of all warts. All 10 patients who completed the course of treatment experienced 75% to 100% clearing of the injected wart, and 5 were noted to have resolution of all warts, including anatomically distinct and untreated lesions. That our results are not based on a prospective, randomized study employing a uniform treatment regimen is a limitation of this study.

Treatment of genital warts is often challenging. Intralesional immunotherapy employing skin recall antigens is effective in a significant number of patients and should be considered by dermatologists as a treatment option. Intralesional immunotherapy may be of particular benefit in men, based on the observation of lower response rates to imiquimod. In any individual, the possibility of response in untreated and anatomically distinct warts is a distinct advantage. A prospective study will be necessary to allow comparison of response rates with intralesional immunotherapy for genital warts and other treatment modalities.

Correspondence: Dr Horn, Department of Dermatology, University of Arkansas for Medical Sciences, 4301 W Markham, No. 576, Little Rock, AR 72205 (hornthomas@uams.edu).

Financial Disclosure: Drs Horn and Johnson have obtained a US patent (6 350 451) and have significant ownership interest in a start-up company formed through the University of Arkansas for Medical Sciences Biomedical Biotechnology Center. This company was created to market a product based on use of the antigens described in this article. Neither author has received payment to perform the work, and the company has not supported any portion of the research described in this article.