Extragenital warts on immunocompetent persons usually resolve spontaneously over time and pose no medical risk. Nevertheless, patients frequently request removal of warts for cosmetic or other reasons. Because little objective evidence is available to guide the logical treatment of uncomplicated warts, Gibbs and colleagues systematically reviewed all relevant randomized controlled trials for evidence of treatment efficacy.

They searched electronic databases and registries of controlled trials plus the references of published trials and review articles to identify all relevant trials. Trials were assessed for quality based on such factors as sample size, concealment of treatment allocation, blinding of outcome assessment, management of withdrawals or subjects lost to follow-up, and use of intention-to-treat analysis. The principal outcome examined was complete disappearance of the wart. The search identified 45 papers, which included 50 relevant clinical trials. The trials varied greatly in methodology, and only two were considered to be of high quality.

From the 17 trials that included placebo groups, the average cure rate of placebo was calculated to be 30 percent after 10 weeks. In comparison, the pooled cure rate for salicylic acid preparations was 75 percent with an odds ratio of 3.9. Most preparations used 15 to 26 percent salicylic acid, with or without lactic acid. Minor skin irritations were reported, but there was only one case of a serious side effect (cellulitis in a patient treated with 60 percent salicylic acid plus monochloroacetic acid).

Most trials of cryotherapy compared different techniques rather than comparing cryotherapy with other treatments or placebo. Data from four trials led to the conclusion that aggressive cryotherapy provided cure rates of 52 percent, significantly more effective than the 31 percent reported for gentle cryotherapy. Pain or blistering was reported in about 64 percent of aggressive regimens involving 10-second application compared with 44 percent of patients treated gently with shorter exposures. About 5 percent of patients in the aggressive cryotherapy group withdrew because of side effects. The highest rate of adverse effects occurred in regimens requiring frequent treatments, but the three trials examining frequency of treatment found no significant difference in long-term cure rates between treatments given at two-, three-, or four-week intervals. When cryotherapy was compared with placebo or no treatment in two small trials, no significant difference in cure rates could be demonstrated. Likewise, no significant difference could be determined between cryotherapy and salicylic acid in two trials.

Among many other treatments studied in small trials, evidence of benefit was only found for topical immunotherapy using dini-trochlorobenzene and for photodynamic therapy plus salicylic acid. Both of these treatments were associated with significant adverse effects.

The authors conclude that evidence-based treatment of warts is not currently possible because of the scarcity of high-quality studies of the alternative strategies. Results from small studies generally could not be pooled because of differences in methodology. They report that the best evidence supports use of salicylic acid or dinitrochlorobenzene as topical therapy. Although cryotherapy is widely used, this treatment is not supported by compelling or consistent evidence.