A systematic review and network meta-analysis 4 assessing comparative clinical effectiveness for interventions used in the treatment of anogenital warts (AGWs) included 37 RCTs. Carbon dioxide laser therapy is the most effective treatment for achieving complete clearance of AGWs at the end of treatment. Of patient-applied topical treatments, podophyllotoxin 0.5% solution was found to be the most effective at achieving complete clearance, and was associated with a statistically significant difference compared with imiquimod 5% cream and polyphenon E 10% ointment (p<0.05). Few data were available on recurrence of AGWs after complete clearance. In terms of recurrence, no statistically significant difference in risk of recurrence at a maximum follow-up of 6 months was found between podophyllotoxin 0.5% solution and any of cryotherapy, imiquimod 5% cream and surgical excision, with surgical excision identified as the most effective treatment for reducing risk of recurrence after complete clearance.
Another network meta-analysis 5 evaluating the efficacy of topical treatments and ablative procedures for the management of AGWs included 70 RCTs involving 9 931 patients. Surgery achieved the best complete lesion response compared to placebo, see table T1.
| Intervention | Complete lesion response compared with placebo | |
|---|---|---|
| RR | 95% CI | |
| Podophyllin solution | 5.65 | 3.12-10.25 |
| Imiquimod | 4.75 | 2.86-7.89 |
| Surgery | 10.54 | 4.53-24.52 |
| Cryotherapy | 4.34 | 2.50-7.53 |
| Electrosurgery | 7.10 | 3.47-14.53 |
| CO2 laser | 5.62 | 3.00-10.54 |
A systematic review 3 evaluated the clinical effectiveness and cost-effectiveness of interventions for the treatment of anogenital warts. 60 randomised controlled trials (RCTs) evaluating 19 interventions were included. Analysis by mixed-treatment comparison (MTC) indicated that ablative techniques were typically more effective than topical interventions at completely clearing warts at the end of treatment. Podophyllotoxin 0.5% solution was found to be the most effective topical treatment evaluated. Networks for other outcomes included fewer treatments, which restrict conclusions on the comparative effectiveness of interventions. Podophyllotoxin 0.5% solution first line followed by carbon dioxide (CO2) laser therapy second line if warts did not clear was most likely to be considered a cost-effective use of resources at a willingness to pay of £20,000-30,000 per additional quality-adjusted life-year gained. Probability (percentage) of complete clearance at another time point by treatment (sensitivity analysis): Placebo/no treatment 7.9, imiquimod 5% cream 44.7, cryotherapy 52.4, cryotherapy plus podophyllotoxin 0.15% cream 57.5, electrotherapy 65.5.
A Cochrane review [Abstract] 2 included 10 studies with a total of 1734 subjects. 6 trials were funded by industry. Six trials (1294 participants) compared the use of imiquimod vs placebo. There was very low quality evidence that imiquimod was superior to placebo in achieving complete and partial regression (RR 4.03, 95% CI 2.03 to 7.99; RR 2.56, 95% CI 2.05 to 3.20, respectively). However, one better quality multicenter RCT (RR 2.30, 95% CI 1.41 to 3.74; n=534) favoured imiquimod over placebo. When compared with placebo, the effects of imiquimod on recurrence (RR 2.76, 95% CI 0.70 to 10.91), appearance of new warts (RR 0.76, 95% CI 0.58 to 1.00) and frequency of systemic adverse reactions (RR 0.91, 95% CI 0.63 to 1.32) were imprecise.Two trials (105 participants) compared the use of imiquimod versus any other patient-applied treatment (podophyllotoxin and podophyllin). The estimated effects of imiquimod on complete regression (RR 1.09, 95% CI 0.80 to 1.48), partial regression (RR 0.77, 95% CI 0.40 to 1.47), recurrence (RR 0.49, 95% CI 0.21 to 1.11) or the presence of local adverse reactions (RR 1.24, 95% CI 1.00 to 1.54) were imprecise (very low quality evidence).
A topic in Clinical Evidence 1 summarizes the results of one systematic review (search date 2000, 5 RCTs, 588 people with genital warts without HIV infection and 1 RCT (100 people) with HIV infection) and one subsequent RCT. The review found that, in people without HIV, imiquimod cream (1-5%) increased clearance rates compared with placebo (AR for clearance with imiquimod 51% vs 6% with placebo, RR 8.3, 95% CI 5.2 to 13.0, NNT 3). The subsequent RCT found similar results. The RCT on people with HIV found no difference between imiquimod and placebo.
Primary/Secondary Keywords