A systematic review and network meta-analysis 2 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 3 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 T2.
| 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. Results for complete clearance without recurrence are shown in table (T1). 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.
| Intervention | Comparator, Odd ratios =OR (95% CrI) | ||||
|---|---|---|---|---|---|
| Cryotherapy | Placebo/no treatment | Imiquimod 5% cream | Electrotherapy | Cryotherapy plus podophyllotoxin 0.15% cream | |
| Cryotherapy | - | - | - | - | - |
| Placebo/no treatment | 0.09 (0.001 to 0.47) | ||||
| Imiquimod 5% cream | 0.78 (0.35 to 1.51) | 1336 (1.42 to 489.9) Median OR 15.47 | - | - | - |
| Electrotherapy | 2.22 (0.53 to 6.49) | 4860 (5.90 to 970.5) Median OR 36.48 | 3.27 (0.60 to 10.85) | - | - |
| Cryotherapy plus podophyllotoxin 0.15% cream | 1.31 (0.64 to 2.41) | 2120 (2.38 to 811.9) Median OR 26.42 | 1.93 (0.63 to 4.62) | 0.89 (0.16 to 2.79) | - |
A topic in Clinical Evidence 1 summarizes the results of RCTs on cryotherapy. There were no placebo-controlled trials. Two trials comparing cryotherapy to electrosurgery and/or podophyllin. The first trial (n=450) found that cryotherapy was less effective at 6 weeks (clearing warts 79% with cryotherapy vs 94% with electrosurgery, p=0.003) than electrosurgery, but more effective than podophyllin (clearance with podophyllin 41%, p<0.0001). The second trial (n=42) comparing cryotherapy and electrosurgery at 2 week intervals until warts were completely cleared found no difference at 3 months' follow-up. Two trials found cryosurgery as effective as trichloroacetic acid (clearance 70% vs 64%, 81% vs 89%).
A randomized controlled trial 2 compared CO(2) laser therapy versus cryotherapy in treatment of genital warts. 160 patients, with external genital warts, were divided into two equal groups treated with CO(2)-laser or cryotherapy. Clearance and recurrence rates were evaluated for 3 months.Complete clearance was achieved in 76 lesions (95%) treated by CO(2)-laser and 37 lesions (46.2%) treated by cryotherapy (p < 0.001). In the CO(2)-laser group, lesions required only one treatment to clear while in the cryotherapy group, lesions required two (12%) even up to three (12.2%) treatments for some patients to clear completely. Laser therapy was associated with less recurrence rate compared to cryotherapy (0.05% Vs 0.18%).
Comment: The quality of evidence was downgraded by inconsistency of results.
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