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Evidence summaries

Cryotherapy for Genital Warts

Cryotherapy appears to be effective for external genital warts but appears to be less effective than laser or electrotherapy. Level of evidence: "B"

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.

Results for complete clearance without recurrence

InterventionComparator, Odd ratios =OR (95% CrI)
CryotherapyPlacebo/no treatmentImiquimod 5% creamElectrotherapyCryotherapy plus podophyllotoxin 0.15% cream
Cryotherapy-----
Placebo/no treatment0.09 (0.001 to 0.47)
Imiquimod 5% cream0.78 (0.35 to 1.51)1336 (1.42 to 489.9) Median OR 15.47---
Electrotherapy2.22 (0.53 to 6.49)4860 (5.90 to 970.5) Median OR 36.483.27 (0.60 to 10.85)--
Cryotherapy plus podophyllotoxin 0.15% cream1.31 (0.64 to 2.41)2120 (2.38 to 811.9) Median OR 26.421.93 (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.

    References

    • Buck H. What are the effects of treatments for external genital warts.? Genital warts. Clinical Evidence 2005;13:2005-2015.
    • Azizjalali M, Ghaffarpour G, Mousavifard B. CO(2) Laser therapy versus cryotherapy in treatment of genital warts; a Randomized Controlled Trial (RCT). Iran J Microbiol 2012;4(4):187-90.[PubMed]
    • Thurgar E, Barton S, Karner C et al. Clinical effectiveness and cost-effectiveness of interventions for the treatment of anogenital warts: systematic review and economic evaluation. Health Technol Assess 2016;20(24):v-vi, 1-486.[PubMed]

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