Comparative Efficacy and Safety of Non-Cryotherapy Treatments Versus Cryotherapy for Plantar Warts: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background/Objectives: To systematically evaluate and compare the clinical efficacy and safety of non-cryotherapy modalities versus standard liquid nitrogen cryotherapy for the treatment of plantar warts, while exploring the influence of specific cryotherapy procedural parameters and intervention-related subgroup characteristics on treatment outcomes. Methods: A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted according to PRISMA guidelines. We searched four major databases from inception until 1 July 2026. The primary outcome was complete clearance. Secondary outcomes included partial clearance, recurrence, and treatment-related adverse events. Pooled risk ratios (RR) with 95% confidence intervals (CI) were calculated using random-effects models. Results: Thirty-one RCTs involving 2313 patients were included. No statistically significant difference was detected between non-cryotherapy modalities and cryotherapy in complete clearance rates (RR = 1.09, 95% CI: 0.98-1.20; p = 0.10; I2 = 0.00%) or recurrence outcomes (RR = 0.90, 95% CI: 0.56-1.44; p = 0.66). Partial clearance significantly favored cryotherapy (RR = 0.65, 95% CI: 0.44-0.95; p = 0.03), particularly in subgroup analyses using two freeze-thaw cycles and treatment intervals of every two weeks. Regarding safety, topical therapies demonstrated significantly lower erythema rates than cryotherapy, while no statistically significant differences were observed in blistering, scarring, or secondary bacterial infection. Conclusions: No statistically significant difference was detected between non-cryotherapy modalities and cryotherapy regarding complete clearance or recurrence of plantar warts. Cryotherapy may offer better partial clearance under optimized treatment parameters, whereas topical therapies may be better tolerated in selected patients.