SLR - July 2023 - Anna Kapustina, DPM, MS, PGY1
Title: Efficacy of cryotherapy for plantar warts: A systematic review and meta‐analysis.Reference: García-Oreja S, Álvaro-Afonso FJ, Tardáguila-García A, López-Moral M, García-Madrid M, Lázaro-Martínez JL. Efficacy of cryotherapy for plantar warts: A systematic review and meta-analysis. Dermatol Ther. 2022 Jun;35(6): e15480.
Level of evidence: I
Reviewed By: Anna Kapustina, DPM, MS, PGY1
Residency Program: Southern Arizona Veterans Affairs Healthcare System
Podiatric relevance:
Plantar warts are common (incidence 14%) benign lesions caused by human papilloma virus infection of skin cells. They can be infectious, painful, unpleasant and, in severe cases, lead to cellulitis. There is no set treatment protocol, and no single treatment has shown to be highly effective. Cryotherapy is a treatment of choice due to its wide availability and cost-effectiveness. Potential side effects of cryotherapy include pain due to perilesional tissue destruction, scar formation, dyspigmentation, healing complications, and recurrence. According to the literature, cryotherapy by itself produces a lower cure rate of 45.61%, compared to laser (79.36%), cantharidin1%-podophyllotoxin5%-salicylic acid30% (CPS) formulation (97.82%), or topical antivirals (72.45%). The purpose of this study is to compare cryotherapy to alternative treatment methods.
Methods:
Multiple randomized controlled trials (RCTs) of level 1b (A) on cryotherapy used as treatment of plantar warts, in males/females, published in English/Spanish, between 1984 and 2020 were included in this study. Unrecorded cure rates and common/genital warts were excluded. The following outcomes were collected for each study: type of the study, demographics, topical intervention, treatment type, complete cure rate, and number of treatment sessions. The studies were assessed for levels of evidence and types of bias.
Results:
After screening 153 articles, 14 RTCs were selected for this meta-analysis with a mean of 77 subjects per study. Meta-analysis was conducted using four sub-groups: 1) keratolytic agents (self-treatment with 50% salicylic acid, 40% trichloroacetic acid (TCA), CPS formulation, or 10% formaldehyde), 2) antivirals (5% acyclovir cream), chemotherapy (intralesional bleomycin), retinoids (adapalene 0.1% gel), 3) physical treatments (electrodesiccation and CO2 laser), 4) placebo/duct tape. The results showed no significant inferiority/superiority of cryotherapy compared to keratolytic agents, as well as physical treatments, as well as placebo/duct tape. Also, no difference was found between cryotherapy application protocols (two rounds of 10 seconds versus four rounds of 5 seconds of freeze-thaw cycles). However, cryotherapy compared to antivirals, chemotherapy, and retinoids, favored antivirals and chemotherapy over cryotherapy. Cryotherapy spray compared to intralesional cryotherapy favored intralesional cryotherapy.
Conclusion:
The limitations of this study were high or medium levels of bias, which prevented proper randomization and possibly affected the results. The total cure rate was the only factor analyzed. The other aspects, such as partial clearance, number of sessions, time to cure, patient satisfaction, quality of life during treatments, cost-effectiveness, were not considered. Overall, lack of studies limited analysis of long term follow up and the ability to estimate recurrence rates. In conclusion, this study has shown the evidence of the superiority of antivirals and chemotherapy over cryotherapy in the treatment of plantar warts. However, no evidence supports the superiority or inferiority of cryotherapy compared to other treatments. More high quality, low-biased studies on this topic are needed in the future.