Key Publications Common Warts

Common Warts Publications

Common Warts Background Information

  • Wart (Plantar, Verruca Vulgaris, Verrucae). Al Aboud AM, Nigam PK. StatPearls. 2020.
  • Warts are benign lesions that occur in the mucosa and skin. Warts are caused by the human papillomavirus (HPV), with over 100 types of HPV identified. HPV may occur at any site. The primary manifestations of HPV infection include common warts, genital warts, flat warts, deep palmoplantar warts (Myrmecia), focal epithelial hyperplasia, Epidermodysplasia verruciformis, and Plantar cysts. Warts may be transmitted by direct or indirect contact. Events that disrupt the normal epithelial barrier increase the likelihood of developing warts. Treatment may be difficult. Warts often resolve spontaneously within a few years. Some high-risk HPV subtypes are associated with malignancies, including types 6, 11, 16, 18, 31, and 35. Malignant transformation usually is seen in patients with genital warts and immunocompromised patients. HPV types 5, 8, 20, and 47 have oncogenic potential leading to epidermodysplasia verruciformis.
  • https://www.ncbi.nlm.nih.gov/books/NBK431047/
  • Treatment success in cutaneous warts: morphology and human papillomavirus type matter. Hogendoorn GK, Bruggink SC, deKoning MNC, et al. British Journal of Dermatology. 2018; 178(1): 253-260.
  • Background: Cutaneous warts have a cure rate after therapy of no more than approximately 50%. Recently, we developed and validated a standard assessment tool for warts (Cutaneous WARTS diagnostic tool, CWARTS) based on phenotypical characteristics.
  • Objectives: To assess whether patient and morphological wart characteristics predict the human papillomavirus (HPV) type in a specific wart and whether these characteristics as well as the HPV type predict a favourable treatment response.
  • Methods: Photographs were used to score nine morphological wart characteristics using the newly developed CWARTS tool. Genotyping of 23 wart-associated HPV types was performed using the hyperkeratotic skin lesion-polymerase chain reaction/multiplex genotyping assay. The results were correlated with a favourable response to treatment with monochloroacetic acid, cryotherapy or a combination of cryotherapy and salicylic acid. Odds ratios were calculated using logistic regression in a generalized estimating equations model.
  • Results: Black dots (capillary thrombosis) strongly predicted the presence of any HPV type in a wart. From all characteristics tested, the HPV type most strongly predicted the treatment response when the warts were treated with monochloroacetic acid or a combination of cryotherapy and salicylic acid with a significantly decreased treatment response if the warts contained HPVs of the alpha genus (HPV2, HPV27 or HPV57). When cryotherapy alone was used for common warts, HPV type did not play a role, but cryotherapy was less effective in the presence of callus and when the wart was located deeper in the skin.
  • Conclusions: Morphological characteristics of the warts and the HPV genotype influence treatment outcome and thus potentially influence future treatment decisions for common and plantar warts.
  • https://onlinelibrary.wiley.com/doi/full/10.1111/bjd.15758

Current Management of Common Warts

Treatment Landscape of Common Warts

Topical Treatments for cutaneous warts. Kwok CS, Gibbs S, Bennett C, Holland R, Abbott R. Cochrane Database of Systematic Reviews. 9; 1-180.

  • Background: Viral warts are a common skin condition, which can range in severity from a minor nuisance that resolve spontaneously to a troublesome, chronic condition. Many different topical treatments are available.
  • Objectives: To evaluate the efficacy of local treatments for cutaneous non-genital warts in healthy, immunocompetent adults and children.
  • Search methods: We updated our searches of the following databases to May 2011: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library, MEDLINE (from 2005), EMBASE (from 2010), AMED (from 1985), LILACS (from 1982), and CINAHL (from 1981). We searched reference lists of articles and online trials registries for ongoing trials.
  • Selection criteria: Randomised controlled trials (RCTs) of topical treatments for cutaneous non-genital warts.
  • Data collection and analysis: Two authors independently selected trials and extracted data; a third author resolved any disagreements.
  • Main results: We included 85 trials involving a total of 8815 randomised participants (26 new studies were included in this update). There was a wide range of different treatments and a variety of trial designs. Many of the studies were judged to be at high risk of bias in one or more areas of trial design. Trials of salicylic acid (SA) versus placebo showed that the former significantly increased the chance of clearance of warts at all sites (RR (risk ratio) 1.56, 95% CI (confidence interval) 1.20 to 2.03). Subgroup analysis for different sites, hands (RR 2.67, 95% CI 1.43 to 5.01) and feet (RR 1.29, 95% CI 1.07 to 1.55), suggested it might be more effective for hands than feet. A meta-analysis of cryotherapy versus placebo for warts at all sites favoured neither intervention nor control (RR 1.45, 95% CI 0.65 to 3.23). Subgroup analysis for different sites, hands (RR 2.63, 95% CI 0.43 to 15.94) and feet (RR 0.90, 95% CI 0.26 to 3.07), again suggested better outcomes for hands than feet. One trial showed cryotherapy to be better than both placebo and SA, but only for hand warts. There was no significant difference in cure rates between cryotherapy at 2-, 3-, and 4-weekly intervals. Aggressive cryotherapy appeared more effective than gentle cryotherapy (RR 1.90, 95% CI 1.15 to 3.15), but with increased adverse effects. Meta-analysis did not demonstrate a significant difference in effectiveness between cryotherapy and SA at all sites (RR 1.23, 95% CI 0.88 to 1.71) or in subgroup analyses for hands and feet. Two trials with 328 participants showed that SA and cryotherapy combined appeared more effective than SA alone (RR 1.24, 95% CI 1.07 to 1.43). The benefit of intralesional bleomycin remains uncertain as the evidence was inconsistent. The most informative trial with 31 participants showed no significant difference in cure rate between bleomycin and saline injections (RR 1.28, 95% CI 0.92 to 1.78).Dinitrochlorobenzene was more than twice as effective as placebo in 2 trials with 80 participants (RR 2.12, 95% CI 1.38 to 3.26).Two trials of clear duct tape with 193 participants demonstrated no advantage over placebo (RR 1.43, 95% CI 0.51 to 4.05).We could not combine data from trials of the following treatments: intralesional 5-fluorouracil, topical zinc, silver nitrate (which demonstrated possible beneficial effects), topical 5-fluorouracil, pulsed dye laser, photodynamic therapy, 80% phenol, 5% imiquimod cream, intralesional antigen, and topical alpha-lactalbumin-oleic acid (which showed no advantage over placebo).We did not identify any RCTs that evaluated surgery (curettage, excision), formaldehyde, podophyllotoxin, cantharidin, diphencyprone, or squaric acid dibutylester.
  • Authors’ conclusions: Data from two new trials comparing SA and cryotherapy have allowed a better appraisal of their effectiveness. The evidence remains more consistent for SA, but only shows a modest therapeutic effect. Overall, trials comparing cryotherapy with placebo showed no significant difference in effectiveness, but the same was also true for trials comparing cryotherapy with SA. Only one trial showed cryotherapy to be better than both SA and placebo, and this was only for hand warts. Adverse effects, such as pain, blistering, and scarring, were not consistently reported but are probably more common with cryotherapy. None of the other reviewed treatments appeared safer or more effective than SA and cryotherapy. Two trials of clear duct tape demonstrated no advantage over placebo. Dinitrochlorobenzene (and possibly other similar contact sensitisers) may be useful for the treatment of refractory warts.
  • https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD001781.pub3/full
    • Paid access
  • The effectiveness of cutaneous Wart Resolution with Current Treatment Modalities. Ringin SA. J Cutan Aesthet Surg. 2020; 13(1): 24–30.
  • Non-venereal warts are a frequent dermatological presentation with potential spontaneous regression in immunocompetent adults and children within 2 years. Evidence shows that conventional wart treatments are not a guaranteed treatment modality and can carry concerns regarding safety.
  • The aim of this literature review was to identify the most effective treatments for wart resolution to guide clinical practice while identifying areas for further research. A systematic literature review was performed to determine the current treatment modalities for non-anogenital cutaneous warts in immunocompetent individuals and their effectiveness. Articles were categorized into one of eight groups depending on anatomical location, population age, or recalcitrant status with ranked levels of evidence.
  • This literature review highlights a variety of treatments for non-venereal warts shown to be effective. In this instance where optimal evidence-based treatments are not available, clinical experience determines the most appropriate clinical practice. Further reproducible immunotherapy research on wart resolution is required to enable clear comparisons of these treatment modalities to conventional methods. Future clinical practice will require the human papillomavirus type to target the wart treatment accordingly; however, further research is required to determine these correlations
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7335473/

Cantharidin Use in Common Warts

  • Efficacy and Safety of Topical Cantharidin Treatment for Molluscum Contagiosum and Warts: A Systematic Review. Vakharia PP, Chopra R, Silverberg NB, Silverberg JI. American Journal of Clinical Dermatology. 2018;19(6):791-803.
  • Background and objective: Topical cantharidin is routinely used for the treatment of molluscum contagiosum and warts. The objective of this systematic review is to assess the efficacy and safety of topical cantharidin treatment for molluscum contagiosum and warts.
  • Methods: We performed a systematic review of studies assessing topical cantharidin treatment of molluscum contagiosum or warts. We searched the databases of Cochrane, EMBASE, GREAT, LILACS, MEDLINE, and Scopus. Two authors performed the study selection and data extraction.
  • Results: Twenty studies (1958-2018) met inclusion/exclusion criteria. Twelve studies assessed warts, and eight studies assessed molluscum contagiosum. Overall, 1752 patients were included (range 0.3-62 years; specified in 15 studies). Clearance rates with topical cantharidin for molluscum contagiosum were variable (range 15.4-100%). Significant clearance of warts with maintenance of clearance was demonstrated with topical cantharidin alone. Topical cantharidin in combination with podophyllotoxin and salicylic acid demonstrated efficacy for plantar warts (pediatric and adult; clearance rate range 81-100%; four studies had 100% clearance), with the majority clearing after a single treatment. Satisfaction with cantharidin therapy was high, especially in molluscum contagiosum. Pain (7-85.7%), blistering (10-100%), and hyper-/hypopigmentation (1.8-53.3%) were the most commonly occurring adverse effects with cantharidin treatment.
  • Conclusion: Topical cantharidin demonstrated clearance of warts, particularly in combination with podophyllotixin and salicylic acid, and modest benefit for pediatric molluscum contagiosum with good tolerability and safety.
  • https://link.springer.com/article/10.1007%2Fs40257-018-0375-4
    • Paid access
  • Cantharidin Treatment of Digital and Periungual Warts. Epstein JH and Epstein WL. California Medicine. 1960; 93(1):11-12.
  • Seventy-six digital and periungual warts in 40 patients were treated topically with cantharidin, a potent blistering agent. The material, dissolved in equal parts of acetone and collodion, was applied directly to the warts. Occlusion facilitated blistering. No pretreatment was required. The warts were re-treated at weekly intervals until clinically cured.
  • Fifty-six per cent of digital warts and 33 per cent of periungual warts cleared after a single application of cantharidin. Few required more than three treatments. Observation was continued for more than six months in more than half of the cases. Cure was lasting in about 70 per cent of the cases in which the long term result was known.
  • Cantharidin ranks with liquid nitrogen in effectiveness, but it is painless to apply and does not cause scarring. For these reasons it is especially useful in children.
  • The main disadvantage is pain and tenderness at the treated site for two to four days in some patients. This can be avoided by careful application of the drug. Occasionally new warts appear at the edge of the cantharidin blister. They are best treated by curettage and desiccation.
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1578244/

Use of VP-102 in Common Warts*

  • COVE-1: A Phase 2, Open-Label Study to Evaluate Efficacy, Safety, and Tolerability of a Proprietary Drug-Device Combination Product Containing 0.7% w/v Cantharidin (VP-102) for Topical Treatment of Common Warts. Guenthner S, McFalda W, Kwong P, et al. Fall Clinical October 19, 2019, Las Vegas, NV.
  • Background and Objective: Studies have shown variable effectiveness of compounded cantharidin in the treatment of common warts (verruca vulgaris) due to a lack of standardized treatment regimens, quality of ingredients and formulations, and large-scale clinical trials. This Phase 2 study’s objective was to evaluate the efficacy, safety, tolerability, and optimal regimen of VP-102 in the treatment of common warts.  VP-102 is a proprietary drug-device combination product containing a topical formulation with 0.7% (w/v) cantharidin in a single-use delivery device.
  • This study included subjects with up to six common warts (≤10mm in diameter, <3mm in height, excluding genital, palmar/plantar and subungual warts) in two treatment Cohorts. Cohort 1 (n=20) included subjects ≥2 years old for dermal application of VP-102 occluded with transparent surgical tape for 24 hours to all treatable wart sites once every 14 days until complete clearance or up to 4 treatments, followed by wart clearance and safety assessments at Day 84. Cohort 2 (n=35) included subjects ≥12 years old had wart paring to remove thick scale prior to application of VP-102 with occlusive tape for 24 hours, with clinic visits to measure safety and efficacy assessments and apply VP-102 every 21 days for up to 4 treatments, followed by a safety and efficacy assessment at D84. Safety and efficacy of warts treated prior to D84 was also measured during follow up visits on days 105, 126, and 147 in Cohort 2.
  • Results: The percentage of subjects with complete clearance of all treatable common warts at D84 was 19% (4/21) for Cohort 1 and 51% (18/35) for Cohort 2.  Percentages of complete clearance for follow-up visits for Cohort 2 were 45.7%, 40%, and 40% for days 105, 126 and 147, respectively. The most common treatment emergent AE’s included application site vesicles, pain, pruritus, erythema and scab, and most AEs were mild or moderate in severity.  AEs listed were considered related to pharmacodynamic action of the active ingredient cantharidin, a topical vesicant.
  • Conclusions: VP-102 showed a favorable tolerability and acceptable safety profile, as well as efficacy in complete clearance of common warts from baseline to D84, as well as follow up visits.   Due to higher percentage of patients with complete clearance the treatment regimen for Cohort 2 will be utilized in future studies.  Studies were sponsored by Verrica Pharmaceuticals Inc.

https://cdn.verrica.com/wp-content/uploads/2020/06/06221047/COVE-Poster_10.17.2019_11.10-Compressed.pdf

*VP-102 has not been approved by the FDA.