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QUESTION: In healthy people with clinically observed viral warts, are common topical treatments or cryotherapy more effective than placebo or no treatment for improving clinical cure?
Studies were identified by searching electronic databases that included Medline (1966 to May 2000), EMBASE/Excerpta Medica (1980 to August 2000), and CINAHL (1982 to March 1999); hand searching 8 relevant journals; and by reviewing bibliographies of relevant articles. Experts in the field and pharmaceutical companies were contacted for unpublished studies.
Studies in any language were selected if they were randomised controlled trials (RCTs) of local treatments (all topical, intralesional, and surgical treatments, including cryotherapy but not systemic or psychological treatments) in people with clinically observed non-genital viral warts.
Data were extracted on study setting, sample size, key components of the intervention, study quality and outcomes. The main outcome was clinical cure (defined as complete disappearance of elevated/warty skin) at the end of a treatment period.
50 RCTs met the selection criteria. Meta-analyses were done using random effects models. (1) Simple topical agents containing salicylic acid and/or lactic acid for 6–12 weeks (13 RCTs): meta-analysis of 6 RCTs showed that the cure rate was higher in the treatment group than in the placebo group (table). (2) Cryotherapy (16 RCTs): meta-analysis of 2 RCTs that compared cryotherapy with placebo showed that the groups did not differ for cure rate (table). (3) Intralesional bleomycin (4 RCTs): the only RCT that used participants as the unit of analysis showed that the bleomycin and placebo groups did not differ for cure rate (table). (4) Topical 5-fluorouracil (3 RCTs): the cure rate was greater in the 5-fluorouracil group than in the placebo group in only1 RCT that made the comparison (table). (5) Intralesional interferons (6 RCTs): meta-analysis of 3 RCTs that compared interferon α with placebo showed that the groups did not differ for cure rate (table). (6) Dinitrochlorobenzene (DNCB) (2 RCTs): meta-analysis showed that the cure rate was greater in the DNCB group than in the placebo group (table). (7) Photodynamic treatment (PDT) (4 RCTs): 1 high quality RCT reported that the cure rate was greater in the aminolaevulinic PDT group than in the placebo PDT group (56% v 42% of warts, p<0.05).
In healthy people with viral non-refractory warts, common topical applications containing salicylic acid and/or lactic acid are more effective than placebo for improving clinical cure. Evidence on the effectiveness of cryotherapy is inconclusive.
Viral warts are common complaints. Although they are painful over a pressure point, the main reason for seeking treatment is cosmetic appearance. In addition to over the counter topical treatments, cryotherapy is available from physicians who widely believe that it is more effective. The trial by Focht et al and the systematic review by Gibbs et al raise a number of methodological issues that have been discussed elsewhere.1–2 Both studies call into question the effectiveness of freezing warts with liquid nitrogen. Should physicians abandon cryotherapy?
In the trial, duct tape was found to be more effective than cryotherapy, but the absolute effectiveness of cryotherapy was difficult to determine because no placebo group was used. In the systematic review, the average placebo cure rates were 30% in the 17 trials that used a placebo group. Surprisingly little is known about the longer term natural history of viral warts. A study by Massing and Epstein of 1000 institutionalised children suggested that over two thirds of warts (single and multiple) disappeared without any form of treatment after 2 years.3 Similar 2 year clearance rates have been reported elsewhere,4 reinforcing the point that “no treatment” must remain a viable option to many patients, or that at least a “no treatment” group should be included in future clinical studies to assess the additional benefit of treatment.
Thirteen years ago, Glover commented in a review of warts that “the knowledge of the disease and its treatments is often inversely proportional to the frequency of the disease”.5 The well done systematic review on local treatments by Gibbs et al confirms that little has changed since Glover threw down the gauntlet. The history of RCTs for viral warts is largely a shambles, characterised by a profusion of small poor quality studies that do not take several important factors into account. These include age of patient, location of the warts on the feet or hands, type of wart, duration of wart and previous treatment, source of participants (from primary or secondary care), as well as factors relating to the intervention such as timing, duration, and frequency of cryotherapy. Long term studies are needed to capture wart recurrences.1 Altman goes on to discuss design options for future RCTs, such as within patient comparisons and the importance of considering individual people and not warts as the unit of analysis.2
In the meantime, as we await better evidence, when faced with someone presenting with a wart, it may be prudent to first consider doing nothing given the high rate of natural resolution of some warts. Then we should try out treatments that are best supported by the available evidence base and those with the least propensity to cause harm, such as topical salicylic acid gels or duct tape. Cryotherapy could be reserved as a third option should these 2 fail.
For correspondence: Dr S Gibbs, Ipswich Hospital NHS Trust, Ipswich, UK.
Source of funding: Norfolk Health Authority UK.
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