LAUSR

Human papillomaviruses (HPVs) are ubiquitous and implicated in numerous benign, premalignant and malignant cutaneous conditions. External genital warts are frequently distressing to patients and often challenging for physicians to treat. In this issue of the BJD, Jung et al. review topically applied treatments for external genital warts in nonimmunocompromised patients. Theirs is one of the first network meta-analyses (NMAs) on the subject. A NMA compares multiple treatments using both direct and indirect comparisons across trials, which can be helpful when studies that directly compare treatments do not exist. Previous conventional meta-analyses on this subject have cited small numbers of direct comparisons as a limiting factor. Jung et al. examined four outcomes: clearance, recurrence, adverse events, and patients with severe adverse events or who withdrew for treatment-related adverse events. Partial clearance was not evaluated. Previous studies have generally not found a significant difference in rates of complete clearance between topically applied therapies. The conclusions reached by Jung et al. may provide some welcome direction to physicians. All agents were shown to be superior to placebo. Podophyllotoxin 0 5% solution was significantly superior to imiquimod 5% cream for wart clearance [odds ratio (OR) 1 94, 95% confidence interval (CI) 1 02– 3 71], but was also associated with a higher overall rate of adverse events. This finding was supported by another recently published NMA assessing topical and ablative therapies. In practice, compared with imiquimod, podophyllotoxin has a shorter indicated duration of therapy (4 weeks vs. 16 weeks) and is less expensive. However, the patient must apply the solution precisely to each wart as opposed to spreading cream over an affected area. This could be difficult for patients with vision or dexterity issues, or who have warts in the perianal area. Sinecatechins 15% ointment was found to be inferior to imiquimod 5% cream with respect to clearance (OR 0 21, 95% CI 0 12–0 34). Although both agents are used for 16 weeks, sinecatechins are applied three times daily as opposed to once daily, which may affect patient adherence. In terms of recurrence, no difference between treatments was noted. Although many postulate that the use of an agent which provokes an immune response may provide decreased rates of recurrence compared with a cytodestructive agent, little evidence currently exists to support this idea. The use of physically destructive (cryotherapy or curettage/ excision) modalities in combination with topically applied treatments is generally felt to be advantageous compared with monotherapy, but published evidence in this area is also limited. Further research is still very much needed in immunocompromised populations, for whom successful treatment can be exceptionally difficult. The impact of access and cost also remains an important variable that is challenging to study on a global basis. Although prophylactic administration of the HPV immunization is ideal, evidence continues to grow, mostly in the form of case reports and small case series, indicating that administration of the immunization post-HPV exposure may prevent and/or mitigate further benign, premalignant and malignant HPV-mediated disease. Physicians often struggle to determine the ‘best’ treatment plan to treat external genital warts. In practice, the ‘best’ treatment plan often lies at the intersection of patient preference, physician familiarity, access and cost.