Topically Applied Treatments for External Genital Warts in Nonimmunocompromised Patients

A Systematic Review and Network Meta-analysis

J.M. Jung; C.J. Jung; W.J. Lee; C.H. Won; M.W. Lee; J.H. Choi; S.E. Chang


The British Journal of Dermatology. 2020;183(1):24-36. 

In This Article

Abstract and Introduction


Selecting a topical treatment from among the numerous topical agents for external genital warts remains challenging without clear evidence. Our aim was to evaluate comparatively the efficacy and safety of topical agents for external genital warts using a network meta-analysis. We included all randomized controlled trials that evaluated any topically applied treatment for external genital warts. Using the R package netmeta, network meta-analyses were performed with a frequentist approach. We identified 41 relevant studies comprising 6371 patients. Among conventional agents, podophyllotoxin 0·5% solution (odds ratio 1·94, 95% confidence interval 1·02–3·71) was significantly more efficacious than imiquimod 5% cream for lesion clearance; however, it was associated with a higher overall adverse event rate. Sinecatechins 15% ointment (odds ratio 0·21, 95% confidence interval 0·12–0·34) was significantly less efficacious than imiquimod 5% cream. Idoxuridine, polyhexamethylene biguanide, cidofovir and SB 206 showed comparable therapeutic efficacies with conventional therapies. None of the treatments were significantly different from each other with respect to recurrence, patients with severe adverse events, or patients who withdrew because of treatment-related adverse events. Conventional modalities were efficacious and well tolerated, although each of them had their advantages and disadvantages. Additional efficacy and safety studies are warranted for unconventional agents.


The detrimental impact of genital warts on patients' quality of life and psychosocial well-being has widely been recognized.[1–5] In addition, the socioeconomic burden of genital warts is significant, because they are among the most common sexually transmitted infections.[6]

Several treatment modalities are currently available for external genital warts. Although physical destruction leads to high clearance rates,[7,8] the outcomes vary depending on the proficiency of the clinician. Moreover, physical destruction is associated with extreme pain and high recurrence rates,[9] and modalities such as electrosurgery and laser surgery may cause human papillomavirus (HPV) transmission if HPV particles are present in the smoke plume.[10] Topical therapies can be easily applied by physicians or the patients themselves. Topically applied therapies have typically longer treatment duration than physical methods.[11] However, because they are primarily field directed, they offer advantages when treating multiple lesions, which have a substantial risk of latent HPV presence in the clinically normal epithelium beyond the warts.[12]

Topically applied therapeutic agents for external genital warts include imiquimod, podophyllotoxin, sinecatechins, trichloroacetic acid (TCA) with podophyllin, and unconventional or newly emerging modalities, such as cidofovir gel, idoxuridine, polyhexamethylene biguanide, sodium nitrite with citric acid, and SB206 12%. The lack of head-to-head comparative analysis of various therapies renders choice of treatment a clinical challenge. Therefore, we performed a network meta-analysis (NMA) that provided direct, indirect and mixed evidence[13] to compare multiple treatments simultaneously regarding their efficacy and safety.