Topical Imiquimod vs Surgery for Vulvar High-Grade Squamous Intraepithelial Neoplasia

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In an Austrian phase III trial reported in The Lancet, Trutnovsky et al found that topical imiquimod was noninferior to surgery as measured by complete clinical response in patients with vulvar high-grade squamous intraepithelial lesions.

Study Details

In the multicenter trial, 107 evaluable patients with vulvar high-grade squamous intraepithelial lesions (intention to treat [ITT] population) were randomly assigned between June 2013 and January 2020 to receive imiquimod (n = 54) or surgery (n = 53). Imiquimod was self-administered in a slowly escalating dosage scheme up to three times per week for a period of 4 to 6 months. Patients who had not achieved a complete clinical response at 4 months were requested to continue application until complete clinical response, with a maximum duration of 6 months. Surgery consisted of excision or ablation.

The primary endpoint was complete clinical response at 6 months. The primary analysis was performed in the per-protocol population, consisting of 46 patients in the imiquimod group and 52 in the surgery group. Noninferiority of imiquimod was established if the upper bound of the 95% confidence interval (CI) for the difference did not exceed 20%.

Key Findings

In the per-protocol population, complete clinical response at 6 months was achieved in 37 (80%) of 46 patients in the imiquimod group vs 41 (79%) of 52 patients in the surgical group after one surgical intervention, with noninferiority of imiquimod being shown (difference =  –0.016, 95% CI = –0.15 to –0.18, P = .0056). In the ITT population, complete clinical response was achieved in 39 patients (72%) vs 42 patients (79%), with a trend toward noninferiority observed (difference = –0.07, 95% CI = –0.23 to –0.09, P = .065). Human papillomavirus testing at 6 months in 45 patients in the imiquimod group and 43 in the surgery group showed positive results in 15 (33%) vs 11 patients (26%; P = .43).

Questionnaires assessing psychosexual distress, sexual activity, and fear of progression showed no significant differences between study groups at 6 or 12 months and no significant difference in treatment satisfaction between groups. Patient diaries indicted that the highest vulvar pain was experienced in the first month after surgery and that vulvar pruritus was highest during the first 2 months of imiquimod treatment. Vulvar erosion or erythema and general complaints such as fatigue were reported more frequently in the imiquimod group. Median analgesic drug intake was higher in the surgery group.

The investigators concluded, “Imiquimod is a safe, effective, and well-accepted alternative to surgery for women with vulvar high-grade squamous intraepithelial lesions and can be considered as first-line treatment.”

Gerda Trutnovsky, MD, of the Department of Obstetrics and Gynaecology, Medical University of Graz, is the corresponding author for The Lancet article.

Disclosure: The study was funded by the Austrian Science Fund and Austrian Gynaecological Oncology group. For full disclosures of the study authors, visit