van Seters M et al. (2008) Treatment of vulvar intraepithelial neoplasia with topical imiquimod. N Engl J Med 358: 1465–1473

Surgical treatment of vulvar intraepithelial neoplasia (VIN) can cause disfigurement of the vulva and does not always prevent recurrence or progression because the most common cause of these lesions, human papillomavirus (HPV), is not eliminated. A less-invasive and more-effective treatment is, therefore, required. To address this need, van Seters et al. investigated the efficacy of a topical formulation of imiquimod, an immune-response modifier that is known to promote apoptosis in tumor cells.

A total of 52 patients (age range 22–71 years) with predominantly grade 2–3 VIN were randomly assigned to either imiquimod 5% or placebo cream. Both creams were self-administered to lesions twice weekly for 16 weeks. HPV-positive lesions were detected in 25 patients in each group at baseline. Lesion size was measured every 4 weeks and biopsies were performed at baseline and at 20 weeks.

At the end of the study period, 21 (81%) of 26 patients treated with imiquimod achieved a >25% reduction in lesion size; none of the patients in the placebo group reached this end point. In addition, a complete response (100% reduction in lesion size) was observed in 9 of the imiquimod-treated patients, all of whom remained disease-free at 12 months' follow-up. HPV was eradicated in 15 lesions treated with imiquimod but in only 2 placebo-treated lesions (P <0.001). Regression of histological grade was observed in 18 patients treated with imiquimod, compared with 1 patient in the placebo group. Imiquimod treatment also provided notable relief of itching and pain over the duration of the study and follow-up period. The authors recommend imiquimod 5% cream as first-line therapy for patients with VIN.