title: Treatment of vulvar intraepithelial neoplasia with topical imiquimod.
abstract: BACKGROUND
  Alternatives to surgery are needed for the treatment of vulvar intraepithelial neoplasia. We investigated the effectiveness of imiquimod 5% cream, a topical immune-response modulator, for the treatment of this condition.
  
  
  METHODS
  Fifty-two patients with grade 2 or 3 vulvar intraepithelial neoplasia were randomly assigned to receive either imiquimod or placebo, applied twice weekly for 16 weeks. The primary outcome was a reduction of more than 25% in lesion size at 20 weeks. Secondary outcomes were histologic regression, clearance of human papillomavirus (HPV) from the lesion, changes in immune cells in the epidermis and dermis of the vulva, relief of symptoms, improvement of quality of life, and durability of response. Reduction in lesion size was classified as complete response (elimination), strong partial response (76 to 99% reduction), weak partial response (26 to 75% reduction), or no response (< or =25% reduction). The follow-up period was 12 months.
  
  
  RESULTS
  Lesion size was reduced by more than 25% at 20 weeks in 21 of the 26 patients (81%) treated with imiquimod and in none of those treated with placebo (P<0.001). Histologic regression was significantly greater in the imiquimod group than in the placebo group (P<0.001). At baseline, 50 patients (96%) tested positive for HPV DNA. HPV cleared from the lesion in 15 patients in the imiquimod group (58%), as compared with 2 in the placebo group (8%) (P<0.001). The number of immune epidermal cells increased significantly and the number of immune dermal cells decreased significantly with imiquimod as compared with placebo. Imiquimod reduced pruritus and pain at 20 weeks (P=0.008 and P=0.004, respectively) and at 12 months (P=0.04 and P=0.02, respectively). The lesion progressed to invasion (to a depth of <1 mm) in 3 of 49 patients (6%) followed for 12 months (2 in the placebo group and 1 in the imiquimod group). Nine patients, all treated with imiquimod, had a complete response at 20 weeks and remained free from disease at 12 months.
  
  
  CONCLUSIONS
  Imiquimod is effective in the treatment of vulvar intraepithelial neoplasia. (Current Controlled Trials number, ISRCTN11290871 [controlled-trials.com].).
authors.affiliation: Department of Gynecology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Manon
authors.initials: M
authors.lastname: van Seters
authors.forename: Marc
authors.initials: M
authors.lastname: van Beurden
authors.forename: Fiebo J W
authors.initials: FJ
authors.lastname: ten Kate
authors.forename: Ilse
authors.initials: I
authors.lastname: Beckmann
authors.forename: Patricia C
authors.initials: PC
authors.lastname: Ewing
authors.forename: Marinus J C
authors.initials: MJ
authors.lastname: Eijkemans
authors.forename: Marjolein J
authors.initials: MJ
authors.lastname: Kagie
authors.forename: Chris J M
authors.initials: CJ
authors.lastname: Meijer
authors.forename: Neil K
authors.initials: NK
authors.lastname: Aaronson
authors.forename: Alex
authors.initials: A
authors.lastname: Kleinjan
authors.forename: Claudia
authors.initials: C
authors.lastname: Heijmans-Antonissen
authors.forename: Freek J
authors.initials: FJ
authors.lastname: Zijlstra
authors.forename: Matthé P M
authors.initials: MP
authors.lastname: Burger
authors.forename: Theo J M
authors.initials: TJ
authors.lastname: Helmerhorst
mesh_terms: D000287:Administration, Topical; D000328:Adult; D000368:Aged; D000634:Aminoquinolines / Q000008:administration & dosage* / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001706:Biopsy; D002278:Carcinoma in Situ / Q000188:drug therapy* / Q000473:pathology; D004279:DNA, Viral / Q000302:isolation & purification; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000077271:Imiquimod; D008875:Middle Aged; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification; D030361:Papillomavirus Infections / Q000188:drug therapy*; D011788:Quality of Life; D014846:Vulvar Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000634:Aminoquinolines; D000970:Antineoplastic Agents; D004279:DNA, Viral; D000077271:Imiquimod