title: Medical interventions for high grade vulval intraepithelial neoplasia.
abstract: BACKGROUND
  Vulval intraepithelial neoplasia (VIN) is a pre-malignant condition of the vulval skin; its incidence is increasing in women under 50 years. VIN is graded histologically as low grade or high grade. High grade VIN is associated with infection with human papilloma virus (HPV) infection and may progress to invasive disease. There is no consensus on the optimal management of high grade VIN. The high morbidity and high relapse rate associated with surgical interventions call for a formal appraisal of the evidence available for less invasive but effective interventions for high grade VIN.
  
  
  OBJECTIVE
  To evaluate the effectiveness and safety of medical interventions for high grade VIN.
  
  
  METHODS
  We searched the Cochrane Gynaecological Cancer Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 3), MEDLINE and EMBASE (up to September 2010). We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field.
  
  
  METHODS
  Randomised controlled trials (RCTs) that assessed medical interventions, in adult women diagnosed with high grade VIN.
  
  
  METHODS
  Two review authors independently abstracted data and assessed risk of bias. Where possible the data were synthesised in a meta-analysis.
  
  
  RESULTS
  Four trials met our inclusion criteria: three assessed the effectiveness of topical imiquimod versus placebo in women with high grade VIN; one examined low versus high dose indole-3-carbinol in similar women. Meta-analysis of three trials found that the proportion of women who responded to treatment at 5 to 6 months was much higher in the group who received topical imiquimod than in the group who received placebo (relative risk (RR) = 11.95, 95% confidence interval (CI) 3.21 to 44.51). A single trial showed similar results at 12 months in (RR = 9.10, 95% CI 2.38 to 34.77). Only one  trial reported adverse events, which were more common in the imiquimod group. One trial found no significant differences in quality of life (QoL) or body image between the imiquimod and placebo groups.
  
  
  CONCLUSIONS
  Imiquimod appears to be effective, but its safety needs further examination. Its use is associated with side effects which are tolerable, but more extensive data on adverse effects are required. Long term follow-up should be mandatory in view of the known progression of high grade VIN to invasive disease. Alternative medical interventions, such as cidofovir, should be explored.
authors.affiliation: Obstetrics and Gynaecology, Queen Elizabeth The Queen Mother Hospital, St Peter's Road, Margate, Kent, UK, CT9 4AN.
authors.forename: Litha
authors.initials: L
authors.lastname: Pepas
authors.forename: Sonali
authors.initials: S
authors.lastname: Kaushik
authors.forename: Andrew
authors.initials: A
authors.lastname: Bryant
authors.forename: Andy
authors.initials: A
authors.lastname: Nordin
authors.forename: Heather O
authors.initials: HO
authors.lastname: Dickinson
mesh_terms: D000287:Administration, Topical; D000328:Adult; D000634:Aminoquinolines / Q000008:administration & dosage* / Q000009:adverse effects; D016588:Anticarcinogenic Agents / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002278:Carcinoma in Situ / Q000473:pathology / Q000628:therapy*; D005260:Female; D006801:Humans; D000077271:Imiquimod; D007211:Indoles / Q000008:administration & dosage*; D016032:Randomized Controlled Trials as Topic; D014846:Vulvar Neoplasms / Q000473:pathology / Q000628:therapy*
chemical_list: D000634:Aminoquinolines; D016588:Anticarcinogenic Agents; D000970:Antineoplastic Agents; D007211:Indoles; C016517:indole-3-carbinol; D000077271:Imiquimod