Primary imiquimod treatment versus surgery for vulvar intraepithelial neoplasia - pitvin study. a randomized clinical trial

Introduction/Background*Surgery is the standard treatment for HPV-associated high-grade vulvar intraepithelial neoplasia (HSIL/VIN), but recurrences occur in about 50% of patients. Imiquimod, a topical immune response modifier, alters the local immune response in favour of HPV clearance and has been shown to be an effective treatment. The aim of this study was to compare the safety, effectiveness and acceptance of primary imiquimod treatment with surgical treatment of HSIL/VIN.MethodologyThis was a multicentre randomised controlled trial of women with histologically confirmed HSIL/VIN. Exclusion criteria were clinical suspicion of microinvasion, a history of vulvar cancer, severe dermatosis, pregnancy, and any active treatment for VIN within the previous three months. Patients were randomized to primary topical treatment or surgery at a ratio of 1:1 and stratified by unifocal or multifocal disease. Treatment with imiquimod was self-administered for a period of 4 months with possible extension to 6 months. Surgical treatment consisted of excision or ablation and was performed according to the standard procedures of the trial site. Clinical assessment, colposcopy, ands vulvar punch-biopsy were performed at baseline and 6 months.Result(s)*Between June 2013 and January 2020 a total of 110 patients, aged between 19 and 82 years, were enrolled at six hospitals in Austria. 85 women (78%) had unifocal and 24 (22%) multifocal VIN; 21 (19%) had received previous treatment for VIN. The primary endpoint, clinical response to treatment at 6 months, could be assessed in 107 patients. By intention to treat analysis, 39/56 (73.6%) patients randomized to imiquimod had a complete clinical response, compared with 42/54 (77.8%) randomized to surgery. By per-protocol analysis 37/46 women (80.4%) using imiquimod had complete clinical response which was confirmed by histology in 33 cases (89.2%). In the per protocol surgery group 41/52 (78.8%) women had complete clinical response. Primary or secondary surgery revealed invasive disease in five patients (3 pT1a, 2 pT1b). Invasive disease was not identified in any patient with per- protocol imiquimod treatment. There was no difference in treatment satisfaction between the two groups (Imiquimod: median(min, max)= 31.0 (9.0, 32.0) and surgery: median(min, max)= 31.0 (12.0, 32.0)).Conclusion*Primary treatment with imiquimod is a safe, effective and well accepted alternative to surgery in women with HSIL/VIN.