Introduction/Background In a recently published randomized, placebo-controlled phase II trial, we showed that topical imiquimod (IMQ) therapy is an efficacious and feasible treatment for selected patients with high-grade squamous intraepithelial lesion (HSIL). Aim of the present study was to investigate the non-inferiority of a 16-week topical IMQ therapy compared to large loop excision of the transformation zone (LLETZ) in patients diagnosed with cervical intraepithelial neoplasia (CIN) 2/3 (HSIL).

Methodology Phase III randomized, controlled, multicenter, open, non-inferiority trial performed by Austrian Gynecologic Oncology group (AGO-Austria). Patients with histologically proven CIN 2 (older than 30 years) and CIN3 and satisfactory colposcopy were randomized (1:1) to topical IMQ treatment or LLETZ. Successful treatment was defined as negative HPV high-risk test (Roche cobas) result 6 months after start of the treatment. Secondary endpoints were long-term success of treatment and histological outcome.

Results In total 93 patients were randomized and received the allocated treatment. The trial was stopped early due to poor accrual. CIN 2 and 3 at inclusion was present in 17 and 76 patients. In the IMQ group negative HPV test at 6 months after treatment start was observed in 66.7% of patients compared to 69.1% in LLETZ group (ITT analysis, rate difference 2.4%, 95% CI: -16.9 to -21.0). Negative HPV test at 12 months after treatment start was observed in 56.9% (IMQ) compared to 52.4% (LLETZ) of patients. In the IMQ group histologic regression 6 months after treatment was observed in 72.7% of patients. Complete resection was observed in 84.4% in the LLETZ group.

Conclusion IMQ and LLETZ treatment seem to result in similar rates of negative HPV test results. We observed major difficulties in recruiting participants in the present academic RCT.

Disclosure The present academic trial was partly funded by the Anniversary Fund of the Oesterreichische Nationalbank (OeNB). Stephan Polterauer, Alexander Reinthaller and Christoph Grimm have received honoraria for consultation from AstraZeneca, Celgene, MSD, PharmaMar, Roche,Roche Diagnostics, Meda Pharma, Tesaro, Vifor Pharma, outside the submitted work. Andreas Gleiss, Melanie Fraunschiel, Regina Berger, Gerhard Bogner, Olaf Reich, Gerda Trutnovsky, Stephan Aberle, Reinhard Horvat, Julia Ganhoer-Schimboeck, and Andreas Widschwendter have nothing to disclose.