Topical Imiquimod Versus Conization to Treat Cervical Intraepithelial Neoplasia
Topical Imiquimod Versus Conization to Treat Cervical Intraepithelial Neoplasia
The purpose of this study is to investigate the non-inferiority of a topical Imiquimod
 therapy in patients with persistent CIN 2/3 when compared to standard therapy, i.e.
 conization A randomized, controlled, non-inferiority AGO-Austria trial
Background: Alternatives to surgery are needed for the treatment of cervical intraepithelial
 neoplasia (CIN). CIN is associated with persistent human papillomavirus (HPV) infection and
 is known to be a potential precursor of cervical cancer. The incidence of CIN has been
 increasing during the last decades, especially among young women. Patients diagnosed with
 (persistent) high-grade CIN (CIN2/3) are treated with conization. Conization can be regarded
 as a safe procedure but peri- and postoperative complications (infections, bleeding, preterm
 birth) occur. This raises the need for a conservative treatment alternative for patients with
 high-grade CIN. Preliminary data: Imiquimod (IMQ), a toll-like receptor 7 agonist, is an
 immune modulating substance approved for the therapy of superficial skin lesions (e.g.
 basalioma, actinic keratosis) and HPV associated disease (e.g. anogenital condylomata
 acuminata and vulvar intraepithelial neoplasia). In a randomized, placebo-controlled phase II
 trial, we previously showed that topical IMQ therapy is an efficacious and feasible treatment
 for selected patients with CIN 2/3. Methods: In the present open, randomized, non-inferiority
 trial 500 women with CIN 2/3 will be included. This non-profit, patient-oriented clinical
 research project will be conducted as an Austrian Gynecologic Oncology Group (AGO-Austria)
 trial. Participants will be randomized to either 16 weeks treatment with topical IMQ (new
 treatment) or to standard therapy i.e. conization (active control). This study investigates
 the non-inferiority of the new treatment, compared to surgical standard treatment. The
 primary endpoint is the rate of successful treatment, defined as negative HPV test result six
 months after treatment start. Six months after start of therapy the primary study endpoint is
 assessed using HPV genotyping. In addition clinical examinations including colposcopy, HPV
 genotyping, cytology, and if indicated colposcopy-guided biopsies of the uterine cervix will
 be performed. In addition, rates of CIN persistence/recurrence 6, 12, 18, and 24 months after
 start of the treatment and rates of negative HPV test results 12 and 24 months after start of
 the treatment will be evaluated in both treatment groups.

 Rationale: The need for a conservative treatment modality for patients diagnosed with CIN is
 obvious, as many young women need surgical treatment. In this randomized controlled, trial we
 will investigate the non-inferiority of a topical IMQ treatment compared to surgical standard
 treatment in selected patients diagnosed with CIN 2/3.
Inclusion criteria:

 1. Women aged ≥18 years diagnosed with histologically verified CIN 3 and women aged ≥ 30
 years diagnosed with CIN 2

 2. Satisfactory colposcopy

 3. Signed informed consent

 4. Negative pregnancy test

 5. Appropriate contraception method for fertile women during active study period

 6. Adequate compliance

 Exclusion criteria:

 1. Adenocarcinoma in situ

 2. History of previous conization

 3. Malignant disease at the time of inclusion

 4. Colposcopy suspicious for invasive disease

 5. Pregnancy and lactation period

 6. Known allergy or intolerance to IMQ

 7. Contraindications to conization or IMQ

 8. Symptoms of a clinically relevant disease

 9. Known HIV infection

 10. Evidence of a clinically significant immunodeficiency

 11. Current, reported participation in another experimental, interventional protocol