Topical 5-Fluorouracil and Imiquimod for the Treatment of High-Grade Cervical Intraepithelial Neoplasia: Protocol for a Randomised Open-Label Controlled Trial (TOPFIT-CIN Study)

Background There has been a long-standing interest in developing a safe, effective topical therapy for treating high-grade cervical intraepithelial neoplasia (CIN2/3). Combining 5-Fluorouracil (5-FU) and Imiquimod as a topical application may synergistically target CIN lesions while minimising adverse effects associated with excisional procedures. However, more research is still needed to understand the potential of these agents when combined as a treatment for CIN 2/3. Aim The “TOPFIT-CIN” study will assess the efficacy and safety of topical 5-FU/imiquimod compared to loop electrosurgical excision procedure (LEEP), as standard of care, in treating patients with CIN 2/3. Methods This is a study protocol for a non-inferiority, randomised, open-label, controlled trial that will be conducted at the gynecologic oncology, cytology and colposcopy clinics of the Lagos University Teaching Hospital (LUTH) in Lagos, Nigeria over two years (July 2025 to June 2027). At baseline, n = 90 sexually active women aged 30–65 years and diagnosed with high-grade CIN lesions (CIN 2 or CIN 3) confirmed by colposcopy biopsy will be randomised to receive either weekly topical application of 5-FU/Imiquimod cream or LEEP. The primary endpoint is the proportion of participants achieving treatment response (complete regression of CIN2/3 lesions at 3 months post-treatment initiation) between treatment arms. The data analysis will be conducted on an intention-to-treat and per-protocol basis. The comparison of treatment response and secondary outcomes (abnormal cervical cytology reversal, HPV clearance, adverse events, and CIN2/3 recurrence) between the two treatment arms will be performed using the generalised linear model to estimate the relative risks (RR) and 95% confidence intervals (95% CI). Statistical significance will be reported as P  < 0.05. Discussion The “ TOPFIT-CIN” study will evaluate the efficacy of topical 5-FU/ imiquimod compared to LEEP in treating patients with CIN 2/3. If proven effective, topical 5-FU and imiquimod combination therapy could offer a non-invasive alternative to traditional excisional procedures, particularly in resource-limited settings where access to specialised surgical care is limited. In addition, by mitigating the risks associated with invasive procedures such as LEEP and cold-knife conisation (CKC), this new treatment approach could improve patient outcomes, preserve fertility, and alleviate the economic burden of cervical cancer treatment on healthcare systems worldwide. Registration : PACTR202505720883384 (12th May 2025).