Feasibility of adjuvant self-administered intravaginal 5-fluorouracil cream following primary treatment of cervical intraepithelial neoplasia grade 2 or 3 among women living with HIV in Kenya: study protocol for a pilot trial.

Background: Women living with HIV (WLWH), the majority of whom live in low- and middle-income countries (LMICs), are at higher risk of cervical precancer, known as cervical intraepithelial neoplasia (CIN), and are up to six times more likely to get cervical cancer. Current CIN treatment methods, primarily ablation or excision, have high treatment failure rates among WLWH, up to 30% for CIN grade 2 or 3 (CIN2/3) at 24 months following ablation. Without strong follow-up many WLWH with treatment failure are at risk of developing invasive cervical cancer, highlighting the urgent need for improved CIN treatment methods. Prior studies in high-income countries (HICs) have demonstrated that 5-Fluorouracil (5-FU) cream, an antimetabolite drug that is easily accessible in LMICs, can be used intravaginally as adjuvant therapy following primary CIN2/3 treatment in WLWH to reduce CIN2/3 recurrence. While the safety, acceptability, and efficacy of self-administered 5-FU for cervical precancer treatment has been demonstrated in HICs, it has not been studied among WLWH in LMICs who bear the greatest burden of cervical cancer. Methods: We are conducting a Phase I pilot study investigating the feasibility of using 5-FU cream as an adjuvant, self-administered intravaginal therapy following cervical intraepithelial neoplasia grade 2/3 (CIN2/3) treatment among WLWH in Kenya (ClinicalTrials.gov NCT05362955). Twelve participants will be enrolled in this single-arm study. Participants will self-administer 2g of 5% 5-FU cream intravaginally every other week for eight applications. The primary objective is to determine safety, defined as the type, frequency, and severity of adverse events (AEs) using a standardized grading scale. The secondary objectives are uptake, tolerability, adherence, and acceptability. Results: There are no results at this time as this is an ongoing study. Discussion: To achieve the World Health Organization (WHO) 90/70/90 global cervical cancer elimination goals, which include 90% of women with cervical precancer adequately treated by 2030, it is essential to employ innovative and resource-appropriate strategies to improve cervical precancer treatment among WLWH. The use of 5-FU as adjuvant therapy following current screen & treat programs may be a feasible and scalable strategy to optimize outcomes in this high-risk group. This clinical trial will provide important feasibility data to inform future randomized efficacy trials in LMICs. Trial registration: ClinicalTrials.gov identifier: NCT05362955.