Misoprostol to Optimize Prevention of Cancer of the Cervix: A Randomized Trial (MISOPCx Project)

Cervical cancer is the leading cause of cancer morbidity and mortality among women in low-and-middle-income countries (LMICs) such as in Africa where screening by visual inspection with acetic acid (VIA) is the primary strategy. Although in 2021 the World Health Organization (WHO) recommended human papillomavirus (HPV) testing as the preferred screening test in all settings, VIA will remain the most common screening test for the foreseeable future in many LMICs, and the main triage test after the transition to HPV screening. However, incomplete visualization of the transformation zone (TZ) of the cervix (Type 3 TZ) which accounts for about 15% of women undergoing cervical cancer screening, is associated with missed lesions during VIA. Therefore, interventions to increase complete visualization of the TZ (i.e., conversion), reducing Type 3 TZ at VIA, remain a priority for cervical cancer prevention. Prostaglandin E1 (misoprostol), with cervical modulating effects, is a promising intervention due to wide availability, low cost ($1/dose), single vaginal dose, benign side effects, and small trials suggesting efficacy. However, misoprostol efficacy remains uncertain and it is unclear whether it will vary by duration of misoprostol, age/menopause, parity or previous precancer treatment, or whether such a program is acceptable, particularly in Africa, a region with the highest risk of cervical cancer. To address these gaps, and building on our preliminary data, we propose a double-blind RCT (N=420) to evaluate the effectiveness and acceptability of misoprostol to convert Type 3 TZ in patients attending a screening program in Cameroon. The ultimate goal is to prevent cervical cancer and morbidity by improving detection of pre-/cancerous lesions. Aim 1: Test the effectiveness of vaginal misoprostol 600 mcg vs. placebo to convert Type 3 TZ. Hypothesis 1: In women with Type 3 TZ, misoprostol given up to 6hrs prior to VIA will increase the rate of conversion by over 50% (primary outcome) and detect more cervical pre-/cancer lesions (secondary outcome). Sub Aim 1a: Identify optimal timing of misoprostol placement prior to same day evaluation to optimize efficacy and other factors that influence the rate of conversion of Type 3 TZ. Hypothesis 1a: Cumulatively, conversion rates at 4-6 hours after misoprostol will not be materially higher than at 2-3 hours and conversion rates will vary by maternal age, parity, prior pre-cancer treatment and menopausal status. Aim 2: Examine the acceptability and satisfaction of integrating misoprostol for Type 3 TZ into a cervical cancer screening program in Africa from patient and health care worker perspectives. Hypothesis 2: Patients with Type 3 TZ and clinical providers will have high acceptability and satisfaction rates with this approach. Cameroon is a low-resource setting with a high burden of cervical cancer and has a VIA-based comprehensive prevention program which provides a framework for the proposed study. If successful, this simple inexpensive intervention will reduce the risk of missed cervical lesions and improve early treatment and prevention cervical cancer.