Optimizing ablation of cervical precancer with ethyl cellulose ethanol to enable translation to women in low and middle-income countries

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Abstract Cervical cancer affects the lives of half a million women worldwide each year, and over half of these women die. Preventative solutions that are widely used in wealthy countries are not practical for use in medically underserved regions due to sophisticated technologies and expertise needed to sustain these solutions. Thus, alternative protocols that employ low-cost, simple-to-use technologies are needed to prevent cervical cancer. Our vision is to develop high quality, low-cost interventions that will be effective in low and middle-income countries (LMICs) to address shortcomings of current solutions for cervical cancer prevention. The Calla Health Foundation is developing the tools needed to help meet the WHO metrics for cervical cancer elimination in the next 100 years. Under fast track SBIR funding (R44CA240019), we are developing tools for point-of-care screening and diagnosis. However, screening and diagnosis alone will not lead to decreases in cervical cancer mortality if access to point-of-care treatment remains limited. While Loop Electrosurgical Excision procedure (LEEP) is the most widely used treatment in high-income settings, cryotherapy is more commonly used in LMICs. Recently, thermocoagulation has gained acceptance for ablation of cervical pre-cancer as it does not require consumables (continuous supply of pressurized liquid nitrogen for cryotherapy) or a stable power supply (for LEEP). However, thermocoagulation is limited by bioheat transfer and therefore the depth of necrosis it can achieve. To develop a complementary therapeutic approach to thermocoagulation, the goal of our Phase I SBIR grant was to establish an injectable low-cost ablative therapy based on controlled delivery of a ubiquitous agent, ethanol to treat cervical pre-cancer. Specifically, we developed a new formulation of ethanol using a polymer called ethyl cellulose (EC) to act as a slow-release gel limiting off target toxicity and an automated injector to reliably deliver ethanol into the region of interest. Moving forward, the goal of our Phase II SBIR grant is to develop beta versions of the automated injector, develop packaging and quality control metrics for EC-ethanol, and assess if a combinatorial therapy in which sequential EC-ethanol ablation and thermocoagulation are applied to the cervix is synergistic and enhances efficacy. This work will include the following specific aims: 1) evaluate usability and repeatability of hand-held injectors for EC-ethanol delivery; 2) establish EC-ethanol stability and potency testing plan and release criteria; 3) assess safety and efficacy of sequential EC-ethanol ablation and thermocoagulation compared to monotherapies; and 4) assess clinical workflow and population health impact of monotherapies and combinatorial therapy.