ABSTRACT Cervical cancer affects the lives of half a million women worldwide each year. Over half of these women die, even though cervical cancer is highly preventable through vaccination or early screening, diagnosis, and treatment of cervical pre-cancer. Cervical cancer prevention consists of three visits in the U.S.: 1) screening using the Papanicolaou smear; 2) colposcopy followed by biopsy of cervical abnormalities for women with positive screening results; 3) treatment by excising the lesion using a Loop Electrosurgical Excision Procedure (LEEP) for women with cervical pre-cancer. This three-visit model is not practical for use in medically underserved regions due to the technologies and expertise needed and patient attrition between clinic visits. Our team has already developed a novel Pocket colposcope and machine learning algorithms that when combined provide high-quality, magnified visualization and automated diagnosis with comparable performance to standard-of-care colposcopy. However, screening and diagnosis alone will not lead to decreases in cervical cancer mortality if access to point-of-care treatment is limited. Recently, the thermocoagulator has gained acceptance for ablation of cervical pre-cancer lesions as it does not require consumables (continuous supply of pressurized liquid nitrogen for cryotherapy) or a stable power supply (for LEEP). However, low-cost thermocoagulators have frequent failures based on reports of field-testing and the more reliable versions cost more than $10k. To address these well-documented shortcomings, our group is working to establish a low-cost ablative therapy using a ubiquitous agent, ethanol to treat cervical pre-cancer. While ethanol ablation has a long history of clinical use, its direct injection into tissue leads to non-uniform distribution and hence low efficacy in the region of interest. We propose a new formulation of ethanol using a polymer called ethyl cellulose (generally regarded as safe by the FDA), which will act as a slow release gel without off target toxicity, and an automated injector to control delivery of ethanol-ethyl cellulose (EEC) into the region of interest. The goal of this Phase I SBIR grant is to establish controlled delivery of EEC for cervical pre-cancer treatment using a combination of tissue surrogates and ex vivo and in vivo models of the swine cervix to induce a zone of necrosis that is consistent with thermocoagulation, a commonly used ablation method. In Aim 1, an automated needle injector will be designed for reproducible EEC delivery in tissue surrogates by maximizing the ratio of distributed to injected volume and minimizing back flow and crack formation. In Aim 2, the automated needle injector will be tested in ex vivo swine cervices to establish the distribution of the agent within the defined region of interest and also to determine the number of injections needed to achieve optimal coverage. In Aim 3, the injector safety and efficacy will be tested in in vivo swine cervices to establish the distribution volume and zone of necrosis caused by EEC. The results from the Phase I SBIR will set the foundation for development of alpha and beta versions of the automated needle injector, quality control assessment and packaging of the EEC injectate, and submission of an IND for EEC to the FDA.

The goal of this SBIR is for PIs from academic and small business institutions to work in partnership to develop a technological strategy that will transform treatment of cervical pre-cancer in low-resource communities. The proposed research is significantly relevant to public health, as the developed technologies will contribute to the improvement of cervical cancer prevention, and thus a reduction in the mortality rate of this imminently preventable disease.