Topical ethanol gel to precisely treat low-grade cervical dysplasia - Although cervical cancer is a preventable disease, there remains significant incidence and mortality in regions of the U.S. with less access to routine healthcare. The burden of cervical cancer in the U.S. falls disproportionately on women in safety net settings, where lack of access to preventive vaccines, as well as the resources needed to screen, diagnose, and treat cervical dysplasia before it becomes cancer, continue to impede efforts to reduce cervical incidence and mortality. While Loop Electrosurgical Excision Procedure (LEEP) is routinely used in the U.S. to treat high-grade dysplasia, low-grade dysplasia is typically not treated as it can resolve on its own, and women can regularly be examined for progression assuming they have access to routine healthcare. However, providers in safety net settings prefer to treat women with persistent low-grade dysplasia as many women are lost to follow-up care, meaning they do not come back for repeat screenings. For women with persistent low-grade dysplasia, the only option for therapy, outside of LEEP (which is often inaccessible), are ablative therapies such as cryotherapy and thermocoagulation. However, these ablation methods remove the entire transformation zone even if women only have lowgrade dysplasia. Full ablation of the cervix carries risk of cervical insufficiency, and also these methods (cryotherapy and thermocoagulation) are often not available at the point of care as they require consumables that are hard to procure, particularly in rural communities, and may not reach all dysplastic cells. Thus, there is a need to develop accessible technologies that are specifically designed for safety net environments that only ablate the lesion while leaving normal cervical tissue intact. To address this need, we propose to develop a topical formulation of gel ethanol ablation specifically designed for treating lowgrade dysplasia. We have an exciting new formulation of methyl cellulose-based ethanol gel that rapidly forms under mixing and sticks to surfaces including wet tissue phantoms. The formulation has a clear solgel transition demonstrating gel formation and maintains viscoelastic solid-like properties at body temperature. To test that the gel adequately ablates low-grade dysplasia, unique approaches must be employed due to the paucity of animal models of cervical dysplasia. Specifically, we will develop and use a unique combination of models, which include ex vivo swine cervices, a novel in vitro, human anatomy relevant model of low-grade cervical dysplasia, and a pelvic model to assess the ease of application. Our specific aims include: 1) formulate affordable ethanol gel for local release up to 24h and long shelf life, 2) evaluate efficacy of ethanol ablation in ex vivo swine cervices and a human in vitro model, and 3) design gel applicator and cup device to maintain localized ethanol release at the cervix.
