Portable, low-cost cryotherapy system that does not require consumable cryogen gas for the treatment of cervical precancerous lesions

Abstract While cervical cancer deaths have dramatically fallen in high-income countries, cervical cancer is one of the leading causes of cancer deaths in low- and middle-income countries (LMICs). Cervical cancer accounted for 341,800 deaths in 2020, with approximately 90% of these deaths occurring in LMICs. Treatments for precancerous lesions are highly effective for preventing cancer progression, so the key is to identify and treat lesions early. However, most low-income countries that offer cervical cancer screening lack accessible treatment services. The lack of readily accessible treatment options means referral of patients to larger hospitals, which is an obstacle to proper treatment, leading to disease progression to cancer. While loop electrosurgical excision procedure is the gold standard in the treatment of lesions, it requires highly trained clinicians and an operating environment rarely found in LMIC clinics. The World Health Organization recommends cryotherapy for cervical precancer treatment in LMICs, but the key drawback for current cryotherapy systems is their dependence on consumable cryogen gas. Access to a cryogen gas supply is unreliable, consumable gas costs are high, and heavy and bulky gas cylinders limit portability to remote clinics. Other LMIC-targeted options have been attempted, but they were poorly adopted due to high cost and discontinued manufacturer support (CryoPen) or insufficient depth of tissue necrosis for fully effective treatment (heat-based thermal ablation). Taken together, no single system exists to provide an appropriate and cost-effective solution that is suitable for widespread LMIC use. With an LMIC-appropriate treatment solution, cervical cancer mortality could be reduced by 33% (~300,000 deaths) by 2030. With NIH SBIR Phase I support, Ananya Health’s goal is developing the Ala System, a portable, battery-powered, closed-loop cryotherapy system for the treatment of cervical precancerous lesions in LMICs. By recirculating the cryogen fluid in a closed-loop system, the Ala System eliminates the need for consumable cryogen gas. The rechargeable battery allows for treatment independent of electrical grid availability. Preliminary studies have shown we can achieve tissue-freezing temperatures on an ovine uterus tissue model with a battery- powered closed-loop prototype. For this proposal, first, we will use a benchtop cervical model to further optimize system parameters to meet the established cervical tissue cryotherapy requirement: ≥5 mm depth of tissue reaches ≤-20°C for ≥1 min in a ≤5 min procedure (Specific Aim 1). Second, we will make in-person visits to two LMIC clinical sites to interview and observe ≥6 clinicians to identify critical User Needs and system requirements to ensure the Ala System design will suit the clinical, usability, and operational needs of primary care facilities in LMICs (Specific Aim 2). The development work in Phase I will lay the foundation for final device testing, user design validation, and regulatory approvals via FDA 510(k) in Phase II, followed by widespread deployment of the Ala System through global NGOs and local and regional LMIC organizational partnerships.