title: A Non-Gas-Based Cryotherapy System for the Treatment of Cervical Intraepithelial Neoplasia: A Mixed-Methods Approach for Initial Development and Testing.
abstract: Gas-based cryotherapy is the most widely used treatment strategy for cervical intraepithelial neoplasia (CIN) in low-resource settings, but reliance on gas presents challenges in low- and middle-income countries (LMICs). Our team adapted the original CryoPen Cryosurgical System, a cryotherapy device that does not require compressed gas and is powered by electricity, for use in LMICs.
  
  
  
  A mixed-methods approach was used involving both qualitative and quantitative methods. First, we used a user-centered design approach to identify priority features of the adapted device. U.S.-based and global potential users of the adapted CryoPen participated in discussion groups and a card sorting activity to rank 7 features of the adapted CryoPen: cost, durability, efficacy and safety, maintenance, no need for electricity, patient throughput, and portability. Mean and median rankings, overall rankings, and summary rankings by discussion group were generated. In addition, results of several quantitative tests were analyzed including bench testing to determine tip temperature and heat extraction capabilities; a pathology review of CIN grade 3 cases (N=107) to determine target depth of necrosis needed to achieve high efficacy; and a pilot study (N=5) investigating depth of necrosis achieved with the adapted device to assess efficacy.
  
  
  
  Discussion groups revealed 4 priority themes for device development in addition to the need to ensure high efficacy and safety and low cost: improved portability, durability, ease of use, and potential for cure. Adaptions to the original CryoPen system included a single-core, single-tip model; rugged carrying case; custom circuit to allow car battery charging; and sterilization by high-level disinfection. In bench testing, there were no significant differences in tip temperature or heat extraction capability between the adapted CryoPen and the standard cryotherapy device. In 80% of the cases in the pilot study, the adapted CryoPen achieved the target depth of necrosis 3.5 mm established in the pathology review.
  
  
  
  The LMIC-adapted CryoPen overcomes barriers to standard gas-based cryotherapy by eliminating dependency on gas, increasing portability, and ensuring consistent freeze temperatures. Further testing and evaluation of the adapted CryoPen will be pursued to assess scalability and potential impact of this device in decreasing the cervical cancer burden in LMICs.
authors.affiliation: Obstetrics, Gynecology & Women's Health Institute, Cleveland Clinic Lerner College of Medicine, Cleveland, OH, USA. bhisubmissions@gmail.com.|Basic Health International, New York, NY, USA, and San Salvador, El Salvador.
authors.forename: Miriam
authors.initials: M
authors.lastname: Cremer
authors.affiliation: Basic Health International, New York, NY, USA, and San Salvador, El Salvador.|University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA.
authors.forename: Proma
authors.initials: P
authors.lastname: Paul
authors.affiliation: Basic Health International, New York, NY, USA, and San Salvador, El Salvador.
authors.forename: Katie
authors.initials: K
authors.lastname: Bergman
authors.affiliation: CryoPen, Inc., Covington, LA, USA.|Department of Family Medicine, Louisiana State University Health Science Center, New Orleans, LA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Haas
authors.affiliation: Basic Health International, New York, NY, USA, and San Salvador, El Salvador.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Maza
authors.affiliation: Department of Gynecology, National Institute for Neoplastic Diseases, Lima, Peru.
authors.forename: Albert
authors.initials: A
authors.lastname: Zevallos
authors.affiliation: National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, MD, USA.
authors.forename: Miguel
authors.initials: M
authors.lastname: Ossandon
authors.affiliation: Basic Health International, New York, NY, USA, and San Salvador, El Salvador.
authors.forename: Jillian D
authors.initials: JD
authors.lastname: Garai
authors.affiliation: Basic Health International, New York, NY, USA, and San Salvador, El Salvador.|Mel & Enid Zuckerman College of Public Health, University of Arizona, Tucson, AZ, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Winkler
mesh_terms: D017679:Cryotherapy / Q000379:methods*; D005260:Female; D006801:Humans; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000628:therapy*; D002578:Uterine Cervical Dysplasia / Q000628:therapy*