Performance, Safety, and Efficacy of a New Cryotherapy Device for Cervical Dysplasia [Part II]
Performance, Safety, and Efficacy of a New Cryotherapy Device for Cervical Dysplasia [Part II]
Globally, cervical cancer is the second most common cancer for women and kills approximately
 250,000 women every year, with the annual number of deaths expected to increase to 410,000 by
 2030. The majority (88%) of these deaths occur in low- and middle-income countries (LMICs)
 where screening and prevention services are limited. Prevention of cervical cancer by
 identification and treatment of cervical cancer precursors is key, since treatment resources
 for invasive disease are scarce. A cervical cancer screening program cannot be effective
 unless it is linked with a proven intervention to prevent the development of cervical cancer.
 The World Health Organization (WHO) recently released the WHO guidelines for screening and
 treatment of precancerous lesions for cervical cancer prevention, which recommends a
 screen-and-treat approach for cervical cancer prevention, with cryotherapy being the first
 choice of treatment for women who have a positive screen. However, these programs are still
 slow to be implemented in part due to the current high cost and low efficiency of cryotherapy
 equipment that is often prone to breaking. Jhpiego, an affiliate of Johns Hopkins University
 (JHU), has developed a new cryotherapy device, CryoPop, that is one tenth the cost of current
 equipment while also ten times more efficient. Once proven safe, feasible and effective,
 CryoPop could save tens of thousands of lives in low- and middle-income countries each year
 by preventing cervical cancer.
The World Health Organization (WHO) Guidelines for screening and treatment of precancerous
 lesions for cervical cancer prevention recommends a screen- and-treat approach for cervical
 cancer prevention, with cryotherapy being the first choice of treatment for women who have a
 positive screen. Cryotherapy using nitrous oxide (N2O) or carbon dioxide (CO2) to induce
 cryonecrosis of dysplastic tissues followed by regeneration of normal cervical epithelium is
 the most common intervention used in LMICs because it is simple and safe enough for
 competently-trained mid-level providers such as nurses and midwives to operate, and can be
 performed without anesthesia or electricity. Adverse effects after cryotherapy are relatively
 uncommon and generally minor, reported in 1-2% of women. A recent meta-analysis of 77 studies
 (with moderate to high quality evidence) regarding the effectiveness of cryotherapy found
 cure rates of 92% and 85%, respectively, in CIN 2 and CIN 3. Cure was defined as normal
 cytology or disease-free state (generally with colposcopy +/- biopsy) at the follow-up visit,
 implying absence of persistent disease or recurrent lesions after treatment and length of
 follow-up varied from 3 months to 10 years. A more recent systematic review and meta-analyses
 of benefits and harms of cryotherapy, as well as Loop Electrosurgical Excision Procedure
 (LEEP) and cervical conization (167 studies) found a residual/ recurrence rate of cervical
 dysplasia (CIN 2-3) of 5% at 12 months' follow-up. Major and minor adverse events occurred in
 less than 1% of women and were fewer with cryotherapy than with the other approaches. Limited
 data suggests that preterm delivery in subsequent pregnancy may be increased (<2%) with
 cryotherapy or LEEP.

 Cost, reliability, durability, portability and reparability are all factors that prohibit the
 scale-up necessary for current cryotherapy methods to match the volume of population-based
 screening needed to achieve a marked decrease in cervical cancer morbidity and mortality.
 Each cryotherapy unit costs approximately $2,000-$7500, resulting in approximately 80% or
 more of the treatment cost of cryotherapy being directly attributed to equipment cost. The
 design involves many custom parts available only through the manufacturers, which are all
 based in the US or Europe. This prohibits local repairs and limits the life of the product to
 only one or two years (or even less when spare parts are not available). Additionally, the
 current technology requires huge amount of N20 or CO2 requiring large gas cylinders which are
 heavy and costly-the cost to refill a CO2 tank can be up to $200.

 The subject of this proposal, CryoPop, is a new technology specifically designed for LMIC
 settings and more appropriate to support see-and-treat efforts because of its low cost,
 portability, reparability and durability. The CryoPop device is currently expected to cost
 one half of the price of current devices while also using one tenth of the CO2 supply,
 thereby substantially reducing the recurring cost of refilling a smaller and more portable
 gas supply with far greater efficiency in the use of CO2. Moreover, this device is designed
 to have minimal moving components which at the same time are inexpensive to replace and easy
 to repair in- situ by the providers themselves. Finally, the CryoPop is not tethered to the
 gas canister during the procedure, adding more safety to the treatment procedure by not
 having to be concerned over tank or gas line placement.The goal is to have a device for the
 frontline where screening is happening and provide the unique opportunity of minimizing if
 not preventing loss to follow-up of screen-positive women.

 This will accelerate access to cervical cancer prevention and treatment services by enabling
 implementation of single-visit approach (SVA) to rural, underdeveloped regions, most of which
 have never had cervical cancer prevention (CECAP) programs.

 This clinical trial is Part 2 of a 2-part research study. Part 1 of this research study is
 registered under:

 1UH2CA189923-01 Performance, Safety, and Efficacy of a New Cryotherapy Device for Cervical
 Dysplasia NCT02367625
Inclusion Criteria:

 1. Must be 30-49 years old

 2. High-grade squamous intraepithelial lesion of the cervix (CIN 2/3), confirmed on
 histology

 3. Eligible for cryotherapy based on size of lesion (occupies <75% of cervix) and fully
 visible on colposcopy or visual inspection with acetic acid (VIA)

 4. Willing and able to provide consent.

 Exclusion Criteria:

 1. Menopausal

 2. History of hysterectomy

 3. Known HIV+ or active cervical infections

 4. Lesion occupies >75% of cervix and/or extends into the endo cervical canal

 5. Pregnancy