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Comparison of Depth of Necrosis Using Cryotherapy by Gas and Number of Freeze Cycles

Cremer, Miriam MD, MPH1; Ditzian, Lauren MS2; Winkler, Jennifer L. MPH3; Jerónimo, José MD3; Singleton, Jered BA3; Franco, Henry Valdivia MD4; Maza, Mauricio MD, MPH2; Conlisk, Elizabeth MS, PhD5; Gage, Julia PhD, MPH6; Castle, Philip PhD, MPH2,7,8; Santos, Carlos MD4

Journal of Lower Genital Tract Disease: January 2015 - Volume 19 - Issue 1 - p 1–6
doi: 10.1097/LGT.0000000000000042
Original Articles: Cervix and HPV Clinical Research

Objective: This study aimed to establish the noninferiority of a single-freeze application with CO2 or N2O compared with the standard double freeze with N2O for cryotherapy treatment.

Materials and Methods: Sixty women undergoing hysterectomy for reasons other than cervical cancer or precancer were randomized to 1 of 3 techniques as follows: (1) double freeze with N2O, (2) single freeze with N2O, or (3) single freeze with CO2. The cervix was separated and cut into anterior and posterior segments, and the deepest area of necrosis was recorded. Comparisons were made using regression analysis. The margin of noninferiority was defined as 0.8 mm.

Results: On the anterior lip, a single freeze with N2O was noninferior to a double freeze of the same gas, but on the posterior lip, the single freeze was not. The single freeze of CO2 did not provide sufficient depth of necrosis in either lip to infer noninferiority versus the double freeze with N2O.

Conclusions: A single freeze with N2O is noninferior to a double-freeze technique in the anterior but not the posterior lip. However, the result for posterior lips was close to reaching statistical significance. In addition, CO2 had approximately 1 mm shallower depth of necrosis compared with N2O techniques; however, the clinical implications are unknown. Given the extensive use of CO2 globally, further clinical evaluation is needed.

This study found that a single freeze of N2O may be as effective as a double freeze to achieve a sufficient depth of necrosis for cervical ablation.

1University of Pittsburgh Medical Center, Pittsburgh, PA; 2Basic Health International, New York, NY; 3Program for Appropriate Technology in Health (PATH), Seattle, WA; 4Instituto Nacional de Enfermedades Neoplásicas, Lima, Peru; 5Hampshire College, Amherst, MA; 6Department of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville; and 7Global Cancer Initiative, Chestertown, MD; and 8Global Coalition Against Cervical Cancer, Arlington, VA

Reprint requests to: Carlos Santos, MD, Instituto Nacional de Enfermedades Neoplásicas, Departamento de Ginecologia, Ave Angamos Este 2520, Lima 34, Peru. E-mail:

The authors have declared they have no conflicts of interest.

This study was supported by PATH and Einhorn Family Charitable Trust.

Copyright © 2015 by the American Society for Colposcopy and Cervical Pathology