Recommendation 4Should cryotherapy using a double versus single freeze technique be used in women with histologically confirmed CIN?

Recommendation: The expert panel suggests double freeze using a 3 minute freeze, 5 minute thaw, 3 minute freeze cycle over single freeze cryotherapy.
Population: Women with histologically confirmed CIN
Intervention: Double versus single freeze
FactorDecisionExplanation
High or moderate evidence
(is there high or moderate quality evidence?)

The higher the quality of evidence, the more likely is a strong recommendation.
□ Yes
☒ No
⊕⊕○○There is moderate to low quality evidence from both randomized and observational controlled studies for recurrence rates. There is low quality evidence for other outcomes which were considered critical and important for decision-making (e.g. severe adverse events, cervical cancer). There is uncertainty for fertility and other obstetrical outcomes, and HIV acquisition/transmission was not measured.
Certainty about the balance of benefits versus harms and burdens
(is there certainty?)

The larger the difference between the desirable and undesirable consequences and the certainty around that difference, the more likely a strong recommendation. The smaller the net benefit and the lower the certainty for that benefit, the more likely is a conditional/weak recommendation.
□ Yes
☒ No
Risks may be reduced with double-freeze cryotherapy
  • Recurrence rates of CIN I, CIN II–III and all CINs may be reduced with double-freeze technique
    • CIN II–III, OR 0.40 (0.22 to 0.75)
    • CIN I, OR 0.70 (0.21 to 2.28)
    • All CIN, OR 0.37 (0.21 to 0.63)
  • There may be little difference in cervical cancer rates based on absolute risks
  • There may be little difference in serious adverse events between double and single freeze cryotherapy, but there may be fewer people experiencing pain with double-freeze cryotherapy and more minor infections
  • It is unclear whether there is little difference in fertility/obstetric outcomes
Certainty in or similar values
(is there certainty or similarity?)

The more certainty or similarity in values and preferences, the more likely a strong recommendation.
☒ Yes
□ No
  • High value was placed on CIN recurrence, incidence of cervical cancer, serious adverse events, resource use, and acceptability to the patient and providers
  • Low value was placed on minor adverse events and fertility
Resource implications
(are resources worth expected benefits?)

The lower the cost of an intervention compared to the alternative that is considered and other costs related to the decision – that is, the fewer resources consumed – the more likely is a strong recommendation.
☒ Yes
□ No
More resources for double freeze but benefits worth the resources
  • Both interventions utilize the same equipment/ supplies
  • Additional resources are required (provider time, patient time, more gas) for double freeze
Overall strength of recommendationConditional

References (see Annex C)

11,13,15,20,21,47,49,67,68,80,85,87,90,94

From: Appendix B, Summary tables for each recommendation

Cover of WHO Guidelines: Use of Cryotherapy for Cervical Intraepithelial Neoplasia
WHO Guidelines: Use of Cryotherapy for Cervical Intraepithelial Neoplasia.
Copyright © 2011, World Health Organization.

All rights reserved. Publications of the World Health Organization are available on the WHO web site (www.who.int) or can be purchased from WHO Press, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel.: +41 22 791 3264; fax: +41 22 791 4857; e-mail: tni.ohw@sredrokoob).

Requests for permission to reproduce or translate WHO publications – whether for sale or for noncommercial distribution – should be addressed to WHO Press through the WHO web site (http://www.who.int/about/licensing/copyright_form/en/index.html).

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.