Recommendation 1bShould cryotherapy versus LEEP (loop electrosurgical excision procedure) be used in women with histologically confirmed CIN?

Recommendation: In settings where LEEP/LLETZ is available and accessible, the expert panel suggests treatment with LEEP/LLETZ
Population: Women with histologically confirmed CIN
Intervention: Cryotherapy versus LEEP
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 quality evidence from both randomized and observational controlled studies for recurrence rates. However, 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		Benefits of LEEP were greater, and harms were fewer or similar
  • Recurrence rates of CIN I, CIN II–III and all CINs are probably greater with cryotherapy
    • CIN II–III, OR 3.3 (1.04 to 10.46)
    • CIN I, OR 2.74 (0.62 to 12.07)
    • All CIN, OR 2.14 (1.05 to 4.33)
  • Cryotherapy may be less acceptable to patients than LEEP
  • There may be little difference in serious adverse events between cryotherapy and LEEP, but there may be fewer minor adverse events (such as pain) with cryotherapy
  • It is unclear whether there is a 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		Similar values across women
  • High value was placed on CIN recurrence, serious adverse events and acceptability to the patient
  • Low value was placed on minor adverse events
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, fewer resources consumed – the more likely is a strong recommendation.		☒ Yes
□ No		More resources required for LEEP
  • Need for more skilled providers to perform LEEP
  • Need for more or expensive equipment/supplies for LEEP; electrical supply for LEEP
  • Need for local anaesthesia with LEEP
Overall strength of recommendationConditional

References (see Annex C)

Recommendation: In settings where LEEP/LLETZ is available and accessible, the expert panel suggests treatment with LEEP/ LLETZ over cryotherapy.
Population: Women with histologically confirmed CIN who are HIV-positive
Intervention: Cryotherapy versus LEEP
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 low quality evidence for recurrence rates. But very-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 around acceptability, 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 greater with cryotherapy
  • Recurrence rates of CIN II–III and all CINs may be greater with cryotherapy
    • CIN II–III, OR 3.6 (0.85 to 15.32)
    • All CIN, OR 3.89 (1.54 to 9.85)
  • The difference between cryotherapy and LEEP is uncertain for prevention of cervical cancer.
  • It is uncertain whether there are differences in major or minor adverse events between cryotherapy and LEEP.
  • There is uncertainty about fertility/obstetric outcomes, acceptability and HIV transmission.
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, serious adverse events and acceptability to the patient
  • Low value was placed on minor adverse events
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 required for LEEP
  • Need for more skilled providers to perform LEEP
  • Need for more or expensive equipment/supplies for LEEP
  • Need for local anaesthesia with LEEP
Overall strength of recommendationConditional

References (see Annex C)

1,17,24,39,45,46,51,56,59,78,89,97

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.

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