Systematic reviews and meta-analyses of benefits and harms of cryotherapy, LEEP, and cold knife conization to treat cervical intraepithelial neoplasia

Int J Gynaecol Obstet. 2016 Mar;132(3):266-71. doi: 10.1016/j.ijgo.2015.07.026. Epub 2015 Nov 28.


Background: Cervical intraepithelial neoplasia (CIN) stage 2-3 is a premalignant lesion that can progress to cervical cancer in 10-20 years if untreated.

Objectives: To conduct systematic reviews of randomized and nonrandomized studies for effects of cryotherapy, loop electrosurgical excision procedure (LEEP), and cold knife conization (CKC) as treatment for CIN 2-3.

Search strategy: Medline, Embase, and other databases were searched to February 2012 for benefits, and to July 2012 for harms. Additionally, experts were contacted. Keywords for CIN, cervical cancer, and the treatments were used.

Selection criteria: Studies of nonpregnant women 18 years or older not previously treated for CIN were included.

Data collection and analysis: Two investigators independently screened and collected data. Relative risks and proportions were calculated and evidence assessed using GRADE (Grading of Recommendations Assessment, Development and Evaluation).

Main results: Recurrence rate was 5.3% 12 months after cryotherapy or LEEP, and 1.4% after CKC. There seemed to be little or no differences in frequency of complications after LEEP or cryotherapy, but they occurred more often after CKC. Evidence suggests premature delivery is most common with CKC, but it also occurs after LEEP and cryotherapy.

Conclusions: Despite a comprehensive search, there is very low quality evidence and often no evidence for important outcomes, including reproductive outcomes and complications. Studies assessing these outcomes are needed.

Keywords: Cervical intraepithelial neoplasia; Cold knife conization; Cryotherapy; Loop electrical excision procedure; Meta-analysis; Review; Uterine cervical neoplasms.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Conization* / adverse effects
  • Cryotherapy* / adverse effects
  • Electrosurgery* / adverse effects
  • Female
  • Humans
  • Neoplasm Staging
  • Postoperative Complications*
  • Practice Guidelines as Topic
  • Premature Birth / etiology
  • Randomized Controlled Trials as Topic
  • Uterine Cervical Dysplasia / pathology
  • Uterine Cervical Dysplasia / surgery*
  • Uterine Cervical Neoplasms / prevention & control*
  • World Health Organization