title: Systematic reviews and meta-analyses of benefits and harms of cryotherapy, LEEP, and cold knife conization to treat cervical intraepithelial neoplasia.
abstract: BACKGROUND
  Cervical intraepithelial neoplasia (CIN) stage 2-3 is a premalignant lesion that can progress to cervical cancer in 10-20 years if untreated.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  Studies of nonpregnant women 18 years or older not previously treated for CIN were included.
  
  
  METHODS
  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).
  
  
  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.
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada.
authors.forename: Nancy
authors.initials: N
authors.lastname: Santesso
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada; Departments of Internal Medicine/Nephrology and Biomedical and Health Informatics, University of Missouri-Kansas City, Kansas City, MO, USA.
authors.forename: Reem A
authors.initials: RA
authors.lastname: Mustafa
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada.
authors.forename: Wojtek
authors.initials: W
authors.lastname: Wiercioch
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada.
authors.forename: Rohan
authors.initials: R
authors.lastname: Kehar
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada.
authors.forename: Shreyas
authors.initials: S
authors.lastname: Gandhi
authors.affiliation: Evidence-Based Medicine Centre, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.
authors.forename: Yaolong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Adrienne
authors.initials: A
authors.lastname: Cheung
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada.
authors.forename: Jessica
authors.initials: J
authors.lastname: Hopkins
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada; Population Health Research Institute, McMaster University, Hamilton, ON, Canada.
authors.forename: Rasha
authors.initials: R
authors.lastname: Khatib
authors.affiliation: Evidence-Based Medicine Centre, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Ma
authors.affiliation: Faculty of Medicine, University of Science and Technology, Irbid, Jordan.
authors.forename: Ahmad A
authors.initials: AA
authors.lastname: Mustafa
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada.
authors.forename: Nancy
authors.initials: N
authors.lastname: Lloyd
authors.affiliation: Department of Clinical Epidemiology, 2nd Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
authors.forename: Darong
authors.initials: D
authors.lastname: Wu
authors.affiliation: Reproductive Health and Research, World Health Organization, Geneva, Switzerland.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Broutet
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada; Department of Medicine, McMaster University, Hamilton, ON, Canada. Electronic address: holger.schunemann@mcmaster.ca.
authors.forename: Holger J
authors.initials: HJ
authors.lastname: Schünemann
mesh_terms: D019092:Conization / Q000009:adverse effects; D017679:Cryotherapy / Q000009:adverse effects; D004598:Electrosurgery / Q000009:adverse effects; D005260:Female; D006801:Humans; D009367:Neoplasm Staging; D011183:Postoperative Complications; D017410:Practice Guidelines as Topic; D047928:Premature Birth / Q000209:etiology; D016032:Randomized Controlled Trials as Topic; D002583:Uterine Cervical Neoplasms / Q000517:prevention & control*; D014944:World Health Organization; D002578:Uterine Cervical Dysplasia / Q000473:pathology / Q000601:surgery*
keywords: Cervical intraepithelial neoplasia; Cold knife conization; Cryotherapy; Loop electrical excision procedure; Meta-analysis; Review; Uterine cervical neoplasms