Surgery for cervical intraepithelial neoplasia

Surgery for cervical intraepithelial neoplasia (Review)
Martin-Hirsch PL, Paraskevaidis E, Kitchener H
This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library2007, Issue 4 Surgery for cervical intraepithelial neoplasia (Review)
Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
PLAIN LANGUAGE SUMMARY CRITERIA FOR CONSIDERING STUDIES FOR THIS REVIEW SEARCH METHODS FOR IDENTIFICATION OF STUDIES DESCRIPTION OF STUDIES METHODOLOGICAL QUALITY . . . . . . . . . . . . . . .
AUTHORS' CONCLUSIONS POTENTIAL CONFLICT OF INTEREST . . . . . . . . . . . . . .
Characteristics of included studies . . . . . . . . . . . . . . .
Comparison 01. Single Freeze Cryotherapy versus Double Freeze Cryotherapy . . . . . . .
Comparison 02. Laser Ablation versus Cryotherapy . . . . . . . . . . . .
Comparison 03. Laser Conisation versus Knife Conisation Comparison 04. Laser Conisation versus Laser Ablation Comparison 05. Laser Conisation versus Loop Excision Comparison 06. Laser Ablation versus Loop Excision Comparison 07. Knife Conisation versus Loop Excision Comparison 08. Radical Diathermy versus LLETZ Comparison 09. Radial Diathermy versus Cryotherapy . . . . . . . . . . .
Comparison 10. Cold Coagulation versus Cryotherapy . . . . . . . . . . .
Comparison 11. Knife Cone Biopsy: Haemostatic Sutures versus None GRAPHS AND OTHER TABLES Analysis 01.01. Comparison 01 Single Freeze Cryotherapy versus Double Freeze Cryotherapy, Outcome 01 Residual Disease within 12 months Analysis 02.01. Comparison 02 Laser Ablation versus Cryotherapy, Outcome 01 Residual Disease (All Grades of CIN) Analysis 02.02. Comparison 02 Laser Ablation versus Cryotherapy, Outcome 02 Residual Disease (CIN1) . .
Analysis 02.03. Comparison 02 Laser Ablation versus Cryotherapy, Outcome 03 Residual Disease (CIN2) . .
Analysis 02.04. Comparison 02 Laser Ablation versus Cryotherapy, Outcome 04 Residual Disease (CIN3) . .
Analysis 02.05. Comparison 02 Laser Ablation versus Cryotherapy, Outcome 05 Peri-operative Severe Pain . .
Analysis 02.06. Comparison 02 Laser Ablation versus Cryotherapy, Outcome 06 Peri-operative Severe Bleeding Analysis 02.07. Comparison 02 Laser Ablation versus Cryotherapy, Outcome 07 Vaso-motor Symptoms . . .
Analysis 02.08. Comparison 02 Laser Ablation versus Cryotherapy, Outcome 08 Malodorous Discharge . . .
Analysis 02.09. Comparison 02 Laser Ablation versus Cryotherapy, Outcome 09 Adequate Colposcopy at Follow-up Analysis 02.10. Comparison 02 Laser Ablation versus Cryotherapy, Outcome 10 Cervical Stenosis at Follow-up Analysis 03.01. Comparison 03 Laser Conisation versus Knife Conisation, Outcome 01 Residual Disease (All Grades of Analysis 03.02. Comparison 03 Laser Conisation versus Knife Conisation, Outcome 02 Primary Haemorrhage Analysis 03.03. Comparison 03 Laser Conisation versus Knife Conisation, Outcome 03 Secondary Haemorrhage Analysis 03.04. Comparison 03 Laser Conisation versus Knife Conisation, Outcome 04 Adequate Colposcopy at Follow- Surgery for cervical intraepithelial neoplasia (Review)
Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
Analysis 03.05. Comparison 03 Laser Conisation versus Knife Conisation, Outcome 05 Cervical Stenosis at Follow-up Analysis 03.06. Comparison 03 Laser Conisation versus Knife Conisation, Outcome 06 Significant Thermal Artifact Prohibiting Interpretation of Resection Margin Analysis 04.01. Comparison 04 Laser Conisation versus Laser Ablation, Outcome 01 Residual Disease (All Grades of Analysis 04.02. Comparison 04 Laser Conisation versus Laser Ablation, Outcome 02 Peri-operative Severe Bleeding .
Analysis 04.03. Comparison 04 Laser Conisation versus Laser Ablation, Outcome 03 Secondary Haemorrhage Analysis 04.04. Comparison 04 Laser Conisation versus Laser Ablation, Outcome 04 Adequate Colposcopy at Follow-up Analysis 05.01. Comparison 05 Laser Conisation versus Loop Excision, Outcome 01 Residual Disease Analysis 05.02. Comparison 05 Laser Conisation versus Loop Excision, Outcome 02 Duration of Procedure Analysis 05.03. Comparison 05 Laser Conisation versus Loop Excision, Outcome 03 Peri-operative Severe Pain Analysis 05.04. Comparison 05 Laser Conisation versus Loop Excision, Outcome 04 Secondary Haemorrhage Analysis 05.05. Comparison 05 Laser Conisation versus Loop Excision, Outcome 05 Significant Thermal Artefact on Analysis 05.06. Comparison 05 Laser Conisation versus Loop Excision, Outcome 06 Depth of Thermal Artifact .
Analysis 05.07. Comparison 05 Laser Conisation versus Loop Excision, Outcome 07 Adequate Colposcopy Analysis 05.08. Comparison 05 Laser Conisation versus Loop Excision, Outcome 08 Cervical Stenosis Analysis 06.01. Comparison 06 Laser Ablation versus Loop Excision, Outcome 01 Residual Disease Analysis 06.02. Comparison 06 Laser Ablation versus Loop Excision, Outcome 02 Peri-operative Severe Pain . .
Analysis 06.03. Comparison 06 Laser Ablation versus Loop Excision, Outcome 03 Secondary Haemorrhage Analysis 06.04. Comparison 06 Laser Ablation versus Loop Excision, Outcome 04 Primary Haemorrhage Analysis 07.01. Comparison 07 Knife Conisation versus Loop Excision, Outcome 01 Residual Disease Analysis 07.02. Comparison 07 Knife Conisation versus Loop Excision, Outcome 02 Primary Haemorrhage Analysis 07.03. Comparison 07 Knife Conisation versus Loop Excision, Outcome 03 Adequate Colposcopy at Follow-up Analysis 07.04. Comparison 07 Knife Conisation versus Loop Excision, Outcome 04 Cervical Stenosis Analysis 08.01. Comparison 08 Radical Diathermy versus LLETZ, Outcome 01 Duration of blood loss . . .
Analysis 08.02. Comparison 08 Radical Diathermy versus LLETZ, Outcome 02 Blood stained / watery discharge Analysis 08.03. Comparison 08 Radical Diathermy versus LLETZ, Outcome 03 Yellow discharge . . . .
Analysis 08.04. Comparison 08 Radical Diathermy versus LLETZ, Outcome 04 White discharge . . . .
Analysis 08.05. Comparison 08 Radical Diathermy versus LLETZ, Outcome 05 Upper Abdominal Pain . . .
Analysis 08.06. Comparison 08 Radical Diathermy versus LLETZ, Outcome 06 Lower Abdominal Pain . . .
Analysis 08.07. Comparison 08 Radical Diathermy versus LLETZ, Outcome 07 Deep Pelvic Pain . . . .
Analysis 08.08. Comparison 08 Radical Diathermy versus LLETZ, Outcome 08 Vaginal Pain Analysis 09.01. Comparison 09 Radial Diathermy versus Cryotherapy, Outcome 01 Residual Disease at 12 months .
Analysis 10.01. Comparison 10 Cold Coagulation versus Cryotherapy, Outcome 01 Residual Disease at 24 months .
Analysis 11.01. Comparison 11 Knife Cone Biopsy: Haemostatic Sutures versus None, Outcome 01 Primary Analysis 11.02. Comparison 11 Knife Cone Biopsy: Haemostatic Sutures versus None, Outcome 02 Secondary Analysis 11.03. Comparison 11 Knife Cone Biopsy: Haemostatic Sutures versus None, Outcome 03 Cervical Stenosis Analysis 11.04. Comparison 11 Knife Cone Biopsy: Haemostatic Sutures versus None, Outcome 04 Adequate Analysis 11.05. Comparison 11 Knife Cone Biopsy: Haemostatic Sutures versus None, Outcome 05 Dysmenorrhoea Surgery for cervical intraepithelial neoplasia (Review)
Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
Surgery for cervical intraepithelial neoplasia (Review)
Martin-Hirsch PL, Paraskevaidis E, Kitchener H
This record should be cited as:
Martin-Hirsch PL, Paraskevaidis E, Kitchener H. Surgery for cervical intraepithelial neoplasia. Cochrane Database of Systematic Reviews
1999, Issue 3. Art. No.: CD001318. DOI: 10.1002/14651858.CD001318.
This version first published online: 26 July 1999 in Issue 3, 1999.
Date of most recent substantive amendment: 19 May 1999
A B S T R A C T
Background
Cervical intra-epithelial neoplasia is treated by local ablation or lower morbidity excision techniques. Choice of treatment depends on
the severity of the disease.
Objectives
The objective of this review was to assess the effects of alternative surgical treatments for cervical intra-epithelial neoplasia.
Search strategy
We searched the Cochrane Gynaecological Cancer Group trials register and MEDLINE up to July 1997. Update: in July 2004 a further
search was conducted.
Selection criteria
Randomised and quasi-randomised trials of alternative surgical treatments in women with cervical intra-epithelial neoplasia.
Data collection and analysis
Trial quality was assessed and two reviewers abstracted data independently.
Main results
Twenty eight trials were included. Seven surgical techniques were tested in various comparisons. No significant difference in eradication
of disease was shown, other than between laser ablation and loop excision. This was based on one trial where the quality of randomisation
was doubtful. Large loop excision of the transformation zone appeared to provide the most reliable specimens for histology with the
least morbidity. Morbidity was lower than with laser conisation, although all five trials did not provide data for every outcome. There
were not enough data to assess the effect on morbidity compared with laser ablation.
Authors' conclusions
The evidence suggests that there is no obviously superior surgical technique for treating cervical intra-epithelial neoplasia.
No clear evidence to show any optimal surgical technique is superior for treating pre-cancerous cervix abnormalities.
Cervical pre-cancer (cervical intraepithelial neoplasia) can be treated in different ways depending on the severity of the disease. Lessinvasive treatments not requiring a hospital stay may be used, but a general anaesthetic is occasionally needed, especially if the tumourhas spread locally or previous out-patient treatment has failed. Surgery can be done with a knife, laser or cutting with a loop (anelectrically charged wire). This review found there was not enough evidence to compare techniques and that more research is needed.
Surgery for cervical intraepithelial neoplasia (Review)
Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
B A C K G R O U N D
Laser Conisation:
This procedure can be performed under general or local analgesia.
Current treatment for cervical intra-epithelial neoplasia (CIN) is A highly focused laser spot is used to make an ectocervical cir- by local ablative therapy or by excisional methods depending on cumferential incision to a depth of 1 cm. Small hooks or retrac- the nature and extent of disease. Traditionally prior to colposcopy, tors are then used to manipulate the cone to allow deeper incision all lesions were treated by knife excisional cone biopsy or by abla- to complete the endocervical incision. Haemostasis if required is tive radical point diathermy. Knife cone biopsy and radical point generally achieved by laser coagulation by defocusing the beam. A diathermy are usually performed under general anaesthesia and are disadvantage of laser conisation is that the cone biopsy specimen now not the preferred treatment of choice as various more conser- might suffer from thermal damage making histological evaluation vative local ablative and excisional therapies can be performed in of margins impossible.
an out-patient setting.
Treatment success of laser cone biopsy is reported as 93 to 96%(Bostofte 1986; Tabor 1990) in non randomised studies. The ma- Patients are suitable for ablative therapy provided that: jor advantages are accurate tailoring of the size of the cone, low (1) the entire Transformation Zone can be visualised (satisfactory blood loss in most cases, and less cervical trauma than knife cut (2) there is no suggestion of micro-invasive or invasive disease;(3) there is no suspicion of glandular disease; Loop Excision of The Transformation Zone:
(4) the cytology and histology correspond.
Large Loop Excision of the Transformation Zone is often abbre- Excisional treatment is mandatory for a patient with an unsatisfac- viated to LLETZ in the UK or LEEP (Loop Electrosurgical Exci- tory colposcopy, suspicion of invasion or glandular abnormality.
sional Procedure) in the U.S.A. A wire loop electrode on the end There is now a trend to utilise low morbidity excisional methods of an insulated handle is powered by an electrosurgical unit. The either laser conisation or Large Loop Excision of the Transforma- current is designed to achieve a cutting and a coagulation effect tion Zone (LLETZ) in place of destructive ablative methods. Exci- simultaneously. Power should be sufficient to excise tissue without sional methods offer advantages over destructive methods in that causing thermal artefact. The procedure can be performed under they can define the exact nature of disease and the completeness local analgesia.
of excision/destruction of the transformation zone. Incomplete Treatment success of LLETZ is reported as 97.4% (Murdoch excision/destruction of the transformation zone is an important 1984), 98% (Prendeville 1989), 95.9% (Bigrigg 1990), 95.9% indicator of patients at risk of treatment failure or recurrence of (Luesley 1990), 94.9% (Whiteley 1990), 91%(Murdoch 1992) and 94% (Wright et al 1992) in non randomised studies.
The treatment modalities included in this review are described A laser beam is used to destroy the tissue of the transformationzone. Laser destruction of tissue can be controlled by the length Knife cone biopsy:
of exposure. Defocusing the beam permits photocoagulation of Traditionally broad deep cones were performed for most cases of bleeding vessels in the cervical wound.
CIN. Excision of a wide and deep cone of the cervix is associated Treatment success of laser ablation is reported as 95% (Wright with significant short and long term morbidity (peri-operative, 1984) and 96% (Jordan 1985).
primary and secondary haemorrhage, local and pelvic infection,cervical stenosis and mid-trimester pregnancy loss (Jordan 1984; Leiman 1980; Luesley 1985). A less radical approach is now gener- A circular metal probe is placed against the transformation zone.
ally adopted tailoring the width and depth of the cone according to Hypothermia is produced by the evaporation of compressed re- colposcopic findings. The procedure is invariably performed un- frigerant gas passing through the base of the probe. The cryonecro- der general anaesthesia. Peri-operative haemostasis can be difficult sis is achieved by crystallization of intracellular water. The effect to achieve and various surgical techniques have been developed to tends to be patchy as sub-lethal tissue damage tends to occur at reduce this. Routine ligation of the cervical vessels is commonly the periphery of the probe.
performed. This technique also allows manipulation of the cervix In non-controlled studies the success of treatment of CIN3 varied during surgery. Sturmdorf sutures have been advocated by some between 77% and 93%, 87% (Benedet 1981), 77% (Hatch 1981), surgeons to promote haemostasis, others recommend circumfer- 82% (Kaufman 1978), 84% (Ostergard 1980), and 93% (Popkin ential locking sutures, electrocauterisation or cold coagulation or et al 1978).
vaginal compression packing.
Utilising a DOUBLE freeze-thaw-freeze technique improves the Treatment success (i.e. no residual disease on follow-up) of knife reliability in the observational study by Creasman 1984 .
cone biopsy is reported as 90 to 94% (Bostofte 1986; Larson 1983; Rapid ice-ball formation indicates that the depth of necrosis will Tabor 1990) in non randomised studies.
extend to the periphery of the probe. The procedure can be asso- Surgery for cervical intraepithelial neoplasia (Review)
Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
ciated with unpleasant vasomotor symptoms.
(4) Knife Conisation(5) Cryotherapy This systematic review examines the efficacy and morbidity of lo-cal ablative and excisional therapies for eradicating disease. The Types of outcome measures
effectiveness and morbidity of the various forms of treatment have (1) Residual disease detected on follow-up examination been generally evaluated by uncontrolled observational studies.
Hence direct comparison of treatment effects of alternative treat- (2) Characteristics and Morbidity ments is unreliable because of variable patient selection, treatment (a) duration of treatment outcomes and follow-up criteria. We have therefore only included (b) peri-operative severe pain trials which appear to be randomised thus reducing selection bias (c) peri-operative severe bleeding, primary and secondary haem- and providing more reliable results. Randomised trials are the only reliable and valid method of generating truly comparable compar- (d) Depth and presence of thermal artifact ison groups.
(e) Adequate colposcopy at follow-up(f ) Cervical Stenosis at follow-up O B J E C T I V E S
(1) To assess the efficacy of alternative surgical treatments for CIN at eradicating disease.
See: methods used in reviews.
(2) To assess the characteristics and morbidity associated with dif-ferent therapies with regards to: A computerised MEDLINE search was conducted to identify all (a) duration of treatment; registered randomised trials comparing surgical treatments for (b) peri-operative pain; CIN before July 1997. Update: in July 2004 a further search was (c) peri-operative bleeding, primary and secondary haemorrhage; (d) depth and presence of thermal artefact; The method for identifying trials was as follows: (e) adequate colposcopy at follow-up; 1 RANDOMIZED-CONTROLLED TRIAL in PT (f ) cervical Stenosis at follow-up.
2 RANDOMIZED-CONTROLLED-TRIALS3 RANDOM-ALLOCATION4 DOUBLE-BLIND-METHOD 5 SINGLE-BLIND-METHOD 6 CLINICAL-TRIAL in PT7 explode CLINICAL-TRIALS Types of studies
8 (clin* near trial*) in TI9 (clin* near trial*) in AB Randomised controlled trials (RCTs) using alternative surgical 10 (singl* or doubl* or trebl* or tripl*) near (blind* or mask*) treatments of CIN were identified by a computerised literature 11 (#10 in TI) or (#10 in AB) search, tracing references listed in the relevant articles and a man- ual search of appropriate journals. A trial was eligible for inclusion 13 placebo* in TI if it dealt with the ability of a surgical treatment for CIN or inves- 14 placebo* in AB tigated the morbidity associated with it, and contained a control group which the authors claimed was created by a randomised procedure. The computerised MEDLINE search was conducted 17 RESEARCH-DESIGN to identify all registered randomised trials comparing alternative surgical treatments for CIN before July 1997. Update: in July 2004 a further search was undertaken.
or #13 or #14 or #15 or #16 or #17 Types of participants
19 explode GENITAL NEOPLASMS, FEMALE Women with CIN confirmed by biopsy and undergoing surgical 21 TG=ANIMAL not (TG=HUMAN and TG=ANIMAL)22 #20 not #21 Types of intervention
(1) Laser Ablation (2) Laser Conisation Surgery for cervical intraepithelial neoplasia (Review)
Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
Our search strategy was similar to the one that is advocated by (1) Residual disease the Cochrane Collaboration (Dickersin 1994) Seven RCTs reported the incidence of residual disease. The studyby Berget (Berget 1991) used the same group of patients as the Sixteen journals thought to be most likely to contain relevant study by (Berget 1987) hence the former publication was used in publications were hand searched, (Acta Cytologica, Acta the analysis as it contained longer and more consistent follow-up Obstetrica Gynecologica Scandanavia, Acta Oncologica, data. None of the trials produced results that reached statistical American Journal of Obstetrics and Gynaecology, British Journal significance. Meta-analysis failed to demonstrate a significant dif- of Cancer, British Journal of Obstetrics and Gynaecology, ference between the two treatments OR 0.96 (95% CI 0.67 to British Medical Journal, Cancer, Cytopathology, Diagnostic Cytopathology, Gynaecologic Oncology, International Journal ofCancer, International Journal of Gynaecological Cancer, Journal Stratification of disease revealed an apparent significant difference of Family Practice, Lancet, Obstetrics and Gynaecology).
between the two treatment options when treating CIN1 OR 3.33(95%CI 1.1 to 10.1), and a non-significant difference for CIN2OR 1.58 (95% CI 0.69 to 3.2) and CIN3 OR 0.8 (95% CI 0.39 (2) Peri-operative severe pain RCTs were analysed for the method of randomisation, inclusion Laser ablation was associated with a higher incidence of severe criteria, number of women included, treatment intervention (and peri-operative severe pain OR 2.38 (95% CI 0.9 to 6.28).
variations in technique), duration of follow-up and out-comesresidual disease and morbidity.
(3) Peri-operative severe bleedingLaser ablation was associated with significantly more peri-opera-tive severe bleeding OR 7.45 (95% CI 1.68 to 33).
(4) Vaso-motor symptomsOne study (Townsend 1983) reported the incidence of vaso-mo- See Characteristics of Included Studies.
tor symptoms (principally light headedness). Cryosurgery causedsignificantly more symptoms OR 0.11 (95% CI 0.04 to 0.28).
(5) Malodorous dischargeTwo trials (Berget 1987; Townsend 1983) provided sufficient Twenty eight RCTs were identified: data to allow analysis of the incidence of malodorous vaginal dis- The method of randomisation (an important source of bias) was charge. Laser ablation caused significantly less symptoms OR 0.23 not described in 11 studies (Berget 1987; Berget 1991; Bostofte (95%CI 0.15 to 0.35) 1986; Jobson 1984; Kirwan 1985; Kristensen 1990; Kwikkel (6) Adequate colposcopy 1985; Larsson 1982; Paraskevaidis 1994; Takac 1999;Townsend Three studies (Berget 1987; Jobson 1984; Ferenczy 1985) reported 1983). Twelve trials were truly randomised (Alvarez 1994; Cromp- on adequate colposcopy at follow-up in the two treatment groups.
ton 1994; Duggan 1999, Giacalone 1999, Gilbert 1989; Healey Laser ablation was associated with a significantly higher adequate 1996; Mathevet 1994; Mitchell 1998; Oyesanya 1993; Parting- colposcopy rate compared to cryosurgery OR 4.64 (95% CI 2.98 ton 1989; Santos 1996, Schantz 1984) using a genuine random method of treatment allocation and five trials were quasi-ran-domised (Ferenczy 1985; Girardi 1994; Gunasekera 1990, O'Shea (7) Cervical stenosis 1986, Singh 1988). Quasi-randomisation was by alternate assign- Berget (Berget 1987) reported on the incidence of cervical stenosis.
ment, by birth date, or by file number.
Laser ablation was associated with a higher rate of cervical stenosisbut not significantly so when compared to cryotherapy OR 1.96 Update: in July 2004 a further search did not identify any new (95% CI 0.52 to 7.44).
Laser conisation compared with knife conisation
(1) Residual disease (all grades)
In two trials (Bostofte 1986; Mathevet 1994), the direction ofeffect suggested that there was more residual disease in the knife Single Freeze compared to doube freeze cryotherapy
cone group but no conclusions can be made as the CIs are wide The study by Schantz 1984 demonstrated that the double freeze OR 0.63 (95% CI 0.2 to 1.93).
technique had a lower residual disease rate odds ratio (OR) 2.93 (2) Primary haemorrhage (95% confidence interval (CI) 2.93 to 8.60).
Two trials reported data on primary haemorrhage (Bostofte 1986; Laser ablation compared with cryotherapy
Kristensen 1990). The incidence of secondary haemorrhage in Surgery for cervical intraepithelial neoplasia (Review)
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cone biopsies performed with and without Sturmdorf sutures were (2) Duration of procedure combined. Laser conisation was associated with a lower incidence Three studies measured the duration of treatment (Crompton of primary haemorrhage OR 0.51 (95% CI 0.23 to 1.16).
1994; Oyesanya 1993; Paraskevaidis 1994). All demonstrated asignificant increased difference in operating time WMD 11.76 (3) Secondary haemorrhage (95% CI 10.6 to 12.9).
Three trials (Kristensen 1990; Larsson 1982; Mathevet 1994) re-ported on secondary haemorrhage. They produced heterogeneous (3) Peri-operative severe pain results. There was no significant difference OR 0.81 (95% CI 0.35 Oyesanya (Oyesanya 1993) demonstrated that there were signifi- cantly more women complaining of severe pain during laser con- (4) Satisfactory colposcopy at follow-up isation OR 7.81 (95% 2.03 to 29.3). However the trial by San- Two trials (Bostofte 1986; Mathevet 1994) reported on satisfactory tos (Santos 1996) did not demonstrate any significant difference.
colposcopy at follow-up examination. Laser conisation produced There was insufficient data in the trial by Crompton (Crompton a significantly higher adequate colposcopy rate OR 2.73 (95% CI 1994) to include in the analysis, their assessment of pain by linear 1.47 to 5.08).
analogue scales did not demonstrate any difference in pain scores.
The final meta-analysis was OR 5.36 (95%CI 1.02 to 17.2).
(5) Cervical stenosis at follow-upFour trials (Bostofte 1986; Kristensen 1990; Larsson 1982; Math- (4) Secondary haemorrhage evet 1994) reported on cervical stenosis at follow-up. All trials The trials did not demonstrate any significant difference OR 0.89 demonstrated the same direction of effect. Laser conisation re- (95% CI 0.34 to 2.34).
sulted in significantly less cervical stenosis at follow-up examina-tion OR 0.39 (95% CI 0.25 to 0.61).
(5) Significant thermal artefactMathevet and Oyesanya (Mathevet 1994; Oyesanya 1993) (6) Ectocervical and endocervical margins with disease demonstrated significantly more thermal artefact in laser cone One trial (Mathevet 1994) reported on the presence of thermal biopsy specimens OR 2.82 (95%CI 1.56 to 5.1).
artefact prohibiting interpretation of resection margins. As ex-pected knife cone biopsy produced no such cases compared to 14 (6) Depth of thermal artefact out of 37 laser cones OR 11.4 (95% CI 3.54 to 36).
Paraskevaidis (Paraskevaidis 1994) demonstrated a significant dif-ference in depth of thermal artefact WMD 0.27 (95%CI 0.19 to Laser conisation compared with laser ablation
(1) Residual disease (all grades)Only one trial (Partington 1989) reported on this outcome. There (7) Adequate colposcopy at follow-up was no significant difference demonstrated OR 0.73 (95% CI 0.19 Mathevet (Mathevet 1994) demonstrated that loop excision pro- duced more adequate colposcopes at follow-up OR 0.27 (95% CI (2) Significant peri-operative bleeding 0.08 to 0.89).
Only one trial (Partington 1989) reported on this outcome. There However, Santos (Santos 1996) did not a significant difference, was no significant difference demonstrated OR 1.55 (95% CI 0.42 the final meta-analysis being OR 0.94 (95% CI 0.59 to 1.54) (8) Cervical stenosis at follow-up (3) Secondary haemorrhage Mathevet and Santos (Mathevet 1994; Santos 1996) did not Only one trial (Partington 1989) reported on this outcome. There demonstrate any significant difference OR 1.15 (95% CI 0.57 to was no significant difference demonstrated OR 2.17 (95%CI 0.73 Laser ablation compared to loop excision
(4) Adequate colposcopy at follow-up (1) Residual disease Only one trial (Partington 1989) reported on this outcome. Laser Three trials reported residual disease (Alvarez 1994; Gunasekera ablation appeared to produce more adequate colposcopes at fol- 1990; Mitchell 1998). There was no difference in residual disease low-up than laser conisation OR 0.25 (95% CI 0.06 to 1.27).
rates OR 0.99 (95% CI 0.63 to 1.55).
Laser conisation compared to LLETZ
(2) Severe peri-operative pain (1) Residual disease Two trials reported on the incidence of severe peri-operative pain Three trials reported on residual disease at follow-up (Mathevet (Alvarez 1994; Gunasekera 1990). They produced heterogeneous 1994; Oyesanya 1993; Santos 1996). They produced heteroge- results, the final meta-analysis demonstrating a higher incidence neous results. The largest trials by Oyesanya and Santos demon- of women complaining of severe pain during laser ablation OR strated more residual disease in the laser conisation group, but this 4.4 (95% CI 1.86 to 10.4).
just failed to achieve significance. The final meta-analysis was OR1.22 (95% 0.71 to 2.12).
(3) Primary haemorrhage Surgery for cervical intraepithelial neoplasia (Review)
Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
The trials by Alvarez, Gunasekera and Mitchell (Alvarez 1994; (2) Secondary haemorrhage Gunasekera 1990; Mitchell 1998) did not demonstrate any sig- Gilbert and Kristensen (Gilbert 1989; Kristensen 1990) demon- nificant difference OR 1.56 (95% CI 0.35 to 7.00).
strated that routine sutures significantly increase the risk of sec-ondary haemorrhage OR 3.81 (95%CI 1.11 to 13.15).
(4) Secondary haemorrhageThe trials by Alvarez, Gunasekera and Mitchell (Alvarez 1994; (3) Cervical stenosis at follow-up Gunasekera 1990; Mitchell 1998) did not demonstrate any sig- Gilbert and Kristensen (Gilbert 1989; Kristensen 1990) demon- nificant difference OR 1.05 (95% CI 0.33 to 3.30) strated no difference in cervical stenosis OR 1.05 (95% CI 0.48to 2.3).
Knife cone biopsy compared to loop excision
(1) Residual disease
(4) Adequate colposcopy at follow-up Five randomised trials evaluated knife cone biopsy and loop ex- Gilbert (Gilbert 1989) demonstrated that avoidance of routine cision. (Duggan 1999, Giacalone 1999, Girardi 1994, Mathevet suturing reduced inadequate colposcopy rates.
1994). The trials sugested that there might be a higher residualdisease rate after loop excision but this was only just statistically (5) Dysmenorrhoea significant OR 0.43 (95% CI 0.18 to 1.0).
Gilbert and Kristensen (Gilbert 1989; Kristensen 1990) demon-strated that routine sutures increased the risk of dysmenorrhoea (2) Primary haemorrhage OR 2.42 (95%CI 0.95 to 6.15).
There was no clear evidence that there there was any difference inthis outcome (Girardi 1994, Giacalone 1999, Takac 1999).
(3) Adequate colposcopy at follow-up D I S C U S S I O N
The studies by Giacalone 1999, Duggan 1999, Girardi 1994,Mathevet 1994, sugested that loop excision significantly had bet- Reports of non randomised case series suffer from case selection ter adequate colposcopy rates OR 0.64 (95% CI 0.4 to 1.01). The bias and biases towards the operators' skills, hence direct compar- study by Takac 1999 agreed with these findings but there was in- isons of treatments from such data is not ideal.
sufficient data to include their results in this analysis.
The incidence of treatment failures following surgical treatment (4) Cervical stenosis.
of CIN has been demonstrated by case series reports as illustrated There was no clear evidence that either method reduced the cer- in the Background section to be low. The vast majority of RCTs vical stenosis rates.
evaluating the differences in treatment success are grossly under-powered to demonstrate a significant difference between treatment Radical diathermy versus LLETZ
techniques and no real conclusions can be drawn on differences Only one trial compared these two treatments (Healey 1996).
of treatment effect. The reports from randomised and non-ran- There was no significant difference with respect to duration of the domised studies suggest that most surgical treatments have around following symptoms: blood loss , watery discharge, white or yellow 90% success rate, in these circumstances several thousand women discharge, upper or lower abdominal pain, deep pelvic pain. There would have to be treated to demonstrate a signicant difference be- was significantly more vaginal pain when using radical diathermy.
tween two techniques. It might be the case that if a well conducted Radial diathermy compared to cryotherapy
mega-trial was conducted no difference in treatment effect would (1) Residual disease be demonstrated.
There was only one study O'Shea 1986 which compared these two The RCTs and meta-analyses have demonstrated some clear dif- treatment modalities. Cryotherapy appeared to be less effective ferences in morbidity and these should be considered as significant compared to radial diathermy OR 0.33 (95%CI 0.09 to 1.16).
outcomes when deciding upon optimum management.
Cold coagulation compared to cryotherapy
We have used a pragmatic approach to RCTs included in the com- (1) Residual disease parisons. Slight variations of surgical technique occur in some of There was only one study Singh 1988 which compared these two the comparisons which reflects the differences in clinical practice.
treatment modalities. There appeared to be no significant differ- If we considered that these differences did not seriously differ from ence in the two treatments OR 1.4 (95% CI 0.33 to 5.88).
other interventions in the comparison, then the trial was consid-ered in the analysis. For example, when we compared laser ablation Knife cone biopsy with or without haemostatic sutures
to cryotherapy, we included trials using single and double freeze (1) Primary haemorrhage Kristensen (Kristensen 1990) demonstrated that routine Sturm-dorf sutures reduced the risk of primary haemorrhage OR 0.18 (1) Double versus single freeze technique cryotherapy (95% CI 0.05 to 0.71), however this effect was not demonstrated The evidence suggests that cryotherapy should only be used with a by Gilbert (Gilbert 1989) OR 1.0 (95% CI 0.34 to 2.9).
double freeze technique to ensure higher success at treating disease.
Surgery for cervical intraepithelial neoplasia (Review)
Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
(2) Laser ablation compared with cryotherapy demonstrated no There was no difference in residual disease rates between the two overall difference in residual disease after treatment for CIN.
Cryosurgery appears to have a lower success rate but the majority There was no significant difference in primary or secondary haem- of authors used a single freeze thaw technique. Although Creas- orrhage but there appeared to be an increased chance of haemor- man (Creasman 1984) demonstrated that using a double freeze rhage after laser ablation.
thaw freeze technique improves results towards those achieved by (7) Knife cone biopsy compared to Loop excision destructive and excisional methods.
(a) Four randomised trials evaluated knife cone biopsy and loop However, analysis of results demonstrated that there was no signif- excision. (Duggan 1999, Giacalone 1999, Girardi 1994, Mathevet icant difference for the treatment of CIN 1 and 2 but laser ablation 1994). The trials sugested that there might be a higher residual appeared to be better but not significantly so at treating CIN3.
disease rate after loop excision but this was only just statistically We therefore cannot recommend cryosurgery for the treatment of significant OR.
high grade disease. The clinicians choice of treatment of low grade (b) Primary haemorrhage.
disease must therefore be influenced by the side effects related to The studies by Giacalone 1999, Duggan 1999, Girardi 1994, the treatments.
Mathevet 1994 sugested that loop excision significantly had better Laser ablation was associated with significantly more per-operative adequate colposcopy rates OR 0.64 (95% CI 0.4 to 1.01). There and significant post operative bleeding and cryosurgery was asso- was no clear evidence of that there was any difference in primary ciated with significantly more vaso-motor symptoms. Laser abla- haemorrhage or cervical stenosis rates.
tion produced significantly more adequate colposcopes (transfor-mation zone seen in its entirety) at follow-up and cervical stenosis (8) Radical diathermy versus LLETZ appeared to be less common after this treatment.
There was no significant difference in these two modalities with (3) Only one trial (Mathevet 1994) evaluated residual disease after regards to the majority of side effects. Residual disease rates were laser conisation or knife conisation. There was no significant dif- not an outcome measure in the single trial identfied.
ference between the two groups. Primary haemorrhage appeared (9) Radial diathermy compared to cryotherapy to be substantially less in the laser conisation but failed to reach The residual disease rate was greater after cryotherapy.
significance, the direction of effect was similar with regards to sec-ondary haemorrhage. Significant thermal artefact prevented inter- (10) Cold coagulation compared to Cryotherapy pretation of resection margins in 38% of laser cones compared to There was no significant difference with regards to persistence of none in the knife cones. Laser conisation produced significantly more adequate colposcopes (transformation zone seen in its en- (11) Haemostatic sutures tirety) at follow-up and cervical stenosis was significantly less com- Haemostatic sutures significantly reduced the risk of primary mon after this treatment.
haemorrhage but increased the risk of secondary haemorrhage, (4) Only one trial compared laser conisation with laser ablation dysmenorrhoea, cervical stenosis and inadequate follow-up col- for ectocervical lesions (Partington 1989). There was no signifi- poscopy in the study compared with no routine haemostatic su- cant difference with respect to residual disease at follow-up. Laser tures and vaginal packing.
conisation appeared to increase peri-operative bleeding and sec-ondary haemorrhage but neither outcome achieved significance.
Laser conisation appeared to reduce adequate colposcopy at fol- Implications for practice
(5) Only four trials compared laser conisation with LLETZ(Crompton 1994; Mathevet 1994; Oyesanya 1993; Santos 1996).
The evidence from the 28 RCTs identified suggests that there is There was no significant difference with respect to residual dis- no overwhelming superior surgical technique for eradicating CIN.
ease at follow-up but the direction of effect suggested that LLETZ Cryotherapy appears to be an effective treatment of low grade might have the advantage. Laser conisation takes significantly disease but not of high grade disease.
longer to perform, the depth of thermal artefact and incidence of Choice of treatment of ectocervical situated lesions must therefore significant thermal damage are all significantly increased.
be based on cost, morbidity and whether excisional treatments (6) Laser ablation compared to LLETZ was evaluated by three tri- provide more reliable biopsy specimens for assessment of disease als. Alvarez 1994 was included in the comparison but its method- compared to colposcopic directed specimens taken before ablative ology differed from the trials by Gunasekera and Mitchell (Gu- therapy. Colposcopic directed biopsies have been shown to under- nasekera 1990; Mitchell 1998). Alvarez performed LLETZ on all diagnose micro-invasive disease compared with excisional biopsies the patients randomised to that group whereas laser ablation was performed by knife or loop excision, particularly if high grade dis- only performed if colposcopic directed biopsies were performed.
ease is present (Anderson 1986; Chappatte 1991). However, the Surgery for cervical intraepithelial neoplasia (Review)
Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
accuracy of colposcopic directed biopsies compared to excisional versus LLETZ or Laser Ablation after confirmation of disease by biopsies is not the objective of this review.
representative biopsy.
Many physicians now adopt a policy of performing a diagnos- Cryotherapy is easy to use, cheap and as demonstrated is associated tic colposcopy and LLETZ treatment at the same out-patient ap- with low morbidity and should be considered a viable alternative pointment. Unfortunately adopting this approach often results in for the treatment of low grade disease particularly where resources a high false positive loop excision rate. In these circumstances, are limited.
women would have had unnecessary treatment. Prior colposcopic Laser Ablation appears to cause more peri-operative severe pain, directed biopsy reduces the false negative loop excision rate. This and perhaps more primary and secondary haemorrhage compared trial would evaluate patient satisfaction, cost implications of 'see to loop excision. The trials with adequate randomisation methods and treat' versus deferred treatment and evaluate the efficacy of suggest that there is no difference in residual disease between the the two most widely used surgical techniques for CIN i.e. laser two treatments. It could be suggested that LLETZ is the superior ablation or LLETZ.
as it is equipment is cheaper and it also permits confirmation ofdisease status by providing an excision biopsy.
Laser conisation takes longer to perform, requires greater opera- I N T E R E S T
tive training, more expensive investment in equipment, producesmore peri-operative pain, greater depth and severe thermal arte- fact than loop excision. We would therefore recommend the use ofLLETZ rather than laser excision unless the lesion is endocervical.
In this situation, a narrow and deep cone biopsy can be performedreducing tissue trauma and providing a clear resection margin.
Knife cone biopsy still has a place if invasion or glandular dis-ease is suspected. In both diseases adequate resection margins free of disease are important for prognosis and management. In suchcases, LLETZ or laser conisation can induce thermal artefact so External sources of support
that accurate interpretation of margins is not possible.
Implications for research
• No sources of support supplied We would advocate a large multi-centre trial of sufficient power Internal sources of support
to evaluate the role of primary 'see and treat' LLETZ treatment • No sources of support supplied R E F E R E N C E S
References to studies included in this review
by carbon dioxide or cold knife in the treatment of cervical intra-ep- Alvarez 1994 {published data only}
ithelial neoplasia. Acta Obstetricia et Gynecologica Scandinavica 1986; Alvarez R, Helm W, Edwards P, Naumann W, Partridge E, Shingle- ton H, et al. Prospective randomised trial of LLETZ versus laser ab- Crompton 1994 {published data only}
lation in patients with cervical intra-epithelial neoplasia. Gynecologic Crompton A, Johnson N. Which is more painful? A randomised trial comparing loop with laser excision of the cervical transformation Berget 1987 {published data only}
zone. Gynecologic Oncology 1994;52:392–4.
Berget A, Andreason B, Bock, Bostofte E, Hobjorn S, Isager-Sally L,et al. Outpatient treatment of cervical intra-epithelial neoplasia: the Dey 2002 {published data only}
CO2 laser versus cryotherapy: a randomised trial. Acta Obstetricia et Dey, P, Gibbs A, Arnold D, Saleh N, Hirsch P, Woodman C. Loop diathermy excision compared with cervical laser vaporisation for thetreatment of intraepithelial neoplasia: a randomised controlled trial.
Berget 1991 {published data only}
BJOG : an international journal of obstetrics and gynaecology April Berget A, Andreason B, Bock J. Laser and cryosurgery for cervical intraepithelial neoplasia. Acta obstetricia et gynecologica Scandinavica
1991;70:231–5.
Duggan 1999 {published data only}
Bostofte 1986 {published data only}
Duggan B, Felix J, Muderspach L, Gebhardt J, Groshen S, Morrow Bostofte E, Berget A, Falck Larsen J, Pedersen H, Rank F. Conisation P, et al. Cold-Knife conization versus conization by loop electrosur- Surgery for cervical intraepithelial neoplasia (Review)
Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
gical excision procedure: a randomized, prospective study. American Mitchell 1998 {published data only}
Journal of Obstetrics and Gynecology 1999;180:276–82.
Mitchell M, Tortolero-Luna G, Cook E, Whittaker L, Rhodes-Mor-ris H, Silva E. A randomized clinical trial of cryotherapy, laser va- Ferenczy 1985 {published data only}
porization and loop electrosurgical excision for the treatment of squ- Ferenczy A. Comparison of cryo- and carbon dioxide laser therapy mous intra-epithelial lesions of the cervix. Obstetrics and Gynaecology for cervical intraepithelial neoplasia. Obstetrics and Gynecology 1985; Giacalone 1999 {published data only}
O'Shea 1986 {published data only}
Giacalone PL, Laffargue F, Aligier N, Roger P, Combecal J, Daures O'Shea R, Need J, Pomeroy G. Cryotherapy versus electrocoagula- JP. Randomized study comparing two techniques of conization: cold tion diathermy for cervical intraepithelial neoplasia- a prospective knife versus loop excision. Gynecologic Oncology 1999;75(3):356–60.
randomised trial. Colposcopy and gynecologic laser surgery 1986;2(3):
159–61.
Gilbert 1989 {published data only}
Gilbert L, Sunders N, Stringer R, Sharp F. Hemostasis and cold knife Oyesanya 1993 {published data only}
cone biopsy: a prospective randomized trial comparing a suture versus Oyesanya O, Amersinghe C, Manning E. Out patient excisional man- non-suturing technique. Obstetrics and Gynecology 1989;74:640–3.
agement of cervical Intra-epithelial neoplasia: A prospective random-ized comparison between loop diathermy excision and laser excisional Girardi 1994 {published data only}
conisation. American Journal of Obstetrics and Gynecology 1993;168:
Girardi F, Heydarfadai M, Koroschetz F, Pickel H, Winter R. Cold- knife conisation versus loop excision : histolopathologic and clinical
results of a randomised trial. Gynecologic Oncology 1994;55:368–70.
Paraskevaidis 1994 {published data only}
Paraskevaidis E, Kichener H, Malamou-Mitsi V, Agnanti N, Lois D.
Gunasekera 1990 {published data only}
Thermal tissue damage following laser and large loop conisation of Gunasekera C, Phipps J, Lewis B. Large loop excision of the trans- the cervix. Obstetrics and Gynecology 1994;84:752–4.
formation zone (LLETZ) compared to carbon dioxide treatment ofCIN: a superior mode of treatment. British Journal of Obstetrics and Partington 1989 {published data only}
Partington C, Turner M, Soutter W, Griffiths, Krausz T. Laser vapor-ization versus laser excision conisation in the treatment of cervical Healey 1996 {published data only}
intraepithelial neoplasia. Obstetrics and Gynecology 1989;73:775–9.
Healey M, Warton B, Taylor N. Postoperative symptoms followingLLETZ of radical cervical diathermy with fulguration: A randomised Santos 1996 {published data only}
double-blind study. The Australian & New Zealand Journal of Obstet- Santos C, Galdos R, Alvarez M, Velarde C, Barriga O, Dyer R, et rics & Gynaecology 1996;36:179–81.
al. One-session management of cervical intraepithelial neoplasia: A
solution for developing countries. Gynecologic Oncology 1996;61:11–
Jobson 1984 {published data only}
Jobson V, Homesley H. Comparison of cryosurgery and carbon diox-ide laser ablation for the treatment of CIN. Colposcopy and Gyneco- Schantz 1984 {published data only}
logic Laser Surgery 1984;1:173–80.
Schantz A, Thormann L. Cryosurgery for Dysplasia of the uterine
ectocervix. Acta Obstetricia et Gynecologica Scandinavica 1984;63:
Kirwan 1985 {published data only}
Kirwan P, Smith I, Naftalin N. A study of cryosurgery and CO2laser in treatment of carcinoma in situ (CINIII) of the uterine cervix.
Singh 1988 {published data only}
Singh p, Loke k, Hii J, Sabaratnam A, Lim-Tan S, Kitchener H,et al. Cold coagulation versus cryotherapy for treatment of cervical Kristensen 1990 {published data only}
intraepithelial neoplasia: results of a prospective randomized trial.
Kristensen G, Jensen L, Holund B. A randomised trial comparing Colposcopy and gynecologic laser surgery 1988;4(4):211–21.
two methods of cold knife conisation with laser conisation. Obstetrics
and Gynecology 1990;76:1009–13.
Takac 1999 {published data only}
Takac I, Gorisek B. Cold knife conization and loop excision for cer- Kwikkel 1985 {published data only}
vical intraepithelial neoplasia. Tumori 1999;85:243–6.
Kwikkel H, Helmerhorst T, Bezemer P, Quaak M, Stolk J. Laseror cryotherapy for cervical intra-epithelial neoplasia: a randomised Townsend 1983 {published data only}
study to compare efficacy and side effects. Gynecologic Oncology 1985; Townsend D, Richart R. Cryotherapy and carbon dioxide laser man- agement of CIN: A controlled comparison. Obstetrics and Gynecology Larsson 1982 {published data only}
Larsson G, Alm P, Grudsell H. Laser conisation versus cold knife
conisation. Surgery, gynecology & obstetrics 1982;154:59–61.
References to studies awaiting assessment
Mathevet 1994 {published data only}
Mathevet P, Dargent D, Roy M, Beau G. A randomised prospective Lisowski-P, Knapp-P, Zbroch-T, Kobylec-M, Knapp-P. The effective- study comparing three techniques of conisation: cold knife, laser, and ness of conservative treatment of cervical lesions using the LLETZ LEEP. Gynecologic Oncology 1994;54:175–9.
and CO2 laser. Przeglad Lekarski 1999;56:72–5.
Surgery for cervical intraepithelial neoplasia (Review)
Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
Larson 1983
Larson G. Conisation for preinvasive and invasive carcinoma. Acta Anderson M. Are we vaporizing microinvasive lesions?. RCOG Peri- Obstetricia et Gynecologica Scandinavica. Supplement 1983;114:1–40.
natology Press 1986:127–31.
Leiman 1980
Benedet 1981
Leiman G, Harrison N, Rubin A. Pregnancy following conisation of Benedet J, Nickerson K, White G. Laser therapy for cervical intraep- the cervix: complications related to cone biopsy. American Journal of ithelial neoplasia. Obstetrics and Gynecology 1981;57:188.
Obstetrics and Gynecology 1980;136:14–8.
Bigrigg 1990
Luesley 1985
Bigrigg MA, Codling BW, Pearson P, Read MD, Swingler GR. Col- Luesley D, McCrum A, Terry P, Wade-Evans T. Complications of poscopic diagnosis and treatment of cervical dysplasia at a single cone biopsy related to the dimensions of the cone and the influence visit. Experience of low-voltage diathermy loop in 1000 patients. The of prior colposcopic assessment. British Journal of Obstetrics and Gy- Luesley 1990
Bostofte E, Berget A, Larsen J, Pedersen P, Rank F. Conisation by Luesley D, Cullimore J, Redman C. Loop excision of the cervical carbon dioxide laser or cold knife in the treatment of cervical intraep- transformation zone in patients with abnormal cervical smears. BMJ ithelial neoplasia. Acta Obstetricia et Gynecologica Scandinavica 1986; Murdoch 1992
Murdoch J, Grimshaw R, Morgan P, Monaghan J. The impact of Chappatte O, Byrne D, Raju K, Nayagam M, Kenney A. Histological loop diathermy on management of early invasive cervical cancer.
differences between colposcopic-directed biopsy and loop excision of International journal of gynecological cancer : official journal of the the transformation zone: a cause for concern. Gynecologic Oncology International Gynecological Cancer Society 1992;2:129.
Ostergard D. Cryosurgical treatment of cervical intraepithelial neo- Creasman W, Hinshaw W, Clarke-Pearson D. Cyrosurgery in the plasia. Obstetrics and Gynecology 1980;56:233.
management of cervical intraepithelial neoplasia. Obstetrics and Gy- Popkin et al 1978
Popkin D, Scali V, Ahmed M. Cryosurgery for the treatment of Hatch 1981
cervical intrraepithelial neoplasia. American Journal of Obstetrics and Hatch K, Shingleton H, Austin M. Cryosurgery of cervical intraep- ithelial neoplasia. Obstetrics and Gynecology 1981;57:692.
Jordan 1984
Prendeville W, Cullimore J, Norman S. Large loop excision of the Jordan J. Symposia on cervical neoplsaia, excisional methods. Col- transformation zone (LLETZ): a new method of management for poscopy & gynecologic laser surgery 1984;1:271.
women with cervical intraepithelial neoplasia. British Journal of Ob- Jordan 1985
stetrics and Gynaecology 1989;96:1054.
Jordan J, Woodman C, Mylotte M, Emens J, Williams D. The treat- Tabor 1990
ment of cervical intraepithelial neoplasia by laser vaporisation. British Tabor A, Berget A. Cold knife and laser conisation for cervical in- Journal of Obstetrics and Gynaecology 1985;92:394–5.
traepithelial neoplasia. Obstetrics and Gynecology 1990;76:633–5.
Kaufman 1978
Kaufman R, Irwin J. The cryosurgical therapy of cervical intraepithe- Whiteley P, Olah K. Treatment of cervical intraepithelial neoplasia: lial neoplasia. American Journal of Obstetrics and Gynecology 1978; experience with low voltage diathermy loop. American Journal of Ob- stetrics and Gynecology 1990;162:1272.
Characteristics of included studies
Alvarez 1994
True randomisation, allocation by computer generation (sealed envelopes) 375 women with cervical smears suggesting CIN 2 or 3, or 2 smears equivalent to CIN1Women with adequte colposcopy included with entire lesion visible, not pregnant Surgery for cervical intraepithelial neoplasia (Review)
Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
Characteristics of included studies (Continued )
Women with vaginitis, lesion extending to vagina, evidence of invasion excluded.
Primary LLETZColposcopic directed biopsy and endocervical curettage, Only if positive Laser Ablation of TransformationZone Histological status of LLETZ or colposcopic specimensOperators impression of significant peri-operative bleedingWomen's subjective opinion of peri-operative painWomen's subjective opinion of post-operative severe discomfort, heavy discharge, severe bleedingResidual disease ( cytology) at 3 and 6 months 195 randomised to LLETZ, 180 to LaserAll women had paracervical 1% lidocaine with 1:100,000 ephidrineLLETZ group: 6 treated by laser ablation due to technical problems, 4 failed to attend for treatmentLaser group: 66 women did not require treatment, 114 required treatment4 women were treated by LLETZ , 2 by cryosurgery due to technical problems Allocation concealment Berget 1987
Method of randomisation not stated 204 women with entire squamo-columnar junction visibleCIN 1 on 2 biopsies 3-6 months apart, CIN 2 or 3 not extending 3 mm into cryptsNo extension onto vagina or lesion or 12.5 mm into canal Operators impression of significant peri-operative bleeding >25ccWomen's subjective opinion of peri-operative pain (mild, moderate severe, Severe being that the womanwould not consider the treatment again)Women's subjective opinion of post-operative discomfort, heavy discharge, bleeding(None, Mild, Moderate, Severe)Post operative cervical stenosisSatisfactory folow-up colposcopy at 3 monthsResidual diseasse ( histological) at 3 months (all women)Residual disease (histological) at 9 and 15 months ( incomplete follow-up data) 103 randomised to Laser, 101 randomised to CryotherapyLaser performed ablated 2 mm lateral to transformation zone to a depth of 5-7mmCryo coagulation (DOUBLE freeze thaw freze technique) or more if the iceball did not exceed the probe(25mm) by 4 mm.
Local analgesia was not routinely administered Allocation concealment Berget 1991
Method of randomisation not stated 204 women with entire squamo-columnar junction visibleCIN 1 on 2 biopsies 3-6 months apart, CIN 2 or 3 not extending 3 mm into cryptsNo extension onto vagina or lesion or 12.5 mm into canal Residual diseasse ( histological) at 3, 9, 15, 21, 33, 45, 80 months 103 randomised to laser, 101 to cryotherapy Surgery for cervical intraepithelial neoplasia (Review)
Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
Characteristics of included studies (Continued )
6 laser and 2 cryotherapy women refused to be followed upWomen were offered repeat treatment with the same method of treatment as part of protocol. 3 laser and 6cryotherapy women refused repeat treatment.
Laser performed ablated 2 mm lateral to transformation zone to a depth of 5-7mmCryo coagulation (DOUBLE freeze thaw freeze technique) or more if the iceball did not exceed the probe(25mm) by 4 mm.
Local analgesia was not routinely administered Allocation concealment Method of randomisation not stated 123 women with CIN1,2,3 Laser ConisationKnife Conisation DurationPeri-operative bleeding (quanity mls)Post-operative bleeding (primary requiring treatment and Secondary)Post-operative pain (use of analgesics)Adequate colposcopyCervical stenosis ( failure to pass cotton swab)Women complaining of dysmenorrhoeaResidual disease (3-36 months) All procedures performed under general anaesthesiaKnife cone biopsy women had vaginal packing for 24 hours and 3 gms Tranexamic acid for 10 days. Sturmdorfsutures were not used, lateral cervical arteries usedLaser conization women did not have vaginal packing or Tranexamic acid59 women randomised to laser conisation, 64 to knife conisation Allocation concealment True randomisation, allocation by computer generation (sealed envelopes) 80 women recruited with CIN3Women with a history of previous cervical surgery, peri- or post menopausal or whose lesion extends tovagina Laser ConisationLLETZ Subjective scoring of pain by attendant nurseSubjective scoring of pain by women by linear analogue scalePeri-operative bleeding (none, spotting, requiring coagulation)Operative time All women had intra-cervical 4mls 2% lignocaine with 0.3 IU /mls Octapressin prior to treatment(1 spoiled data sheet) Allocation concealment True randomisation, allocation by computer 239 women with CIn I,II,III Surgery for cervical intraepithelial neoplasia (Review)
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Characteristics of included studies (Continued )
Laser AblationLLETZ Residual / Recurent disease,Primary Haemorrhageduration of pregnancy 134 allocated to laser ablation. 120 received allocated treatment.
155 allocated to LLETZ151 received allocated treatment Allocation concealment Duggan 1999
True randomisation,allocation by computer 180 women recruited with all grades of CIN with the following inclusion criteria1) unsatisfactoery colposcopy with positive biopsy2) endocervical curettage with positive biopsy3) possible microinvasion on biopsy LLETZKnife conisation Adequate colposcopy.
Cervical stenosisIncomplete resection marginsResidual disease at 3 months Quasi-randomisation, allocation by alternate assignment 294 women with CIN 1,2,3CIN present on ectocervix with or without marginal extension inrto cervical canal Significant Peri-operative bleedingAdequate Colposcopy at Follow-upResidual Disease 147 randomised to laser, 147 to cryotherapyWomen were offered repeat treatment with the same method of treatment as part of protocol. 3 laser and 6cryotherapy women refused repeat treatment.
Data included in comparison is for one treatment onlyLaser performed ablated 5 mm lateral to lesion to a depth of 5mmCryo coagulation (SINGLE freeze thaw technique) iceball extending 5 mm lateral to lesion.
Local analgesia was not routinely administered Allocation concealment True randomisation,allocation by random number tables and sealed envelopes Surgery for cervical intraepithelial neoplasia (Review)
Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
Characteristics of included studies (Continued )
78 women with CIN 2,3 Knife conisationLLETZ Residual DiseaseCervical stenosisAdequate Colposcopy 78 women randomisedOnly 66 available for follow-up38 Knife Cone28 Laser Excision Allocation concealment Gilbert 1989
True randomisation: sealed envelopes 200 women undergoing knife cone biopsy Lateral haemostatic sutures and interrupted sutures if indicatedVaginal pack with Monsels solution Duration of surgical procedureOperative blood lossPrimary haemorrhageSecondary haemorrhage Girardi 1994
Quasi-randomisation, allocation by odd/even birth dates 90 women with CIN 2 or 3 or persistant CIN1 LLETZKnife conisation Incomplete resection margins (endocervical, ectocervical or both)Primary haemorrhage requiring treatmentResidual disease at 3 months 38 women randomised to loop excision, 52 to knife conisationAll women had pre-operative intracervical local analgesia and vasopressin2 women with incomplete resection of endocervical disease had vaginal hysterectomy Allocation concealment Quasi-randomisation, allocation by unit number 199 women with CIN 2 or 3Women with a history of previous cervical surgery or squamo-columnar junction not completely visible,suspicion of invasion or glandular disease excluded Laser ablationLLETZ Duration of procedure (insuffient data for analysis)Peri-operative blood loss (subjective assessed by operator mild, moderate, severe) Surgery for cervical intraepithelial neoplasia (Review)
Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
Characteristics of included studies (Continued )
Primary haemorrhageSecondary haemorrhageAcceptability of procedure/ pain (subjectively scored by womenn : not unpleasant, moderate, very unpleasant)Residual disease at 6 months 98 women randomised to LLETZ, 101 to laser ablationAll women had paracervical 2% lignocaine with 1:100,000 adrenaline Allocation concealment Healey 1996
True randomisation, allocation by sealed envelopes 55 women with CIN Radical diathermyLLETZ Duration of blood lossDuration of watery/ blood stained dischargeDuration of yellow dischargeDuration of upper abdominal painDuration of lower abdominal painDuration of deep pelvic painDuration of vaginal pain Jobson 1984
Method of randomisation not stated 125 women with CIN 1,2,3Women with satisfactory colposcopy, negative endocervical curettage, reproductive years Vasovagal reactionPatient acceptance (would patient have repeat treatment)Satisfactory colposcopy at 4 monthsResidual disease at 4 and 12 months 42 women were randomised to laser ablation, 39 to cryotherapy and completed protocolLaser performed ablated 2 mm lateral to transformation zone to a depth of 5-7mm. Women had pre-operativeoral ibuprofen.
Cryo coagulation (DOUBLE freeze thaw freeze technique) or more if the iceball did not exceed the probe(28mm) by 4-5mm. With or without analgesia Allocation concealment Kirwan 1985
Method of randomisation not stated 106 women with CIN 3Adequate colposcopy and no extension to vagina Residual disease at 4 and 10 months Surgery for cervical intraepithelial neoplasia (Review)
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Characteristics of included studies (Continued )
71 women were randomised to laser ablation, 35 to cryotherapyLaser performed ablated transformation zone to a depth of 7mmCryo coagulation ( DOUBLE freeze thaw freeze technique) .
Allocation concealment Method of randomisation not stated 183 women with CIN2 or 3 Knife cone with anterior+posterior Sturmdorf suturesKnife cone without haemostatic sutures but with vaginal packing for 6-8 hoursLaser cone Resection margins free of diseasePrimary haemorrhageSecondary haemorrhageCervical stenosisDysmenorrhoea 62 women randomised to knife cone with sutures, 60 women to knife cone with packing, 61 to laser coneAll procedures performed under general anaesthesiaAll procedures performed with lateral sutures and intra-cervical vasopressin Allocation concealment Kwikkel 1985
Method of randomisation not stated 105 women with CIN1,2,3Adquate colposcopy, no suspicion of invasion Peri-operative painPeri-operative bleedingResidual disease at 3-18 months Laser performed ablating the transformation zone to a depth of 6-7mmCryo coagulation (DOUBLE freeze thaw freeze technique) using a probe (18mm)2 women in cryotherapy group, 2 women in laser group lost to follow-up Allocation concealment Larsson 1982
Method of randomisation not stated 110 women with CIN3 Laser conisationKnife conisation Peri-operative blood loss (insufficient data for analysis)Primary haemorrhage (bleeding requiring intervention in first 4 days)Secondary haemorrhage (bleeding after 4th day) 55 women were randomised to laser conisation, 55 to knife conisationAll procedures performed under general anaesthesiaBood loss estimated by alkaline haematin extraction from swabs etc Allocation concealment Surgery for cervical intraepithelial neoplasia (Review)
Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
Characteristics of included studies (Continued )
True randomisation, allocation by sealed envelopes 110 women with CIN 1,2,3Squamo-columnar junction NOT completely visible Knife coneLaser coneLLETZ Ectocervical resection margin involved with diseaseEndocervical resection margin involved with diseasePresence of thermal artifact not permitting evaluation of resection marginsPeri-operative bleeding requiring haemostatic sutures (loop+laser only)Secondary haemorrhageCervical stenosisSatisfactory colposcopyResidual disease at 6 months 37 women were randomised to knife conisation, 37 to laser conisation, 36 to loopAll 3 treatments performed as an out-patient procedure with 10-20 mls 1% xylocaine with ephidrine.
At knife conisation haemostasis was achieved by Sturmdorf sutures, laser cone by laser coagulation andMonsels solution, loop excision by coagulation and Monsels solution Allocation concealment True randomisation, allocation by computer generation 498 women with CIN 1,2,3Women over 18 yrs, using contraception, biopsy proven CIN, staisfactory colposcopy with lesion entirelyvisible CryotherapyLaser ablationLoop Excision Residual diseasePrimary haemorrhageSecondary haemorrhage 139 women were randomised to cryotherapy, 121 to laser ablation, 130 to loop excision Allocation concealment O'Shea 1986
Quasi-randomisation, allocation by odd/even birth dates 57 women with fuuly visible CIN 1 and 2 proven by biopsy Residual disease at 12 months 30 women randomised to CryotherapySome of these women had single , and some had double freeze technique 27 women to diathermy Allocation concealment Surgery for cervical intraepithelial neoplasia (Review)
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Characteristics of included studies (Continued )
True randomisation, allocation by sealed envelopes 300 women with CIN 1,2,3Women with adequate colposcopy, no evidence of invasion Laser conisationLLETZ Duration of treatmentPatient subjective assesment of pain (none/minimal, moderate, severe)Peri-operative blood loss (difference in weight of blood stained / dry swabs)Secondary haemorrhagePresence of thermal artifact not permitting evaluation of resection marginsDysmenorrhoeaResidual disease at 3-12 months 150 women randomised to laser conisation, 150 to loop excisionIntra-cervical 6mls Citanest (0.5% prilocaine with Octapressin) used pre-operatively Allocation concealment Method of randomisation not stated 40 women undergoing elective hysterectomy Laser conisationLLETZ Duration of procedureDepth of thermal injury Allocation concealment True randomisation, allocation by sealed envelopes 100 women with CIN 1,2,3Women with adequate colposcopy , no evidence of invasion, lesion no more than 5mm into canal Laser conisationLaser ablation Duration of treatmentSignificant peri-operative bleedingWomen's subjective opinion of peri-operative pain (mild, moderate, severe)Secondary haemorrhage (seen in out-patients)Secondary haemorrhage (required admission)Adequate colposcopyCervical stenosisDysmennorrhoeaResidual disease at 6, 12 , 24 months 50 women randomised to laser conisation, 50 women randomised to laser ablationHaemostasis achieved by pressure with a cotton swab or Monsel solutionLaser Excision 2mm margin to lesion and to a depth of 2-3mmLaser ablation to a depth of 10mmIntra-cervical 3% prilocaine with Octapressin used pre-operatively Surgery for cervical intraepithelial neoplasia (Review)
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Characteristics of included studies (Continued )
Allocation concealment Santos 1996
True randomisation, allocation by random tables 447 women with CIN 1,2,3Women with suspicion of invasion, extensive lesion, pregnant were excluded LLETZLaser conisation Residual diseaseSignificant peri-operative bleedingSecondary haemorrhageCervical stenosis at follow-upSatisfactory colposcopy at follow-up 145 women randomised to laser conisation, 147 to loopIntra-cervical 6mls 2% lidocaine with 1:80,000 ephidrine used preoperatively Allocation concealment Schantz 1984
True randomisation, allocation by random tables 142 women with ectocervical CIN 1 and 2 Single FreezeDouble FreezeCryotherapy Residual Disease at 6 months 61 underwent single freeze,81 underwent double freeze Allocation concealment Singh 1988
Quasi-randomisation, by alternate file number 161 women with CIN 1,2,3 Residual disease at 24 months 92 randomised to cold coagulation69 to cryotherapyWomen with inadequate colposcopy or possibility of invasion excluded.
Treatment repeated with modality that patient was randomised to, if initial treatment failed Allocation concealment Takac 1999
Method of randomisation not stated 240 women with CIN 1,2,3.
All procedues were done as in-patients Surgery for cervical intraepithelial neoplasia (Review)
Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
completeness of excision (endo / ectocervial diseaseinvolvement)adequatecolposcopy ratesafter treatmentPrimary haemorrhage 120 randomised to Knife cone120 randomised to LLETZ Allocation concealment Method of randomisation not stated 200 women with CIN 1,2,3Adequate colposcopy, no evidence of invasion Severe crampsVasomotor symptomsResidual disease at 6 months.
100 women randomised to laser ablation, 100 randomised to cryotherapyCryo coagulation (SINGLE freeze thaw technique) using a probe (18mm) with iceball extending 5 mmbeyond abnormal epitheliumLaser ablation of all transformation zone Allocation concealment CIN: cervical intraepithelial neoplasiaLLETZ: large loop excision of the transformation zone A N A L Y S E S
Comparison 01. Single Freeze Cryotherapy versus Double Freeze Cryotherapy
Effect size
01 Residual Disease within 12 Peto Odds Ratio 95% CI 2.93 [1.00, 8.60] Comparison 02. Laser Ablation versus Cryotherapy
Effect size
01 Residual Disease (All Grades of Peto Odds Ratio 95% CI 0.96 [0.67, 1.36] 02 Residual Disease (CIN1) Peto Odds Ratio 95% CI 3.33 [1.10, 10.11] 03 Residual Disease (CIN2) Peto Odds Ratio 95% CI 1.49 [0.69, 3.20] 04 Residual Disease (CIN3) Peto Odds Ratio 95% CI 0.80 [0.39, 1.65] 05 Peri-operative Severe Pain Peto Odds Ratio 95% CI 2.38 [0.90, 6.28] 06 Peri-operative Severe Bleeding Peto Odds Ratio 95% CI 7.45 [1.68, 33.05] 07 Vaso-motor Symptoms Peto Odds Ratio 95% CI 0.11 [0.04, 0.28] 08 Malodorous Discharge Peto Odds Ratio 95% CI 0.23 [0.15, 0.35] Surgery for cervical intraepithelial neoplasia (Review)
Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
09 Adequate Colposcopy at Peto Odds Ratio 95% CI 4.64 [2.98, 7.23] 10 Cervical Stenosis at Follow-up Peto Odds Ratio 95% CI 1.44 [0.46, 4.55] Comparison 03. Laser Conisation versus Knife Conisation
Effect size
01 Residual Disease (All Grades of Peto Odds Ratio 95% CI 0.63 [0.20, 1.93] 02 Primary Haemorrhage Peto Odds Ratio 95% CI 0.51 [0.23, 1.16] 03 Secondary Haemorrhage Peto Odds Ratio 95% CI 0.81 [0.35, 1.86] 04 Adequate Colposcopy at Peto Odds Ratio 95% CI 2.73 [1.47, 5.08] 05 Cervical Stenosis at Follow-up Peto Odds Ratio 95% CI 0.39 [0.25, 0.61] 06 Significant Thermal Artifact Peto Odds Ratio 95% CI 11.40 [3.59, 36.19] Prohibiting Interpretation ofResection Margin Comparison 04. Laser Conisation versus Laser Ablation
Effect size
01 Residual Disease (All Grades of Peto Odds Ratio 95% CI 0.73 [0.19, 2.87] 02 Peri-operative Severe Bleeding Peto Odds Ratio 95% CI 1.55 [0.42, 5.70] 03 Secondary Haemorrhage Peto Odds Ratio 95% CI 2.17 [0.73, 6.48] 04 Adequate Colposcopy at Peto Odds Ratio 95% CI 0.25 [0.05, 1.27] Comparison 05. Laser Conisation versus Loop Excision
Effect size
01 Residual Disease Peto Odds Ratio 95% CI 1.22 [0.71, 2.12] 02 Duration of Procedure Weighted Mean Difference (Fixed) 95% CI 11.76 [10.60, 12.91] 03 Peri-operative Severe Pain Peto Odds Ratio 95% CI 5.36 [1.62, 17.72] 04 Secondary Haemorrhage Peto Odds Ratio 95% CI 0.89 [0.34, 2.34] 05 Significant Thermal Artefact Peto Odds Ratio 95% CI 2.82 [1.56, 5.10] 06 Depth of Thermal Artifact Weighted Mean Difference (Fixed) 95% CI 0.27 [0.19, 0.35] 07 Adequate Colposcopy Peto Odds Ratio 95% CI 0.94 [0.59, 1.52] 08 Cervical Stenosis Peto Odds Ratio 95% CI 1.15 [0.57, 2.33] Comparison 06. Laser Ablation versus Loop Excision
Effect size
01 Residual Disease Peto Odds Ratio 95% CI 1.16 [0.76, 1.76] 02 Peri-operative Severe Pain Peto Odds Ratio 95% CI 4.40 [1.86, 10.43] 03 Secondary Haemorrhage Peto Odds Ratio 95% CI 1.05 [0.33, 3.30] Surgery for cervical intraepithelial neoplasia (Review)
Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
04 Primary Haemorrhage Peto Odds Ratio 95% CI 1.56 [0.35, 7.00] Comparison 07. Knife Conisation versus Loop Excision
Effect size
01 Residual Disease Peto Odds Ratio 95% CI 0.43 [0.18, 1.00] 02 Primary Haemorrhage Peto Odds Ratio 95% CI 1.05 [0.47, 2.33] 03 Adequate Colposcopy at Peto Odds Ratio 95% CI 0.64 [0.40, 1.01] 04 Cervical Stenosis Peto Odds Ratio 95% CI 1.08 [0.38, 3.04] Comparison 08. Radical Diathermy versus LLETZ
Effect size
01 Duration of blood loss Weighted Mean Difference (Fixed) 95% CI -1.20 [-5.20, 2.80] 02 Blood stained / watery Weighted Mean Difference (Fixed) 95% CI 0.80 [-3.84, 5.44] 03 Yellow discharge Weighted Mean Difference (Fixed) 95% CI -1.10 [-6.43, 4.23] 04 White discharge Weighted Mean Difference (Fixed) 95% CI -1.60 [-6.74, 3.54] 05 Upper Abdominal Pain Weighted Mean Difference (Fixed) 95% CI -0.30 [-1.86, 1.26] 06 Lower Abdominal Pain Weighted Mean Difference (Fixed) 95% CI 0.50 [-5.84, 6.84] 07 Deep Pelvic Pain Weighted Mean Difference (Fixed) 95% CI 1.00 [-2.49, 4.49] Weighted Mean Difference (Fixed) 95% CI 10.50 [5.37, 15.63] Comparison 09. Radial Diathermy versus Cryotherapy
Effect size
01 Residual Disease at 12 months Peto Odds Ratio 95% CI 0.33 [0.09, 1.16] Comparison 10. Cold Coagulation versus Cryotherapy
Effect size
01 Residual Disease at 24 months Peto Odds Ratio 95% CI 1.40 [0.33, 5.88] Comparison 11. Knife Cone Biopsy: Haemostatic Sutures versus None
Effect size
01 Primary Haemorrhage Peto Odds Ratio 95% CI 0.52 [0.23, 1.20] 02 Secondary Haemorrhage Peto Odds Ratio 95% CI 2.69 [1.34, 5.39] 03 Cervical Stenosis Peto Odds Ratio 95% CI 3.85 [2.45, 6.04] 04 Adequate Colposcopy at Peto Odds Ratio 95% CI 0.26 [0.15, 0.45] Peto Odds Ratio 95% CI 2.88 [1.55, 5.36] I N D E X T E R M S
Medical Subject Headings (MeSH)
Cervical Intraepithelial Neoplasia [∗surgery]; Conization; Cryosurgery; Laser Surgery; Uterine Cervical Neoplasms [∗surgery] Surgery for cervical intraepithelial neoplasia (Review)
Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
MeSH check words
C O V E R S H E E T
Surgery for cervical intraepithelial neoplasia Martin-Hirsch PL, Paraskevaidis E, Kitchener H Contribution of author(s)
Information not supplied by author Issue protocol first published
Review first published
Date of most recent amendment
Date of most recent
What's New
Update: in July 2004 a further search did not identify any new RCTs Date new studies sought but
none found
Date new studies found but not
Information not supplied by author Date new studies found and
Information not supplied by author Date authors' conclusions
Information not supplied by author Mr Pierre Martin-HirschConsultant GynaecologistDepartment of Obstetrics and GynaecologySharoe Green HospitalSharoe Green LanePrestonLancashirePR2 8DUUKE-mail: [email protected]: + 44 1772716565Fax: + 44 1772710162 Cochrane Library number
Cochrane Gynaecological Cancer Group Editorial group code
Surgery for cervical intraepithelial neoplasia (Review)
Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
Comparison 01 Single Freeze Cryotherapy versus Double Freeze Cryotherapy, Outcome 01
Residual Disease within 12 months
Surgery for cervical intraepithelial neoplasia 01 Single Freeze Cryotherapy versus Double Freeze Cryotherapy 01 Residual Disease within 12 months 2.93 [ 1.00, 8.60 ] 2.93 [ 1.00, 8.60 ] Total events: 10 (Single Freeze), 5 (Double Freeze) Test for heterogeneity: not applicable Test for overall effect z=1.95 Comparison 02 Laser Ablation versus Cryotherapy, Outcome 01 Residual Disease (All Grades
Surgery for cervical intraepithelial neoplasia 02 Laser Ablation versus Cryotherapy 01 Residual Disease (All Grades of CIN) 2.01 [ 0.63, 6.45 ] 0.46 [ 0.18, 1.15 ] 0.92 [ 0.22, 3.94 ] 0.60 [ 0.18, 1.98 ] 2.45 [ 0.96, 6.27 ] 0.68 [ 0.37, 1.24 ] 1.63 [ 0.62, 4.27 ] 0.96 [ 0.67, 1.36 ] Total events: 73 (), 74 (Control) Test for heterogeneity chi-square=10.83 df=6 p=0.09 I² =44.6% Test for overall effect z=0.23 Surgery for cervical intraepithelial neoplasia (Review)
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Comparison 02 Laser Ablation versus Cryotherapy, Outcome 02 Residual Disease (CIN1)
Surgery for cervical intraepithelial neoplasia 02 Laser Ablation versus Cryotherapy 02 Residual Disease (CIN1) 1.24 [ 0.07, 21.66 ] 1.00 [ 0.14, 7.26 ] 3.79 [ 0.04, 350.61 ] 10.52 [ 1.80, 61.58 ] 7.39 [ 0.15, 372.38 ] 3.33 [ 1.10, 10.11 ] Total events: 11 (), 3 (Control) Test for heterogeneity chi-square=3.67 df=4 p=0.45 I² =0.0% Test for overall effect z=2.12 Comparison 02 Laser Ablation versus Cryotherapy, Outcome 03 Residual Disease (CIN2)
Surgery for cervical intraepithelial neoplasia 02 Laser Ablation versus Cryotherapy 03 Residual Disease (CIN2) 3.95 [ 0.77, 20.24 ] 1.00 [ 0.14, 7.32 ] 0.54 [ 0.05, 5.50 ] 1.28 [ 0.34, 4.78 ] 1.53 [ 0.25, 9.27 ] 1.49 [ 0.69, 3.20 ] Total events: 17 (), 13 (Control) Test for heterogeneity chi-square=2.30 df=4 p=0.68 I² =0.0% Test for overall effect z=1.01 Surgery for cervical intraepithelial neoplasia (Review)
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Comparison 02 Laser Ablation versus Cryotherapy, Outcome 04 Residual Disease (CIN3)
Surgery for cervical intraepithelial neoplasia 02 Laser Ablation versus Cryotherapy 04 Residual Disease (CIN3) 0.81 [ 0.11, 6.28 ] 0.22 [ 0.06, 0.79 ] 1.65 [ 0.16, 17.49 ] 2.27 [ 0.28, 18.55 ] 1.45 [ 0.44, 4.80 ] 0.80 [ 0.39, 1.65 ] Total events: 16 (), 18 (Control) Test for heterogeneity chi-square=6.14 df=4 p=0.19 I² =34.9% Test for overall effect z=0.60 Comparison 02 Laser Ablation versus Cryotherapy, Outcome 05 Peri-operative Severe Pain
Surgery for cervical intraepithelial neoplasia 02 Laser Ablation versus Cryotherapy 05 Peri-operative Severe Pain 8.24 [ 0.85, 80.33 ] 7.54 [ 0.77, 74.22 ] 1.21 [ 0.36, 4.07 ] 2.38 [ 0.90, 6.28 ] Total events: 12 (), 5 (Control) Test for heterogeneity chi-square=3.31 df=2 p=0.19 I² =39.6% Test for overall effect z=1.75 Surgery for cervical intraepithelial neoplasia (Review)
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Comparison 02 Laser Ablation versus Cryotherapy, Outcome 06 Peri-operative Severe
Surgery for cervical intraepithelial neoplasia 02 Laser Ablation versus Cryotherapy 06 Peri-operative Severe Bleeding 7.32 [ 0.45, 117.82 ] 7.44 [ 0.46, 119.51 ] 7.54 [ 0.77, 74.22 ] 7.45 [ 1.68, 33.05 ] Total events: 7 (), 0 (Control) Test for heterogeneity chi-square=0.00 df=2 p=1.00 I² =0.0% Test for overall effect z=2.64 Comparison 02 Laser Ablation versus Cryotherapy, Outcome 07 Vaso-motor Symptoms
Surgery for cervical intraepithelial neoplasia 02 Laser Ablation versus Cryotherapy 07 Vaso-motor Symptoms 0.11 [ 0.04, 0.28 ] 0.11 [ 0.04, 0.28 ] Total events: 0 (), 20 (Control) Test for heterogeneity: not applicable Test for overall effect z=4.70 Surgery for cervical intraepithelial neoplasia (Review)
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Comparison 02 Laser Ablation versus Cryotherapy, Outcome 08 Malodorous Discharge
Surgery for cervical intraepithelial neoplasia 02 Laser Ablation versus Cryotherapy 08 Malodorous Discharge 0.38 [ 0.20, 0.71 ] 0.14 [ 0.08, 0.26 ] 0.23 [ 0.15, 0.35 ] Total events: 26 (), 86 (Control) Test for heterogeneity chi-square=4.96 df=1 p=0.03 I² =79.9% Test for overall effect z=6.67 Comparison 02 Laser Ablation versus Cryotherapy, Outcome 09 Adequate Colposcopy at
Surgery for cervical intraepithelial neoplasia 02 Laser Ablation versus Cryotherapy 09 Adequate Colposcopy at Follow-up 3.61 [ 1.99, 6.53 ] 8.36 [ 3.23, 21.65 ] 4.92 [ 1.93, 12.57 ] 4.64 [ 2.98, 7.23 ] Total events: 260 (), 196 (Control) Test for heterogeneity chi-square=2.17 df=2 p=0.34 I² =8.0% Test for overall effect z=6.78 Surgery for cervical intraepithelial neoplasia (Review)
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Comparison 02 Laser Ablation versus Cryotherapy, Outcome 10 Cervical Stenosis at Follow-
Surgery for cervical intraepithelial neoplasia 02 Laser Ablation versus Cryotherapy 10 Cervical Stenosis at Follow-up 1.96 [ 0.52, 7.44 ] 0.59 [ 0.06, 5.71 ] 1.44 [ 0.46, 4.55 ] Total events: 7 (), 5 (Control) Test for heterogeneity chi-square=0.81 df=1 p=0.37 I² =0.0% Test for overall effect z=0.62 Comparison 03 Laser Conisation versus Knife Conisation, Outcome 01 Residual Disease (All
Grades of CIN)
Surgery for cervical intraepithelial neoplasia 03 Laser Conisation versus Knife Conisation 01 Residual Disease (All Grades of CIN) 0.67 [ 0.19, 2.44 ] 0.50 [ 0.05, 5.00 ] 0.63 [ 0.20, 1.93 ] Total events: 5 (), 8 (Control) Test for heterogeneity chi-square=0.05 df=1 p=0.83 I² =0.0% Test for overall effect z=0.81 Surgery for cervical intraepithelial neoplasia (Review)
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Comparison 03 Laser Conisation versus Knife Conisation, Outcome 02 Primary Haemorrhage
Surgery for cervical intraepithelial neoplasia 03 Laser Conisation versus Knife Conisation 02 Primary Haemorrhage 0.30 [ 0.10, 0.92 ] 0.96 [ 0.29, 3.21 ] 0.51 [ 0.23, 1.16 ] Total events: 7 (), 20 (Control) Test for heterogeneity chi-square=1.89 df=1 p=0.17 I² =47.0% Test for overall effect z=1.59 Comparison 03 Laser Conisation versus Knife Conisation, Outcome 03 Secondary
Surgery for cervical intraepithelial neoplasia 03 Laser Conisation versus Knife Conisation 03 Secondary Haemorrhage 1.25 [ 0.45, 3.49 ] 0.13 [ 0.02, 0.93 ] 1.00 [ 0.14, 7.40 ] 0.81 [ 0.35, 1.86 ] Total events: 9 (), 17 (Control) Test for heterogeneity chi-square=4.06 df=2 p=0.13 I² =50.7% Test for overall effect z=0.50 Surgery for cervical intraepithelial neoplasia (Review)
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Comparison 03 Laser Conisation versus Knife Conisation, Outcome 04 Adequate Colposcopy
at Follow-up
Surgery for cervical intraepithelial neoplasia 03 Laser Conisation versus Knife Conisation 04 Adequate Colposcopy at Follow-up 2.98 [ 1.43, 6.21 ] 2.21 [ 0.70, 7.01 ] 2.73 [ 1.47, 5.08 ] Total events: 53 (), 34 (Control) Test for heterogeneity chi-square=0.18 df=1 p=0.67 I² =0.0% Test for overall effect z=3.18 Comparison 03 Laser Conisation versus Knife Conisation, Outcome 05 Cervical Stenosis at
Surgery for cervical intraepithelial neoplasia 03 Laser Conisation versus Knife Conisation 05 Cervical Stenosis at Follow-up 0.26 [ 0.10, 0.69 ] 0.61 [ 0.31, 1.22 ] 0.29 [ 0.12, 0.69 ] 0.27 [ 0.07, 1.15 ] 0.39 [ 0.25, 0.61 ] Total events: 22 (), 81 (Control) Test for heterogeneity chi-square=3.04 df=3 p=0.39 I² =1.2% Test for overall effect z=4.14 Surgery for cervical intraepithelial neoplasia (Review)
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Comparison 03 Laser Conisation versus Knife Conisation, Outcome 06 Significant Thermal
Artifact Prohibiting Interpretation of Resection Margin
Surgery for cervical intraepithelial neoplasia 03 Laser Conisation versus Knife Conisation 06 Significant Thermal Artifact Prohibiting Interpretation of Resection Margin 11.40 [ 3.59, 36.19 ] 11.40 [ 3.59, 36.19 ] Total events: 14 (), 0 (Control) Test for heterogeneity: not applicable Test for overall effect z=4.13 Comparison 04 Laser Conisation versus Laser Ablation, Outcome 01 Residual Disease (All
Grades of Disease)
Surgery for cervical intraepithelial neoplasia 04 Laser Conisation versus Laser Ablation 01 Residual Disease (All Grades of Disease) 0.73 [ 0.19, 2.87 ] 0.73 [ 0.19, 2.87 ] Total events: 4 (), 5 (Control) Test for heterogeneity: not applicable Test for overall effect z=0.45 Surgery for cervical intraepithelial neoplasia (Review)
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Comparison 04 Laser Conisation versus Laser Ablation, Outcome 02 Peri-operative Severe
Surgery for cervical intraepithelial neoplasia 04 Laser Conisation versus Laser Ablation 02 Peri-operative Severe Bleeding 1.55 [ 0.42, 5.70 ] 1.55 [ 0.42, 5.70 ] Total events: 6 (), 4 (Control) Test for heterogeneity: not applicable Test for overall effect z=0.66 Comparison 04 Laser Conisation versus Laser Ablation, Outcome 03 Secondary
Surgery for cervical intraepithelial neoplasia 04 Laser Conisation versus Laser Ablation 03 Secondary Haemorrhage 2.17 [ 0.73, 6.48 ] 2.17 [ 0.73, 6.48 ] Total events: 10 (), 5 (Control) Test for heterogeneity: not applicable Test for overall effect z=1.39 Surgery for cervical intraepithelial neoplasia (Review)
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Comparison 04 Laser Conisation versus Laser Ablation, Outcome 04 Adequate Colposcopy
at Follow-up
Surgery for cervical intraepithelial neoplasia 04 Laser Conisation versus Laser Ablation 04 Adequate Colposcopy at Follow-up 0.25 [ 0.05, 1.27 ] 0.25 [ 0.05, 1.27 ] Total events: 45 (), 49 (Control) Test for heterogeneity: not applicable Test for overall effect z=1.68 Comparison 05 Laser Conisation versus Loop Excision, Outcome 01 Residual Disease
Surgery for cervical intraepithelial neoplasia 05 Laser Conisation versus Loop Excision 01 Residual Disease 0.49 [ 0.05, 4.86 ] 1.56 [ 0.81, 2.98 ] 0.73 [ 0.23, 2.31 ] 1.22 [ 0.71, 2.12 ] Total events: 31 (), 26 (Control) Test for heterogeneity chi-square=1.91 df=2 p=0.38 I² =0.0% Test for overall effect z=0.72 Surgery for cervical intraepithelial neoplasia (Review)
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Comparison 05 Laser Conisation versus Loop Excision, Outcome 02 Duration of Procedure
Surgery for cervical intraepithelial neoplasia 05 Laser Conisation versus Loop Excision 02 Duration of Procedure Weighted Mean Difference (Fixed) Weighted Mean Difference (Fixed) 4.28 [ 2.29, 6.27 ] 21.70 [ 19.73, 23.67 ] Paraskevaidis 1994 9.00 [ 6.96, 11.04 ] 11.76 [ 10.60, 12.91 ] Test for heterogeneity chi-square=158.68 df=2 p=<0.0001 I² =98.7% Test for overall effect z=19.95 Comparison 05 Laser Conisation versus Loop Excision, Outcome 03 Peri-operative Severe
Surgery for cervical intraepithelial neoplasia 05 Laser Conisation versus Loop Excision 03 Peri-operative Severe Pain 7.81 [ 2.08, 29.36 ] 1.03 [ 0.06, 16.51 ] 5.36 [ 1.62, 17.72 ] Total events: 10 (), 1 (Control) Test for heterogeneity chi-square=1.67 df=1 p=0.20 I² =40.1% Test for overall effect z=2.75 Surgery for cervical intraepithelial neoplasia (Review)
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Comparison 05 Laser Conisation versus Loop Excision, Outcome 04 Secondary Haemorrhage
Surgery for cervical intraepithelial neoplasia 05 Laser Conisation versus Loop Excision 04 Secondary Haemorrhage 0.97 [ 0.13, 7.20 ] 1.50 [ 0.26, 8.76 ] 0.62 [ 0.15, 2.51 ] 0.89 [ 0.34, 2.34 ] Total events: 8 (), 9 (Control) Test for heterogeneity chi-square=0.61 df=2 p=0.74 I² =0.0% Test for overall effect z=0.23 Comparison 05 Laser Conisation versus Loop Excision, Outcome 05 Significant Thermal
Artefact on Biopsy
Surgery for cervical intraepithelial neoplasia 05 Laser Conisation versus Loop Excision 05 Significant Thermal Artefact on Biopsy 1.38 [ 0.53, 3.59 ] 4.38 [ 2.06, 9.30 ] 2.82 [ 1.56, 5.10 ] Total events: 39 (), 16 (Control) Test for heterogeneity chi-square=3.46 df=1 p=0.06 I² =71.1% Test for overall effect z=3.43 Surgery for cervical intraepithelial neoplasia (Review)
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Comparison 05 Laser Conisation versus Loop Excision, Outcome 06 Depth of Thermal
Surgery for cervical intraepithelial neoplasia 05 Laser Conisation versus Loop Excision 06 Depth of Thermal Artifact Weighted Mean Difference (Fixed) Weighted Mean Difference (Fixed) Paraskevaidis 1994 0.27 [ 0.19, 0.35 ] 0.27 [ 0.19, 0.35 ] Test for heterogeneity: not applicable Test for overall effect z=6.58 Comparison 05 Laser Conisation versus Loop Excision, Outcome 07 Adequate Colposcopy
Surgery for cervical intraepithelial neoplasia 05 Laser Conisation versus Loop Excision 07 Adequate Colposcopy 0.27 [ 0.08, 0.89 ] 1.19 [ 0.71, 1.99 ] 0.94 [ 0.59, 1.52 ] Total events: 121 (), 124 (Control) Test for heterogeneity chi-square=4.94 df=1 p=0.03 I² =79.8% Test for overall effect z=0.24 Surgery for cervical intraepithelial neoplasia (Review)
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Comparison 05 Laser Conisation versus Loop Excision, Outcome 08 Cervical Stenosis
Surgery for cervical intraepithelial neoplasia 05 Laser Conisation versus Loop Excision 08 Cervical Stenosis 0.42 [ 0.08, 2.33 ] 1.41 [ 0.65, 3.07 ] 1.15 [ 0.57, 2.33 ] Total events: 18 (), 16 (Control) Test for heterogeneity chi-square=1.59 df=1 p=0.21 I² =37.0% Test for overall effect z=0.38 Comparison 06 Laser Ablation versus Loop Excision, Outcome 01 Residual Disease
Surgery for cervical intraepithelial neoplasia 06 Laser Ablation versus Loop Excision 01 Residual Disease 0.71 [ 0.34, 1.49 ] 3.27 [ 1.03, 10.39 ] 1.58 [ 0.52, 4.86 ] 1.09 [ 0.56, 2.11 ] 1.16 [ 0.76, 1.76 ] Total events: 50 (), 47 (Control) Test for heterogeneity chi-square=5.11 df=3 p=0.16 I² =41.3% Test for overall effect z=0.68 Surgery for cervical intraepithelial neoplasia (Review)
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Comparison 06 Laser Ablation versus Loop Excision, Outcome 02 Peri-operative Severe Pain
Surgery for cervical intraepithelial neoplasia 06 Laser Ablation versus Loop Excision 02 Peri-operative Severe Pain 0.22 [ 0.01, 4.07 ] 5.86 [ 2.38, 14.44 ] 4.40 [ 1.86, 10.43 ] Total events: 19 (), 4 (Control) Test for heterogeneity chi-square=4.44 df=1 p=0.04 I² =77.5% Test for overall effect z=3.37 Comparison 06 Laser Ablation versus Loop Excision, Outcome 03 Secondary Haemorrhage
Surgery for cervical intraepithelial neoplasia 06 Laser Ablation versus Loop Excision 03 Secondary Haemorrhage 7.32 [ 0.75, 71.19 ] 0.54 [ 0.14, 2.04 ] 1.05 [ 0.33, 3.30 ] Total events: 6 (), 6 (Control) Test for heterogeneity chi-square=3.76 df=1 p=0.05 I² =73.4% Test for overall effect z=0.08 Surgery for cervical intraepithelial neoplasia (Review)
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Comparison 06 Laser Ablation versus Loop Excision, Outcome 04 Primary Haemorrhage
Surgery for cervical intraepithelial neoplasia 06 Laser Ablation versus Loop Excision 04 Primary Haemorrhage 0.20 [ 0.01, 3.62 ] 7.39 [ 1.03, 53.29 ] 0.15 [ 0.00, 7.33 ] 1.56 [ 0.35, 7.00 ] Total events: 4 (), 3 (Control) Test for heterogeneity chi-square=5.71 df=2 p=0.06 I² =65.0% Test for overall effect z=0.58 Comparison 07 Knife Conisation versus Loop Excision, Outcome 01 Residual Disease
Surgery for cervical intraepithelial neoplasia 07 Knife Conisation versus Loop Excision 01 Residual Disease 0.30 [ 0.08, 1.09 ] 0.43 [ 0.11, 1.68 ] 0.97 [ 0.13, 7.20 ] 0.43 [ 0.18, 1.00 ] Total events: 8 (), 16 (Control) Test for heterogeneity chi-square=0.92 df=2 p=0.63 I² =0.0% Test for overall effect z=1.97 Surgery for cervical intraepithelial neoplasia (Review)
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Comparison 07 Knife Conisation versus Loop Excision, Outcome 02 Primary Haemorrhage
Surgery for cervical intraepithelial neoplasia 07 Knife Conisation versus Loop Excision 02 Primary Haemorrhage 0.72 [ 0.09, 5.50 ] 1.10 [ 0.18, 6.76 ] 1.13 [ 0.42, 3.04 ] 1.05 [ 0.47, 2.33 ] Total events: 14 (), 12 (Control) Test for heterogeneity chi-square=0.16 df=2 p=0.92 I² =0.0% Test for overall effect z=0.13 Comparison 07 Knife Conisation versus Loop Excision, Outcome 03 Adequate Colposcopy at
Surgery for cervical intraepithelial neoplasia 07 Knife Conisation versus Loop Excision 03 Adequate Colposcopy at Follow-up 1.15 [ 0.52, 2.58 ] 0.28 [ 0.11, 0.75 ] 0.93 [ 0.40, 2.13 ] 0.27 [ 0.08, 0.89 ] 0.64 [ 0.40, 1.01 ] Total events: 128 (), 132 (Control) Test for heterogeneity chi-square=7.55 df=3 p=0.06 I² =60.3% Test for overall effect z=1.92 Surgery for cervical intraepithelial neoplasia (Review)
Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
Comparison 07 Knife Conisation versus Loop Excision, Outcome 04 Cervical Stenosis
Surgery for cervical intraepithelial neoplasia 07 Knife Conisation versus Loop Excision 04 Cervical Stenosis 0.55 [ 0.11, 2.79 ] 1.71 [ 0.44, 6.57 ] 1.08 [ 0.38, 3.04 ] Total events: 9 (Knife Cone), 8 (LLETZ) Test for heterogeneity chi-square=1.11 df=1 p=0.29 I² =10.2% Test for overall effect z=0.14 Favours treatment Comparison 08 Radical Diathermy versus LLETZ, Outcome 01 Duration of blood loss
Surgery for cervical intraepithelial neoplasia 08 Radical Diathermy versus LLETZ 01 Duration of blood loss Weighted Mean Difference (Fixed) Weighted Mean Difference (Fixed) -1.20 [ -5.20, 2.80 ] -1.20 [ -5.20, 2.80 ] Test for heterogeneity: not applicable Test for overall effect z=0.59 Surgery for cervical intraepithelial neoplasia (Review)
Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
Comparison 08 Radical Diathermy versus LLETZ, Outcome 02 Blood stained / watery
Surgery for cervical intraepithelial neoplasia 08 Radical Diathermy versus LLETZ 02 Blood stained / watery discharge Weighted Mean Difference (Fixed) Weighted Mean Difference (Fixed) 0.80 [ -3.84, 5.44 ] 0.80 [ -3.84, 5.44 ] Test for heterogeneity: not applicable Test for overall effect z=0.34 Comparison 08 Radical Diathermy versus LLETZ, Outcome 03 Yellow discharge
Surgery for cervical intraepithelial neoplasia 08 Radical Diathermy versus LLETZ 03 Yellow discharge Weighted Mean Difference (Fixed) Weighted Mean Difference (Fixed) -1.10 [ -6.43, 4.23 ] -1.10 [ -6.43, 4.23 ] Test for heterogeneity: not applicable Test for overall effect z=0.40 Comparison 08 Radical Diathermy versus LLETZ, Outcome 04 White discharge
Surgery for cervical intraepithelial neoplasia 08 Radical Diathermy versus LLETZ 04 White discharge Weighted Mean Difference (Fixed) Weighted Mean Difference (Fixed) -1.60 [ -6.74, 3.54 ] -1.60 [ -6.74, 3.54 ] Test for heterogeneity: not applicable Test for overall effect z=0.61 Surgery for cervical intraepithelial neoplasia (Review)
Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
Comparison 08 Radical Diathermy versus LLETZ, Outcome 05 Upper Abdominal Pain
Surgery for cervical intraepithelial neoplasia 08 Radical Diathermy versus LLETZ 05 Upper Abdominal Pain Weighted Mean Difference (Fixed) Weighted Mean Difference (Fixed) -0.30 [ -1.86, 1.26 ] -0.30 [ -1.86, 1.26 ] Test for heterogeneity: not applicable Test for overall effect z=0.38 Comparison 08 Radical Diathermy versus LLETZ, Outcome 06 Lower Abdominal Pain
Surgery for cervical intraepithelial neoplasia 08 Radical Diathermy versus LLETZ 06 Lower Abdominal Pain Weighted Mean Difference (Fixed) Weighted Mean Difference (Fixed) 0.50 [ -5.84, 6.84 ] 0.50 [ -5.84, 6.84 ] Test for heterogeneity: not applicable Test for overall effect z=0.15 Comparison 08 Radical Diathermy versus LLETZ, Outcome 07 Deep Pelvic Pain
Surgery for cervical intraepithelial neoplasia 08 Radical Diathermy versus LLETZ 07 Deep Pelvic Pain Weighted Mean Difference (Fixed) Weighted Mean Difference (Fixed) 1.00 [ -2.49, 4.49 ] 1.00 [ -2.49, 4.49 ] Test for heterogeneity: not applicable Test for overall effect z=0.56 Surgery for cervical intraepithelial neoplasia (Review)
Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
Comparison 08 Radical Diathermy versus LLETZ, Outcome 08 Vaginal Pain
Surgery for cervical intraepithelial neoplasia 08 Radical Diathermy versus LLETZ Weighted Mean Difference (Fixed) Weighted Mean Difference (Fixed) 10.50 [ 5.37, 15.63 ] 10.50 [ 5.37, 15.63 ] Test for heterogeneity: not applicable Test for overall effect z=4.01 Comparison 09 Radial Diathermy versus Cryotherapy, Outcome 01 Residual Disease at 12
Surgery for cervical intraepithelial neoplasia 09 Radial Diathermy versus Cryotherapy 01 Residual Disease at 12 months 0.33 [ 0.09, 1.16 ] 0.33 [ 0.09, 1.16 ] Total events: 3 (Radial Diathermy), 9 (Cryotherapy) Test for heterogeneity: not applicable Test for overall effect z=1.73 Favours Cryotherapy Favours Diathermy Comparison 10 Cold Coagulation versus Cryotherapy, Outcome 01 Residual Disease at 24
Surgery for cervical intraepithelial neoplasia 10 Cold Coagulation versus Cryotherapy 01 Residual Disease at 24 months 1.40 [ 0.33, 5.88 ] 1.40 [ 0.33, 5.88 ] Total events: 85 (Cold Coagulation), 61 (Cryotherapy) Test for heterogeneity: not applicable Test for overall effect z=0.46 Favours Cryotherapy Surgery for cervical intraepithelial neoplasia (Review)
Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
Comparison 11 Knife Cone Biopsy: Haemostatic Sutures versus None, Outcome 01 Primary
Surgery for cervical intraepithelial neoplasia 11 Knife Cone Biopsy: Haemostatic Sutures versus None 01 Primary Haemorrhage 1.00 [ 0.34, 2.90 ] 0.18 [ 0.05, 0.71 ] 0.52 [ 0.23, 1.20 ] Total events: 8 (), 15 (Control) Test for heterogeneity chi-square=3.75 df=1 p=0.05 I² =73.3% Test for overall effect z=1.53 Sturmdorf Sutures Comparison 11 Knife Cone Biopsy: Haemostatic Sutures versus None, Outcome 02
Surgery for cervical intraepithelial neoplasia 11 Knife Cone Biopsy: Haemostatic Sutures versus None 02 Secondary Haemorrhage 2.29 [ 0.99, 5.31 ] 3.81 [ 1.11, 13.15 ] 2.69 [ 1.34, 5.39 ] Total events: 25 (), 9 (Control) Test for heterogeneity chi-square=0.45 df=1 p=0.50 I² =0.0% Test for overall effect z=2.79 Sturmdorf Sutures Surgery for cervical intraepithelial neoplasia (Review)
Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
Comparison 11 Knife Cone Biopsy: Haemostatic Sutures versus None, Outcome 03 Cervical
Surgery for cervical intraepithelial neoplasia 11 Knife Cone Biopsy: Haemostatic Sutures versus None 03 Cervical Stenosis 7.34 [ 4.22, 12.76 ] 1.05 [ 0.48, 2.30 ] 3.85 [ 2.45, 6.04 ] Total events: 97 (), 46 (Control) Test for heterogeneity chi-square=15.75 df=1 p=<0.0001 I² =93.6% Test for overall effect z=5.84 Sturmdorf Sutures Comparison 11 Knife Cone Biopsy: Haemostatic Sutures versus None, Outcome 04 Adequate
Colposcopy at Follow-up
Surgery for cervical intraepithelial neoplasia 11 Knife Cone Biopsy: Haemostatic Sutures versus None 04 Adequate Colposcopy at Follow-up 0.26 [ 0.15, 0.45 ] 0.26 [ 0.15, 0.45 ] Total events: 42 (), 75 (Control) Test for heterogeneity: not applicable Test for overall effect z=4.72 Sturmdorf Sutures Surgery for cervical intraepithelial neoplasia (Review)
Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd
Comparison 11 Knife Cone Biopsy: Haemostatic Sutures versus None, Outcome 05
Surgery for cervical intraepithelial neoplasia 11 Knife Cone Biopsy: Haemostatic Sutures versus None 3.31 [ 1.44, 7.62 ] 2.42 [ 0.95, 6.15 ] 2.88 [ 1.55, 5.36 ] Total events: 34 (), 14 (Control) Test for heterogeneity chi-square=0.24 df=1 p=0.62 I² =0.0% Test for overall effect z=3.33 Sturmdorf Sutures Surgery for cervical intraepithelial neoplasia (Review)
Copyright 2007 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd

Source: http://www.conadico.org.mx/boletin/ene13_d.pdf