Microwave therapy for cervical ectropion
Abstract
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:
To evaluate the efficacy and the potential side effects of microwave in the treatment of cervical ectropion.
Background
The terms cervical ectopy or cervical ectropion have replaced that of cervical erosion. It is also sometimes referred to as the transformation zone of the cervix. A cervical ectropion occurs when, due to hormonal changes, the columnar epithelium moves onto the vaginal portion of the cervix. A cervical ectropion appears red and may have an inflamed appearance due to the columnar epithelium being thinner than squamous epithelium. This makes the underlying blood vessels more apparent. Along with the reddened appearance the columnar epithelium may also secrete more mucus which if abundant may cause a vaginal discharge (Chang 1991).
In the west, cervical ectropion is considered as a physiological process not requiring treatment. However, in China, cervical ectropion is considered as one of the most common types of chronic cervicitis, and it is thought that severe cervical ectopion may even result in infertility (Dalgic 2001). As a result, treatment for cervical ectropion is widely used in many hospitals in China.
It is reported that between 20 to 50% in urban and rural Chinese women of reproductive age have cervical ectropion (Zhang 1995; Cai 1997; Peng 2002;Xiao 2003; Zhang 2003). In Chinese literature the occurrence of cervical ectropion is not thought to be caused solely by estrogenic hormonal changes but inflammation and trauma have also been implicated in the aetiology (Wang 2000).
Inflammatory ectropion presents as a defect or degeneration and necrosis of cervical squamous epithelium combined with infiltration of great amounts of inflammatory cells in histopathology. On a smear, superficial, intermediate and basement cells can be found, and also degenerated and necrotic cells, mild dyskaryotic cells, large amounts of neutrophils, small amounts of monocytes, lymphocytes, plasmocytes and macrophages can be seen (Tang 1995).
Clinical macroscopic examination describes three grades based on size I, II and III and on severity of the lesion and the growing speed of columnar epithelium,‐ simple pattern, granular pattern and mamilla pattern (Yue 2005).
Macroscopically it may be difficult to distinguish cervical ectopion from cervical intraepithelial neoplasia (CIN), cancer in situ. Thus a cervical smear for cytological examination should be routinely performed to exclude dysplasia. In addition colposcopy and biopsy may also be needed for, histopathologic examination.
Presently, there is still controversy on whether intervention should be taken for inflammatory cervical ectropion. In China, there have been several management approaches. These include topical treatment with laser coagulation, infrared light, interferon‐alpha suppository (Aoping suppository), combine microwave tissue coagulation (MTC) with interferon‐alpha suppository, electrocautery, and cryotherapy etc. These are only performed after excluding malignancy and specific or nonspecific cervical or vaginal infection. The purpose of treatment is to induce the necrosis and exfoliation of the columnar epithelium at the affected site and also repairing by neoformative squamous epithelium. This in turn is considered likely to reduce the chance of abnormal metaplasia and infection.
Microwave is a kind of electromagnetic waves with frequency up to 2.45 billion HZ, and it can function by giving rise to biophysical effect at the target site through internal heating effect and non‐heating effect. Unlike the external heating of other physical treatment, microwave tissue coagulation (MTC) is an internal heating taking human tissue as the heat source. When the microwave electrode touches the local lesion, a microwave magnetic field can be formed in the tissue and small‐scope high temperature can be produced instantly, inducing degeneration, coagulation and necrosis of the local tissue protein. New squamous cells then migrate from peripheral tissue and repair the wound. The non‐heating effect of microwave can induce dilation of local blood vessel, acceleration of blood flow, and enhancement of tissue metabolism, and in turn promote the elimination of inflammatory products thus playing a synergistic action in the therapy (Guan 2004).
Although many methods including microwave treatment have been used for cervical ectropion clinically, there is no systematic review for the efficacy of the treatments.
Objectives
To evaluate the efficacy and the potential side effects of microwave in the treatment of cervical ectropion.
Methods
Criteria for considering studies for this review
Types of studies
Only truly randomized controlled trials (RCTs) will be included. Pseudo and quasi randomized controlled trials will be excluded.
Types of participants
Women of 18 to 60 years old with cervical ectropion, who are symptomatic with mucopurulent vaginal discharge, and or contact bleeding.
Diagnosed by vaginal examination & graded by ectropion size and tissue pattern.
Diagnostic criteria
Macroscopic examination: discriminating acute with chronic cervicitis.
Three grades based on erosion size: I grade, size of ectropion covers one/third of cervix; II grade, from one/third to two/third; III grade, over two/third. Based on the severity of the lesion and the growing speed of columnar epithelium: simple pattern, granular pattern and mamilla pattern. Simple pattern: the surface of the ectropion is planus and covered by simple columnar epithelium, Granular pattern: the surface is not smooth and the glandular epithelium is hyperplastic accompanied by hyperplastic mesenchyma. Mamilla pattern: the surface is more severely uneven.
Exclusion criteria
Excluding asymptomatic ectropion.
Excluding women who are pregnant or post‐menopausal.
Excluding women with intraepithelial neoplasia (CIN1, 2, 3, cancer in situ or early uterine cervix cancer which diagnosis through Papanicolaou test and/or histological examination or colposcopy.
Excluding women with vaginal or cervical infection (vulvovaginal candidiasis, bacterial vaginosis, trichomonas vaginitis, chlamydial or gonococcal infection)
Types of interventions
Microwave tissue coagulation (MTC) versus no treatment or other treatments such as laser coagulation, infrared light, interferon‐alpha suppository (Aoping suppository), combine MTC with interferon‐alpha suppository, electrocautery, and cryotherapy, respectively.
Types of outcome measures
Main outcome measures
1) Relief of symptoms ‐vaginal discharge and/or contact bleeding as assessed by woman and/or health professional.
2) Quality of life/satisfaction.
3) Appearance of cervix.
Assessment criterion of curative effect
1) Healing well: cervix has become smooth and glossy, ectropion has disappeared or lesion of cervical surface has become squamous metaplasia, the newborn squamous epithelium colors in iodine testing.
2) Not‐healing well: Reduction in the grade of cervix ectropion or no change after treating.
Additional outcome measure
1) The rate of bleeding during operation;
Follow‐up duration
For measurement of cervical ectropion, the follow‐up duration 8 to 12 weeks is adequate.
For symptoms of vaginal discharge and/or contact bleeding (and quality of life/satisfaction), the follow‐up duration of more than three months is adequate.
Search methods for identification of studies
Electronic databases
We will search the Cochrane Menstrual Disorders & Subfertility Group Controlled trials register, Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library (Issue 1, 2006), MEDLINE (1966 to December 2005), EMBASE (1974 to December 2005; The Chinese Biomedical Database (CBM to disc.1978 to December 2005), The Chinese Medical Current Contents (CMCC), CAJ Full‐text Database (1994 to December 2005), Chinese Scientific Journals Database (1989 to December 2005).
The detailed search strategies for each major electronic database are listed in Additional tables 01, 02 and 03.
Additional searches
We will also search related literatures on the internet with search engines such as "google"; search the references listed of articles; and handsearch relevant Chinese journals which are most likely to publish trials on cervical ectropion.
We will contact experts in this field and search the related conference literature. We will not apply any language restrictions.
01‐MEDLINE Search strategy
1 RANDOMIZED CONTROLLED TRIAL
2 CONTROLLED CLINICAL TRIAL
3 RANDOMIZED CONTROLLED TRIALS
4 RANDOM ALLOCATION
5 DOUBLE BLIND METHOD
6 SINGLE BLIND METHOD
7 #1 or #2 or #3 or #4 or #5 or #6
8 ANIMALS not HUMAN
9 #7 not #8
10 CLINICAL TRIAL
11 explode CLINICAL TRIALS/ all subheadings
12 clin* near25 trial*
13 (singl* or doubl* or trebl* or tripl*) near25 (blind* or mask*)
14 PLACEBOS
15 placebo*
16 random*
17 RESEARCH DESIGN
18 #10 or #11 or #12 or #13 or #14 or #15 or #16 or #17
19 #18 not #8
20 #19 not #9
21 explode Evaluation‐Studies/ all subheadings
22 FOLLOW UP STUDIES
23 PROSPECTIVE STUDIES
24 control* or prospectiv* or volunteer*
25 COMPARATIVE STUDY
26 #21 or #22 or #23 or #24 or #25
27 #26 not #8
28 #27 not (#9 or #20)
29 #9 or #20 or #28
30 Cervix‐Erosion/ all subheadings
31 Cervicitis/ all subheadings
32 cervi* erosion*
33 cervicitis
34 Cervi* ectopy or cervi* ectropion
35 columnar ectopy
36 cervi* disease*
37 cervi* infect*
38 #30 or #31 or #32 or #33 or #34 or #35 or #36 or #37
39 Microwaves/ all subheadings
40 Radio‐Waves/ all subheadings
41 microwave*
42 radio wave*
43 Diathermy
44 #39 or #40 or #41 or #42 or #43
45 Laser‐Coagulation/ all subheadings
46 Light‐Coagulation/ all subheadings
47 Infrared‐Rays/ adverse‐effects , therapeutic‐use
48 explode Interferon‐alpha/ all subheadings
49 explode Cautery / all subheadings
50 "Cryotherapy"/ all subheadings
51 "Cryosurgery"/ all subheadings
52 #45 or #46 or #47 or #48 or #49 or #50 or #51
53 laser*
54 light Coagulation or Infrared Ray*
55 interferon* or IFN or aoping suppository
56 cryotherap* or cryosurgery or cautery
57 electrocoagulation or electrocautery or thermocoagulation or electrosurgery
58 no treat*
59 #53 or #54 or #55 or #56 or #57 or #58
60 #44 or #52 or #59
* 61 #29 and #38 and #60
02‐EMBASE Search strategy
1 RANDOMIZED CONTROLLED TRIAL
2 CONTROLLED CLINICAL TRIAL
3 RANDOMIZED CONTROLLED TRIALS
4 RANDOM ALLOCATION
5 DOUBLE BLIND METHOD
6 SINGLE BLIND METHOD
7 #1 or #2 or #3 or #4 or #5 or #6
8 ANIMALS not HUMAN
9 #7 not #8
10 CLINICAL TRIAL
11 'clinical trial'/exp
12 clin* near25 trial*
13 (singl* or doubl* or trebl* or tripl*) near25 (blind* or mask*)
14 PLACEBOS
15 placebo*
16 random*
17 RESEARCH DESIGN
18 #10 or #11 or #12 or #13 or #14 or #15 or #16 or #17
19 #18 not #8
20 #19 not #9
21 'evaluation'/exp
22 FOLLOW UP STUDIES
23 PROSPECTIVE STUDIES
24 control* or prospectiv* or volunteer*
25 COMPARATIVE STUDY
26 #21 or #22 or #23 or #24 or #25
27 #26 not #8
28 #27 not (#9 or #20)
29 #9 or #20 or #28
30 'uterine‐cervix‐erosion'/exp
31 'uterine cervicitis'/exp
32 cervi* erosion*
33 cervicitis
34 cervi* ectopy or cervi* ectropion
35 columnar ectopy
36 cervi* infect*
37 #30 OR #31 OR #32 OR #33 OR #34 or #35 or #36
38 'microwave therapy'/exp
39 'diathermy'/exp
40 'laser'/exp
41 'alpha‐interferon'/exp
42 'infrared radiation'/exp
43 'cryosurgery'/exp
44 'electrocoagulation'/exp
45 'electrosurgery'/exp
46 'cauterization'/exp
47 #38 or #39 or #40 or #41 or #42 or #43 or #44 or #45 or #46
48 microwave* OR MTC
49 microwave tissue coagulation
50 Diathermy
51 laser*
52 interferon* or IFN
53 aoping suppository
54 light Coagulation
55 Infrared Ray*
56 cryotherap* or cryosurgery or cautery
57 electrocoagulation or electrocautery or thermocoagulation or electrosurgery
58 #48 or #49 or #50 or #51 or #52 or #53 or #54 or #55 or #56 or #57
59 #47 or #58
60 #29 and #37 and #59
Data collection and analysis
Study selection
We will develop a standardised data extraction form and pilot this for consistency and completeness. Two review authors (LYL, TJY) will independently consider trials for inclusion, and evaluate their methodological quality and extract trial data independently.
Assessment of methodological quality
The criteria for evaluation of the quality of randomized controlled trial according to Cochrane Handbook for Systematic Reviews of Interventions.
Two review authors (LYL, TJY) will independently evaluate their methodological quality.
1. Quality of allocation concealment will be noted: e.g centralised, third party, envelopes. Papers with unsatisfactory concealment will be excluded.
2. Number of women recruited, randomised, excluded, analysed or lost to follow up
3. Location of trial; single or multicenter
4. Whether an intention to treat analysis was done
5. Whether a power calculation was done
6. Source of funding. The included studies will be classified into one of three categories and presented in a table.
Data extraction
Two review authors (LYL, MB) will independently enter data onto a data extraction form. Discrepancies will be resolved by a third review author (YK). Missing data will be obtained from authors wherever possible. Data will be checked and entered into RevMan by one review aiuthor.
Data analysis
Abstracted data will be analysed following the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2005). We will use Revman software to complete the data analysis. We expect both event (dichotomous) and continuous data. We plan to pool (meta‐analyse) the results of individual studies only if they are clinically similar with respect to their participants, interventions and clinical criteria for defining outcomes.
For dichotomous data, two‐by‐two tables will be generated for each trial and expressed as a risk ratio (RR) with 95% confidence intervals (CI). The data will be meta‐analysed with RevMan software, using the Peto‐modified Mantel‐Haenszel method. Published graphs will display the results of the fixed‐effect approach unless there is statistical heterogeneity, in which case the random‐effects model will be used. However unless the results are robust to both models, they will need to be treated with caution. The results may be converted to absolute measures, such as the number needed to treat (NNT).
Continuous data will be expressed as weighted mean differences (WMD) and 95% confidence intervals, and if appropriate will be combined in meta‐analysis. Meta‐analytic methods for continuous data assume that the underlying distribution of the measurements is normal. The ratio of the mean to its standard deviation gives a crude method of assessing skew: if this ratio is less than 1.65 for any group in a trial, the results will not be pooled but will be reported in text in the other Data of the review. Results will also be reported in other Data where results are reported in the publication as median and range with non‐parametric tests of significance.
We plan to assess statistical heterogeneity (variation) between the results of different studies included in meta‐analyses by inspecting the scatter in the data points on the graphs and the overlap in their confidence intervals, and by checking the I‐squared (I2) quantity. This quantity describes the percentage of total variation across studies that is due to heterogeneity rather than chance.
We plan to conduct sensitivity analyses to examine the effect of methodological differences between the trials, provided there are sufficient trials (> 5). This may help to explain any significant heterogeneity we may detect (defined for this review as I2 > 50%). We plan to explore the effect of including only trials with adequate methodology. Adequate methodology is defined for this purpose as adequate allocation concealment, blinding, analysis by intention to treat and losses to follow up of less than 20%.
Potential publication bias will be tested for by using a funnel plot or other corrective analytical methods, provided there are sufficient trials.
