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      Defining the short-term disease recurrence after loop electrosurgical excision procedure (LEEP)

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          Abstract

          Background

          The goal of cervical cancer screening is to identify dysplastic lesions for subsequent excision in order to prevent invasive disease. There is clinical equipoise, on how to best follow women for disease surveillance after treatment with some Canadian provinces exclusively performing colposcopy and some utilizing Human Papilloma Virus (HPV) testing in addition to cervical cytology. Loop Electrosurgical Excision Procedure (LEEP) is used to treat pre-invasive HPV-mediated disease and patients are typically followed for 12 months after disease excision. This study aims to quantify the prevalence of high-grade disease at the time of the second follow-up colposcopy visit, in a practice setting that utilizes laser ablation in addition to LEEP.

          Methods

          In a retrospective cohort study, consecutive patient charts were accessed through the electronic medical record system, ARIA, at the Tom Baker Cancer Centre, in Calgary, Alberta, from January 2010 to December 2015. Data was extracted and a REDCap database was used to compile pertinent information from charts meeting inclusion criteria. Descriptive and analytic statistics were performed.

          Results

          Of the 303 patients identified, 221 patients met inclusion criteria. 86% of these patients met discharge criteria from colposcopy after the second follow up visit. 31 (14%) were seen in a subsequent visit for abnormal findings. Of these, 7 (3.2%) underwent further treatment for high-grade disease/Cervical Intraepithelial Neoplasia (CIN 2/3). Of the 31, 23 (10.6%) had a third – negative – visit, resulting in discharge from colposcopy. One patient had a repeat LEEP for persistent Low-Grade Squamous Intraepithelial Lesion (LSIL).

          Conclusion

          In summary, our data demonstrates a prevalence of 3.2% of high-grade disease at the time of a second colposcopic follow up visit after treatment, in a setting which frequently utilizes laser ablation in combination with LEEP, for large lesions. This recurrence rate is consistent with most published literature on recurrence rates of CIN2/3.

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          Most cited references20

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          Chapter 9: Clinical applications of HPV testing: a summary of meta-analyses.

          More than ever, clinicians need regularly updated reviews given the continuously increasing amount of new information regarding innovative cervical cancer prevention methods. A summary is given from recently published meta-analyses on three possible clinical applications of human papillomavirus (HPV)-DNA testing: triage of women with equivocal or low-grade cytological abnormalities; prediction of the therapeutic outcome after treatment of cervical intraepithelial neoplasia (CIN) lesions, and last not but not least, primary screening for cervical cancer and pre-cancer. Consistent evidence is available indicating that HPV-triage with the Hybrid Capture-2 assay (HC2) is more accurate (significantly higher sensitivity, similar specificity) than repeat cytology to triage women with equivocal Pap smear results. When triaging women with low-grade squamous intraepithelial lesions (LSIL), a reflex HC2 test does not show a significantly higher sensitivity, but a significantly lower specificity compared to a repeat Pap smear. After treatment of cervical lesions, HPV testing easily detects (with higher sensitivity and not lower specificity) residual or recurrent CIN than follow-up cytology. Primary screening with HC2 generally detects 23% (95% confidence interval, CI: 13-23%) more CIN-2, CIN-3, or cancer compared to cytology at cut-off atypical squamous cells of undetermined significance (ASCUS) or LSIL, but is 6% (95% CI: 4-8%) less specific. By combined HPV and cytology screening, a further 4% (95% CI: 3-5%) more CIN-3 lesions can be identified but at the expense of a 7% (95% CI: 5-9%) loss in specificity, in comparison with isolated HC2 screening. Sufficient evidence exists to recommend HPV testing in triage of women with atypical cytology and in surveillance after treatment of CIN lesions. In the United States, recently reviewed knowledge has resulted in the approval of combined cytology and HC2 primary screening in women older than 30 years. However, in Europe, cytology-based screening still remains the standard screening method. The European screening policy will be reviewed based on the longitudinal results of randomised population trials which are currently underway.
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            Systematic reviews and meta-analyses of benefits and harms of cryotherapy, LEEP, and cold knife conization to treat cervical intraepithelial neoplasia.

            Cervical intraepithelial neoplasia (CIN) stage 2-3 is a premalignant lesion that can progress to cervical cancer in 10-20 years if untreated.
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              Incomplete excision of cervical intraepithelial neoplasia and risk of treatment failure: a meta-analysis.

              Over 60,000 women are treated for cervical intraepithelial neoplasia (CIN) each year in England, most by excision. Management of women who have incomplete excision is controversial and the subject of much debate. Consequently, the completeness of excision is often ignored in the planning of subsequent treatment. We aimed to assess the effect of completeness of excision on the risk of post-treatment disease. We undertook a meta-analysis of studies published between Jan 1, 1960, and Jan 31, 2007, that studied the risk of post-treatment disease (ie, CIN of any grade or invasive cancer) in relation to completeness of excision. Studies were included if they described treatment of CIN by excision; numbers of women with involved margins; prevalence of and numbers of women with post-treatment disease in relation to margin status. Criteria for post-treatment disease had to be stated as a defined abnormal cytology or histology. Studies were excluded if they described treatment of cervical glandular intraepithelial disease (CGIN); if all or nearly all women had reflex hysterectomy done soon after initial treatment; if women were immunosuppressed (eg, if they were HIV-positive); or if no control group with disease-free margins was used. The endpoint of our analysis was the relative risk (RR) of post-treatment disease in those whose treatment histology suggested that excision was complete compared with those in whom excision was incomplete or uncertain. RR meta-analysis was done by use of a random effects model. The initial Medline search identified 1756 publications, from which 125 publications were short-listed. Of these, 65 and one unpublished study met our inclusion criteria; therefore, 66 studies were included in this meta-analysis. These studies described findings in 35,109 women of whom 8091 (23%) had at least one margin of the excision biopsy involved with disease. After incomplete excision, RR of post-treatment disease of any grade was 5.47 (95% CI 4.37-6.83) and RR of high-grade disease (ie, CIN 2 or 3, or high-grade squamous intraepithelial lesion) was 6.09 (3.87-9.60) compared with the reference group who had complete excision. High-grade post-treatment disease occurred in 597 of 3335 (18%) women who had incomplete excision versus 318 of 12 493 (3%) women who had complete excision. Incomplete excision of CIN exposes women to a substantial risk of high-grade post-treatment disease. Some of these women would be safer with a second treatment, especially if deep margins are involved, but most will need close follow-up for at least 10 years. Every effort should be made to avoid incomplete excision. Adding extensive ablation in the treatment crater to compensate for inadequate excision should be avoided because this might delay detection of inadequately treated invasive disease and because the effectiveness of additional ablation to destroy any residual CIN cannot be assessed. Furthermore, extensive ablation does not decrease any risk of preterm delivery in subsequent pregnancies.
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                Author and article information

                Contributors
                nicholas.papalia@albertahealthservices.ca
                Journal
                BMC Womens Health
                BMC Womens Health
                BMC Women's Health
                BioMed Central (London )
                1472-6874
                26 February 2020
                26 February 2020
                2020
                : 20
                : 34
                Affiliations
                [1 ]GRID grid.22072.35, ISNI 0000 0004 1936 7697, Department of Obstetrics and Gynaecology, , University of Calgary, ; 1108-1500 7th Street SW, Calgary, AB T2R 1A7 Canada
                [2 ]GRID grid.413574.0, ISNI 0000 0001 0693 8815, Department of Obstetrics and Gynaecology, , Alberta Health Services, ; Calgary, Canada
                Author information
                https://orcid.org/0000-0002-6031-0161
                Article
                901
                10.1186/s12905-020-00901-1
                7045470
                32102650
                2025f21a-eb6f-4df0-b4fd-cd9382ac79b8
                © The Author(s) 2020

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 17 August 2019
                : 11 February 2020
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2020

                Obstetrics & Gynecology
                leep,follow-up,colposcopy,hsil,cin2–3,hpv
                Obstetrics & Gynecology
                leep, follow-up, colposcopy, hsil, cin2–3, hpv

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