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      Residual disease and risk factors in patients with high-grade cervical intraepithelial neoplasia and positive margins after initial conization

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          The purpose of this study was to determine the clinicopathologic predictors of residual disease in patients with high-grade cervical intraepithelial neoplasia (CIN) and margin involvement after initial conization.


          Data from 145 patients who underwent subsequent surgery for high-grade CIN with positive margins were retrospectively analyzed.


          After subsequent surgery, residual disease was diagnosed in 47 (34.2%) patients, of whom five had invasive cervical carcinoma, 31 had CIN 3, nine had CIN 2, and two had CIN 1. Multivariate analysis revealed that only age ≥35 years ( P=0.033), major abnormal cytology ( P=0.002), and pre-cone high-risk human papillomavirus load ≥300 relative light units ( P=0.011) were significant factors associated with residual disease.


          Age ≥35 years, major abnormal cytology, and pre-cone high-risk human papillomavirus load ≥300 relative light units were the only significant factors predicting post-cone residual disease. Appropriate application of these predictive factors may avoid delayed treatment and overtreatment.

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          Most cited references 19

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          2012 updated consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors.

          A group of 47 experts representing 23 professional societies, national and international health organizations, and federal agencies met in Bethesda, MD, September 14-15, 2012, to revise the 2006 American Society for Colposcopy and Cervical Pathology Consensus Guidelines. The group's goal was to provide revised evidence-based consensus guidelines for managing women with abnormal cervical cancer screening tests, cervical intraepithelial neoplasia (CIN) and adenocarcinoma in situ (AIS) following adoption of cervical cancer screening guidelines incorporating longer screening intervals and co-testing. In addition to literature review, data from almost 1.4 million women in the Kaiser Permanente Northern California Medical Care Plan provided evidence on risk after abnormal tests. Where data were available, guidelines prescribed similar management for women with similar risks for CIN 3, AIS, and cancer. Most prior guidelines were reaffirmed. Examples of updates include: Human papillomavirus-negative atypical squamous cells of undetermined significance results are followed with co-testing at 3 years before return to routine screening and are not sufficient for exiting women from screening at age 65 years; women aged 21-24 years need less invasive management, especially for minor abnormalities; postcolposcopy management strategies incorporate co-testing; endocervical sampling reported as CIN 1 should be managed as CIN 1; unsatisfactory cytology should be repeated in most circumstances, even when HPV results from co-testing are known, while most cases of negative cytology with absent or insufficient endocervical cells or transformation zone component can be managed without intensive follow-up.
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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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              Risk factors for cervical intraepithelial neoplasia recurrence after conization: a 10-year study.

              To evaluate the risk factors potentially involved in the development of cervical intraepithelial neoplasia (CIN) recurrence after cervical conization in a long-term follow-up period. Consecutive patients with histologically proven CIN who had undergone either cold knife conization or a loop electrosurgical excision procedure were enrolled and scheduled for serial follow-up examinations over a 10-year period. Data were stored in a digital database. Multivariate analysis was performed to identify factors for recurrence. Between January 1999 and December 2009, 282 patients fulfilled the inclusion criteria and were included in the final statistical analysis. After a median follow-up of 26.7 months (range 6-100), 64 (22.7%) women developed histologically confirmed recurrence. The 2-year recurrence-free survival was 83.7% and 66.7% for women with negative and positive margins, respectively (p=0.008). The 5-year recurrence-free survival was 75.4% and 50.3% for patients with negative and positive margins, respectively (p=0.0004). Positive surgical margin was the most important independent predictor of recurrence [HR 2.5 (95%CI 1.5-4.5), p=0.0007; Wald 11.338]. After multinomial logistic regression the indication for conization based on persistent CIN1 was the only independent predictor for negative margin [OR 0.3 (95%CI 0.1-0.7), p=0.008]. Our study demonstrated that the surgical margin status represents the most important predictor for CIN recurrence after conization. After excisional therapy, close follow-up is mandatory for the early detection of recurrent disease. The identification of risk factors for recurrence may guide clinical decision-making on expectant management versus re-intervention. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

                Author and article information

                Ther Clin Risk Manag
                Ther Clin Risk Manag
                Therapeutics and Clinical Risk Management
                Therapeutics and Clinical Risk Management
                Dove Medical Press
                21 May 2015
                : 11
                : 851-856
                [1 ]Department of Gynecology, Fourth Affiliated Hospital, School of Medicine, Zhejiang University, Yiwu, People’s Republic of China
                [2 ]Department of Gynecologic Oncology, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China
                [3 ]Second Hospital of Shandong University, Jinan, People’s Republic of China
                Author notes
                Correspondence: Weiguo Lü, Department of Gynecologic Oncology, Women’s Hospital, School of Medicine, Zhejiang University, Xueshi Road 2, Hangzhou 310006, People’s Republic of China, Tel +86 571 8706 1501 ext 1005, Fax +86 571 8706 1878, Email lbwg@ 123456zju.edu.cn ; lwg@ 123456hzcnc.com

                *These authors contributed equally to this work

                © 2015 Fu et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License

                The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                Original Research


                predictor, cervical intraepithelial neoplasia, positive margin, conization, residual disease


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