The Management For The High-grade Cervical Intraepithelial Neoplasia Patients With Positive Margins After The Conization:a Meta Analysis

Background: Cervical intraepithelial neoplasia(CIN)is a group of precancerous lesions associated with cervical cancer.Currently,the guidelines of European and American recommend the conization as the preferred procedure for the high-grade cervical intraepithelial neoplasia patients.However,after the initial conization,the positive margins could be found sometimes in clinical practice.The NCCN Clinical Practice Guidelines to Cervical Cancer in 2018(1st edition)published by the National Comprehensive Cancer Network(NCCN)of the United States recommended the IA1 stage of cervical cancer patients with positive margins after the initial conization without lymphatic vessel infiltration to cone again to evaluate Infiltration depth and eliminate higher level lesions.At present,the best management strategy for high grade CIN patients with positive margins after the initial conization has not yet reached a consensus.Although the relevant clinical guidelines are recommended,but the level of evidence-based medical evidence is low.Most scholars believe that the positive margin is an important factor in residual or recurrence of lesions.But this does not mean that there are residual lesions.It is controversial.We could choose actively surgical treatment or closely follow-up.It is one of the hot issues in clinical practice.Objectives: To objectively evaluate the outcomes of the high-grade cervical intraepithelial neoplasia patients with positive margins after the initial conization for different clinical management and provide medical evidence for further clinical treatment.Methods: Search Chinese and English databases,including Pub Med,Medline,Cochrane Library,the Chinese Biomedicine Literature Database,the CNKI Database,the Wanfang Database and the VIP Database about different clinical management for the high-grade cervical intraepithelial neoplasia patients with positive margins after the initial conization.According to the established criteria of literature inclusion and exclusion,we could collect data and make statistical analysis.The retrieval time range was set to build the database until February 2018.The languages were Chinese and English.The Rev Man5.3 statistical software provided by the International Cochrane Collaboration was used for Meta-analysis.Calculated the odds ratio(OR)and 95% confidence interval(CI)for each study and the combined OR value.Main results: 1.20 retrospective cohort studies included 18 Chinese articles and 2 English articles.The NOS scores of them were higher than 5 points,which were considered as high quality researches.The total number of patients was 1,903,of which 472 patients were in the follow-up group and 1,431 patients in the surgical treatment group.2.Outcomes of the Meta-analysis: The combined OR and 95% CI of follow-up group and surgery group in the recurrence rate of low grade and above lesions,the recurrence rate of high grade lesions: 0.18[0.10,0.32],0.13[0.05,0.35];The combined OR and 95% CI of follow-up group and conization group in the recurrence rate of low grade and above lesions:0.30[0.12,0.75];The combined OR and 95% CI of follow-up group and hysterectomy group in the recurrence rate of low grade and above lesions,the recurrence rate of high grade lesions:0.17[0.07,0.37],0.12[0.03,0.47];The combined OR and 95% CI of conization group and hysterectomy group in the recurrence rate of low grade and above lesions,the recurrence rate of high grade lesions,the residual rate of low grade and above lesions in secondary surgical specimens,the residual rate of high grade lesions in secondary surgical specimens and the rate of over-treatment:2.91[1.09,7.77],4.44[0.71,27.60],0.87[0.52,1.47],1.24[0.81,1.91],0.81[0.52,1.24].The results showed that the secondary operation could significantly reduce the residual and recurrence of the high-grade cervical intraepithelial neoplasia patients with positive margins after the conization.The repeated conization or total hysterectomy could achieve good therapeutic effect and there was no significant difference between them.Conclusion: 1.The high-grade cervical intraepithelial neoplasia patients with positive margins after the initial conization should continue with surgical treatment and repeated conization should be preferred.2.Repeated conization could find the undiagnosed infiltrating cancer,which is a safe,effective,ideal and conservative surgical procedure.3.Hysterectomy is still an important treatment.