Menopausal status is associated with a high risk for residual disease after cervical conization with positive margins.

Cervical cancer is the second most common malignant neoplasm in women worldwide. High-grade cervical intraepithelial neoplasia (CIN 2/3) is associated with a high risk of developing cervical cancer and is typically treated with conization (cold knife or loop electrosurgical excision procedure (LEEP)). The status of the endocervical cone margin is associated with a major risk for persistence/recurrence of this disease [ 1 – 2 ]. It is estimated that the rate of recurrence two years after treatment in patients without compromised margins is approximately 4 to 18% with an average of 8% [ 3 ]. However, in patients with positive margins, this risk of recurrence is typically higher, and some studies report rates of approximately 52% [ 1 – 4 ]. The ideal follow-up for patients with positive margin involvement after conization is controversial among experts. Some patients who have positive margins will not present residual disease, whereas another portion will still have residual disease in subsequent resection specimens [ 2 , 5 – 7 ]. Thus, some experts suggest clinical follow-up with colposcopy and cytology, whereas others indicate surgical treatment, such as reconization or hysterectomy. The decision is often made based on age, reproductive desire, availability of appropriate follow-up, or presence of other concomitant gynecological problems that can be an indication of hysterectomy, including fibroids, uterine prolapse, or other associated pathologies, such as endometriosis [ 7 ]. If the choice of treatment is new conization or hysterectomy, a portion of women will undergo these procedures unnecessarily because they do not have a residual lesion. This unnecessary surgery increases the risks and complications and highly affects their gestational future, i.e., premature preterm labor, premature rupture of membranes or the need for a surrogate uterus in patients who undergo hysterectomy [ 2 , 5 – 7 ]. Alternatively, if surgery is not performed, there is a risk of inadequately treating a large number of patients who have CIN 2/3 with a risk of malignancy. The estimated prevalence of positive margins after conization could be greater than 30% [ 2 , 7 ]; thus, many researchers are searching for risk factors that may be associated with persistence/recurrence of CIN 2/3 that could facilitate the identification of the correct treatment for each patient. The identification of these predictors is fundamental to determine the correct follow-up in patients with positive endocervical margins. The aim of this study was to determine the demographic and clinicopathological predictors for residual disease in hysterectomy specimens in women after conization for CIN 2/3 with endocervical cone margin involvement.

Hysterectomy specimens from a total of 80 patients were analyzed; 37 (46.3%) had no persistence of CIN 2/3 (no residual disease group) and 43 (53.7%) had persistence of CIN 2/3 (residual disease group). The analysis of demographic and clinical characteristics as possible risk factors for the presence of residual lesions at hysterectomy (age, parity, previous cesarean, previous abortion, race, menstrual cycles, body mass index) is presented in Table 1 . No statistical difference was observed between the no residual disease group and residual disease group. a Student’s t-test or chi-square test. b Body mass index. c Chi-square test or Fisher’s exact test. d Only 63 women were included in this analysis, since the remainder were already in menopause Analysis of cone surgical characteristics as possible risk factors for the presence of residual lesions at hysterectomy (cone height, cone width, conization time until hysterectomy) is presented in Table 2 . None of these variables were associated with residual disease. a Student’s t-test. The analysis of menopausal status, a visible squamocolumnar junction (SCJ) and type of conization (LEEP or cold knife) as possible risk factors for the presence of residual lesions at hysterectomy is presented in Table 3 . We found that menopausal status was strongly associated with a high risk of persistence of residual disease 81.2% (OR 4.9, CI 1.27–18.9), P = 0.014. a Chi-square test b P-value of the risk estimate (odds ratio) The logistic regression analysis for the presence of residual lesions at hysterectomy (dependent variable: residual disease, independent variables: menopausal status and cone depth) is presented in Table 4 . Menopausal status was associated with residual disease ( P = 0.04), whereas cone depth was not (P = 0.550).

To summarize, in the present study, we identified that menopausal status exhibited an important association with persistent residual disease. These results indicate that repeat cervical conization rather than cytopathology and colposcopy during follow-up is viable for patients with endocervical margin involvement with CIN 2/3 after conization. Besides that, we have to remember that the squamocolumnar junction is not visible in the majority of menopausal patients after conization. Notably, conization specimens with endocervical margin involvement exhibit a persistence rate greater than 80% in menopausal women. Patients without these characteristics can undergo more conservative follow-up treatment.

This cross-sectional study was conducted in patients with CIN 2/3 who had positive endocervical margin involvement after conization and underwent a total hysterectomy. The study was conducted at the Gynecologic Oncology Service of the Hospital de Clínicas de Porto Alegre (HCPA), University Hospital, Department of Obstetrics and Gynecology, from 2000 to 2015. The study was approved by the Ethics Committee of the Comitê Nacional de Ética em Pesquisa and by the Comitê de Ética em Pesquisa do Hospital de Clínicas de Porto Alegre (HCPA) (institutional review board equivalent). The data were collected through the electronic medical records of the institution (HCPA) while preserving the patients' anonymity and the research ethics committee waived the requirement for informed consent because the study used previously stored data. Eligible patients for this study included women who underwent hysterectomy as a treatment option after having a positive endocervical margin for CIN 2/3 in cervix cone specimens after treatment with a cold knife or LEEP. In total, 128 patients were selected for inclusion in this study. Of these, 48 cases were excluded based on the following exclusion criteria: patients underwent hysterectomy for another indication, such as myomectomy, abnormal uterine bleeding, cervical stenosis or another indication; presence of a disease that could affect the immune system, such as HIV or an immunological disease; chronic use of corticoids or immunosuppressive drugs; chemotherapy or radiotherapy; and patients with low-grade dysplasia at conization. Eighty patients were eligible for this study. After initial conization, the selected patients had returned for a consultation and were informed that the endocervical margin was compromised. It was explained that they would need a new procedure, either a new conization or a hysterectomy if they did not want to preserve the fertility potential. All these patients underwent total hysterectomy for positive endocervical margin involvement of CIN 2/3 after conization because they had already completed their fertility and follow up with a specialist was difficult due to their geographic location. The hysterectomy specimens of these patients were divided into two groups: women with residual disease (residual disease group) and women with no residual disease (no residual disease group). Data with a normal distribution were analyzed using Student’s t-test or ANOVA for independent samples and Levene’s test for equality of variances. The chi-square test was used for categorical variables. A logistic regression model was used to determine the association between various patient characteristics and residual disease in the multivariate analysis. The threshold for statistical significance was 5%. Statistical tests were performed using the Statistical Package for the Social Sciences 20 (SPSS Inc., Chicago, IL, USA). Moreover, we performed an analysis to verify the power calculation. Our results showed sufficient power with a Fisher's test of 87.8% and a Mid-P test of 91.6% using our data. Therefore, our findings are robust and valuable, considering adequate power greater than 80%.

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