Date Published: June 4, 2019
Publisher: Public Library of Science
Author(s): João Paolo Bilibio, Heleusa Ione Monego, Márcia Luiza Appel Binda, Ricardo dos Reis, Magdalena Grce.
We aimed to determine demographic and clinicopathological predictors for residual disease in women with cervical intraepithelial neoplasia (CIN 2/3) with endocervical cone margin involvement.
A cross-sectional study was conducted. The eligible patients were women who underwent hysterectomy as a treatment option after having a positive endocervical margin for CIN 2/3 in cervix conization specimens from 2000 to 2015. The patients were divided into two groups based on the persistence of CIN 2/3 and absence of CIN 2/3 in hysterectomy specimens. Demographic, clinical and histology information were collected in both groups. A total of 80 patients were eligible for the study; 37 (46.3%) had no persistence of CIN 2/3 and 43 (53.7%) had persistence of CIN 2/3 in the hysterectomy specimens. Demographic, clinical, and cone specimen characteristics, and a visible squamocolumnar junction and type of conization were analyzed as possible risk factors for the presence of residual lesions at hysterectomy, and none of these variables were associated with residual disease. Menopausal status was strongly associated with a high risk of persistent residual disease 81.2% (OR 4.9, CI 1.27–18.9), P = 0.014. In the multivariate analysis, only a menopausal status (P = 0.04) was associated with a high risk of persistent lesions.
This analysis found that menopausal status exhibited an important association with persistent residual disease. Menopausal women with endocervical margin involvement exhibit a greater than 80% risk of persistent lesions.
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% . However, in patients with positive margins, this risk of recurrence is typically higher, and some studies report rates of approximately 52% [1–4].
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.
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.
In this study, approximately 53% of women who underwent hysterectomy for endocervical cone margin involvement of CIN 2/3 after conization exhibited persistent disease in hysterectomy specimens. This finding demonstrates a high prevalence of residual disease if endocervical margin involvement was noted after conization. This result is similar to findings of other studies that reported persistence rates of approximately 45–55% in this situation [1, 4, 8]. In this study, menopausal status was strongly associated with a high risk of persistent disease: 81.2% in menopausal women versus 46.9% in nonmenopausal women. Other studies have previously demonstrated menopausal status as a risk factor for persistent lesions. Xiang et al evaluated the incidences of margin involvement after electrosurgical knife and there were three factors associated with positive margins: age greater than 50 years (odds ratio 3.0), postmenopausal status (odds ratio, 3.1) and microinvasive disease (OR, 2.7) . Similar results were found in other studies that also evaluated factors associated with positive cone margin status after electrosurgical knife and also concluded that increased age are associated with persistent/recurrent disease [2, 10]. These three studies described above only included patients who performed electrosurgical knife, different from ours, that we include patients who performed electrosurgical and cold knife.
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.