Abstract
Background/Aim: Conization in patients with cervical intraepithelial neoplasia is associated with longer time required to conceive, a higher risk of preterm delivery, and a myriad of obstetric complications. This study assessed whether operator sex and experience correlate with cone volume, depth, and resection margins in patients wishing to conceive and the general patient population. Patients and Methods: This retrospective single center cohort study included 141 women who had undergone conization for cervical dysplasia in 2020 and 2021. Loop size selection was guided by the preoperative colposcopy report and intraoperative diluted Lugol staining. The hemiellipsoid cone volume was compared for subgroups in three categories: patients operated on by residents vs. board-certified gynecologists; patients operated on by female vs. male surgeons; patients who wished to pursue future pregnancy after conization vs. those who did not. Results: Female surgeons excised insignificantly less cervical tissue compared with their male counterparts (p=0.08). In the subgroup of patients without the wish to conceive, male surgeons tended to excise significantly bigger volumes during conization (p=0.008). No significant difference (p=0.74) regarding volume of resected tissue was evidenced when comparing residents to board-certified surgeons, both in patient subgroups with (p=0.58) and without (p=0.36) a wish to conceive. Male surgeons tended to resect higher volumes (p=0.012) if board-certified compared to their board-certified female colleagues. Conclusion: There were insignificant differences regarding cone depth and volume or incomplete resection when stratified by operator experience and sex. However, male gynecologists removed significantly larger cone volumes in the subgroup of patients who did not pursue future pregnancy.
Cervical cancer remains a serious threat to women’s health with 24,874 deaths reported in Europe in 2008 (1). The incidence of cervical intraepithelial neoplasia (CIN), being a premalignancy, is significantly more difficult to ascertain. Worryingly, most high-grade premalignant cervical lesions are diagnosed in young women aged 25 to 35 (2).
Several techniques are used for CIN treatment, but these can be divided into two broad categories: excision and ablation. Large loop excision of the transformation zone (LLETZ) is currently considered the mainstay amongst CIN excision techniques (3, 4). It has been used for more than three decades and has been definitively proven to be a superior approach when it comes to CIN management as compared to observation (5, 6). However, the fact is that even women treated for CIN adhering to the current best practice recommendations remain at increased risk of developing cervical cancer compared to those without CIN [relative risk (RR)=2.57-4.24] (7). Patients with incomplete CIN excision are at even higher risk of persistent/recurrent disease (8-10). Incomplete resection usually warrants repeat surgery. Some researchers have postulated that cone volume and cone length are predictors of margin positivity (11-13). By extension, a more radical approach to CIN excision might lead to a lower incidence of cervical cancer during follow-up.
However, research of the female reproductive physiology over the past decade has shed new light on the importance of an adequate cervix for fertility (14). Women with a history of treatment for CIN were found to take longer to conceive when compared with women who had no treatment or had a colposcopy only (15). Also, conization has been associated with a higher risk of preterm delivery, in particular cervical insufficiency, premature rupture of membranes (PROM), preterm premature rupture of membranes (PPROM), lower birth weight, a higher neonatal intensive care unit (NICU) admission rate, and perinatal mortality (16-20). Preterm birth and lower birthweight have been most consistently reported to occur when the mothers had been subjected to conization before pregnancy. Some researchers have found that an increase in cone depth and volume was associated with increased risk of preterm labor (21). Not all studies found that conization was associated with adverse fertility outcomes (22-24).
Surgeons have even been found to inadvertently remove less cervical tissue during conization if the patient was considering becoming pregnant in the future (25). Other factors, such as surgical experience and the instruments and techniques used, may also have an impact on cone volume. Some previous studies report that residents tend to remove excessive amounts of tissue that has a high rate of histologic artefacts when compared to more experienced surgeons (26, 27). Also, it has been demonstrated that cone dimensions have generally been decreasing over the years due to more sophisticated instruments and techniques (22). This has occurred without any increase in the incidence of cervical cancer after the conization.
Whether operator sex influences the cone volume, cancer persistence/recurrence rate or infertility and obstetric complications remains to be elucidated. Recent studies are rather divergent in trends regarding operator-dependence. Some reports stated that women have had better surgical outcomes when operated on by female surgeons as compared to male ones (28, 29). Conversely, some studies have shown that male surgeons tend to be less radical when it comes to breast cancer surgery compared to their female colleagues (30). The aim of this study was to determine how operator sex affects the rate of incomplete resections and/or the volume of tissue removed during conization.
Patients and Methods
This is a retrospective cohort study that included all women who had undergone LLETZ for cervical dysplasia in 2020 and 2021 at the Department of Gynecology and Obstetrics of the Mannheim University Hospital, University of Heidelberg, Mannheim, Germany. The study was approved by the Ethics Committee of the Mannheim Medical Faculty of the University of Heidelberg, (approval no. 2022-814, issued March 09, 2022).
A Microsoft Excel database was compiled and contains information about patients’ demographic factors and obstetric personal histories, family planning decisions, expertise/experience of the operating surgeon (resident versus board-certified–which includes consultants, fellows and attending doctors), cone dimensions (height, width and depth, volume), resection margin status, preoperative histology, preoperative Pap smear, preoperative human papillomavirus (HPV) status.
All residents have been supervised during surgery by an experienced colleague. Loop size selection was guided by the preoperative colposcopy report and intraoperative diluted Lugol staining to the cervix. The smallest loop to allow a complete resection was chosen.
Assuming that the tissue samples were hemiellipsoid, the cone volume was calculated using the formula (1/2) × (4/3) × π × (length/2) × (width/2) × depth, as previously described (31). In cases where an additional cone was necessary during the index procedure or in those where several pieces of tissue were resected, the volumes were added.
Data were analyzed using the methods of descriptive statistics with continuous variables represented as medians and ranges and discrete variables represented as ratios and percentages. Three subdivisions were made and compared–one was patients operated on by residents vs. those operated on by board-certified colleagues; the other was patients operated on by female surgeons vs. those operated on by male surgeons; the third was patients who wished to pursue future pregnancy after conization and those who did not. Continuous approximately normally distributed variables were compared using a t-test. Continuous non-normally distributed variables were compared using a Mann–Whitney U (MWU) test. Discrete variables were compared using a chi-square test or a Fisher’s test depending on the number of expected observations in each cell. The impact of the above-mentioned parameters on cone depths and volumes was additionally investigated by a categorical data analysis using cut-off values of 10 mm and 2,500 mm3, respectively. A two-sided p-value of <0.05 was used. We used IBM’s SPSS v 21.0 (IBM Corp., Armonk, NY, USA) for data analysis.
Results
The study included 141 patients. Fifty-three patients (37.6%) were operated on by residents, whereas 88 (62.4%) were treated by board-certified gynecologists. The majority of women (n=99, 70.2%) were operated on by females (Table I). The youngest patient was 20 years old and the oldest 69 years old, while the median age was 39 years. The age distribution had a slight right skew (skewness=0.64).
Characteristics of patients undergoing conization performed by residents and board-certified gynecologists or female and male gynecologists.
There were no statistically significant differences in any of the baseline characteristics of the patients when those operated on by male surgeons were compared to those operated on by female surgeons. The same is true when the subgroup operated on by residents was compared to the one operated on by more experienced surgeons (Table I).
Approximately fifty-eight percent of patients had given birth before being subjected to conization, whereas 45.4% desired to have more children in the future. The most common PAP smear findings were IIID and IVa-36.9% and 43.3%, respectively. One hundred and twenty-two patients (86.5%) tested positive for high-risk HPV.
The cumulative resected volume distribution was monomodal and had a significant right skew (skewness=0.9), which is evident in Figure 1. The volumes resected ranged from 162 to 6,869 mm3 and the median of the distribution was found to be 1,813 mm3. Ninety-six patients (68.1%) had more than 2,500 mm3 of cervical tissue removed.
Frequency distribution of cumulative resection volumes.
Data on the characteristics of the excised tissue and any residual neoplastic tissue with comparisons in regard to operator sex and experience are presented in Table II. The median cumulative resection depth was 9 mm overall (3 mm-22 mm). Fifty-four women (38.3%) had more than 10 mm of tissue removed in regard to cone depth. Twenty-six patients (18.4%) had positive resection margins.
Comparison of large loop excision of the transformation zone (LLETZ) findings between conizations performed by residents and staff or female and male gynecologists.
As shown in Figure 2A, female surgeons removed less cervical tissue but the difference between male and female surgeons in this respect did not achieve statistical significance (MWU=1683.5, p=0.08). Statistical significance was not achieved even when the only significant outlier (in the female surgeon subpopulation) was excluded from the calculation. However, when only patients not wishing to have more children were evaluated, male surgeons tended to be significantly more radical during conization than female ones (MWU=368.5, p=0.008) (Figure 2B).
Box plots representing the differences in cumulative resection volume between surgeons A) with regard to surgeon’s sex, and B) with regard to surgeon’s sex and desire of the patients to have more children in the future.
Interestingly, there seems to be no statistically significant difference (MWU=2253, p=0.74) in the volume of resected tissue when residents are compared to more experienced surgeons (Figure 3A). The same was true when patient subgroups desiring to have more children (MWU=459, p=0.58) and those who did not (MWU=577.5, p=0.36) were analyzed (Figure 3B).
Box plots representing the differences in cumulative resection volume between surgeons A) with regard to experience, and B) with regard to experience and the patient‘s desire to have more children in the future.
Male surgeons tended to get more radical (MWU=650.5, p=0.012) with experience, which is evident from Figure 4. Most residents in our Department of Gynecology were female at the time, thus only four surgeries were performed by male residents. When a chi-square test was done to evaluate differences in surgical experience between sexes, a statistically significant difference was detected (Χ2=20.1, p<0.001). The difference was based on the fact, as stated previously, that expected counts and observed counts differed in the male group since there were only four surgeries performed by male residents.
Box plots representing the differences in cumulative resection volume between surgeons with regard to experience and sex.
Discussion
We have not been able to demonstrate any statistically significant differences between cumulative conization volumes or depths when patient subgroups were compared based on operator sex or experience. Even though male surgeons tended to remove larger volumes when it comes to absolute numbers (2,488 vs. 1,752 mm3), this trend did not reach statistical significance (p=0.08). However, male surgeons did excise larger volumes of tissue in the subpopulation of patients not desiring to have more children in future (p=0.008). Other authors have found male surgeons to be more sparing when it comes to breast cancer excision but published scientific literature on sex differences between surgeons is scarce at best (30, 32). Our findings confirm data from the only study examining differences in the sex of the residents performing LLETZ, which had shown no statistically significant differences (33). The fact that most of the male surgeons in our hospital at the time were experienced surgeons, makes it difficult to decisively discern whether the observed difference was due to sex differences or experience. We found no differences in the observed tissue volumes when residents were compared to more experienced surgeons (p=0.74). However, the fact that residents had been supervised by experienced operators during the procedure might constitute a relevant confounder in this regard. On the other hand, the data confirm the safety of resident-performed procedures in this setting, as the fraction of positive margins was not higher than that in the group of more experienced gynecologists. Also, no differences when it comes to the depth of the excised tissue were observed when male and female surgeons were compared (p=0.39) or when residents and non-residents were compared (p=0.8). The same was true for positive margins when surgeons were compared by sex (p=0.61) and by experience (p=0.66). Other authors have mostly found residents to be more aggressive when it comes to cervical tissue excision even though they tended not to remove all of the cancerous tissue and to traumatize tissue samples making a definitive pathologic diagnosis difficult (26, 27, 34).
Limitations. Our study has several limitations. We did not compile follow-up data concerning patients that did try to conceive after conization as well as those who became pregnant at any point after the procedure; this being a consequence of the retrospective study design with inclusion of very recent conizations. Also, patients were not asked to report other untoward long-term effects like dyspareunia. The study was not adequately powered to analyze differences in patient subpopulations.
Conclusion
No significant differences were found in terms of cone depth and volume as well as incomplete resection when stratified by operator experience and sex. However, male gynecologists removed significant larger cone volumes in the subpopulation of patients who did not pursue future pregnancy.
Footnotes
Authors’ Contributions
Conception and design of the study: Sa.Sp.; data collection: I.S.M., Sa.Sp.; data analysis & interpretation: I.S.M, St.St., Sa.Sp., M.S.; statistical analysis: C.W., St.St.; manuscript preparation phase 1 - drafting the article: St.St., I.S.M.; manuscript preparation phase 2-revising it critically for important intellectual content: Sa.Sp., M.S.; final approval of the version to be submitted: all Authors.
Conflicts of Interest
The Authors have no conflicts of interest to disclose in relation to this study.
- Received January 20, 2023.
- Revision received February 2, 2023.
- Accepted February 3, 2023.
- Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY-NC-ND) 4.0 international license (https://creativecommons.org/licenses/by-nc-nd/4.0).
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