Lugol’s solution reduces positive resection margins and residual disease after the loop electrosurgical excision procedure

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There remains a concern regarding the residual disease if resection is incomplete. However, few studies have so far examined the methods to improve the complete resection of the entire lesion with LEEP, eg, applying Lugol’s solution during LEEP. We examined whether the use of Lugol’s solution reduces the proportion of positive resection margins after the loop electrosurgical excision procedure (LEEP). Methods: A total of 1,751 consecutive women with cervical intraepithelial neoplasia (CIN) who underwent LEEP at three university hospitals were retrospectively retrieved from the database. Outcomes included positive resection margins and residual disease pathologically confirmed within 6 months after LEEP. Results: Positive resection margins were noted in 345 (19.7%) cases. Among 1,507 women followed up, residual disease was diagnosed in 100 (6.6%) cases (69/308 cases with positive margins; 31/1,199 cases with negative margins). The Lugol’s solution group was less likely to have positive resection margins (11.8% vs. 25.5%; P < 0.01), to require additional surgical intervention (5.4% vs. 10.2%; P < 0.01), and to have residual disease (4.9% vs. 8.0%; P = 0.02). A multiple logistic regression analysis demonstrated that Lugol’s solution reduced the proportion of positive resection margins (adjusted odds ratio [aOR], 0.31), and that age 50 years or older (aOR, 1.64), pre-conization cervical cytology (aOR, 1.53), high-risk HPV (aOR 1.75), and CIN 2–3 (aOR, 2.65) were independent risk factors for margin positivity ( P < 0.01 for all except high-risk HPV). Conclusions: Lugol’s solution optimizes CIN treatment by reducing the proportion of positive resection margins and residual disease after LEEP. Resection margins Conization Cervical intraepithelial neoplasm Residual tumors Figures Figure 1 Introduction The gold standard of treatment for cervical intraepithelial neoplasia (CIN) is cervical conization because CIN involves the risk of progression to cervical cancer [1]. The loop electrosurgical excision procedure (LEEP) is preferred over ablative or cold knife conization methods because it has comparable diagnostic power, provides good surgical margins, and is relatively bloodless [2–4]. However, an excisional procedure does not always remove the entire transformation zone (TZ), where CIN mainly develops, particularly in cases with large TZs or deep endocervical lesions [5, 6]. The presence of positive resection margins does not necessarily indicate the need for further immediate action other than careful observation in most cases [7, 8]. Nevertheless, the fundamental goal should be to remove the whole CIN during the initial conization because the risk of residual or recurrent disease is higher for the cases with incomplete excision [5, 9]. According to the colposcopy tutorial provided by the International Agency for Research on Cancer of the World Health Organization, Lugol’s solution can be used to outline the CIN extent before LEEP [10]. In order to reduce the risk of residual disease and its progression and avoid the obstetric complication associated with the repetitive surgical intervention, LEEP aims to remove the whole lesion and TZ as much as possible [6, 11, 12]. Lugol’s solution seems to be a reasonable and inexpensive tool for acquiring disease-free margins at the time of LEEP. However, Lugol’s solution is often disregarded by physicians or is unavailable in many hospitals, especially in South Korea since the test of Lugol’s staining was categorized to “non-specific” categories of “abnormal colposcopic findings” showing poor reliability for detecting CINs [13]. No previous studies have examined the substantive benefits of Lugol’s solution for LEEP. Therefore, we conducted a retrospective study to determine the role of Lugol’s solution in reducing resection margin positivity in LEEP specimens. Methods 1.Study population This was a retrospective observational study. We collected the clinic-pathological and surgical data of 1,992 consecutive patients who underwent LEEP in the Department of Obstetrics and Gynecology of three university hospitals; Seoul National University Hospital (SNUH) from 2012 January to 2013 December (N = 523), Yeonsei University Gangnam Severance Hospital (YUGSH) from 2008 January to 2015 February (N = 853), and Dongguk University Ilsan Hospital (DUIH) from 2005 September to 2017 February (N = 616), respectively. A total of 236 patients who had a histological diagnosis other than CIN, such as benign conditions including condyloma (N = 130), adenocarcinoma in situ (N = 10), or invasive carcinoma including adenocarcinoma (N = 4) or invasive squamous cell carcinoma (N = 89), and metastatic or other malignancies (N = 3) were excluded. Five patients who had a previous history of conization were also excluded. Finally, only 1,751 patients with a histological diagnosis of CIN after LEEP were enrolled in our study (Fig. 1 ), consisting of 443 from SNUH, 756 from YUGSH and 552 from DUIH. The histological grade was categorized as CIN 1 or CIN 2–3. 2. Data Collection The data included patient age, use (yes or no) of Lugol’s solution, LEEP results (histology, margin status, and involved margin sites), follow-up data for at least six months of the initial LEEP, including the type of subsequent management (either immediate subsequent surgical management or follow-up with a Pap test with or without a human papillomavirus test), and subsequent histological diagnosis by cervical biopsy (if available). The initial definite histological diagnosis was determined by colposcopy-guided cervical biopsy and LEEP. The resection margin status was categorized as negative, positive, or uncertain. Positive resection margins were defined as the presence of any CIN grades in any of the sites along the resection margin. The involved resection margin sites were categorized as the ectocervix, endocervix, deep, multiple, or uncertain. Multiple positive resection sites were diagnosed when CIN was detected in two or more margins. As the clinical practice protocol, all treated women should undergo post-LEEP follow-up every 3 to 6 months, which consists of cervical cytology with or without HPV test for 2 years. In particular, patients with positive resection margins underwent either immediate subsequent surgery or first follow-up at 3- to 4-month post-LEEP. The patients who had available follow-up data for at least 6 months after the initial LEEP were finally analyzed for residual diseases. Residual disease was defined as the presence of any CIN grades pathologically confirmed by cervical biopsy or surgical management within 6 months after LEEP. 3. Statistical Analysis The primary outcome of this study was the proportion of positive resection margin in LEEP specimens. The secondary outcome was residual disease. Categorical variables were described as frequencies and percentages, whereas continuous variables were described as median and range for non-parametric variables and as mean and standard deviations for parametric variables. Group difference between two groups (e.g., Lugol’s solution group vs. non-Lugol’s solution group) and each categorical variable was examined using a two-tailed Pearson χ 2 or Fisher’s Exact test with salient dichotomizations. To identify the risk factors for positive resection margins, univariable logistic regression analysis was used and tested all independent variables, including age, pre-conization cervical cytology, high-risk HPV, histology grade, and use of Lugol’s solution. We also performed multiple logistic regression analyses which included the independent factors showing p < 0.05 in the univariable analysis, by calculating the odds ratios and a 95% confidence interval. All statistical analyses were performed using IBM SPSS Statistics for Windows, version 26.0 (IBM Corp., Armonk, N.Y., USA). P < 0.05 was considered statistically significant. Results We retrieved the data of 1,751 consecutive patients (age range, 19–83 years) who were affected by CIN and treated by LEEP from three university hospitals (Fig. 1 ). The clinical and pathological characteristics are summarized in Table 1 . The rate of CIN 2 or 3 was 83.2% (1,456/1,751). The use of Lugol’s solution was 42.5% (745/1,751) among the patients because its use was dependent on the physician’s clinical discretion. Positive resection margins were noted in 345 patients (19.7%). Table 1 Basic characteristics of the eligible study population N (%) No. of patients 1751 (100.0) Age, years old a) median (range) 41 (19–83) Cervical cytology NILM 258 (14.7) ASC-US 410 (23.4) LSIL 264 (15.1) HSIL 402 (23.0) ASC-H 346 (19.8) SCCA 8 (0.5) AGC 10 (0.6) Unavailable 53 (3.0) High-risk HPV Negative 127 (7.3) Positive 1254 (71.6) Unavailable 370 (21.1) Histology grade CIN 1 295 (16.8) CIN 2–3 1456 (83.2) Lugol’s solution Non-Use 1006 (57.5) Use 745 (42.5) Resection margin Negative 1397 (79.8) Positive 345 (19.7) Uncertain 9 (0.5) Abbreviations LEEP, loop electrosurgical excision procedure; HPV, human papillomavirus; NILM, negative for intraepithelial lesion or malignancy; ASC-US, atypical squamous epithelial cells of undetermined significance; LSIL, low-grade squamous intraepithelial lesion; HSIL, high-grade squamous intraepithelial lesion; ASC-H atypical squamous epithelial cells cannot exclude high-grade SIL; SCCA squamous cervical carcinoma; AGC atypical glandular cells; CIN, cervical intraepithelial neopalsia. Data in parentheses are percentages except for age. We observed no statistical difference in patients’ age between the Lugol’s solution and non-Lugol’s solution groups (Table 2 ). Although women in the Lugol’s solution group had a significantly higher rate of CIN 2/3 (P < 0.01), positive resection margins were noted in 11.8% (88/745) and 25.5% (257/1,006) of the patients in the Lugol’s solution group and non-Lugol’s solution group, respectively (P < 0.01). Table 2 Comparison of the two groups with and without use of Lugol’s solution Lugol’s solution group Non-Lugol’s solution group P -value No. of patients 1751 745 1006 Age, years old 0.08 < 50 1332 583 (78.3) 749 (74.5) ≥ 50 419 162 (21.7) 257 (25.5) Cervical cytology 0.32 ≤ LSIL 933 378 (50.7) 555 (55.2) ≥ HSIL 765 329 (44.2) 437 (43.4) Unavailable 53 38 (5.1) 14 (1.4) High-risk HPV 0.04 Negative 128 46 (6.2) 82 (8.1) Positive 1254 569 (76.4) 684 (68.0) Unavailable 369 130 (17.4) 240 (23.9) Histology grade 0.01 CIN 1 295 106 (14.2) 189 (18.8) CIN 2–3 1456 639 (85.8) 817 (81.2) Resection margin < 0.01 Negative 1397 651 (87.4) 746 (74.2) Positive 345 88 (11.8) 257 (25.5) Uncertain 9 6 (0.8) 3 (0.3) Post-LEEP surveillance, N = 1742 a) 739 1003 < 0.01 Immediate surgical management 142 40 (5.4) 102 (10.2) Follow-up with cervical cytology ± HPV tests 1365 632 (85.5) 733 (73.1) Loss of follow-up 235 67 (9.1) 168 (16.7) Residual disease, N = 1507 b) 672 835 0.02 Absent 1360 622 (92.6) 738 (88.4) Present 100 33 (4.9) 67 (8.0) Undetermined 47 17 (2.5) 30 (3.6) Abbreviations HPV, human papillomavirus; LSIL, low-grade squamous intraepithelial lesion; HSIL, high-grade squamous intraepithelial lesion; CIN, cervical intraepithelial neoplasia; LEEP, loop electrosurgical excision procedure Data in parentheses are percentages a) Excluding nine women with uncertain resection margin. b) Excluding nine women with uncertain resection margin and 235 women with loss of follow-up. Two-hundreds thirty-five patients were lost to follow-up, and nine with uncertain resection margin were excluded. A total of 1,507 patients were followed-up; cervical cytology with or without human papillomavirus (HPV) test (N = 1,365) and immediate surgery (N = 142) within 6 months after LEEP. Of these, residual disease was diagnosed in 100 (6.6%) patients: 69 of these patients had positive resection margins (N = 308), whereas 31 had negative resection margins (N = 1,199) [Supplementary Table 1]. Compared to the non-Lugol’s solution group, Lugol’s solution group was less likely to require immediate subsequent surgical procedures (5.4% vs. 10.2%; P < 0.01) or to have the residual disease (4.9% vs. 8.0%; P = 0.02). A logistic regression analysis was conducted to confirm whether the use of Lugol’s solution affected resection margin positivity (Table 3 ). Our univariate analysis demonstrated that age (50 years or older vs. younger than 50 years), pre-conization cervical cytology (≥ high-grade squamous intraepithelial lesion [HSIL] vs. ≤low-grade squamous intraepithelial lesion [LSIL]), pre-conization high-risk HPV (present vs. absent), histological grade (CIN 2/3 vs. CIN 1), and Lugol’s solution (use vs. non-use) were significantly associated with positive resection margins (P < 0.01 for all except for high-risk HPV of P = 0.06). In the multivariable logistic regression analysis, all of these variables were independent risk factors for positive resection margins. The use of Lugol’s solution (adjusted odds ratio [aOR], 0.31; 95% confidence interval [CI], 0.23–0.42; P < 0.01) significantly decreased the proportion of positive resection margins, and age (for 50 years or older, aOR, 1.64; 95% CI, 1.19–2.27), pre-conization cervical cytology (for ≥ HSIL, aOR, 1.53; 95% CI, 1.15–2.03), pre-conization high-risk HPV (for positive high-risk HPV, aOR, 1.75; 95% CI, 1.00-3.07) and histological grade (for CIN 2/3, aOR, 2.65; 95% CI, 1.67–4.22) were significant risk factors for positive resection margins (P < 0.01 for all except for high-risk HPV of P = 0.05). Table 3 Association of age, histology grade, and use of Lugol’s solution with positive resection margins of LEEP specimen Univariable analysis Multivariable analysis Variables N = 1742 a) Unadjusted OR 95% C.I. p -value Adjusted OR 95% C.I. P -value b) Age, years old < 0.01 < 0.01 < 50 1327 Reference Reference ≥ 50 415 1.56 1.20–2.03 1.64 1.19–2.27 Cervical cytology < 0.01 < 0.01 ≤LSIL 931 Reference Reference ≥HSIL 759 1.62 1.27–2.06 1.53 1.15–2.03 High-risk HPV 0.06 0.05 Negative 127 Reference Reference Positive 1248 1.77 1.03–3.05 1.75 1.00-3.07 Histology grade < 0.01 < 0.01 CIN 1 295 Reference Reference CIN 2–3 1447 2.68 1.78–4.03 2.65 1.67–4.22 Lugol’s solution < 0.01 < 0.01 Non-use 1003 Reference Reference Use 739 0.39 0.30–0.51 0.31 0.23–0.42 Abbreviations LEEP, loop electrosurgical excision procedure; C.I., confidence interval; HPV, human papillomavirus; LSIL, low-grade squamous intraepithelial lesion; HSIL, high-grade squamous intraepithelial lesion; CIN, cervical intraepithelial neoplasia a) excluding nine subjects with uncertain resection margin status of LEEP specimen. b) adjusted for all significant variables (age, cervical cytology, high-risk HPV, histology grade, Lugol’s solution) in univariable analysis. We further analyzed 345 cases with positive resection margins and found no differences in age and histological grades between the Lugol’s solution and non-Lugol’s solution groups (Table 4 ). The endocervix was the site that was most frequently involved by CIN (167/345), regardless of whether Lugol’s solution was used. The proportion of positive endocervical margins was much higher in the Lugol’s solution group than in the non-Lugol’s solution group (62.5% vs. 43.6%, respectively). During the 6-month follow-up after LEEP, however, among 308 cases with positive resection margins who underwent follow-up, the rates of residual disease were similar for the Lugol’s and non-Lugol’s solution groups (22.4% vs. 22.4%, respectively). Table 4 Clinopathological characteristics of 345 patients with positive resection margin according to use of Lugol’s solution Subjects with positive resection margins a) Lugol’s solution group Non-Lugol’s solution group P -value No. of patients 345 88 257 Age, years old 0.14 < 50 239 56 (63.6) 183 (71.2) ≥ 50 106 32 (36.4) 74 (28.8) Histology grade 0.06 CIN 1 28 3 (3.4) 25 (9.7) CIN 2–3 317 85 (96.6) 232 (90.3) Involved margin sites 0.03 Ectocervix 77 15 (17.0) 62 (24.1) Endocervix 167 55 (62.5) 112 (43.6) Deep 21 3 (3.4) 18 (7.0) Multiple 80 15 (17.0) 65 (25.3) Residual disease, N = 308 b) 85 223 0.27 Absent 229 61 (71.8) 168 (75.3) Present 69 19 (22.4) 50 (22.4) Undetermined 10 5 (5.9) 5 (2.2) Abbreviations LEEP, loop electrosurgical excision procedure; C.I. confidence interval; CIN, cervical intraepithelial neoplasia. Data in parentheses are percentages a) Excluding nine cases with uncertain resection margin status b) Excluding 37 women with loss to follow-up. Discussion The presence of CIN at the resection margin (positive resection margin) of the LEEP specimen has been known to be a risk factor relating to residual disease and often considered as ‘treatment failure’ mandating repetitive surgery [14]. Management of patients with positive resection margins is still unresolved. As of now, many studies have investigated clinical factors affecting positive resection margins [15, 16] and efforts have been made to develop strategies for optimizing CIN treatment by LEEP [17, 18]. The studies on the Schiller test using Lugol’s solution have focused mainly on its performance in detecting CIN, not on aiding the completely removal of CIN by its role of delineating the TZ [13, 19]. No previous studies have examined the substantive benefits of Lugol’s solution for LEEP, that is, affordable and amenable preoperative preparation. This is the first study to demonstrate that using Lugol’s solution during LEEP significantly reduces the incidence of positive resection margins and residual disease; the proportion of positive resection margins ranged from 11.8% (88/745) in the Lugol’s solution group to 25.5% (257/1,006) in the non-Lugol’s solution group. A systematic review of 93 studies that examined 44,000 women with CIN demonstrated positive resection margins in 23.1% (95% CI, 20.4–25.9) of cases [14, 20]. The European Federation of Colposcopy has set a 20% cutoff for positive resection margins as a quality indicator of good clinical practice among colposcopists [21]. However, more than half of the studies included in this systematic review did not achieve this target [14]. Furthermore, a recent survey conducted by Waxman et al. demonstrated that fewer than half of the members of the American Committee of Obstetrics and Gynecology reported routinely using Lugol’s solution during colposcopic examinations, despite the recommendations of the International Agency for Research on Cancer [22]. In our study, more cases of positive resection margins were observed among those, who underwent LEEP without the routine use of Lugol’s solution as part of the LEEP protocol (11.8% vs 25.5%). Therefore, the results of our study suggest that the routine use of Lugol’s solution can achieve negative resection margins in at least 80% of cases and substantially reduce the incidence of incomplete excision [21]. Additionally, an important finding of our study was that the proportion of endocervical involvement was relatively high regardless of whether Lugol’s solution was used. In the Lugol’s solution group, up to two-thirds of cases with positive resection margins showed involvement of the endocervix. Other authors have reported similarly high proportions of endocervical margin involvement in up to 60 ~ 75% of cases with positive resection margins [23, 24]. Lugol’s solution helps to visualize the TZ of the uterine ectocervix and, therefore, seems to have no role in aiding lesion removal from the endocervix. As women age, the TZ gradually migrates into the endocervical canal, explaining the relatively higher proportion of older patients with cervical intraepithelial neoplasia who have positive resection margins. Among older patients, Lugol’s solution may be used to visualize the TZ, and a small or invisible TZ may indicate a higher likelihood of a deep endocervical lesion. Hence, modified excision methods (i.e., narrow and deep excisions) may be adopted for CIN lesions in patients 50 years or older or in those with small or invisible TZs [25]. Further, another significant outcome of our study was the rate of residual disease, which was 6.6% (100/1,507) for all the cases; 22.4% (69/308) among cases with positive margins, and 2.6% (31/1,199) among cases with negative margins (Supplementary Table 1). The reported risk of residual disease among cases with positive resection margins is approximately 25% [23, 26]. As expected, among patients with positive resection margins, the rate of residual disease was not significantly different between the Lugol’s solution group and non-Lugol’s solution group in our study, showing 22.4% (19/85) and 22.4% (50/223), respectively (Table 4 ). Therefore, we can infer that it is crucial to reduce the rate of positive resection margins with the routine application of Lugol’s solution during LEEP in order to reduce the incidence of residual disease. We further analyzed the patients who had a pathologically confirmed diagnosis within six months of the initial LEEP, unlike other studies reporting the total prevalence of residual disease and recurrent disease without discriminating between the two [23, 27, 28]. Although a substantive proportion of patients was lost to follow-up and underwent no recommended surgical procedures, the results of our study may suggest some possibility of the presence of residual disease that may be attributable to positive resection margins; two-thirds (69.0%, 69/100) of cases with the histologically confirmed residual disease was found in those with positive resection margins. Whether or not a reduction of positive resection margin with routine application of Lugol’s solution translates into a reduced rate of residual disease requires investigation through a well-designed randomized controlled study. Our study had some limitations. First, our study had a retrospective design. Second, the clinical and pathological data regarding the resection margin status and involved margin sites were collected from an archived database. We did not conduct additional reviews of the pathologic slides for this study and the detailed pathology information, i.e., cone specimen dimension, was not available. Unfortunately, we have no complete information on pre- and post-conization cervical cytology and HPV genotypes, known as essential variables for positive resection margin and residual disease of CIN [23, 29]. Third, our study sample excluded nine cases which had uncertain resection margins, mainly resulting from the fragmentation of LEEP specimens. Finally, as we mentioned above, the proportion of cases lost to follow-up was substantial and different between the Lugol’s and non-Lugol’s solution groups. One possible explanation is that during post-LEEP surveillance, some physicians which mostly managed patients without Lugol’s solution, were noted to refer some patients to their district hospitals. All of the limitations may hinder us from postulating generalization of our study results; thus, well-designed randomized controlled study is necessary. Conclusions To the best of our knowledge, this is the first study to demonstrate the substantive benefits of using the Lugol’s solution during LEEP, with a large sample size involving three hospitals, which reduced the impact of any bias from individual hospital treatment protocols. Based on the results of this study, we strongly suggest using Lugol’s solution routinely during LEEP to avoid incomplete excision and the requirement for additional surgical intervention. Declarations Acknowledgements We would like to thank Editage (www.editage.co.kr) for English language editing. Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Availability of data and materials The datasets used and analyzed during the current study are within the manuscript and the raw data are available from the corresponding author on reasonable request. Ethical approval and consent to participate The study design was approved by the institutional review board of three hospitals (Seoul National University Hospital Approval No. H-2003-004-1104, Yonsei University Gangnam Severance Hospital Approval No. 3-2021-0058, and Donguk University Ilsan Hospital Approval No. DUIH 2020-03-020) and confirmed to the ethical guidelines of the World Medical Association Declaration of Helsinki. The need for Informed Consent was waived by the institutional review board of Seoul National University Hospital, Yonsei University Gangnam Severance Hospital, and Donguk University Ilsan Hospital due to the retrospective nature of the study Competing interests The authors declare that they have no competing interests. Consent for publication Not applicable. Author contributions KMJ: Performed the analysis and wrote the paper and prepared figure. LEJ, LS, & CDB: Collected the data and contributed data or analysis tools. LCH: Collected the data, contributed data or analysis tools, and Project administration. RJW: Conceived and designed the analysis, Collected the data, Contributed data or analysis tools, Project administration, Investigation, and Supervision. KJH: Contributed data or analysis tools, and Supervision. All authors contributed to the interpretation of the study, revised and approved the final manuscript. Authors’ information Min-Jeong Kim MD 1 , Eun Ji Lee MD 2 , Seungmee Lee MD 3 , Doo Byung Chay MD, PhD 4 , Chae Hyeong Lee MD, PhD 5 , Ju-Won Roh MD, PhD 1 , Jae-Hoon Kim MD, PhD 6 Author details 1 Department of Obstetrics and Gynecology, CHA Hospital Ilsan Medical Center, Goyang-si, Gyonggi-do, Korea 2 Department of Obstetrics and Gynecology, Chung-Ang University Hospital, Seoul, Korea 3 Department of Obstetrics and Gynecology, Keimyung University School of Medicine, Daegu, Korea 4 Department of Obstetrics and Gynecology, Sahmyook Medical Center, Seoul, Korea 5 Department of Obstetrics and Gynecology, Dongguk University Ilsan Hospital, Goyang-si, Gyonggi-do, Korea 6 Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea References McCredie MR, Sharples KJ, Paul C, Baranyai J, Medley G, Jones RW, Skegg DC: Natural history of cervical neoplasia and risk of invasive cancer in women with cervical intraepithelial neoplasia 3: a retrospective cohort study . 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Petry KU, Nieminen PJ, Leeson SC, Bergeron C, Redman CWE: 2017 update of the European Federation for Colposcopy (EFC) performance standards for the practice of colposcopy . Eur J Obstet Gynecol Reprod Biol 2018, 224 :137–141. Waxman AG, Conageski C, Silver MI, Tedeschi C, Stier EA, Apgar B, Huh WK, Wentzensen N, Massad LS, Khan MJ et al : ASCCP Colposcopy Standards: How Do We Perform Colposcopy? Implications for Establishing Standards . J Low Genit Tract Dis 2017, 21 (4):235–241. Fernandez-Montoli ME, Tous S, Medina G, Castellarnau M, Garcia-Tejedor A, de Sanjose S: Long-term predictors of residual or recurrent cervical intraepithelial neoplasia 2–3 after treatment with a large loop excision of the transformation zone: a retrospective study . BJOG 2020, 127 (3):377–387. Kim HS, Kwon JE, Kim JH, Kim A, Lee NR, Kim M, Lee M, Suh DH, Kim YB: Efficacy of loop electrosurgical excision procedure with cold coagulation for treating cervical intraepithelial neoplasia: A two center cohort study . Obstet Gynecol Sci 2017, 60 (2):200–206. Bae HS, Chung YW, Kim T, Lee KW, Song JY: The appropriate cone depth to avoid endocervical margin involvement is dependent on age and disease severity . Acta Obstet Gynecol Scand 2013, 92 (2):185–192. Binyamin L, Segev M, Peled Y, Krissi H, Sabah G, Raban O, Jakobson-Setton A, Ben-Haroush A, Eitan R: Simple Hysterectomy for Residual Cervical Intraepithelial Neoplasm . J Low Genit Tract Dis 2018, 22 (2):126–128. Cejtin HE, Zimmerman L, Mathews M, Patel A: Predictors of Persistent or Recurrent Disease After Loop Electrosurgical Excision Procedure . J Low Genit Tract Dis 2017, 21 (1):59–63. Fu Y, Chen C, Feng S, Cheng X, Wang X, Xie X, Lu W: Residual disease and risk factors in patients with high-grade cervical intraepithelial neoplasia and positive margins after initial conization . Ther Clin Risk Manag 2015, 11 :851–856. Ouh YT, Cho HW, Kim SM, Min KJ, Lee SH, Song JY, Lee JK, Lee NW, Hong JH: Risk factors for type-specific persistence of high-risk human papillomavirus and residual/recurrent cervical intraepithelial neoplasia after surgical treatment . Obstet Gynecol Sci 2020, 63 (5):631–642. Additional Declarations No competing interests reported. Supplementary Files Additionalfile2.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-1784007","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":117844486,"identity":"3518694d-1eb0-4652-8fbd-e6f40815cecb","order_by":0,"name":"Min-Jeong Kim","email":"","orcid":"","institution":"CHA Hospital Ilsan Medical Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Min-Jeong","middleName":"","lastName":"Kim","suffix":""},{"id":117844487,"identity":"6b96eb9d-d551-4456-b891-e8e8e541cf5c","order_by":1,"name":"Eun Ji Lee","email":"","orcid":"","institution":"Chung-Ang University Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Eun","middleName":"Ji","lastName":"Lee","suffix":""},{"id":117844488,"identity":"277d6019-c429-4a81-bb09-d9a6ac70b22a","order_by":2,"name":"Seungmee Lee","email":"","orcid":"","institution":"Keimyung University School of Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Seungmee","middleName":"","lastName":"Lee","suffix":""},{"id":117844489,"identity":"a49047c3-a16c-45b5-a2b1-39e1de3e151a","order_by":3,"name":"Doo Byung Chay","email":"","orcid":"","institution":"Sahmyook Medical Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Doo","middleName":"Byung","lastName":"Chay","suffix":""},{"id":117844490,"identity":"76657564-b16b-4625-9597-108f8c0d49ec","order_by":4,"name":"Chae Hyeong Lee","email":"","orcid":"","institution":"Dongguk University Ilsan Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Chae","middleName":"Hyeong","lastName":"Lee","suffix":""},{"id":117844491,"identity":"bd0c5951-ffe1-436e-b27a-a1b546a62404","order_by":5,"name":"Ju-Won Roh","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4klEQVRIiWNgGAWjYFACHgYDEMXG3nyAGSbG2ECMFj6eYwnEawEDOYkcA+K0mLf3HijmbbPJY5PI+fi5oGabPAP74QOMM/fg1iJz5lyCMW9bWjEbz9vN0jOO3TZs4ElLYNzwDLcWCaB7jHm3HU5sY8/dxszDdjuBQYLHgPHBAWK0MOQ8Y+b5R5IWjhw2Zt42qJYN+LTwnDEwnPsvLbGN55ixNG/fbcM2oF8OzsCnhb3HzODNGZvE+e3NDz/zfLstz89++ODDHjxagIDNAJULxPg1MDAwPyCgYBSMglEwCkY6AAA92ExaTEBAjQAAAABJRU5ErkJggg==","orcid":"","institution":"CHA Hospital Ilsan Medical Center","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Ju-Won","middleName":"","lastName":"Roh","suffix":""},{"id":117844492,"identity":"c34397be-7571-4d30-82d5-24588904f441","order_by":6,"name":"Jae-Hoon Kim","email":"","orcid":"","institution":"Yonsei University College of Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jae-Hoon","middleName":"","lastName":"Kim","suffix":""}],"badges":[],"createdAt":"2022-06-22 10:29:14","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-1784007/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-1784007/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":23597779,"identity":"a4563c62-4b78-495a-8121-3602ed1948d0","added_by":"auto","created_at":"2022-07-07 16:53:58","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":450654,"visible":true,"origin":"","legend":"\u003cp\u003eFlow chart of eligible study population.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-1784007/v1/9d30283728734281280568c6.png"},{"id":25247740,"identity":"08c13613-340b-4aa8-9d04-6886fd8e46fb","added_by":"auto","created_at":"2022-08-16 08:29:37","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1443876,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1784007/v1/d5501185-111d-4eee-916d-d810bc19f109.pdf"},{"id":23597778,"identity":"9de9ad89-4d70-4077-a922-c79d44f750bf","added_by":"auto","created_at":"2022-07-07 16:53:58","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":16819,"visible":true,"origin":"","legend":"","description":"","filename":"Additionalfile2.docx","url":"https://assets-eu.researchsquare.com/files/rs-1784007/v1/370d3dee8b2f9491e144cc82.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Lugol’s solution reduces positive resection margins and residual disease after the loop electrosurgical excision procedure","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe gold standard of treatment for cervical intraepithelial neoplasia (CIN) is cervical conization because CIN involves the risk of progression to cervical cancer [1]. The loop electrosurgical excision procedure (LEEP) is preferred over ablative or cold knife conization methods because it has comparable diagnostic power, provides good surgical margins, and is relatively bloodless [2\u0026ndash;4]. However, an excisional procedure does not always remove the entire transformation zone (TZ), where CIN mainly develops, particularly in cases with large TZs or deep endocervical lesions [5, 6]. The presence of positive resection margins does not necessarily indicate the need for further immediate action other than careful observation in most cases [7, 8]. Nevertheless, the fundamental goal should be to remove the whole CIN during the initial conization because the risk of residual or recurrent disease is higher for the cases with incomplete excision [5, 9].\u003c/p\u003e \u003cp\u003e According to the colposcopy tutorial provided by the International Agency for Research on Cancer of the World Health Organization, Lugol\u0026rsquo;s solution can be used to outline the CIN extent before LEEP [10]. In order to reduce the risk of residual disease and its progression and avoid the obstetric complication associated with the repetitive surgical intervention, LEEP aims to remove the whole lesion and TZ as much as possible [6, 11, 12]. Lugol\u0026rsquo;s solution seems to be a reasonable and inexpensive tool for acquiring disease-free margins at the time of LEEP. However, Lugol\u0026rsquo;s solution is often disregarded by physicians or is unavailable in many hospitals, especially in South Korea since the test of Lugol\u0026rsquo;s staining was categorized to \u0026ldquo;non-specific\u0026rdquo; categories of \u0026ldquo;abnormal colposcopic findings\u0026rdquo; showing poor reliability for detecting CINs [13]. No previous studies have examined the substantive benefits of Lugol\u0026rsquo;s solution for LEEP. Therefore, we conducted a retrospective study to determine the role of Lugol\u0026rsquo;s solution in reducing resection margin positivity in LEEP specimens.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e1.Study population\u003c/h2\u003e \u003cp\u003eThis was a retrospective observational study. We collected the clinic-pathological and surgical data of 1,992 consecutive patients who underwent LEEP in the Department of Obstetrics and Gynecology of three university hospitals; Seoul National University Hospital (SNUH) from 2012 January to 2013 December (N\u0026thinsp;=\u0026thinsp;523), Yeonsei University Gangnam Severance Hospital (YUGSH) from 2008 January to 2015 February (N\u0026thinsp;=\u0026thinsp;853), and Dongguk University Ilsan Hospital (DUIH) from 2005 September to 2017 February (N\u0026thinsp;=\u0026thinsp;616), respectively. A total of 236 patients who had a histological diagnosis other than CIN, such as benign conditions including condyloma (N\u0026thinsp;=\u0026thinsp;130), adenocarcinoma in situ (N\u0026thinsp;=\u0026thinsp;10), or invasive carcinoma including adenocarcinoma (N\u0026thinsp;=\u0026thinsp;4) or invasive squamous cell carcinoma (N\u0026thinsp;=\u0026thinsp;89), and metastatic or other malignancies (N\u0026thinsp;=\u0026thinsp;3) were excluded. Five patients who had a previous history of conization were also excluded. Finally, only 1,751 patients with a histological diagnosis of CIN after LEEP were enrolled in our study (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), consisting of 443 from SNUH, 756 from YUGSH and 552 from DUIH. The histological grade was categorized as CIN 1 or CIN 2\u0026ndash;3.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch2\u003e2. Data Collection\u003c/h2\u003e\n\u003cp\u003eThe data included patient age, use (yes or no) of Lugol\u0026rsquo;s solution, LEEP results (histology, margin status, and involved margin sites), follow-up data for at least six months of the initial LEEP, including the type of subsequent management (either immediate subsequent surgical management or follow-up with a Pap test with or without a human papillomavirus test), and subsequent histological diagnosis by cervical biopsy (if available). The initial definite histological diagnosis was determined by colposcopy-guided cervical biopsy and LEEP.\u003c/p\u003e \u003cp\u003eThe resection margin status was categorized as negative, positive, or uncertain. Positive resection margins were defined as the presence of any CIN grades in any of the sites along the resection margin. The involved resection margin sites were categorized as the ectocervix, endocervix, deep, multiple, or uncertain. Multiple positive resection sites were diagnosed when CIN was detected in two or more margins.\u003c/p\u003e \u003cp\u003eAs the clinical practice protocol, all treated women should undergo post-LEEP follow-up every 3 to 6 months, which consists of cervical cytology with or without HPV test for 2 years. In particular, patients with positive resection margins underwent either immediate subsequent surgery or first follow-up at 3- to 4-month post-LEEP. The patients who had available follow-up data for at least 6 months after the initial LEEP were finally analyzed for residual diseases. Residual disease was defined as the presence of any CIN grades pathologically confirmed by cervical biopsy or surgical management within 6 months after LEEP.\u003c/p\u003e\n\u003ch2\u003e3. Statistical Analysis\u003c/h2\u003e\n\u003cp\u003eThe primary outcome of this study was the proportion of positive resection margin in LEEP specimens. The secondary outcome was residual disease. Categorical variables were described as frequencies and percentages, whereas continuous variables were described as median and range for non-parametric variables and as mean and standard deviations for parametric variables. Group difference between two groups (e.g., Lugol\u0026rsquo;s solution group vs. non-Lugol\u0026rsquo;s solution group) and each categorical variable was examined using a two-tailed Pearson χ\u003csup\u003e2\u003c/sup\u003e or Fisher\u0026rsquo;s Exact test with salient dichotomizations. To identify the risk factors for positive resection margins, univariable logistic regression analysis was used and tested all independent variables, including age, pre-conization cervical cytology, high-risk HPV, histology grade, and use of Lugol\u0026rsquo;s solution. We also performed multiple logistic regression analyses which included the independent factors showing p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 in the univariable analysis, by calculating the odds ratios and a 95% confidence interval. All statistical analyses were performed using IBM SPSS Statistics for Windows, version 26.0 (IBM Corp., Armonk, N.Y., USA). P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eWe retrieved the data of 1,751 consecutive patients (age range, 19\u0026ndash;83 years) who were affected by CIN and treated by LEEP from three university hospitals (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The clinical and pathological characteristics are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The rate of CIN 2 or 3 was 83.2% (1,456/1,751). The use of Lugol\u0026rsquo;s solution was 42.5% (745/1,751) among the patients because its use was dependent on the physician\u0026rsquo;s clinical discretion. Positive resection margins were noted in 345 patients (19.7%).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBasic characteristics of the eligible study population\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo. of patients\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1751\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(100.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, \u003cem\u003eyears old\u003c/em\u003e\u003csup\u003e\u003cem\u003ea)\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003emedian (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e41 (19\u0026ndash;83)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCervical cytology\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNILM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e258\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(14.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eASC-US\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e410\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(23.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLSIL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e264\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(15.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHSIL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e402\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(23.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eASC-H\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e346\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(19.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSCCA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(0.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAGC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(0.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnavailable\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(3.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHigh-risk HPV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e127\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(7.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1254\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(71.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnavailable\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e370\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(21.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistology grade\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCIN 1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e295\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(16.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCIN 2\u0026ndash;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1456\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(83.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLugol\u0026rsquo;s solution\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-Use\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1006\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(57.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUse\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e745\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(42.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eResection margin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1397\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(79.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e345\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(19.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUncertain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(0.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003e\u003cem\u003eAbbreviations\u003c/em\u003e LEEP, loop electrosurgical excision procedure; HPV, human papillomavirus; NILM, negative for intraepithelial lesion or malignancy; ASC-US, atypical squamous epithelial cells of undetermined significance; LSIL, low-grade squamous intraepithelial lesion; HSIL, high-grade squamous intraepithelial lesion; ASC-H atypical squamous epithelial cells cannot exclude high-grade SIL; SCCA squamous cervical carcinoma; AGC atypical glandular cells; CIN, cervical intraepithelial neopalsia.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003eData in parentheses are percentages except for age.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eWe observed no statistical difference in patients\u0026rsquo; age between the Lugol\u0026rsquo;s solution and non-Lugol\u0026rsquo;s solution groups (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Although women in the Lugol\u0026rsquo;s solution group had a significantly higher rate of CIN 2/3 (P\u0026thinsp;\u0026lt;\u0026thinsp;0.01), positive resection margins were noted in 11.8% (88/745) and 25.5% (257/1,006) of the patients in the Lugol\u0026rsquo;s solution group and non-Lugol\u0026rsquo;s solution group, respectively (P\u0026thinsp;\u0026lt;\u0026thinsp;0.01).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of the two groups with and without use of Lugol\u0026rsquo;s solution\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eLugol\u0026rsquo;s solution\u003c/p\u003e \u003cp\u003egroup\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eNon-Lugol\u0026rsquo;s solution group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo. of patients\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1751\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e745\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e1006\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, \u003cem\u003eyears old\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.08\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1332\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e583\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(78.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e749\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e(74.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge; 50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e419\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e162\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(21.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e257\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e(25.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCervical cytology\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.32\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026le; LSIL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e933\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e378\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(50.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e555\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e(55.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge; HSIL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e765\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e329\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(44.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e437\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e(43.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnavailable\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(5.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e(1.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHigh-risk HPV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.04\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e128\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(6.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e(8.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1254\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e569\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(76.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e684\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e(68.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnavailable\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e369\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e130\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(17.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e240\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e(23.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistology grade\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCIN 1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e295\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e106\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(14.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e189\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e(18.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCIN 2\u0026ndash;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1456\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e639\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(85.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e817\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e(81.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eResection margin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1397\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e651\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(87.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e746\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e(74.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e345\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(11.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e257\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e(25.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUncertain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(0.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e(0.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePost-LEEP surveillance, N\u0026thinsp;=\u0026thinsp;1742\u003csup\u003ea)\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e739\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e1003\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eImmediate surgical management\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e142\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(5.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e102\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e(10.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFollow-up with cervical cytology\u0026thinsp;\u0026plusmn;\u0026thinsp;HPV tests\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1365\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e632\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(85.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e733\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e(73.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLoss of follow-up\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e235\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(9.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e168\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e(16.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eResidual disease, N\u0026thinsp;=\u0026thinsp;1507\u003csup\u003eb)\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e672\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e835\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.02\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbsent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1360\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e622\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(92.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e738\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e(88.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePresent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(4.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e(8.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUndetermined\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(2.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e(3.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003e\u003cem\u003eAbbreviations\u003c/em\u003e HPV, human papillomavirus; LSIL, low-grade squamous intraepithelial lesion; HSIL, high-grade squamous intraepithelial lesion; CIN, cervical intraepithelial neoplasia; LEEP, loop electrosurgical excision procedure\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eData in parentheses are percentages\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003e\u003csup\u003ea)\u003c/sup\u003e Excluding nine women with uncertain resection margin.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003e\u003csup\u003eb)\u003c/sup\u003e Excluding nine women with uncertain resection margin and 235 women with loss of follow-up.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTwo-hundreds thirty-five patients were lost to follow-up, and nine with uncertain resection margin were excluded. A total of 1,507 patients were followed-up; cervical cytology with or without human papillomavirus (HPV) test (N\u0026thinsp;=\u0026thinsp;1,365) and immediate surgery (N\u0026thinsp;=\u0026thinsp;142) within 6 months after LEEP. Of these, residual disease was diagnosed in 100 (6.6%) patients: 69 of these patients had positive resection margins (N\u0026thinsp;=\u0026thinsp;308), whereas 31 had negative resection margins (N\u0026thinsp;=\u0026thinsp;1,199) [Supplementary Table\u0026nbsp;1]. Compared to the non-Lugol\u0026rsquo;s solution group, Lugol\u0026rsquo;s solution group was less likely to require immediate subsequent surgical procedures (5.4% vs. 10.2%; P\u0026thinsp;\u0026lt;\u0026thinsp;0.01) or to have the residual disease (4.9% vs. 8.0%; P\u0026thinsp;=\u0026thinsp;0.02).\u003c/p\u003e \u003cp\u003eA logistic regression analysis was conducted to confirm whether the use of Lugol\u0026rsquo;s solution affected resection margin positivity (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Our univariate analysis demonstrated that age (50 years or older vs. younger than 50 years), pre-conization cervical cytology (\u0026ge;\u0026thinsp;high-grade squamous intraepithelial lesion [HSIL] vs. \u0026le;low-grade squamous intraepithelial lesion [LSIL]), pre-conization high-risk HPV (present vs. absent), histological grade (CIN 2/3 vs. CIN 1), and Lugol\u0026rsquo;s solution (use vs. non-use) were significantly associated with positive resection margins (P\u0026thinsp;\u0026lt;\u0026thinsp;0.01 for all except for high-risk HPV of P\u0026thinsp;=\u0026thinsp;0.06). In the multivariable logistic regression analysis, all of these variables were independent risk factors for positive resection margins. The use of Lugol\u0026rsquo;s solution (adjusted odds ratio [aOR], 0.31; 95% confidence interval [CI], 0.23\u0026ndash;0.42; P\u0026thinsp;\u0026lt;\u0026thinsp;0.01) significantly decreased the proportion of positive resection margins, and age (for 50 years or older, aOR, 1.64; 95% CI, 1.19\u0026ndash;2.27), pre-conization cervical cytology (for \u0026ge;\u0026thinsp;HSIL, aOR, 1.53; 95% CI, 1.15\u0026ndash;2.03), pre-conization high-risk HPV (for positive high-risk HPV, aOR, 1.75; 95% CI, 1.00-3.07) and histological grade (for CIN 2/3, aOR, 2.65; 95% CI, 1.67\u0026ndash;4.22) were significant risk factors for positive resection margins (P\u0026thinsp;\u0026lt;\u0026thinsp;0.01 for all except for high-risk HPV of P\u0026thinsp;=\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAssociation of age, histology grade, and use of Lugol\u0026rsquo;s solution with positive resection margins of LEEP specimen\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"10\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eUnivariable analysis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003eMultivariable analysis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;1742\u003csup\u003ea)\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eUnadjusted OR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e95% C.I.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eAdjusted OR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e95% C.I.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003csup\u003eb)\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, \u003cem\u003eyears old\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1327\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge; 50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e415\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.20\u0026ndash;2.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1.64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1.19\u0026ndash;2.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCervical cytology\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026le;LSIL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e931\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;HSIL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e759\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.27\u0026ndash;2.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1.15\u0026ndash;2.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHigh-risk HPV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.05\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e127\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1248\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.03\u0026ndash;3.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1.00-3.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistology grade\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCIN 1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e295\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCIN 2\u0026ndash;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1447\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.78\u0026ndash;4.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1.67\u0026ndash;4.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLugol\u0026rsquo;s solution\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-use\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1003\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUse\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e739\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.30\u0026ndash;0.51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.23\u0026ndash;0.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"10\"\u003e\u003cem\u003eAbbreviations\u003c/em\u003e LEEP, loop electrosurgical excision procedure; C.I., confidence interval; HPV, human papillomavirus; LSIL, low-grade squamous intraepithelial lesion; HSIL, high-grade squamous intraepithelial lesion; CIN, cervical intraepithelial neoplasia\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"10\"\u003e\u003csup\u003ea)\u003c/sup\u003e excluding nine subjects with uncertain resection margin status of LEEP specimen.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"10\"\u003e\u003csup\u003eb)\u003c/sup\u003e adjusted for all significant variables (age, cervical cytology, high-risk HPV, histology grade, Lugol\u0026rsquo;s solution) in univariable analysis.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eWe further analyzed 345 cases with positive resection margins and found no differences in age and histological grades between the Lugol\u0026rsquo;s solution and non-Lugol\u0026rsquo;s solution groups (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). The endocervix was the site that was most frequently involved by CIN (167/345), regardless of whether Lugol\u0026rsquo;s solution was used. The proportion of positive endocervical margins was much higher in the Lugol\u0026rsquo;s solution group than in the non-Lugol\u0026rsquo;s solution group (62.5% vs. 43.6%, respectively). During the 6-month follow-up after LEEP, however, among 308 cases with positive resection margins who underwent follow-up, the rates of residual disease were similar for the Lugol\u0026rsquo;s and non-Lugol\u0026rsquo;s solution groups (22.4% vs. 22.4%, respectively).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinopathological characteristics of 345 patients with positive resection margin according to use of Lugol\u0026rsquo;s solution\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"10\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"6\" nameend=\"c9\" namest=\"c4\"\u003e \u003cp\u003eSubjects with positive resection margins\u003csup\u003ea)\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eLugol\u0026rsquo;s solution group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003eNon-Lugol\u0026rsquo;s solution group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo. of patients\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e345\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e257\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, \u003cem\u003eyears old\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.14\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e239\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(63.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e183\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e(71.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge; 50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e106\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(36.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e(28.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistology grade\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.06\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCIN 1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(3.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e(9.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCIN 2\u0026ndash;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e317\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(96.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e232\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e(90.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInvolved margin sites\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.03\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEctocervix\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(17.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e(24.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEndocervix\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e167\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(62.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e112\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e(43.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDeep\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(3.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e(7.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMultiple\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(17.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e(25.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eResidual disease, N\u0026thinsp;=\u0026thinsp;308\u003csup\u003eb)\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e223\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.27\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbsent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e229\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(71.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e168\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e(75.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePresent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(22.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e(22.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUndetermined\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(5.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e(2.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"10\"\u003e\u003cem\u003eAbbreviations\u003c/em\u003e LEEP, loop electrosurgical excision procedure; C.I. confidence interval; CIN, cervical intraepithelial neoplasia.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"10\"\u003eData in parentheses are percentages\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"10\"\u003e\u003csup\u003ea)\u003c/sup\u003e Excluding nine cases with uncertain resection margin status\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"10\"\u003e\u003csup\u003eb)\u003c/sup\u003e Excluding 37 women with loss to follow-up.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe presence of CIN at the resection margin (positive resection margin) of the LEEP specimen has been known to be a risk factor relating to residual disease and often considered as \u0026lsquo;treatment failure\u0026rsquo; mandating repetitive surgery [14]. Management of patients with positive resection margins is still unresolved. As of now, many studies have investigated clinical factors affecting positive resection margins [15, 16] and efforts have been made to develop strategies for optimizing CIN treatment by LEEP [17, 18]. The studies on the Schiller test using Lugol\u0026rsquo;s solution have focused mainly on its performance in detecting CIN, not on aiding the completely removal of CIN by its role of delineating the TZ [13, 19]. No previous studies have examined the substantive benefits of Lugol\u0026rsquo;s solution for LEEP, that is, affordable and amenable preoperative preparation.\u003c/p\u003e \u003cp\u003eThis is the first study to demonstrate that using Lugol\u0026rsquo;s solution during LEEP significantly reduces the incidence of positive resection margins and residual disease; the proportion of positive resection margins ranged from 11.8% (88/745) in the Lugol\u0026rsquo;s solution group to 25.5% (257/1,006) in the non-Lugol\u0026rsquo;s solution group.\u003c/p\u003e \u003cp\u003eA systematic review of 93 studies that examined 44,000 women with CIN demonstrated positive resection margins in 23.1% (95% CI, 20.4\u0026ndash;25.9) of cases [14, 20]. The European Federation of Colposcopy has set a 20% cutoff for positive resection margins as a quality indicator of good clinical practice among colposcopists [21]. However, more than half of the studies included in this systematic review did not achieve this target [14]. Furthermore, a recent survey conducted by Waxman et al. demonstrated that fewer than half of the members of the American Committee of Obstetrics and Gynecology reported routinely using Lugol\u0026rsquo;s solution during colposcopic examinations, despite the recommendations of the International Agency for Research on Cancer [22]. In our study, more cases of positive resection margins were observed among those, who underwent LEEP without the routine use of Lugol\u0026rsquo;s solution as part of the LEEP protocol (11.8% vs 25.5%). Therefore, the results of our study suggest that the routine use of Lugol\u0026rsquo;s solution can achieve negative resection margins in at least 80% of cases and substantially reduce the incidence of incomplete excision [21].\u003c/p\u003e \u003cp\u003eAdditionally, an important finding of our study was that the proportion of endocervical involvement was relatively high regardless of whether Lugol\u0026rsquo;s solution was used. In the Lugol\u0026rsquo;s solution group, up to two-thirds of cases with positive resection margins showed involvement of the endocervix. Other authors have reported similarly high proportions of endocervical margin involvement in up to 60\u0026thinsp;~\u0026thinsp;75% of cases with positive resection margins [23, 24]. Lugol\u0026rsquo;s solution helps to visualize the TZ of the uterine ectocervix and, therefore, seems to have no role in aiding lesion removal from the endocervix. As women age, the TZ gradually migrates into the endocervical canal, explaining the relatively higher proportion of older patients with cervical intraepithelial neoplasia who have positive resection margins. Among older patients, Lugol\u0026rsquo;s solution may be used to visualize the TZ, and a small or invisible TZ may indicate a higher likelihood of a deep endocervical lesion. Hence, modified excision methods (i.e., narrow and deep excisions) may be adopted for CIN lesions in patients 50 years or older or in those with small or invisible TZs [25].\u003c/p\u003e \u003cp\u003eFurther, another significant outcome of our study was the rate of residual disease, which was 6.6% (100/1,507) for all the cases; 22.4% (69/308) among cases with positive margins, and 2.6% (31/1,199) among cases with negative margins (Supplementary Table\u0026nbsp;1). The reported risk of residual disease among cases with positive resection margins is approximately 25% [23, 26]. As expected, among patients with positive resection margins, the rate of residual disease was not significantly different between the Lugol\u0026rsquo;s solution group and non-Lugol\u0026rsquo;s solution group in our study, showing 22.4% (19/85) and 22.4% (50/223), respectively (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Therefore, we can infer that it is crucial to reduce the rate of positive resection margins with the routine application of Lugol\u0026rsquo;s solution during LEEP in order to reduce the incidence of residual disease.\u003c/p\u003e \u003cp\u003eWe further analyzed the patients who had a pathologically confirmed diagnosis within six months of the initial LEEP, unlike other studies reporting the total prevalence of residual disease and recurrent disease without discriminating between the two [23, 27, 28]. Although a substantive proportion of patients was lost to follow-up and underwent no recommended surgical procedures, the results of our study may suggest some possibility of the presence of residual disease that may be attributable to positive resection margins; two-thirds (69.0%, 69/100) of cases with the histologically confirmed residual disease was found in those with positive resection margins. Whether or not a reduction of positive resection margin with routine application of Lugol\u0026rsquo;s solution translates into a reduced rate of residual disease requires investigation through a well-designed randomized controlled study.\u003c/p\u003e \u003cp\u003eOur study had some limitations. First, our study had a retrospective design. Second, the clinical and pathological data regarding the resection margin status and involved margin sites were collected from an archived database. We did not conduct additional reviews of the pathologic slides for this study and the detailed pathology information, i.e., cone specimen dimension, was not available. Unfortunately, we have no complete information on pre- and post-conization cervical cytology and HPV genotypes, known as essential variables for positive resection margin and residual disease of CIN [23, 29]. Third, our study sample excluded nine cases which had uncertain resection margins, mainly resulting from the fragmentation of LEEP specimens. Finally, as we mentioned above, the proportion of cases lost to follow-up was substantial and different between the Lugol\u0026rsquo;s and non-Lugol\u0026rsquo;s solution groups. One possible explanation is that during post-LEEP surveillance, some physicians which mostly managed patients without Lugol\u0026rsquo;s solution, were noted to refer some patients to their district hospitals. All of the limitations may hinder us from postulating generalization of our study results; thus, well-designed randomized controlled study is necessary.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eTo the best of our knowledge, this is the first study to demonstrate the substantive benefits of using the Lugol\u0026rsquo;s solution during LEEP, with a large sample size involving three hospitals, which reduced the impact of any bias from individual hospital treatment protocols. Based on the results of this study, we strongly suggest using Lugol\u0026rsquo;s solution routinely during LEEP to avoid incomplete excision and the requirement for additional surgical intervention.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to thank Editage (www.editage.co.kr) for English language editing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and analyzed during the current study are within the manuscript and the raw data are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study design was approved by the institutional review board of three hospitals (Seoul National University Hospital Approval No. H-2003-004-1104, Yonsei University Gangnam Severance Hospital Approval No. 3-2021-0058, and Donguk University Ilsan Hospital Approval No. DUIH 2020-03-020) and confirmed to the ethical guidelines of the World Medical Association Declaration of Helsinki. The need for Informed Consent was waived by the institutional review board of Seoul National University Hospital, Yonsei University Gangnam Severance Hospital, and Donguk University Ilsan Hospital due to the retrospective nature of the study\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eKMJ: Performed the analysis and wrote the paper and prepared figure.\u003c/p\u003e\n\u003cp\u003eLEJ, LS, \u0026amp; CDB: Collected the data and contributed data or analysis tools.\u003c/p\u003e\n\u003cp\u003eLCH: Collected the data, contributed data or analysis tools, and Project administration.\u003c/p\u003e\n\u003cp\u003eRJW: Conceived and designed the analysis, Collected the data, Contributed data or analysis tools, Project administration, Investigation, and Supervision.\u003c/p\u003e\n\u003cp\u003eKJH: Contributed data or analysis tools, and Supervision.\u003c/p\u003e\n\u003cp\u003eAll authors contributed to the interpretation of the study, revised and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors’ information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMin-Jeong Kim MD\u003csup\u003e1\u003c/sup\u003e, Eun Ji Lee MD\u003csup\u003e2\u003c/sup\u003e, Seungmee Lee MD\u003csup\u003e3\u003c/sup\u003e, Doo Byung Chay MD, PhD\u003csup\u003e4\u003c/sup\u003e, Chae Hyeong Lee MD, PhD\u003csup\u003e5\u003c/sup\u003e, Ju-Won Roh MD, PhD\u003csup\u003e1\u003c/sup\u003e, Jae-Hoon Kim MD, PhD\u003csup\u003e6\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor details\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e1\u003c/sup\u003eDepartment of Obstetrics and Gynecology, CHA Hospital Ilsan Medical Center, Goyang-si, Gyonggi-do, Korea\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e2\u003c/sup\u003eDepartment of Obstetrics and Gynecology, Chung-Ang University Hospital, Seoul, Korea\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e3\u003c/sup\u003eDepartment of Obstetrics and Gynecology, Keimyung University School of Medicine, Daegu, Korea\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e4\u003c/sup\u003eDepartment of Obstetrics and Gynecology, Sahmyook Medical Center, Seoul, Korea\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e5\u003c/sup\u003eDepartment of Obstetrics and Gynecology, Dongguk University Ilsan Hospital, Goyang-si, Gyonggi-do, Korea\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e6\u003c/sup\u003eDepartment of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eMcCredie MR, Sharples KJ, Paul C, Baranyai J, Medley G, Jones RW, Skegg DC: \u003cstrong\u003eNatural history of cervical neoplasia and risk of invasive cancer in women with cervical intraepithelial neoplasia 3: a retrospective cohort study\u003c/strong\u003e. \u003cem\u003eLancet Oncol\u003c/em\u003e 2008, \u003cstrong\u003e9\u003c/strong\u003e(5):425\u0026ndash;434.\u003c/li\u003e\n \u003cli\u003eMitchell MF, Tortolero-Luna G, Cook E, Whittaker L, Rhodes-Morris H, Silva E: \u003cstrong\u003eA randomized clinical trial of cryotherapy, laser vaporization, and loop electrosurgical excision for treatment of squamous intraepithelial lesions of the cervix\u003c/strong\u003e. \u003cem\u003eObstet Gynecol\u003c/em\u003e 1998, \u003cstrong\u003e92\u003c/strong\u003e(5):737\u0026ndash;744.\u003c/li\u003e\n \u003cli\u003eMartin-Hirsch PP, Paraskevaidis E, Bryant A, Dickinson HO: \u003cstrong\u003eSurgery for cervical intraepithelial neoplasia\u003c/strong\u003e. \u003cem\u003eCochrane Database Syst Rev\u003c/em\u003e 2013(12):CD001318.\u003c/li\u003e\n \u003cli\u003e. 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There remains a concern regarding the residual disease if resection is incomplete. However, few studies have so far examined the methods to improve the complete resection of the entire lesion with LEEP, eg, applying Lugol’s solution during LEEP. We examined whether the use of Lugol’s solution reduces the proportion of positive resection margins after the loop electrosurgical excision procedure (LEEP). \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eA total of 1,751 consecutive women with cervical intraepithelial neoplasia (CIN) who underwent LEEP at three university hospitals were retrospectively retrieved from the database. Outcomes included positive resection margins and residual disease pathologically confirmed within 6 months after LEEP. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003ePositive resection margins were noted in 345 (19.7%) cases. Among 1,507 women followed up, residual disease was diagnosed in 100 (6.6%) cases (69/308 cases with positive margins; 31/1,199 cases\u0026nbsp;with negative margins). The Lugol’s solution group was less likely to have positive resection margins (11.8% vs. 25.5%;\u0026nbsp;\u003cem\u003eP \u003c/em\u003e\u0026lt; 0.01), to require additional surgical intervention (5.4% vs. 10.2%;\u0026nbsp;\u003cem\u003eP \u003c/em\u003e\u0026lt; 0.01), and to have residual disease (4.9% vs. 8.0%;\u0026nbsp;\u003cem\u003eP \u003c/em\u003e= 0.02). A multiple logistic regression analysis demonstrated that Lugol’s solution reduced the proportion of positive resection margins (adjusted odds ratio [aOR], 0.31), and that age 50 years or older (aOR, 1.64), pre-conization cervical cytology (aOR, 1.53), high-risk HPV (aOR 1.75), and CIN 2–3 (aOR, 2.65) were independent risk factors for margin positivity (\u003cem\u003eP \u003c/em\u003e\u0026lt; 0.01 for all except high-risk HPV). \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusions: \u003c/strong\u003eLugol’s solution optimizes CIN treatment by reducing the proportion of positive resection margins and residual disease after LEEP.\u003c/p\u003e","manuscriptTitle":"Lugol’s solution reduces positive resection margins and residual disease after the loop electrosurgical excision procedure","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-07-07 16:53:56","doi":"10.21203/rs.3.rs-1784007/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"2db271fd-d6b8-4eb7-b671-975558ad81b2","owner":[],"postedDate":"July 7th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2022-08-16T08:29:32+00:00","versionOfRecord":[],"versionCreatedAt":"2022-07-07 16:53:56","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-1784007","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1784007","identity":"rs-1784007","version":["v1"]},"buildId":"-HB7Z8yhvgn0wM9Nzuekk","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}