Adenocarcinoma In Situ of the Uterine Cervix (AIS) Treated by Loop Electrosurgical Excision Procedure Strategy: An Observational Study.

OBJECTIVES: Evaluation of the results of treatment of adenocarcinoma in situ by loop electrosurgical excision procedure and the safety of a conservative strategy. METHODS: Identification of all cases of adenocarcinoma in situ treated by loop electrosurgical excision procedure at our institution and follow-up by a conservative strategy. Completeness of the identification of all cases was secured by data from the National Pathology Registry. The treatment strategy was based on cytologic follow-up performed by a general practitioner and, irrespective of margin status of the cone, only the results of the postoperative surveillance were indicative of further treatment. RESULTS: A total of 224 patients were identified. The overall recurrence rate with a mean follow-up time of 87.8 months was 7.6% (17/224). The recurrence rate in patients with involved margins was significantly higher than in patients with uninvolved margins, 15.7% vs 5.2%, respectively. Six recurrences were diagnosed at first examination 6 months postconization in patients with involved margins. They were treated with hysterectomy in 4 cases and reconization in 1 case. If involvement of margins alone had been an indication of further therapy (hysterectomy or reconization) immediately after conization, the conservative management strategy prevented 46 surgical procedures. Two cases of invasive cancer were diagnosed during follow-up, 150 months and 196 months after primary treatment, and after normal follow-up examinations. These 2 cases must be considered de novo cases and cannot be considered treatment failures. CONCLUSION: The conservative management strategy thus seems safe, and unnecessary surgical procedures were avoided.

Recurrence After Biopsy-Confirmed Cervical High-Grade Intraepithelial Lesion Followed by Negative Conization: A Systematic Review and Meta-analysis.

ABSTRACT: The aim of the study is to assess the recurrence rate (as cervical intraepithelial neoplasia 2+ [CIN2+]) in patients who had a confirmed high-grade squamous intraepithelial lesion (CIN2-3) in a cervical biopsy specimen followed by a negative conization specimen. MATERIALS AND METHODS: A systematic literature review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. Ovid/MEDLINE, Ovid/Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched from inception until January 2023. The study protocol was registered in PROSPERO (ID number CRD42023393951). The search identified 3,089 articles; 1,530 were removed as duplicates, and 1,559 titles and abstracts were assessed for inclusion. The full text of 26 studies was assessed for eligibility, and finally, 12 studies with 1,036 patients were included. All included studies were retrospective cohort studies. A proportion meta-analysis was performed. RESULTS: For patients with negative conization specimens, the recurrence rate as CIN2+ during follow-up was 6% (95% CI, 1.8%-12.1%; I2 = 49.2; p < .0001, 215 patients and 4 studies) in the proportion meta-analysis, ranging from 0.3% to 13.0% for the individual studies. For patients with ≤CIN1 conization specimens, the recurrence rate as CIN2+ during follow-up was 3.6% (95% CI, 1.2%-7%; I2 = 75.1; p < .0001, 991 patients and 10 studies) in the proportion meta-analysis and ranged from 0.6% to 13.0% for the individual studies. CONCLUSIONS: The recurrence rate as CIN2+ for patients with a confirmed high-grade intraepithelial lesion on a cervical biopsy followed by a negative conization specimen is 6%. In patients with negative and CIN1 conization specimens, the recurrence rate is 3.6%.

Risk Factors for Persistence or Recurrence of High-Grade Cervical Squamous Intraepithelial Lesions.

OBJECTIVES: to evaluate whether the colposcopic lesion size , age, kind of surgery, the status of the surgical margins and the expression of the p16 and Ki-67 immunomarkers are risk factors for persistence or recurrence of the lesion. METHODS: a cross-sectional, observational, retrospective study of patients submitted to cold knife conization (CKC) or the loop electrosurgical excision procedure for cervical intraepithelial neoplasia 2 or 3. The colposcopic lesion size, age, surgical method, involvement of the surgical margins, and p16/Ki-67 immunomarker expression were analyzed in relation to lesion persistence and recurrence. RESULTS: seventy-one women were treated with cold knife conization and 200 were treated with loop electrosurgical excision. Of these, 95 had cervical intraepithelial neoplasia 2, 173 had cervical intraepithelial neoplasia 3, 183 had free surgical margins, 76 had compromised margins, and 12 showed damage by processing artifact or fragments. Among the 76 cases with positive margins, 55, 11, and 10 showed endocervical margin involvement, ectocervical margin involvement, and both endocervial and ectocervical margin involvement, respectively. Of the 264 followed-up patients, 38 had persistent or recurrent disease. A multiple logistic regression indicated that positive endocervical margins are the only independent risk factor for the persistence/recurrence of cervical intraepithelial neoplasia. No significant association was identified between the colposcopic lesion size, age, surgery type, or p16/Ki-67 immunomarker expression and lesion persistence or recurrence.

Frequency of post-treatment disease after excisional procedure in stage IA1 squamous cervical carcinoma - a case series.

Early stages of cervical cancer in young women need conservative treatments. Electrosurgical therapies (LLETZ, LEEP, SWETZ, NETZ) have been recommended for these women. However, there are recommendations to perform a second excision when the specimen margins are not free of disease. This can lead to some important complications. This article aims to verify the frequency of residual invasive or microinvasive disease after the excisional procedure in women with IA1CC. Data on women with IA1CC diagnosed between 1990 and 2022, were retrieved from medical records. Post-treatment disease was detected during a second surgical procedure or postoperative follow-up. Among the 69 included women, three (4.3 percent; CI95 percent 0-9.2) had residual microinvasive lesions, while none showed invasive disease during a second procedure or follow-up. Only the age of 37 years or more was significantly related to the presence of preinvasive or microinvasive residual lesions. Nearly 80 percent of the women who underwent a second procedure showed no residual lesions. The absence of invasive disease in a second procedure or during the follow-up of these women and the large proportion of women with no residual lesion questions the need for a new surgical procedure even when the surgical margins of the initial specimen are involved.

The efficacy of pre-operative conization in patients undergoing surgical treatment for early-stage cervical cancer: A meta-analysis.

BACKGROUND: Minimal invasive surgery (MIS) has been reported to increase the risk of cancer relapse and death compared with traditional open surgery in patients with early-stage cervical cancer (CC). Pre-operative conization is a protective procedure that as developed to reduce the risk caused by MIS. METHODS: Relevant publications were identified by searching medical databases prior to the December 31, 2022. The primary aim of this meta-analysis was to evaluate the efficacy of pre-operative conization on disease-free survival (DFS) in early-stage CC. The secondary objective was to assess the efficacy of pre-operative conization on overall survival (OS) in early-stage CC. RESULTS: Twelve studies were eligible for analysis. The pooled result of pre-operative conization showed a significantly improved DFS when compared with non-conization patients (HR, 0.28; 95% CI, 0.19-0.41), furthermore, pre-operative conization improved DFS by 75% (HR, 0.25; 95% CI, 0.13-0.46) in stage IB1 patients. In patients who underwent MIS, pre-operative conization also led to a significant improvement in DFS when compared with non-conization patients (HR, 0.21; 95% CI, 0.09-0.54). However, in patients who underwent pre-operative conization, MIS increased the risk of recurrence by 34% when compared with open abdominal radical hysterectomy (HR, 1.34; 95% CI, 0.41-4.38), although this difference was not statistically significant. Finally, the OS of early-stage CC was not significantly affected by surgical approach or conization. CONCLUSION: Pre-operation conization represents a protective effect and can improve DFS when compared with non-conization in early-stage CC, especially in stage IB CC. There was no statistical evidence to indicate that pre-operation conization could improve OS. High-quality randomized controlled trials are required to verify these results.

Risk factors for recurrence of cervical intraepithelial neoplasia after loop electrosurgical excisional procedure in patients with positive margins.

AIM: Loop electrosurgical excisional procedure (LEEP) is a major treatment method for cervical precancerous lesions. However, recurrence rates were estimated to be 15%, and the risk is increased if a surgical margin is involved by dysplastic cells. This study aimed to identify the risk factors for recurrence of cervical precancerous lesions in patients with positive margins. METHODS: We retrospectively reviewed medical records of patients who underwent LEEP between 2012 and 2014 and had a positive surgical margin. Clinicopathologic factors were collected, including age, parity, menopausal status, smoking, human papilloma virus infection, results of cytology/biopsy/LEEP, and specimen size and volume. RESULTS: A total of 117 patients with positive margins were included, and 26 (22.2%) patients had recurrence. According to a multivariate analysis, the recurrence rates were significantly higher in parous women (adjusted hazard ratio [HR], 2.92; 95% confidence interval [CI], 1.00-8.49), but positive margins at the exocervix (adjusted HR, 0.39; 95% CI, 0.17-0.91) and volume ≥4000 mm3 (adjusted HR, 0.36; 95% CI, 0.16-0.82) showed negative correlation. CONCLUSIONS: The risk of recurrence for cervical precancerous lesions increased in patients with a history of previous delivery, positive margin at the endocervix, and specimen volume of LEEP <4000 mm3 . These results could help gynecologists determine optimal treatment options for patients with positive margins.

Increasing trends of cervical conization with lymph node evaluation for fertility-sparing surgery in early cervical cancer.

OBJECTIVE: To examine uptake, characteristics, and survival outcome of less-radical fertility-sparing surgery with cervical conization and lymph node evaluation (Cone-LN) in reproductive age patients with early cervical cancer. METHODS: This retrospective cohort study examined the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. The study population included 407 patients aged <50 years with stage IA-IB2 (≤4 cm) cervical cancer who received fertility-sparing surgery from 2004 to 2019. The exposure was fertility-sparing surgery type: Cone-LN (n = 196) or trachelectomy with lymph node evaluation (Trach-LN, n = 211). The main co-outcomes were (i) temporal trends of surgery type, assessed with Cochran-Armitage test, and (ii) clinical and tumor characteristics, assessed with multivariable binary logistic regression model. The secondary outcome was overall survival, assessed with inverse probability of treatment weighting propensity score. RESULTS: The number of patients receiving Cone-LN increased from 43.5% in 2004-2007 to 58.4% in 2016-2019 (P-trend = 0.005). Patients receiving conization and sentinel lymph node (SLN) biopsy alone increased from 0% to 14.4% (P-trend < 0.001). In a multivariable analysis, patients in the Cone-LN group were more likely to undergo SLN biopsy (aOR 6.04) compared to those in the Trach-LN group whereas those with adenocarcinoma (aOR 0.49) and T1b tumors (aOR for ≤2 cm 0.21, and aOR for 2.1-4.0 cm 0.10) were less likely to receive Cone-LN. In a propensity score-weighted model, the Cone-LN and Trach-LN groups had comparable overall survival (7-year rates, 98.9% vs 97.8%). Similar associations were observed for patients with squamous, adenocarcinoma / adenosquamous, T1a classification, and T1b(≤2 cm) classification. CONCLUSION: The current population-based analysis suggests that the performance of cervical conization with lymph node evaluation, particularly with SLN biopsy, is gradually increasing for early cervical cancer patients desiring future fertility.

Câncer de colo uterino na gestação / Cervical cancer in pregnancy

PONTOS-CHAVE • A incidência de câncer durante a gestação tem aumentado devido à tendência das mulheres em postergar a gravidez. O câncer de colo de útero é a terceira neoplasia mais comumente diagnosticada durante o período gestacional. • O rastreamento e o diagnóstico devem se dar como nas pacientes não gestantes; a citologia oncótica cervical é o exame obrigatório do pré-natal, e a colposcopia com biópsia pode ser realizada em qualquer período da gestação. • A gestação complicada pelo diagnóstico de um câncer deve sempre ser conduzida em centro de referência e por equipe multidisciplinar. • A interrupção da gestação em situações específicas, para tratamento-padrão, é respaldada por lei. • A quimioterapia neoadjuvante é uma alternativa segura de tratamento durante a gestação, para permitir alcançar a maturidade fetal. Apresenta altas taxas de resposta, sendo relatada progressão neoplásica durante a gestação em apenas 2,9% dos casos. O risco de malformações fetais decorrentes da quimioterapia é semelhante ao da população geral. Contudo, a quimioterapia está associada a restrição de crescimento intraútero, baixo peso ao nascer e mielotoxicidade neonatal. • Na ausência de progressão de doença, deve-se levar a gestação até o termo.

The characteristics of the residual disease after cervical conization: A retrospective analysis from a tertiary gynecological cancer center.

Background: Patients with a biopsy-confirmed cervical intraepithelial neoplasia 2 and 3 have an increased risk of disease progression to invasive cancer and should be treated with an excisional method. However, after treatment with an excisional method, a high-grade residual lesion may remain in patients with positive surgical margins. We aimed to investigate the risk factors for a residual lesion in patients with a positive surgical margin after cervical cold knife conization. Methods: Records of 1008 patients who underwent conization at a tertiary gynecological cancer center were retrospectively reviewed. One hundred and thirteen patients with a positive surgical margin after cold knife conization were included in the study. We have retrospectively analyzed the characteristics of the patients treated with re-conization or hysterectomy. Results: Residual disease was identified in 57 (50.4%) patients. The mean age of the patients with residual disease was 42.47 ± 8.75 years. Age greater than 35 years (P = 0.002; OR, 4.926; 95%CI [Confidence Interval] - 1.681-14.441), more than one involved quadrant (P = 0.003; OR, 3.200; 95% CI - 1.466-6.987), and glandular involvement (P = 0.002; OR, 3.348; 95% CI - 1.544-7.263) were risk factors for residual disease. The rate of high-grade lesion positivity in post-conization endocervical biopsy at initial conization was similar between patients with and without residual disease (P = 0.16). The final pathology of the residual disease was microinvasive cancer in four patients (3.5%) and invasive cancer in one patient (0.9%). Conclusion: In conclusion, residual disease is found in about half of the patients with a positive surgical margin. In particular, we found that age greater than 35 years, glandular involvement, and more than 1 involved quadrant were associated with the residual disease.

Positive pathological margins after loop electrosurgical excision procedure - Management and outcome.

OBJECTIVE: Pathological involvement of cervical conization margins is a risk factor for recurrence, although management of these patients is controversial. We aimed to define risk factors for positive margins and compare recurrence following additional surgical intervention compared to conservative management. METHODS: A retrospective study of all conizations at our center between 2010 and 2019. Univariate analysis identified characteristics associated with positive margins. Women were stratified by mode of management comparing three groups (surveillance, repeat conization or hysterectomy) then two groups (surveillance vs. additional surgery). Kaplan Meyer survival curves compared cumulative recurrence stratified by mode of management. Pathological results of subsequent surgical procedures were examined for residual disease. RESULTS: Of 448 conizations performed, 131 (29.2%) had positive margins which were associated with menopause, high-grade cytology and endocervical gland involvement. Women who underwent surveillance (n = 45) were more likely to be nulliparous, with low-grade histology and less endocervical gland involvement. Women who underwent hysterectomy (n = 61) were more likely to be postmenopausal and parous. Recurrence did not differ significantly in the three-group (p = 0.073) or two-group model (6.4% vs. 7.1% p = 0.869). Kaplan Meyer survival curves depicting cumulative recurrence did not differ significantly in either model (log rank test p = 0.642 for the three-group model, and p = 0.868 for the two-group model). Residual disease was found in 51.6% of hysterectomy specimens and 52.6% of repeat conizations. CONCLUSION: Surveillance is non-inferior to additional surgery in cases with positive conization margins and constitutes a valid option specifically for younger women at risk of future obstetric complications and those susceptible post-hysterectomy complications.

Prognostic Value of Human Papillomavirus Genotyping before and after Cervical Conization for Squamous Intraepithelial Lesion.

INTRODUCTION: We previously reported that preoperative human papillomavirus (HPV) type 16/18 positivity and postoperative high-risk (HR)-HPV test positivity are associated with abnormal postoperative cytology. In this study, we further examined whether preoperative and postoperative HR-HPV genotyping could predict cytological abnormalities and the risk of additional surgery. METHODS: Patients who underwent cervical conization at our hospital between July 2009 and June 2018 were enrolled. HPV genotyping was performed preoperatively for all patients with HPV-positive. The association among preoperative and postoperative HR-HPV genotyping results, the cumulative risk of cytological abnormalities, and additional surgery were evaluated. The endpoint approach was used to investigate the cumulative incidence of additional surgery owing to cytological abnormalities, such as low-grade squamous intraepithelial lesion positivity and recurrence 2 years after cervical conization. RESULTS: Positive and negative histological margins were observed in 21 and 287 of 308 cases, respectively. The cumulative incidence of abnormal cytology and additional surgery was significantly higher in margin-positive cases than that in margin-negative cases. Examination established according to the margin status demonstrated that the postoperative HR-HPV-positive group had a significantly worse prognosis than the HR-HPV-negative group. Additionally, 32 cases, wherein the same genotype detected before and after surgery, demonstrated significantly unfavorable outcomes. Fifteen patients with persistent HPV 16/18 had the worst prognosis than the other types. CONCLUSION: Preoperative and postoperative HR-HPV genotype tests were used to predict the cumulative incidence of abnormal cytology and additional surgery. Particularly, patients with suspected persistent HPV type 16/18 infection are at a high recurrence risk.

Histopathological discrepancies between colposcopy-directed biopsy and LEEP-conization observed during SARS-CoV-2 pandemic.

OBJECTIVES: Long-term exposure to the human papillomavirus (HPV) is a known cause of squamous intraepithelial lesions that lead to cervical cancer. The loop electrosurgical excision procedure (LEEP) conization is an established treatment method. According to the latest recommendations, we present a paper to evaluate the effectiveness of various diagnostic methods of squamous intraepithelial lesions. MATERIAL AND METHODS: We analyzed 229 patients who reported to District Public Hospital in Poznan to undergo LEEP conization in 2019-2021 during the SARS-CoV-2 Pandemic. The analysis included Pap smear/liquid-based cytology, HPV genotyping, colposcopy with targeted biopsy and LEEP-conization. We offered post-treatment HPV vaccination and, as a follow-up, performed HPV re-genotyping after six months. RESULTS: In total, 89.1% of patients were HPV-positive. The coloscopy-directed biopsy (CDB) results show that almost 70% of the patients had high-grade intraepithelial lesions (HSIL). The diagnosis obtained by LEEP-conization showed that half of the women were diagnosed with HSIL and one-third with the low-grade squamous intraepithelial lesion (LSIL). The sensitivity of Pap smear/LBC accounted for 93.7% and was lower than for CDB, which reached 95.1%. Both diagnostic methods tend to underestimate the final diagnosis. CONCLUSIONS: The inclusion of a colposcopic examination in an in-depth diagnostic process in women with abnormal Pap smear results facilitates the identification of patients requiring therapeutic intervention. LEEP-conization may be used without the primary biopsy. It applies to multiparous women in the perimenopausal period, extensive abnormalities, discrepancies in test results, extensive visible abnormalities, and suspicion of invasive cervical cancer in the colposcopic examination.

Recurrence in Cervical High-Grade Squamous Intraepithelial Lesion: The Role of the Excised Endocervical Canal Length-Analysis of 2,427 Patients.

OBJECTIVE: This study aimed to evaluate the influence of the excised canal length on relapse rates of cervical high-grade squamous intraepithelial lesion (HSIL) treated by loop electrosurgical excision procedure and to find a cut-off point, above which lower recurrence rates could be observed, with low probability of compromising future obstetric outcome, and the relationship with other individual factors related to HSIL recurrence. METHOD: This was a retrospective cohort study of 2,427 women diagnosed with cervical intraepithelial neoplasia CIN2+ who underwent cervical conization using the high-frequency loop electrosurgical excision procedure surgery technique, to analyze the role of endocervical canal length associated with individual factors in the recurrent disease after CIN2+ treatment and determine a cut-off point for the excised canal length needed to decrease the risk of disease relapse. RESULTS: In 2,427 cases, the relapse rate of HSIL treated was 12%. Compromised margins of conization, HIV+, and endocervical canal length were related directly to relapses ( p < .001). The cut-off point, by receiver operating characteristic curve, to calculate the endocervical canal length related to relapses was 1.25 cm of canal excised. Canal length of less than 1.25 cm increased the recurrence rate 2.5 times. Compromised margins and HIV+ increased recurrence rates by more than 5 times. CONCLUSION: Cervical HSIL recurrence was directly related to the endocervical canal length: excised canal length of 1.25 cm or more decreases recurrence rate; HIV and compromised margins increase the chance of recurrence by more than 5 times.

Evaluation of the efficacy and safety of 5-aminolevulinic acid-mediated photodynamic therapy in women with high-risk HPV persistent infection after cervical conization.

OBJECTIVE: To evaluate the efficacy and safety of photodynamic therapy (PDT) in women with high-risk human papillomavirus (hr-HPV) persistent infection after cervical conization, including loop electrosurgical excision procedure (LEEP) and cold knife conization (CKC). MATERIALS AND METHODS: The clinicopathological and follow-up data of 76 women with hr-HPV persistent infection after cervical conization (54 cases with LEEP and 22 cases with CKC) were collected. All the women in this group met these criteria: postoperative pathological diagnosis of LEEP/CKC showed high grade squamous intraepithelial lesions (HSIL) with negative incisal margin, hr-HPV persistent infection after LEEP/CKC ≥ 1 year, colposcopy and histopathology showed no intraepithelial lesions before PDT, and 5-aminolaevulinic acid (5-ALA) as photosensitizer treating for 6 times with an interval of 7-10 days. The above patients were followed up 6 months and 12 months after PDT, and the follow-up contents included Roche Cobas HPV classification test, cytology, colposcopy, and pathological examinations. HPV negative conversion rate is an index to evaluate the efficacy of PDT. In addition, we also assessed the safety of PDT. RESULTS: Six months after PDT, the overall HPV clearance rate was 59.21% (45/76). The HPV negative conversion rates in patients ≤ 50 years old group and > 50 years old group were 68.52% (37/54) and 36.36% (8/22), respectively (P=0.009). But there was no significant difference in HPV clearance rate between the HPV16/18 infection group and other hr-HPV infection group (P=0.3326). 12 months after PDT, 1 case underwent hysterectomy because of progression to HSIL, and 7 cases lost follow-up. The overall HPV clearance rate was 88.24% (60/68). The negative conversion rates of HPV16/18 and other hr-HPV infection groups were 76.00% (19/25) and 95.35% (41/43), respectively (P=0.0458). However, the HPV negative conversion rate was not correlated with the patient's age (P=0.2383). The adverse reactions after PDT were mild, mainly manifested as increased vaginal secretions or burning/tingling. CONCLUSIONS: Photodynamic therapy could be an effective treatment for patients with hr-HPV persistent infection after cervical conization and it could promote the negative conversion of hr-HPV and prevent the recurrence progression of cervical intraepithelial neoplasia (CIN) after LEEP/CKC.

HPV Test as Test of Cure After Conization for CIN2+: A Nationwide Register-Based Cohort Study.

OBJECTIVE: The purpose of this study was to assess if cytology can be omitted in the follow-up after treatment for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and if human papillomavirus (HPV) test can be used alone as test of cure (TOC) after stratifying for resection margins. MATERIAL AND METHODS: In this retrospective register-based study, women who had a conization performed in Denmark between January 1 and December 31, 2013, were included. Histology, cytology, and HPV test results were obtained from The Danish Pathology Data Bank for a 3-year follow-up. RESULTS: A total of 5,174 women were included, of whom 6.1% (318/5,174) had histological residual/recurrent disease in the follow-up period. In the group with free margins, 2.6% (73/2,780) had residual/recurrent disease in contrast to 10.2% (245/2,394) in the group with involved margins. In the group with free resection margins and negative HPV test results, residual/recurrent disease was found in 0.5% (13/2,780) compared with 0.3% (9/2,780) in the group with negative HPV test results and normal cytology at 6 months' follow-up. Based on margin status and HPV test result as follow-up, the sensitivity, specificity, and positive and negative predictive values were 95.9%, 43.2%, 10.0%, and 99.4% respectively, and for combined testing (margin status, HPV, and cytology), 97.2%, 41.2%, 9.8%, and 99.6%, respectively. CONCLUSIONS: Using the HPV test at the first post-treatment control as TOC for cervical intraepithelial neoplasia grade 2 or worse after stratifying for resection margins in cone resections yields an equally high sensitivity and negative predictive value as cotesting with cytology. We suggest that women with free resection margins return to the routine screening program after negative HPV test result as TOC at 6 months.

Recurrent Dysplasia After a Loop Electrosurgical Excision Procedure: Local Versus General Anesthesia.

OBJECTIVE: This study aimed to compare the rates of positive specimen margins and postconization recurrent dysplasia between loop electrosurgical excision procedures (LEEPs) performed under general anesthesia (GA) and LEEP under local anesthesia (LA). METHODS: This retrospective cohort study included all consecutive women who underwent LEEP between 2011 and 2019. Collected data included demographics, LEEP indication, cone dimensions, and margin involvement as well as recurrence rate. Women who had undergone previous conization, cold-knife conization, or those who were lost to follow-up during the first 2 years after the procedure were excluded. RESULTS: Overall, 71 women who underwent LEEP under GA and 75 women under LA were included. Demographic characteristics were similar between the groups, as were the rates of preceding abnormal cytology and high-grade dysplasia before conization. Although cone depth and volume were higher for LEEP specimens done under GA compared with LA, the rate of positive specimen margins was comparable both for the endocervical margin (16/71 [22.5%] vs 16/75 [21.3%], respectively; p = .861) and the ectocervical margin (14/71 [19.7%] vs 11/75 [14.7%], respectively; p = .418). During the first 2 years after conization, the rates of high-grade dysplasia (cervical intraepithelial neoplasia ≥ 2) in repeat biopsy and the need for repeat conization were also not significantly different between the GA and LA groups (4.2% vs 1.3%, p = .356; 7.0% vs 9.3%, p = .614, respectively). CONCLUSIONS: Anesthesia mode does not seem to affect the rate of positive LEEP margins and the need for repeat conization. Our study findings suggest that LA should be preferred instead of GA in LEEP.

Predictors of high-grade residual disease after repeat conization in patients with positive surgical margins.

OBJECTIVES: No consensus exists on the subsequent management strategy of patients who exhibit positive surgical margin (PSM) after re-excision of high-grade cervical intraepithelial neoplasia (CIN). The aim of the study is to examine the predictors related to the persistence of high-grade CIN lesions after re-excision, where PSM was left behind. MATERIAL AND METHODS: The present retrospective study included patients with PSM who underwent repeated conization due to residual high-grade CIN lesions between January 2005 and December 2019. The SPSS software v20.0 was used for data interpretation and statistical analysis. P values less than 0.05 were accepted as statistically significant. RESULTS: Repeat conization was performed in 91 patients, 43 (47.3%) presented with PSM with high-grade CIN, 6 (6.5%) presented with micro-invasive carcinoma, and 42 (46.2%) presented with clear surgical margin or CIN 1 at the surgical margin. At the time of conization, patients who presented with lesions > 5 mm in repeat cone specimens, exhibited a significantly higher rate of residual disease (p < 0.001). Besides, the involvement of the endocervical margin with high-grade CIN was the predictor of residual disease in repeat cone specimens (p = 0.006). CONCLUSIONS: In the cone specimen, the presence of lesion size greater than 5 mm and involvement of the endocervical margin were the predictors of high-grade residual disease after re-excision. Whether it is the first or second procedure, great care must be given to excise the lesion entirely at the time of the conization, preferably in one piece.

Identification of women with high grade histopathology results after conisation by artificial neural networks.

BACKGROUND: The aim of the study was to evaluate if artificial neural networks can predict high-grade histopathology results after conisation from risk factors and their combinations in patients undergoing conisation because of pathological changes on uterine cervix. PATIENTS AND METHODS: We analysed 1475 patients who had conisation surgery at the University Clinic for Gynaecology and Obstetrics of University Clinical Centre Maribor from 1993-2005. The database in different datasets was arranged to deal with unbalance data and enhance classification performance. Weka open-source software was used for analysis with artificial neural networks. Last Papanicolaou smear (PAP) and risk factors for development of cervical dysplasia and carcinoma were used as input and high-grade dysplasia Yes/No as output result. 10-fold cross validation was used for defining training and holdout set for analysis. RESULTS: Bas eline classification and multiple runs of artificial neural network on various risk factors settings were performed. We achieved 84.19% correct classifications, area under the curve 0.87, kappa 0.64, F-measure 0.884 and Matthews correlation coefficient (MCC) 0.640 in model, where baseline prediction was 69.79%. CONCLUSIONS: With artificial neural networks we were able to identify more patients who developed high-grade squamous intraepithelial lesion on final histopathology result of conisation as with baseline prediction. But, characteristics of 1475 patients who had conisation in years 1993-2005 at the University Clinical Centre Maribor did not allow reliable prediction with artificial neural networks for every-day clinical practice.

Comparative effectiveness and risk of preterm birth of local treatments for cervical intraepithelial neoplasia and stage IA1 cervical cancer: a systematic review and network meta-analysis.

BACKGROUND: The trade-off between comparative effectiveness and reproductive morbidity of different treatment methods for cervical intraepithelial neoplasia (CIN) remains unclear. We aimed to determine the risks of treatment failure and preterm birth associated with various treatment techniques. METHODS: In this systematic review and network meta-analysis, we searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials database for randomised and non-randomised studies reporting on oncological or reproductive outcomes after CIN treatments from database inception until March 9, 2022, without language restrictions. We included studies of women with CIN, glandular intraepithelial neoplasia, or stage IA1 cervical cancer treated with excision (cold knife conisation [CKC], laser conisation, and large loop excision of the transformation zone [LLETZ]) or ablation (radical diathermy, laser ablation, cold coagulation, and cryotherapy). We excluded women treated with hysterectomy. The primary outcomes were any treatment failure (defined as any abnormal histology or cytology) and preterm birth (<37 weeks of gestation). The network for preterm birth also included women with untreated CIN (untreated colposcopy group). The main reference group was LLETZ for treatment failure and the untreated colposcopy group for preterm birth. For randomised controlled trials, we extracted group-level summary data, and for observational studies, we extracted relative treatment effect estimates adjusted for potential confounders, when available, and we did random-effects network meta-analyses to obtain odds ratios (ORs) with 95% CIs. We assessed within-study and across-study risk of bias using Cochrane tools. This systematic review is registered with PROSPERO, CRD42018115495 and CRD42018115508. FINDINGS: 7880 potential citations were identified for the outcome of treatment failure and 4107 for the outcome of preterm birth. After screening and removal of duplicates, the network for treatment failure included 19 240 participants across 71 studies (25 randomised) and the network for preterm birth included 68 817 participants across 29 studies (two randomised). Compared with LLETZ, risk of treatment failure was reduced for other excisional methods (laser conisation: OR 0·59 [95% CI 0·44-0·79] and CKC: 0·63 [0·50-0·81]) and increased for laser ablation (1·69 [1·27-2·24]) and cryotherapy (1·84 [1·33-2·56]). No differences were found for the comparison of cold coagulation versus LLETZ (1·09 [0·68-1·74]) but direct data were based on two small studies only. Compared with the untreated colposcopy group, risk of preterm birth was increased for all excisional techniques (CKC: 2·27 [1·70-3·02]; laser conisation: 1·77 [1·29-2·43]; and LLETZ: 1·37 [1·16-1·62]), whereas no differences were found for ablative methods (laser ablation: 1·05 [0·78-1·41]; cryotherapy: 1·01 [0·35-2·92]; and cold coagulation: 0·67 [0·02-29·15]). The evidence was based mostly on observational studies with their inherent risks of bias, and the credibility of many comparisons was low. INTERPRETATION: More radical excisional techniques reduce the risk of treatment failure but increase the risk of subsequent preterm birth. Although there is uncertainty, ablative treatments probably do not increase risk of preterm birth, but are associated with higher failure rates than excisional techniques. Although we found LLETZ to have balanced effectiveness and reproductive morbidity, treatment choice should rely on a woman's age, size and location of lesion, and future family planning. FUNDING: National Institute for Health and Care Research: Research for Patient Benefit.

Management of patients with positive margin after conization for high-grade cervical intraepithelial lesions.

BACKGROUND AND OBJECTIVE: To evaluate the clinical efficacy and safety of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) in the treatment of patients with positive margin in comparison to regular follow-up, and a repeat cervical conization. MATERIALS AND METHODS: A retrospective analysis was conducted using 83 patients with pathologically confirmed high-grade cervical intraepithelial neoplasia (CIN) with a positive margin after conization. The management methods and patient prognosis were analyzed and compared. RESULTS: Thirty-five, 33, and 15 patients were treated for regular follow-up, ALA-PDT, and a repeat cervical conization, respectively. About 33.3% (5/15) patients had residual lesions of low-grade CIN and above after recognization. The clinical characteristics of patients in the three groups were similar. The residual lesion rates of patients selected for follow-up, ALA-PDT, and recognization were 34.3% (12/35), 9.1% (3/33), and 0% (0/15), respectively, at 6-month follow-up (p = 0.004). The HPV clearance rates were 31.3%, 66.7%, and 84.6%, respectively (p = 0.01). Further analysis showed that a positive margin in the inscribed margin of the cervical canal (p = 0.022) and persistent HR-HPV positive tests after initial conization (p = 0.003) significantly increased the risk of residual disease. At 2-year follow-up, the recurrence rates of lesions were 3.3% and 26.1% in the ALA-PDT and follow-up groups, respectively (p = 0.021). Notably, the recurrence rates were not significantly different between the ALA-PDT and recognization groups (3.3% vs. 6.7%) (p = 0.561). CONCLUSION: ALA-PDT is an effective treatment for patients with a positive margin after cervical conization for high-grade CIN. Compared with regular follow-up, ALA-PDT can reduce residual and recurrence rate. Moreover, there was no significant difference in the efficacy between AlA-PDT and recognization.