Aerobic vaginitis is associated with carbonic anhydrase IX in cervical intraepithelial neoplasia.

The aim of this study was to analyze the association between vaginal microbiota, carbonic anhydrase IX (CAIX) and histological findings of cervical intraepithelial neoplasia (CIN). The study included 132 females, among them 66 were diagnosed with high-grade intraepithelial lesion (CIN2, CIN3, and cancer), 14 with low-grade disease, and 52 assigned to the control group. An interview focused on the behavior risk factors, together with vaginal fluid pH measurement, wet mount microscopy, detection of Chlamydia trachomatis, and Trichomonas vaginalis were performed. After colposcopy, high-grade abnormalities were detected via direct biopsies and treated with conization procedure. Conuses were immuno-stained with CAIX antibody. The histological findings were CIN1 (n = 14), and CIN2+ (included CIN2 (n = 10), CIN3 (n = 49), and cancer (n = 7; squamous cell carcinomas)). Prevalence of bacterial vaginosis (BV) was similar between the groups. Moderate or severe aerobic vaginitis (msAV) was diagnosed more often among CIN2+ (53.0%) than CIN1 (21.4%). Moderate or strong immunostaining of CAIX (msCAIX) was not detected among CIN1 cases. Thus, msAV was prevalent in CAIX non-stained group (p = 0.049) among CIN2 patients. Co-location of msAV and msCAIX was found in CIN3. Regression model revealed that msAV associated with high-grade cervical intraepithelial neoplasia independently from smoking and the number of partners.

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.

Effects of adding low-dose esketamine to sufentanil and propofol sedation during cervical conization: a single-centre, randomized controlled trial.

BACKGROUND: Cervical conization is a brief but painful procedure that can be performed under sufficient sedation with propofol and opioids. However, this sedation approach comes with a high risk of sedation-related adverse events (SRAEs). Esketamine, an N-methyl-d-aspartate (NMDA) receptor antagonist, causes less cardiorespiratory depression than opioids. The aim of this study was to assess the efficacy and safety of adding a low dose of esketamine to propofol and sufentanil sedation as an opioid-reduced regimen. METHODS: A total of 122 consecutive patients with ASA I-II, body mass index < 30, and STOP-BANG score < 3 who underwent cervical conization were enrolled and randomly divided into Group S and Group ES. Using a closed-loop target-controlled infusion (TCI) pump with a target bispectral index (BIS) value of 60 ± 5, patients in Group S were sedated with 0.2 mcg·kg-1 sufentanil and propofol, while patients in Group ES were sedated with 0.15 mg·kg-1 esketamine, 0.1 mcg·kg-1 sufentanil and propofol. The primary outcome was the incidence and severity of SRAEs, while the secondary outcomes included effectiveness of sedation, awakening time, psychotomimetic side effects, postoperative pain, postoperative nausea and vomiting, and patient and gynaecologist satisfaction. RESULTS: Data from 120 patients were analysed. The incidence of composite SRAEs was significantly higher in Group S than in Group ES (85.0% vs. 56.7%, P < 0.05). Furthermore, the severity of SRAEs was higher in Group S than in Group ES (P < 0.001). There were no significant differences in the effectiveness of sedation, awakening time, psychotomimetic side effects, postoperative pain, postoperative nausea and vomiting, or patient and gynaecologist satisfaction between the two groups. CONCLUSION: Adding low-dose esketamine to propofol and sufentanil sedation reduces the incidence and severity of SRAEs in patients undergoing cervical conization, with equal sedation efficacy, recovery quality, and no additional psychomimetic side effects. TRIAL REGISTRATION: ChiCTR2000040457 , 28/11/2020.

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%.

Endocervical crypt involvement by high-grade cervical intraepithelial neoplasia and its association with high-grade histopathological recurrence after cervical excision in women with negative excision margins: a systematic review and meta-analysis.

BACKGROUND: There is a growing body of evidence suggesting that endocervical crypt involvement by high-grade cervical intraepithelial neoplasia (CIN) may represent a risk factor for disease recurrence after cervical treatment. OBJECTIVES: To provide a systematic review and meta-analysis on whether endocervical crypt involvement by high-grade CIN on the excised cervical specimen is associated with high-grade histopathological recurrence during the follow-up of women after cervical excisional treatment. SEARCH STRATEGY: We searched the Medline, Scopus, Central, and Clinical Trials.gov databases from inception till May 2023. SELECTION CRITERIA: Studies that reported on women with a single cervical treatment with any method of excision for CIN2 or CIN3 lesion, negative excision margins, and whose recurrence was defined histopathologically were included. DATA COLLECTION AND ANALYSIS: Two reviewers independently evaluated study eligibility. We used the fixed effects model for meta-analysis. MAIN RESULTS: There were 4 eligible studies included in the present systematic review that evaluated 1088 women treated with either large loop excision of the transformation zone (LLETZ) or with cold knife conization (CKC). We found no significant association of endocervical crypt involvement by CIN2-3 with high-grade histopathological recurrence at follow-up after cervical excision (OR 1.93; 95% CI 0.51-3.35). The subgroup analysis of women with LLETZ cervical excision showed again no significant association with high-grade histopathological recurrence at follow-up (OR 2.00; 95% CI 0.26-3.74). CONCLUSION: Endocervical crypt involvement by high-grade CIN does not seem to be a risk factor for high-grade histopathological recurrence after cervical excision with negative excision margins.

Robotic radical hysterectomy after conization for patients with small volume early-stage cervical cancer.

Laparoscopy and robotics are recommended for managing gynecological cancer, as they are associated with lower morbidity and comparable outcomes to open surgery. However, in the case of early cervical cancer, new evidence suggests worse oncological outcomes with these approaches compared to open surgery, though the limited number of robotic cases makes it challenging to draw definitive conclusions for this particular approach. The prior conization has been proposed as a strategy to reduce the risk of tumor spillage and contamination during minimally invasive (MIS) radical hysterectomy (RH). Retrospective studies have indicated that undergoing conization before RH is linked to a reduced risk of recurrences, especially in cervical tumors measuring less than 2 cm. Nevertheless, these studies lack the statistical power needed to definitively establish conization as a recommended step before RH. Furthermore, these studies do not have enough cases utilizing the robotic approach and specific conclusions cannot be drawn from this technique. The question of whether a subset of cases would benefit from preoperative conization and whether conization should be performed to recommend MIS over open surgery remains unanswered. Prospective clinical trials involving women diagnosed with early-stage cervical cancer <2 cm, randomized between undergoing conization before robotic RH or without prior conization are mandatory to assess the role of conization before robotic RH in cervical cancer.

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.

Risk stratification of invasive cervical cancer diagnosed after cervical conization.

BACKGROUND: Cervical intraepithelial neoplasia (CIN) diagnosis is based on colposcopy-aided histological examination. However, its accuracy in CIN diagnosis is limited. Some invasive cervical cancers (ICCs) are diagnosed after cervical conization. Therefore, risk stratification of undetected ICC is particularly important for the management of patients with CIN. This study aimed to identify the risk factors for undetected ICC. We especially focused on the association of human papillomavirus (HPV) genotypes. METHODS: We retrospectively reviewed the clinicopathological characteristics (including age, parity, and preoperative diagnosis) and HPV genotypes of 348 patients diagnosed with CIN or adenocarcinoma in situ (AIS) who underwent cervical conization at our hospital between 2008 and 2016. The relationship between preoperative factors, including HPV genotypes and post-conization ICC, was evaluated. RESULTS: Among the 348 patients, 322, 7, and 19 had preoperative CIN3, CIN2, and AIS, respectively; 181 were nulliparous. The median patient age was 41 (23-83) years. HPV genotyping was performed on 237 patients. Overall, post-conization ICC was detected in 16 patients (4.6%). Multivariate analysis showed that nulliparity and HPV16 positivity were the independent risk factors for post-conization ICC (OR: 6.01, P = 0.0302; OR: 5.26, P = 0.0347, respectively). The combination of HPV16 status and parity improved diagnostic accuracy. Seven of 53 HPV16-positive cases (13%) without childbirth history were diagnosed with post-conization ICC. In contrast, none of the HPV16-negative cases with childbirth history was diagnosed with post-conization ICC. CONCLUSION: HPV16 positivity and nulliparity were identified as risk factors for undetected ICC. Careful treatment selection and preoperative scrupulous examination are especially important in these cases.

Effect of Pap Smear Cytology, HPV Genotyping on the Concordance of Colposcopy and Conization Results.

OBJECTIVE: To evaluate the conization results performed due to human papillomavirus (HPV), smear, colposcopy results or clinician's decision and determine the factors that predict ≥CIN2. STUDY DESIGN: Retrospective comparative study. Place and Duration of the Study: Department of Gynaecology and Obstetrics, Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital, Ankara, Turkey, between January 2011 and December 2021. METHODOLOGY: Women with known HPV results who underwent conization in the Gynaecology clinic were retrospectively included. Age, HPV genotypes, conization, and colposcopy results of the patients were recorded. Patients were divided into two groups as those with and without ≥CIN2 and compared in terms of clinicopathological features. RESULTS: Four hundred and twenty eight (82.8%) of the 517 patients were premenopausal and perimenopausal, and 89 (17.2%) of the patients with a median age of 42 years (range: 30-65 years) were postmenopausal. While 374 were HPV 16/18 positive, 143 were non-16/18 HPV positive. Conization result was normal in 202 (39.1%) patients, CIN1 in 129 (25.0%) patients, and CIN 2-3 in 186 (36.0%) patients. In the HPV 16/18 positive group, conization result was normal in 38.2% of patients, CIN1 in 20.9%, and CIN 2-3 in 40.9%; these rates were 41.3%, 35.7%, and 23.1% in the HPV-other group, respectively (p <0.001). In the logistic regression model, age, HPV type (16/18), and smear cytology results (≥ASC-US) were tested as independent factors predicting ≥CIN2. CONCLUSION: HPV 16/18 positivity and smear cytology result (≥ASC-US) were the factors predicting ≥CIN2. Smear and HPV genotyping can make an important contribution to detecting false

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.

Are "additional cuts" effective for positive margins in cervical conization? It varies according to the doctor.

BACKGROUND: High-grade squamous intraepithelial lesion (HSIL) is a disease that is closely related to the development of cervical cancer. In clinical work, cold knife conization and a loop electrosurgical excision procedure (LEEP) are often selected for diagnosis and treatment. OBJECTIVE: In this paper, we aimed to discuss additional cuts, a common practice in cervical conization, and determine whether the doctor's choice to use additional cuts in conization can reduce the occurrence of a positive cone margin. METHODS: From January 2018 to October 2019, 965 patients underwent cervical conization at the First Affiliated Hospital of Dalian Medical University (Dalian, China). Of these, 174 were in the positive cone margin group, and 791 were in the negative cone margin group. Age, preoperative pathology, pathological results of conization, additional cuts, cone depth, and cone volume were studied. Additionally, the additional cut rate and the efficiency of doctors with a habit of additional cuts were analyzed. RESULTS: Of the 965 patients included in the study, the median age was 41 years (range 35-50). Multivariable logistic regression analysis suggested that additional cuts (OR, 2.480; 95% CI 1.608 to 3.826; p = 0.01) and smaller cone depth (OR, 0.591; 95% CI, 0.362 to 0.965, p = 0.036) were independent risk factors for positive margins. Six of the 64 doctors who performed conizations had a habit of making additional cuts, and there was no positive correlation between their additional cut rate and their effective additional cut rate. CONCLUSION: This study showed that a certain proportion of additional cuts can be effectively excised from the positive margin that cannot be removed in the initial conization. The practice of additional cuts in conization tends to be the personal habit of a small number of doctors.

Extensive lesions and a positive cone margin are strong predictors of residual disease in subsequent hysterectomy following conization for squamous intraepithelial lesion grade 2 or 3 study design.

BACKGROUND: This study aimed to determine the predictive factors for post-conization of residual disease in subsequent hysterectomy for cervical intraepithelial neoplasia grade 2 or 3. METHODS: This retrospective study included 267 patients with histologically confirmed cervical intraepithelial neoplasia grade 2 or 3 who underwent hysterectomy within 7 months after conization. Clinical data (e.g., age, menopausal status, gravidity, parity, type of transformation zone, conization method) as well as pathological data pertaining to conization and hysterectomy were collected from medical records. A logistic regression model was used to analyze the relationship between the variables and risk of residual lesions in hysterectomy samples. RESULTS: Overall, 70 (26.2%) patients had residual lesions in their hysterectomy specimens. Univariate analyses revealed that age ≥ 50 years (p=0.019), endocervical gland involvement(p=0.013), positive margin(p < 0.001), and involvement of 3-4 quadrants(p < 0.001) were risk factors for residual lesions. Conversely, postmenopausal status, gravidity ≥ 3, parity ≥ 2, loop electrosurgical excision procedure, and type III transformation zone were not risk factors for residual lesions. A positive margin(p < 0.001) and multiple-quadrant involvement(p < 0.001) were identified as independent risk factors for residual lesions on multivariate analysis. CONCLUSIONS: Multiple-quadrant involvement and a positive cone margin were reliable predictive factors for residual disease. Total hysterectomy or repeated cervical conization should be considered for patients with these two risk factors. The identification of high-risk patients with extensive lesions by colposcopic examination before conization is indispensable, as it will enable surgeons to perform conization with consideration of risk factors and possibly improve the approach used for the excisional procedure. For high-risk patients, colposcope-guided cold-knife conization is preferred when resources permit.

Impact of cervical excisional dimensions on endocervical margins status in adenocarcinoma in situ of the uterine cervix: A multicenter study from the FRANCOGYN group.

OBJECTIVE: Excisional procedures have a central role in the management of adenocarcinoma in situ of the cervix (AIS). We aimed to evaluate the relationship between the excisional specimen dimensions and the endocervical margin status. METHODS: We conducted a multicentric retrospective study in seven French centers. All cases with proven AIS on a colposcopic biopsy and undergoing an excisional procedure afterwards were included in the analysis. We evaluated the impact of excision length, along with the lateral and anteroposterior diameters on the endocervical margin status. An additional subgroup analysis of the impact of maternal age on endocervical margin status was also conducted. RESULTS: Of the 101 cases of AIS diagnosed on initial biopsy, 95 underwent a primary excisional procedure, among which 80% (n = 76/95) had uninvolved endocervical margins and 20% (n = 19/95) had positive endocervical margins. The excisional specimen length was not significantly related to the endocervical margin status. Conversely, both lateral and antero-posterior diameters were significantly correlated with the negative endocervical margins status: OR = 1,19, 95% CI [1.03, 1.40], p = 0.025, for the lateral diameter and OR = 1.34, 95% CI [1.14, 1.64], p = 0.001 for the antero-posterior diameter. The median lateral diameter was 20 mm, IQR (18, 24) in case of endocervical negative margins vs. 18 mm IQR (15, 24) in case of positive endocervical margins (p = 0.039), and the median anteroposterior diameter was 17 mm IQR (15, 20) in case of negative endocervical margins vs 14 mm IQR (11, 15) in case of positive endocervical margins (p = 0.004), respectively.  Additionally, in patients over 45 years old, endocervical margin were more likely to be positive despite similar excisional dimensions (7/17 (41%) of positive endocercival margins before 45 years old vs 12/78 (15%) after, p = 0.039) CONCLUSIONS: Endocervical margin statues were significantly related to the transverse diameters (lateral and anteroposterior diameters), but not to the excision specimen length. Reducing the excised length may lead to fewer post-procedure complications but would still allow to obtain a large proportion of negative endocervical margins.

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.

High-grade vaginal intraepithelial neoplasia after hysterectomy for high-grade cervical intraepithelial neoplasia: Is hysterectomy a "definitive" treatment compared to conization?

AIM: We investigated the frequency of early recurrence of vaginal intraepithelial neoplasia grade 2/3 (VaIN 2/3) (within 2 years) after hysterectomy for cervical intraepithelial neoplasia grade 3 (CIN3). The characteristics of the clinicopathological factors common to them were explored including different surgical methods. METHODS: As a retrospective observational study, a total of 647 CIN3 patients were divided into a conization and hysterectomy group (C group, n = 492; H group, n = 155), and HSIL (CIN2/3 or VaIN2/3) recurrence within 2 years after surgery was evaluated. A stratified analyses was performed. Surgical methods were divided into trans-abdominal, trans-vaginal, and laparoscopic. RESULTS: The recurrence of VaIN3 was detected in four cases (2.6%) in the H group, which was similar to that of CIN2/3 in the C group, 12 out of 491 patients (2.4%). The patients who developed VaIN3 were significantly older than those who did not (median, VaIN3: 71.0; VaIN1 and less: 48.0; p < 0.0001). All VaIN3 cases were detected within 5 months, although majority of cases were negative in the margin (3/4 cases; margin negative). The method of hysterectomy was not related to the VaIN3 recurrence. CONCLUSION: For CIN3 patients for whom hysterectomy is the main treatment, VaIN3 can develop in 2.6% within very shortly after operation even if surgical margin was negative. The elder the age, the higher the risk of early recurrence could be. Laparoscopic surgery is considered to be acceptable methods of hysterectomy.

Cardiopulmonary Adverse Events of Remimazolam versus Propofol During Cervical Conization: A Randomized Controlled Trial.

Purpose: This study aimed to compare the cardiopulmonary safety of remimazolam and propofol in patients undergoing cervical conization. Methods: This was a single-blind, parallel, randomized controlled study. A total of 204 patients scheduled for day surgery of cold knife cervical conization received either remimazolam-alfentanil anesthesia (remimazolam group) or propofol-alfentanil anesthesia (propofol group). The primary outcome was the incidence of intraoperative cardiopulmonary adverse events (a composite outcome of hypotension, bradycardia and hypoxemia). The occurrence of hypotension, bradycardia, hypoxemia and the degree of body movement were secondary outcomes, as well as the moment at which consciousness was lost, the interval between the end of anesthesia and the operating room's release of the patient, and the overall dosage of alfentanil administered during the procedure. Results: The incidence of intraoperative cardiopulmonary adverse events was 45 (44.1%) in the remimazolam group and 72 (70.6%) in the propofol group (absolute risk difference [95% CI], -26.47% [-39.55% to -13.39%]; odds ratio (OR) [95% CI], 0.43 [0.28 to 0.65]; P < 0.001). The remimazolam group showed lower incidences of hypotension and hypoxemia compared to the propofol group (P = 0.01 for both). No significant differences were observed in the overall alfentanil dosages administered, bradycardia, bodily movement, or time to losing consciousness between the two groups. Conclusion: In patients who underwent cold knife cervical conization, remimazolam-alfentanil anesthesia was associated with a reduced incidence of intraoperative cardiopulmonary adverse events compared with propofol-alfentanil anesthesia.

Persistent HPV infection after conization of cervical intraepithelial neoplasia-- a systematic review and meta-analysis.

OBJECTIVE: To systematically evaluate several factors of persistent human papillomavirus (HPV) infection following conization in patients with cervical intraepithelial neoplasia (CIN). METHODS: PubMed, EMBASE and the Cochrane Library were searched from January 1, 1998 to September 10, 2021. Random-effects models for meta-analyses were used and pooled relative risks with 95% confidence intervals were reported. Literature screening, data extraction, and assessment of the risk of bias in the included studies were conducted independently by two researchers. Data analysis was performed with Stata software, version 12.0. RESULTS: A total of 28 studies were included in this study. Meta-analysis revealed that surgical margin and residual disease were positively correlated with persistent HPV infection after conization. Compared with patients infected with other types of HPV, CIN patients with HPV 16 had a higher persistent infection rate (OR = 1.967, 95% CI (1.232-3.140), P < 0.05). CONCLUSIONS: CIN patients who are postmenopausal, have positive surgical margins and residual lesions, and are positive for HPV 16 are prone to persistent HPV infection after conization.

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.

The efficacy of human papillomavirus prophylactic vaccination after conization in preventing cervical intraepithelial neoplasia recurrence: A prospective observational study in China.

High-risk human papillomavirus (hrHPV) infection is the cause of most cervical cancers. Since therapeutic vaccines are not yet available for clinical practice, the administration of HPV prophylactic vaccines in patients with cervical intraepithelial neoplasia (CIN) arouses great interest and its value after excisional treatment of CIN remains unclear. We conducted this prospective cohort study to evaluate the impact of HPV prophylactic vaccination on preventing women from subsequent infection and cervical lesions after excision treatment. 148 patients after loop electrosurgical excision procedure (LEEP) for CIN2+ disease received HPV prophylactic vaccination (6/11/16/18 vaccine, Gardasil®, Merck) after surgery (V-group) and 273 didn't get vaccination (NV-group). The HPV infection rates at the first and second year after LEEP were significantly lower in the V-group than that in NV-group (P = 0.049 and P = 0.026). CIN2+ recurrence was observed in 29 cases (10.62 %) in the NV-group and 2 cases (2.03 %) in the V-group. Logistic regression analysis showed that the HPV16/18 infection, the CIN3 pathology after LEEP and no vaccination after LEEP were significant risk factors of recurrence. Patients without HPV vaccination had a higher CIN2+ recurrence rate (OR = 12.35, 95 % CI 1.919-79.492, P = 0.008). Our study showed the quadrivalent prophylactic HPV vaccination after LEEP had a significantly protective role in the prevention of high-grade squamous intraepithelial lesion recurrence. Further randomized, controlled trials are required in elucidating the efficacy of the prophylactic HPV vaccines using shortly after LEEP in patients with CIN disease.