Risk-stratified management of cervical high-grade squamous intraepithelial lesion based on machine learning.

The concordance rate between conization and colposcopy-directed biopsy (CDB) proven cervical high-grade squamous intraepithelial lesion (HSIL) were 64-85%. We aimed to identify the risk factors associated with pathological upgrading or downgrading after conization in patients with cervical HSIL and to provide risk-stratified management based on a machine learning predictive model. This retrospective study included patients who visited the Obstetrics and Gynecology Hospital of Fudan University from January 1 to December 31, 2019, were diagnosed with cervical HSIL by CDB, and subsequently underwent conization. A wide variety of data were collected from the medical records, including demographic data, laboratory findings, colposcopy descriptions, and pathological results. The patients were categorized into three groups according to their postconization pathological results: low-grade squamous intraepithelial lesion (LSIL) or below (downgrading group), HSIL (HSIL group), and cervical cancer (upgrading group). Univariate and multivariate analyses were performed to identify the independent risk factors for pathological changes in patients with cervical HSIL. Machine learning prediction models were established, evaluated, and subsequently verified using external testing data. In total, 1585 patients were included, of whom 65 (4.1%) were upgraded to cervical cancer after conization, 1147 (72.4%) remained having HSIL, and 373 (23.5%) were downgraded to LSIL or below. Multivariate analysis showed a 2% decrease in the incidence of pathological downgrade for each additional year of age and a 1% increase in lesion size. Patients with cytology > LSIL (odds ratio [OR] = 0.33; 95% confidence interval [CI], 0.21-0.52), human papillomavirus (HPV) infection (OR = 0.33; 95% CI, 0.14-0.81), HPV 33 infection (OR = 0.37; 95% CI, 0.18-0.78), coarse punctate vessels on colposcopy examination (OR = 0.14; 95% CI, 0.06-0.32), HSIL lesions in the endocervical canal (OR = 0.48; 95% CI, 0.30-0.76), and HSIL impression (OR = 0.02; 95% CI, 0.01-0.03) were less likely to experience pathological downgrading after conization than their counterparts. The independent risk factors for pathological upgrading to cervical cancer after conization included the following: age (OR = 1.08; 95% CI, 1.04-1.12), HPV 16 infection (OR = 4.07; 95% CI, 1.70-9.78), the presence of coarse punctate vessels during colposcopy examination (OR = 2.21; 95% CI, 1.08-4.50), atypical vessels (OR = 6.87; 95% CI, 2.81-16.83), and HSIL lesions in the endocervical canal (OR = 2.91; 95% CI, 1.46-5.77). Among the six machine learning prediction models, the back propagation (BP) neural network model demonstrated the highest and most uniform predictive performance in the downgrading, HSIL, and upgrading groups, with areas under the curve (AUCs) of 0.90, 0.84, and 0.69; sensitivities of 0.74, 0.84, and 0.42; specificities of 0.90, 0.71, and 0.95; and accuracies of 0.74, 0.84, and 0.95, respectively. In the external testing set, the BP neural network model showed a higher predictive performance than the logistic regression model, with an overall AUC of 0.91. Therefore, a web-based prediction tool was developed in this study. BP neural network prediction model has excellent predictive performance and can be used for the risk stratification of patients with CDB-diagnosed HSIL.

Postoperative clearance of high-risk human papillomavirus for patients with high-grade squamous intraepithelial lesion: Conization versus hysterectomy.

To compare the clearance rate of high-risk human papillomavirus (HR-HPV) in patients with high-grade squamous intraepithelial lesion (HSIL) after 2 different treatments (conization vs hysterectomy), and investigate the influencing factors. A retrospective cohort was established in HSIL patients with HR-HPV infection treated with conization or hysterectomy from July 2020 to May 2022. Age matching (1:1) was conducted between conization group and hysterectomy group. Chi-square test and t-test were employed to compare baseline and clinical characteristics between the 2 groups (conization vs hysterectomy). In addition, univariate and multivariate logistic regression analyses were conducted to compare the influencing factors for HR-HPV clearance at 6 months after surgery. The HR-HPV clearance rates at 6 months were 70.6% and 73.8% in conization group and hysterectomy group in the matched groups, respectively (P = .755). Similarly, at 12 months, the clearance rates were 78.6% and 76.5% in the matched groups, respectively (P = .844). Considering different age groups among all patients, the HR-HPV clearance rates were 81.8%, 72.9%, 73.5%, and 53.6% in the 20 to 30-year, 31 to 40-year, 41 to 50-year and 51 to 60-year groups at 6 months, respectively, and the clearance rates were 87.5%, 80.6%, 84.5% and 52.9% at 12 months, respectively. For HSIL, the postoperative HPV clearance rates were similar between the 2 groups (conization vs hysterectomy), conization is enough to resect the lesion and eliminate HPV. In addition, we should pay attention to the postoperative HR-HPV status in the older population of the 2 groups.

Fertility-sparing treatment with conization versus radical hysterectomy in patients with early-stage cervical cancer: inverse propensity score weighted analysis.

OBJECTIVE: To report 20 years of experience with fertility-sparing surgery for patients with early-stage cervical cancer, comparing the oncological outcomes with outcomes for those who underwent a radical hysterectomy. METHODS: Patients with pre-operative stage IA1 with lymphovascular space invasion, IA2 and IB1 cervical cancer (any grade) were included (2018 International Federation of Gynecology and Obstetrics staging system). Inclusion criteria comprised age (18-44 years), histology (squamous, adenocarcinoma, or adenosquamous) and absence of previous/concomitant cancer. A thorough counseling about oncological and obstetrical potential risks was mandatory for patients asking for fertility sparing. Results for consecutive patients who underwent fertility-sparing surgery (cervical conization and nodal evaluation) were analyzed and compared with results for patients treated with radical surgery. Oncological outcomes were assessed with a propensity score adjustment with inverse probability of treatment weighting. RESULTS: Overall, 109 patients were included in the study. Ten patients abandoned the fertility-sparing route because of nodal involvement (n=5), margin positive (n=2), or because patients requested radical treatment (n=3). Sentinel node mapping was performed in 19 of 49 (38.8%) patients in the fertility-sparing surgery group. Among the patients in the fertility-sparing group, 6 (12.2%) patients relapsed. 34 (69.4%) patients attempted to conceive. Pre-operative covariates selected to define the probability of having either fertility-sparing or radical surgery were well balanced using inverse probability of treatment weighting. Pathological features were similar between the groups, including grading, histotype, stage, and lymphovascular space invasion. After a median follow-up of 38.8 (range 5-186) months there were no differences in progression-free survival (p=0.32) and overall survival (p=0.74) between the fertility-sparing and radical hysterectomy groups. The results after inverse probability of treatment weighting adjustment did not show significant differences in progression-free survival (p=0.72) and overall survival (p=0.71) between the groups. CONCLUSION: Fertility-sparing surgery based on conization plus laparoscopic lymph node evaluation, may be considered safe and effective for patients with early-stage cervical cancer.

Immunohistochemistry staining of Eag1 and p16/Ki-67 can help improve the management of patients with cervical intraepithelial Neoplasia after cold knife conversion.

BACKGROUND: Immunohistochemistry (IHC) is widely used in the management of patients with cervical intraepithelial neoplasia (CIN) but still has many limitations in clinical practice. We analyzed the correlation of new biomarkers with the severity of CIN and follow-up outcomes in patients after conization to improve the management of patients with CIN. METHODS: IHC staining of Eag1 and p16/Ki-67 was performed on cervical tissue sections from 234 patients with suspected CIN2/3. After a series of follow-ups, including human papillomavirus (HPV) test and thinprep cytologic test (TCT) for 1-2 years, the outcomes were collected. IHC scores of biomarkers and follow-up results were used to analyze the correlation and assess the diagnostic efficiency of biomarkers. RESULTS: The IHC staining intensity of Eag1 and p16/Ki-67 was significantly different from that of the CIN1-3 groups (p < 0.05). Eag1 expression scores were significantly different in the distribution between the two follow-up groups (p < 0.001). ROC curves based on the correlations between the follow-up outcomes and the Eag1 scores and IS of p16/ki-67 showed that Eag1 had a greater AUC (0.767 vs. 0.666). Logistic regression analysis of the combination of biomarkers revealed a greater AUC value than any single biomarker. CONCLUSIONS: Eag1 expression was significantly correlated with CIN grade and follow-up outcomes after conization. IHC staining of combinations of biomarkers of Eag1, p16 and Ki-67 may help us to improve the ability to identify risk groups with abnormal follow-up outcomes after treatment for CIN.

Cold Knife Versus Carbon Dioxide for the Treatment of Preinvasive Cervical Lesion.

Background and Objectives: Cervical cancer (CC) represents a significant health concern worldwide, particularly for younger women. Cold knife (CK) conization and carbon dioxide (CO2) laser conization are two techniques commonly used to remove pre-invasive lesions, offering a potential curative intent in cases of incidental diagnosis of CC. This study aimed to assess the clinical implications and pathological outcomes of CK vs. CO2 laser conization for pre-invasive lesions. Materials and Methods: We retrospectively analyzed women who underwent CO2 or CK conization for high-grade preinvasive lesions (CIN2/3, CIS and AIS) between 2010 and 2022. Patient demographics, surgical details and pathological outcomes were collected. Pregnancy outcomes, including composite adverse obstetric rates, and oncological follow-up data, were also obtained. Results: In all, 1270 women were included; of them, 1225 (96.5%) underwent CO2, and 45 (3.5%) underwent CK conization. Overall, the rate of positive endocervical or deep margins was lower with CO2 laser compared to CK (4.3% vs. 13.3%, p = 0.015). Incidental CC was diagnosed in 56 (4.4%) patients, with 35 (62.5%) squamous and 21 (46.6%) adenocarcinomas. In a multivariate regression model, the relative risk for positive endocervical or deep margins is significantly greater in cases of incidental diagnosis of CC (p < 0.01). In cases of incidental diagnosis of CC, we found that the probabilities of having either positive endocervical or deep margins after CO2 laser or CK conization are similar, with a higher risk in case of adenocarcinoma lesion. Among women with CC, 42 (75%) opted for radical treatment, while 14 (25%) underwent a follow-up. Only one woman (7.1%) in the follow-up group, who had undergone CK conization, experienced a composite adverse obstetric outcome. No recurrences were observed after a median follow-up of 53 months. Conclusions: CO2 laser conization achieved a lower positive margin rate overall. CK and CO2 conization appear to be equivalent oncological options for incidental CC.

Expanding management strategies for cervical precancerous lesions in resource-limited settings: insights from a training center in a district hospital in Ghana.

BACKGROUND: Cervical cancer continues to disproportionately burden women in low/middle-income countries like Ghana. We examined treatment patterns and histopathological outcomes among women screened using visual inspection with acetic acid (VIA) and/or mobile colposcopy who subsequently underwent thermal ablation, large loop excision of the transformation zone (LLETZ), or cold knife conization at the Cervical Cancer Prevention and Training Centre, Battor. We also assessed the prevalence of cervical intraepithelial neoplasia 2+ (CIN2+) or micro-invasive disease and their associated factors for women who underwent excisional treatments. The treatment choices for cervical precancerous lesions suitable for resource-limited settings have also been described from the perspective of a center that manages a heterogenous population. METHODS: We conducted an analysis of secondary data collected between June 2016 and June 2023 among women with positive findings on VIA or mobile colposcopy who subsequently underwent thermal ablation or large loop excision of the transformation zone (LLETZ). The prevalence of histopathology outcomes, including no dysplasia, CIN1 - 3, and micro-invasive disease, were estimated with 95% confidence intervals (CIs). Factors associated with histopathological findings were modeled using multinomial logistic regression. RESULTS: For the study period, 14 (10.6%) of the total 132 participants underwent cervical lesion treatment at outreach locations, all via thermal ablation. The remaining 118 (89.4%) were treated at the Catholic Hospital, Battor using LLETZ (n = 66, 55.9%), thermal ablation (n = 51, 43.2%), and cold knife conization (n = 1, 0.9%). Among 65 women with histopathology reports, the most frequent histopathological finding was no dysplasia (47.7%; 95% CI, 35.1 - 60.5), followed by CIN2 and CIN3 (20.0%; 95% CI, 11.1 - 31.8 each), CIN1 (7.7%; 95% CI, 2.5 - 17.0) and micro-invasion (4.6%; 95% CI, 1.0 - 12.9). Those with micro-invasive disease were significantly older than those with CIN1, CIN2, and CIN3 (p = 0.036, 0.022, 0.009, respectively), but not significantly older than those who showed no dysplasia (p = 0.088). For each unit increase in age, the likelihood of CIN3 was relatively significantly reduced compared to no dysplasia (crude relative risk ratio [RRR] = 0.93; 95% CI, 0.86 - 0.99). This association was neither observed with the remaining histopathological groups nor for parity and persisted after controlling for parity (adjusted RRR = 0.92; 95% CI, 0.85 - 0.99; p = 0.025). CONCLUSION: This paper largely demonstrates treatment options available to women and practitioners in LMICs. The high combined prevalence of high-grade precancerous lesions and micro-invasive disease underscores the need to increase cervical cancer awareness that would enhance screening attendance and hasten efforts at moving from opportunistic to organized screening in Ghana. This will enhance early cervical lesion detection and treatment, while simultaneously re-evaluating and cutting down on unnecessary treatment.

[Analysis of adverse late-term pregnancy outcomes after cervical cold knife conization].

Objective: To investigate the effects of cervical cold knife conization (CKC) on preterm delivery, other pregnancy complications and neonatal outcomes, and explore the relationship between preterm delivery risk and the depth and volume of conization. Methods: The clinical data and pregnancy outcomes of 272 women who underwent CKC in Peking Union Medical College Hospital from January 2002 to March 2018 (conization group) and 1 647 pregnant women who gave birth in Peking Union Medical College Hospital during January to December 2019 (control group) were collected. The preterm delivery, premature rupture of membranes, other pregnancy complications and neonatal outcomes of the two groups were compared, and the relationship between the depth and volume of conization and the risk of preterm delivery in postoperative singleton pregnancy was analyzed. Results: (1) There were no significant differences between the two groups in delivery age, parity, proportion of singleton pregnancy, proportion of assisted reproductive technology (all P>0.05). (2) The rate of preterm delivery in the conization group was significantly higher than that in the control group [14.8% (39/264) vs 5.7% (91/1 589); χ2=28.397, P<0.001]. There were still significant differences in preterm delivery rates between the two groups at <34 weeks and 34-37 weeks (all P<0.01). There was no significant difference in the incidence of premature rupture of membrane between the two groups [23.5% (62/264) vs 23.4% (372/1 589); χ2=0.001, P=0.979], but the incidence of preterm premature rupture of membrane in the conization group was significantly higher than that in the control group [11.4% (30/264) vs 2.2% (35/1 589); χ2=56.132, P<0.001]. (3) The rate of cesarean section in the conization group was higher than that in the control group [59.6% (162/272) vs 38.8% (639/1 647); χ2=41.377, P<0.001]. The birth weight of preterm infants in the conization group was significantly higher than that in the control group [(2 409±680) vs (2 150±684) g; t=2.184, P=0.030]. However, there were no statistically significant differences in the incidence of gestational diabetes mellitus, hypertensive disorders in pregnancy, the birth weight of full-term infants, incidence of small for gestational age infant and neonatal intensive care unit admission rate between the two groups (all P>0.05). (4) The preterm delivery rates of coning depth >15 mm, cone size ≥2 cm3 and cone size <2 cm3 were higher than that in the control group (all P<0.05). When the coning depth ≤15 mm, the preterm delivery rate in the conization group was higher than that in the control group, but there was no significant difference (P=0.620). The rate of preterm delivery of pregnant women with coning depth >15 mm was significantly higher than those with coning depth ≤15 mm (RR=3.084, 95%CI: 1.474-6.453; P=0.001). There was no significant difference in the preterm delivery rate between pregnant women with cone size >2 cm3 and those with cone size ≥2 cm3 (RR=1.700, 95%CI: 0.935-3.092; P=0.077). Conclusion: The risk of preterm delivery and preterm premature rupture of membranes in subsequent pregnancies are increased after cervical CKC, and the risk of preterm delivery is positively correlated with the depth of cervical coning.

Sentinel node mapping, sentinel node mapping plus back-up lymphadenectomy, and lymphadenectomy in Early-sTage cERvical caNcer scheduled for fertilItY-sparing approach: The ETERNITY project.

OBJECTIVE: To investigate the safety of sentinel node mapping for patients with early-stage cervical cancer undergoing cervical conization plus nodal evaluation. METHODS: The ETERNITY project is a retrospective, multi-institutional study collecting data of patients with early-stage cervical cancer undergoing fertility-sparing treatment. Here, we compared outcomes related to three methods of nodal assessment: sentinel node mapping (SNM), SNM plus backup lymphadenectomy (SNM + LND); pelvic lymphadenectomy (LND). RESULTS: Charts of 123 patients (with stage IA1-IB1 cervical cancer) were evaluated. Median patients' age was 34 (range, 22-44) years. SNM, SNM + LND, and LND were performed in 32 (26 %), 31 (25.2 %), and 60 (48.8 %) patients, respectively. Overall, eight (6.5 %) patients were diagnosed with positive nodes. Two (3.3 %), three (9.7 %), and three (9.4 %) patients were detected in patients who had LND, SNM + LND, and SNM respectively. Considering the 63 patients undergoing SNM (31 SNM + LND and 32 SNM alone), macrometastases, micrometastases, and isolated tumor cells were detected in four (3.2 %), three (2.4 %), and one (0.8 %) patients, respectively. All patients with positive nodes discontinued the fertility sparing treatment. Other two patients (one (1.7 %) in the LND group and one (3.1 %) in the SNM group) required hysterectomy even after negative nodal evaluation. After a median follow-up of 53.6 (range, 1.3, 158.0) months, nine (7.3 %) and two (1.6 %) patients developed cervical and pelvic nodes recurrences, respectively. Disease-free (p = 0.332, log-rank test) and overall survival (p = 0.769, log-rank test) were similar among groups. CONCLUSIONS: In this retrospective experience, SNM upholds long-term oncologic effectiveness of LND, reducing morbidity.

Analysis of the clinical characteristics and surgical methods of high-grade squamous intraepithelial lesions of the cervix in postmenopausal women: A retrospective case study.

The purpose of this study was to thoroughly evaluate the clinical features and surgical options for high-grade squamous intraepithelial lesions (HSIL) in postmenopausal women. A total of 308 patients diagnosed with HSIL through colposcopic cervical biopsy and endocervical curettage were included. Their clinical characteristics, surgical treatments, and postoperative pathology were analyzed. Key findings include: 1. Patients with positive preoperative thinprep cytologic test (TCT) results and postoperative pathology indicating HSIL or squamous cell carcinoma (≥HSIL) were significantly more frequent than those with negative preoperative TCT results (P < .05). 2. Univariate analysis indicated significant impacts of TCT, human papillomavirus (HPV) type, transformation zone (TZ) location, and surgical technique on postoperative pathology (P < .05). 3. Logistic regression analysis confirmed significant influences of TCT, HPV type, TZ location, and surgical method on postoperative pathology outcomes (P < .05), showing that each unit increase in TZ raised the probability of ≥HSIL in postoperative pathology by 49.7%. In surgical comparisons, cold knife conization (CKC) and extrafascial hysterectomy resulted in 8.379 and 4.427 times higher probabilities of ≥HSIL in postoperative pathology, respectively, compared to loop electrosurgical excision procedure (LEEP). 4. Surgical methods significantly influenced margin results (P < .05). After LEEP, 17.5% of cases had positive margins, compared to 9.4% after CKC, and 3.7% after extrafascial hysterectomy, indicating the highest rate of positive surgical margins occurred with LEEP. 1. Combined TCT and HPV screening is crucial for cervical cancer prevention, early detection, and management in postmenopausal women. Women with positive results for both TCT and HPV should undergo colposcopic cervical biopsy and endocervical curettage. 2. For patients with TZ3, CKC is the recommended surgical option. 3. CKC is the preferred treatment for postmenopausal women with HSIL, as it effectively diagnoses and treats the lesion, showing superior outcomes in managing postmenopausal HSIL.

Development of a machine learning-based model for predicting positive margins in high-grade squamous intraepithelial lesion (HSIL) treatment by Cold Knife Conization(CKC): a single-center retrospective study.

OBJECTIVES: This study aims to analyze factors associated with positive surgical margins following cold knife conization (CKC) in patients with cervical high-grade squamous intraepithelial lesion (HSIL) and to develop a machine-learning-based risk prediction model. METHOD: We conducted a retrospective analysis of 3,343 patients who underwent CKC for HSIL at our institution. Logistic regression was employed to examine the relationship between demographic and pathological characteristics and the occurrence of positive surgical margins. Various machine learning methods were then applied to construct and evaluate the performance of the risk prediction model. RESULTS: The overall rate of positive surgical margins was 12.9%. Independent risk factors identified included glandular involvement (OR = 1.716, 95% CI: 1.345-2.189), transformation zone III (OR = 2.838, 95% CI: 2.258-3.568), HPV16/18 infection (OR = 2.863, 95% CI: 2.247-3.648), multiple HR-HPV infections (OR = 1.930, 95% CI: 1.537-2.425), TCT ≥ ASC-H (OR = 3.251, 95% CI: 2.584-4.091), and lesions covering ≥ 3 quadrants (OR = 3.264, 95% CI: 2.593-4.110). Logistic regression demonstrated the best prediction performance, with an accuracy of 74.7%, sensitivity of 76.7%, specificity of 74.4%, and AUC of 0.826. CONCLUSION: Independent risk factors for positive margins after CKC include HPV16/18 infection, multiple HR-HPV infections, glandular involvement, extensive lesion coverage, high TCT grades, and involvement of transformation zone III. The logistic regression model provides a robust and clinically valuable tool for predicting the risk of positive margins, guiding clinical decisions and patient management post-CKC.

Follow-up of women with cervical adenocarcinoma in situ treated by conization: A single centre clinical experience.

OBJECTIVE: Hysterectomy has been the historical gold standard final step in the treatment algorithm of adenocarcinoma in situ (AIS) recommended by most North American colposcopy guidelines. AIS disproportionately affects young childbearing age women, therefore a fertility sparing treatment option is desirable. Our study examines the impact of conservative treatment of AIS with conization followed by serial surveillance. METHODS: A retrospective chart review was completed of patients treated for AIS from 2006 to 2020. Charts were identified by pathologic diagnosis of AIS on cervical and uterine specimens. Charts were excluded if AIS was not treated with conization, if AIS was not confirmed on initial conization specimen, or if invasive disease was found at initial conization. RESULTS: 121 patient charts were analyzed. Median age of patients at first conization and hysterectomy was 34.8 and 40.9, respectively. First conization was by Cold Knife Cone in 58% of patients, and by Loop Electrosurgical Excisional Procedure in 42% of patients. Median follow-up period in our study was 609 days. 5% of patients had recurrence, with only one patient who recurred as cancer. One case of recurrence had a positive initial conization margin. Median time to recurrence was 700 days. 47% of patients underwent eventual hysterectomy. Residual AIS was found in 23% of hysterectomy specimens. Adenocarcinoma was diagnosed on hysterectomy specimen in four patients. CONCLUSION: Our study demonstrates the oncologic safety of treating AIS with conization and serial surveillance. Routine hysterectomy completed as a part of the AIS treatment algorithm, as in current clinical guidelines, is unnecessary.

Reduced risk of CIN2+ recurrence in women immunized with a 9-valent HPV vaccine post-excision: Retrospective cohort study.

The main aim of our study was to investigate the specific contribution of a 9-valent human papillomavirus vaccine (9vHPV) to the recurrence risk of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) in women vaccinated post-excision. Therefore, we conducted a retrospective monocentric cohort study in women aged 22-49 years undergoing conization between 2014 and 2023. The 9vHPV-vaccinated women were matched to unvaccinated women for age and follow-up duration in a 1:2 ratio to eliminate allocation bias. The risk of CIN2+ recurrence was estimated by the incidence rate ratio using Poisson regression with adjustment for comorbidities, smoking status, nulliparity, CIN grade, positive cone margin, and HPV genotypes. The CIN2+ recurrence rates in 147 women enrolled in the analysis were 18 and 2 cases per 100,000 person-days for unvaccinated and vaccinated women, respectively, during a mean follow-up period of 30 months (±22 months). A reduction in CIN2+ recurrences by 90% (95% confidence interval: 12-99%) was documented in 9vHPV-vaccinated participants compared to women undergoing only surgical excision. Moreover, vaccinated women with a positive cone margin showed a 42% (though non-significant) reduction in relapse (p = .661). Full post-conization vaccination with the 9vHPV contributed to an additional reduction in the risk of CIN2+ recurrence. This finding is consistent with current knowledge and suggests a high adjuvant effect of the 9vHPV vaccine.

Comparative study of treatment efficacy in severe intraepithelial squamous cell lesions and preinvasive cervical cancer by conization and chlorin e6-mediated fluorescence-assisted systemic photodynamic therapy.

BACKGROUND: Cervical cancer (CC) occupies a leading position in incidence among young women of reproductive age. In this connection, it is urgent to search for the most effective approaches to the diagnosis and treatment of this pathology. The purpose of the study was to evaluate the effectiveness of the PDT method using Cе6 with the control of the photobleaching using video and spectral fluorescence diagnostic methods, to develop the method of fluorescence-assisted systemic photodynamic therapy mediated with chlorin e6 for treatment CIN 3 and CIS. MATERIALS AND METHODS: A randomized comparative clinical study was conducted involving 94 women aged 18 to 49 years with histologically verified severe intraepithelial squamous cell lesions of the cervix or preinvasive cervical cancer. The patients were included in 2 groups: in the first group conization of the cervix was performed with curettage of the remaining part of the cervical canal; patients in the second group underwent the chlorin e6-mediated fluorescence-assisted systemic photodynamic therapy. RESULTS: The absolute majority of patients in the main group after the first course of chlorin e6-mediated fluorescence-assisted systemic photodynamic therapy showed normalization of cytological parameters and colposcopic picture, while women from the comparison group showed signs of cervical lesions statistically significantly more often. These changes corresponded to the dynamics of the proliferation markers expression in the cells of intraepithelial squamous cell lesions. Also, patients of the second group who were planning a pregnancy had better reproductive outcomes after treatment compared to those of the first group. CONCLUSION: In general, higher clinical efficacy and safety of the use of the chlorin e6-mediated fluorescence-assisted systemic photodynamic therapy in the treatment of intraepithelial squamous cell lesions and preinvasive cervical cancer have been established compared to the use of standard treatment methods.

The role of multiple high-risk human papillomavirus infection on the persistence recurrence of high-grade cervical lesions after standard treatment: A systematic review and a meta-analysis.

INTRODUCTION: The role of multiple high-risk human papillomavirus (HR-HPV) infections on the occurrence of persistence/recurrence of high-grade squamous intraepithelial lesion (HSIL) after conization/surgery for cervical intraepithelial neoplasia was evaluated. MATERIAL AND METHODS: A systematic search of Pubmed/Medine, Scopus, Cochrane databases from inception to June 30, 2023 was performed. Three reviewers independently screened the abstracts of the selected studies and extracted data from full-text articles. The data were subsequently tabulated and compared for consistency. The bias associated with each included study was evaluated according to the OSQE method. PROSPERO registration number CRD42023433022. RESULTS: Out of 1606 records screened, 22 full text articles met the inclusion criteria. A total of 8321 subjects treated (loop electrosurgical excision, laser or surgery) because of HSIL were followed-up and included in the meta-analysis. The pooled prevalence of overall persistence and/or recurrence was 17.6 (95% CI: 12.3-23.5) in multiple and 14.3 (95% CI: 10.1-19.2) in single HR-HPV infections detected shortly before or at surgery. The pooled rate of multiple HR-HPV infections was 25% (95% CI: 20.4-30). The odds ratio of histologically confirmed HSIL persistence and/or recurrence was significantly higher (OR: 1.38, 95% CI:1.08-1.75, p = 0.01, heterogeneity = 39%) among multiple than single HR-HPV infections. Increased risk of HSIL persistence/recurrence was more marked among studies with multiple HR-HPVs prevalence ≥25% (12 studies, N = 3476) (OR: 1.47, 95% CI: 1.18-1.84, heterogeneity = 0%) and in those evaluating true histologically confirmed recurrence after at least 6 months of negative follow-up (9 studies, N = 5073) (OR: 1.67, 95% CI: 1.17-2.37, heterogeneity = 37%). Multiple HR-HPVs infection detected during follow-up visits had no effect on the risk of recurrence although the number of included studies was small (4 studies, N = 1248) (OR: 0.98, 95% CI: 0.68-1.39, heterogeneity = 0%). The risk of bias was rated as high in 10 and low-moderate in 12 studies, respectively. In subgroup analysis, the risk of bias of the included studies (low/moderate vs. high), had a small, although not significant effect on the odds ratios of persistence/recurrence of HSIL (OR: 1.57, 95% CI: 1.23-2 for low-moderate risk of bias and OR: 1.06, 95% CI: 0.65-1.75 for high risk of bias; p-value for subgroup differences = 0.17). CONCLUSIONS: Multiple HR-HPVs infections at the time of standard treatment of HSIL entail a small but significant increased risk of persistence/recurrence of HSIL and should be taken into account in the follow-up plan.

Fertility-sparing surgery vs standard surgery for early-stage cervical cancer: difference in 5-year life expectancy by tumor size.

BACKGROUND: Cervical cancer incidence among premenopausal women is rising, and fertility-sparing surgery serves as an important option for this young population. There is a lack of evidence on what tumor size cutoff should be used to define candidacy for fertility-sparing surgery. OBJECTIVE: We sought to describe how the association between fertility-sparing surgery (compared with standard surgery) and life expectancy varies by tumor size among patients with cervical cancers measuring ≤4 cm in largest diameter. Our secondary objective was to quantify the probability of undergoing adjuvant radiotherapy among patients who underwent fertility-sparing surgery as a function of tumor size. STUDY DESIGN: We identified patients in the National Cancer Database aged ≤45 years, diagnosed with stage I cervical cancer with tumors ≤4 cm between 2006 and 2018, who received no preoperative radiation or chemotherapy, and who underwent either fertility-sparing surgery (cone or trachelectomy, either simple or radical) or standard surgery (simple or radical hysterectomy) as their primary treatment. Propensity-score matching was performed to compare patients who underwent fertility-sparing surgery with those who underwent standard surgery. A flexible parametric model was employed to quantify the difference in life expectancy within 5 years of diagnosis (restricted mean survival time) based on tumor size among patients who underwent fertility-sparing and those who underwent standard surgery. In addition, among those who underwent fertility-sparing surgery, a logistic regression model was used to explore the relationship between tumor size and the probability of receiving adjuvant radiation. RESULTS: A total of 11,946 patients met the inclusion criteria of whom 904 (7.6%) underwent fertility-sparing surgery. After propensity-score matching, 897 patients who underwent fertility-sparing surgery were matched 1:1 with those who underwent standard surgery. Although the 5-year life expectancy was similar among patients who had fertility sparing surgery and those who had standard surgery regardless of tumor sizes, the estimates of life-expectancy differences associated with fertility-sparing surgery were more precise among patients with smaller tumors (1-cm tumor: restricted mean survival time difference, -0.10 months; 95% confidence interval, -0.67 to 0.47) than among those with larger tumors (4-cm tumor: restricted mean survival time difference, -0.11 months; 95% confidence interval, -3.79 to 3.57). The probability of receiving adjuvant radiation increased with tumor size, ranging from 5.6% (95% confidence interval, 3.9-7.9) for a 1-cm tumor to 37% (95% confidence interval, 24.3-51.8) for a 4-cm tumor. CONCLUSION: Within 5 years of diagnosis, young patients with stage I cancers measuring ≤4 cm had similar survival outcomes after either fertility-sparing surgery or standard surgery. However, because few patients with tumors >2 cm underwent fertility-sparing surgery, a clinically important survival difference could not be excluded in this population.

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.