Treatment methods for cervical intraepithelial neoplasia in England: A cost-effectiveness analysis.

OBJECTIVE: To compare the cost-effectiveness of different treatments for cervical intraepithelial neoplasia (CIN). DESIGN: A cost-effectiveness analysis based on data available in the literature and expert opinion. SETTING: England. POPULATION: Women treated for CIN. METHODS: We developed a decision-analytic model to simulate the clinical course of 1000 women who received local treatment for CIN and were followed up for 10 years after treatment. In the model we considered surgical complications as well as oncological and reproductive outcomes over the 10-year period. The costs calculated were those incurred by the National Health Service (NHS) of England. MAIN OUTCOME MEASURES: Cost per one CIN2+ recurrence averted (oncological outcome); cost per one preterm birth averted (reproductive outcome); overall cost per one adverse oncological or reproductive outcome averted. RESULTS: For young women of reproductive age, large loop excision of the transformation zone (LLETZ) was the most cost-effective treatment overall at all willingness-to-pay thresholds. For postmenopausal women, LLETZ remained the most cost-effective treatment up to a threshold of £31,500, but laser conisation became the most cost-effective treatment above that threshold. CONCLUSIONS: LLETZ is the most cost-effective treatment for both younger and older women. However, for older women, more radical excision with laser conisation could also be considered if the NHS is willing to spend more than £31,500 to avert one CIN2+ recurrence.

Uterine cervical conisation and chorioamnionitis: A nationwide observational study.

OBJECTIVE: To investigate whether conisation increases chorioamnionitis (CAM) and assess whether this risk differs between preterm and term periods. Furthermore, we estimated mediation effects of CAM between conisation and preterm birth (PTB). DESIGN: A nationwide observational study. SETTING: Japan. POPULATION: Singleton pregnant women derived from the perinatal registry database of the Japan Society of Obstetrics and Gynaecology between 2013 and 2019. METHODS: The association between a history of conisation and clinical CAM was examined using a multivariable logistic regression model with multiple imputation. We conducted mediation analysis to estimate effects of CAM on PTB following conisation. MAIN OUTCOME MEASURES: Clinical CAM. RESULTS: Of 1 500 206 singleton pregnant women, 6961 (0.46%) underwent conisation and 1 493 245 (99.5%) did not. Clinical CAM occurred in 150 (2.2%) and 11 484 (0.8%) women with and without conisation, respectively. Conisation was associated with clinical CAM (odds ratio [OR] 3.09; 95% confidence interval (CI) 2.63-3.64; p < 0.001) (risk difference 1.57%; 95% CI 1.20-1.94). The association was detected among 171 440 women with PTB (OR 3.09; 95% CI 2.57-3.71), whereas it was not significant among 1 328 284 with term birth (OR 0.88; 95% CI 0.58-1.34). OR of total effect of conisation on PTB was 2.71, OR of natural indirect effect (effect explained by clinical CAM) was 1.04, and OR of natural direct effect (effect unexplained by clinical CAM) was 2.61. The proportion mediated was 5.9%. CONCLUSIONS: Conisation increased CAM occurrence. Obstetricians should be careful regarding CAM in women with conisation, especially in preterm period. Bacterial infections may be an important cause of PTB after conisation.

Pregnancy outcome and risk of recurrence after tissue-preserving loop electrosurgical excision procedure (LEEP).

BACKGROUND/PURPOSE: This study aims to investigate whether women with cervical dysplasia after LEEP have an increased risk of pregnancy/childbirth complications or recurrence of dysplasia in an upcoming pregnancy. METHODS: Data from 240 women after LEEP were analysed retrospectively. The reference group consisted of 956 singleton births. Fisher's and Wilcoxon rank tests were used to detect differences between groups. Using logistic regressions, we analysed the effect of surgery-specific aspects of LEEP on pregnancy/childbirth complications and the frequency of CIN recurrences. RESULTS: We found that tissue-preserving LEEP did not lead to premature birth or miscarriage and did not increase the likelihood of CIN recurrence. We did not observe differences regarding preterm birth [< 37 (p < 0.28) < 34 (p < 0.31), < 32 weeks of gestation (p < 0.11)] or birth weight (< 2500 g (p < 0.54), < 2000 g (p < 0.77) between groups. However, women after LEEP exhibit a higher risk of premature rupture of membranes (PROM) at term (p < 0.009) and vaginal infections (p < 0.06). Neither volume nor depth of the removed tissue nor an additional endocervical resection seems to influence the likelihood of premature birth or early miscarriage. Performing an endocervical resection protects against CIN recurrence (OR 0.0881, p < 0.003). CONCLUSIONS: After tissue-preserving LEEP, there is an increased risk of vaginal infections and PROM at term in consecutive pregnancy. LEEP does not affect prematurity or miscarriage. The removal of additional endocervical tissue appears to be a protective factor against recurrence of CIN.

Oncologic results of fertility sparing surgery of cervical cancer: An updated systematic review.

BACKGROUND: Several techniques can be proposed as fertility sparing surgery in young patients treated for cervical cancer but uncertaincies remain concerning their outcomes. Analysis of oncological issues is then the first aim of this review in order to evaluate the best strategy. RESULTS: Data were identified from searches of MEDLINE, Current Contents, PubMed and from references in relevant articles from January 1987 to 15th of September 2021. We carry out an updated systematic review involving 5862 patients initially selected for fertility-sparing surgery in 275 series. FINDINGS: In patients having a stage IB1 disease, recurrence rate/RR in patients undergoing simple conisation/trachelectomy, radical trachelectomy/RT by laparoscopico-vaginal approach, laparotomic or laparoscopic approaches are respectively: 4.1%, 4.7%, 2.4% and 5.2%. In patients having a stage IB2 disease, RR after neoadjuvant chemotherapy or RT by laparotomy are respectively 13.2% and 4.8% (p = .0035). After neoadjuvant treatment a simple cone/trachelectomy was carried out in 91 (30%) patients and a radical one in 210 (70%) cases. But the lowest pregnancy rate is observed in patients undergoing RT by laparotomy (36%). CONCLUSIONS: The choice between these treatments should be based above all, on objective oncological data that strike a balance for each procedure between the best chances for cure and the fertility results. In patients having a stage IB1 disease, oncological results are quite similar according to the procedure used. In patients having a stage IB2 disease, RT by open approach has the lowest RR. Anyway the lowest pregnancy rate is observed in patients undergoing RT by laparotomy.

Video colposcopy versus headlight for large loop excision of the transformation zone (LLETZ): a randomised trial.

PURPOSE: To compare resected cone mass and resection margin status when performing Large Loop Excision of the Transformation Zone (LLETZ) using video colposcopy (LLETZ-VC) versus a headlight (LLETZ-HL) in women with cervical dysplasia. METHODS: Prospective, randomised trial (monocentric) at a specialised cervical dysplasia unit in a University Hospital. Women with a biopsy-proven CIN2 + or persisting CIN1 or diagnostic LLETZ were recruited and randomised. LLETZ was performed either under video colposcopic vision or using a standard surgical headlight. The primary endpoint was resected cone mass. Secondary endpoints were the rate of involved margins, fragmentation of the specimen, procedure time, time to complete haemostasis (TCH), blood loss, pain, intra- and postoperative complications, and surgeon preference. RESULTS: LLETZ-VC and LLETZ-HL (109 women each) had comparable cone masses (1.57 [0.98-2.37] vs. 1.67 [1.15-2.46] grams; P = 0.454). TCH was significantly shorter in the LLETZ-VC arm (60 [41-95.2] vs. 90 [47.2-130.2] seconds; P = 0.008). There was no statistically significant difference in involved resection margins (6/87 [6.5%] vs. 16/101 [13.7%], P = 0.068) and postoperative complications (13/82 [13.7%] vs. 22/72 [23.4%], P = 0.085). Patient-reported outcomes favoured LLETZ-VC with a lower use of analgesics (6/80 [7.0%] vs. 17/87 [16.3%]; P = 0.049). However, LLETZ-VC was more difficult to perform with significantly lower ratings for handling (7 [5-9] vs. 9 [8-10]; P < 0.001) and general satisfaction (7.5 [5-9] vs. 10 [8-10]; P < 0.001). CONCLUSION: Intraoperative video colposcopy for LLETZ has minimal benefits at the cost of surgeons' satisfaction. CLINICAL TRIAL REGISTRATION: NCT04326049 (ClinicalTrials.gov).

Incidence and mortality from cervical cancer and other malignancies after treatment of cervical intraepithelial neoplasia: a systematic review and meta-analysis of the literature.

BACKGROUND: Although local treatments for cervical intraepithelial neoplasia (CIN) are highly effective, it has been reported that treated women remain at increased risk of cervical and other cancers. Our aim is to explore the risk of developing or dying from cervical cancer and other human papillomavirus (HPV)- and non-HPV-related malignancies after CIN treatment and infer its magnitude compared with the general population. MATERIALS AND METHODS: Design: Systematic review and meta-analysis. Eligibility criteria: Studies with registry-based follow-up reporting cancer incidence or mortality after CIN treatment. DATA SYNTHESIS: Summary effects were estimated using random-effects models. OUTCOMES: Incidence rate of cervical cancer among women treated for CIN (per 100 000 woman-years). Relative risk (RR) of cervical cancer, other HPV-related anogenital tract cancer (vagina, vulva, anus), any cancer, and mortality, for women treated for CIN versus the general population. RESULTS: Twenty-seven studies were eligible. The incidence rate for cervical cancer after CIN treatment was 39 per 100 000 woman-years (95% confidence interval 22-69). The RR of cervical cancer was elevated compared with the general population (3.30, 2.57-4.24; P < 0.001). The RR was higher for women more than 50 years old and remained elevated for at least 20 years after treatment. The RR of vaginal (10.84, 5.58-21.10; P < 0.001), vulvar (3.34, 2.39-4.67; P < 0.001), and anal cancer (5.11, 2.73-9.55; P < 0.001) was also higher. Mortality from cervical/vaginal cancer was elevated, but our estimate was more uncertain (RR 5.04, 0.69-36.94; P = 0.073). CONCLUSIONS: Women treated for CIN have a considerably higher risk to be later diagnosed with cervical and other HPV-related cancers compared with the general population. The higher risk of cervical cancer lasts for at least 20 years after treatment and is higher for women more than 50 years of age. Prolonged follow-up beyond the last screening round may be warranted for previously treated women.

Can we predict surgical margin positivity while performing cervical excisional procedures?

We designed this study to evaluate any factors associated with positive surgical margin in conisation specimens and to determine the optimal cone size. The medical records of patients who had undergone a loop electrosurgical excision procedure (LEEP), cold-knife conisation (CKC) and needle excision of the transformation zone (NETZ) procedure were reviewed retrospectively. Two hundred and sixty eight women fulfilled the inclusion criteria. Univariate analyses showed that 'postmenopause', 'HSIL on smear', 'previous colposcopic examination revealing HSIL in endocervical curettage (ECC) material and in two or more ectocervical quadrants' and 'managing with LEEP' were significant predictors of surgical margin positivity. Nulliparous patients showed significantly lower rate of surgical margin positivity. 'Postmenopause', 'previous colposcopic examination revealing HSIL in ECC material and in two or more ectocervical quadrants' and 'HSIL on smear' were identified as independent predictors of surgical margin positivity according to multivariate analyses.IMPACT STATEMENTWhat is already known on this subject? Previous studies demonstrated 'menopause', 'Age ≥50', 'managing with LEEP', 'disease involving >2/3 of cervix at visual inspection', 'training level of the surgeon', 'cytology squamous cell carcinoma' and 'mean cone height' as factors associated with positive surgical margin in conisation specimens.What do the results of this study add? In our study, univariate analyses showed that 'postmenopause', 'HSIL on smear', 'previous colposcopic examination revealing HSIL in endocervical curettage material and in two or more ectocervical quadrants' and 'managing with LEEP' were associated with surgical margin positivity. On the other hand, nulliparous women showed significantly lower rate of surgical margin positivity compared with parous women. Multivariate analyses showed that 'postmenopause', 'previous colposcopic examination revealing HSIL in endocervical curettage material and in two or more ectocervical quadrants' and 'HSIL on smear' were independent predictors of surgical margin positivity in conisation specimens.What are the implications of these findings for clinical practice and/or further research? We can predict high-risk patients with regard to surgical margin positivity. Prediction of high-risk patients and management with a tailored approach may help minimise surgical margin positivity rates.

Effects of cervical conisation on pregnancy outcome: a meta-analysis.

To assess the effect of cervical conisation on pregnancy outcome, a literature search strategy was conducted to identify all of the references lists of the relevant studies. The fixed or random effect model was used to calculate pooled RRs on the basis of heterogeneity. Twenty-seven publications with n cases and m controls were included in the meta-analysis. The results showed that conisation was associated with a higher risk of a preterm delivery (p = .010), PROM (p = .008), and a lower birth weight (p < .001) in overall effect. The subgroup analysis showed that CKC was associated with a significantly increased risk of a preterm delivery (p < .001), and a lower birth weight (p< .001). LLETZ was associated with preterm delivery (p = .004) and a lower birth weight (p = .020). The results suggested that cervical conisation increases the risk of a preterm delivery, PROM, and a lower birth weight, especially in a CKC and LLEETZ procedure. Impact statement What is already known on this subject? Currently, the three main excisional procedures for cervical intraepithelial neoplasia (CIN) treatment are laser conisation, cold-knife conisation (CKC), and a large loop excision of the transformation zone (LLETZ). CKC and LEEP/LLETZ were significantly associated with a preterm delivery and low birth weight, and that former was associated with higher relative risks than the latter one. What do the results of this study add? The present results showed that conisation was associated with a higher risk of a preterm delivery, PROM, and a lower birth weight in overall effect. A subgroup analysis showed that CKC was associated with a significantly increased risk of a preterm delivery, and a lower birth weight. LLETZ was associated with a preterm delivery and lower birth weight. What are the implications of these findings for clinical practice and/or further research? This study is of clinical significance by showing that cervical conisation increases the risk of preterm delivery, PROM, and a lower birth weight, especially in a CKC and a LLEETZ procedure.

The use of colposcopic punch biopsy in the management of abnormal cervical cytology: a 5-year retrospective audit.

The aim of this study was to determine the accuracy of colposcopic punch biopsy to detect cervical epithelial neoplasia (CIN) II + in patients with abnormal cervical cytology and the major colposcopic findings in patients who underwent a loop electrosurgical excision procedure (LEEP), subsequently. A total of 231 patients with abnormal cervical cytology who underwent a colposcopy guided cervical biopsy and subsequent LEEP were analysed. The mean age was 33.4 ± 8.7 years. CIN II + rate on LEEP pathology was significantly higher in patients with high-grade cytology, compared to those with a low-grade cytology (92 vs. 55%, p < .0001). CIN II + was found in 80, 98 and 100% of colpocopic biopsies of patients with LSIL, HSIL and AGC, respectively. The overall concordance rate between a colposcopic biopsy and LEEP was 41% with a kappa coefficient. The overall underestimation of CIN II + was 10.5%. On a patient-based analysis, the sensitivity, specificity, PPV and NPV of colposcopic biopsy were 89.4, 47.1, 79.5 and 66%, respectively. More than two cervical biopsies had 100% sensitivity for CIN II + on LEEP pathology. The specificity and PPV decreased with increasing number of cervical biopsies. A see-and-treat strategy may be considered for high-grade cytologies. Patients with a low-grade cytology should be managed with more than two colposcopic biopsies.

Pathological discrepancy between colposcopic directed cervical biopsy and conisation results: A five years experience of a single center in Turkey.

OBJECTIVE: To analyze the clinical outcomes and treatment strategies of patients who underwent conisation in a tertiary hospital clinic. METHODS: The study was designed as a retrospective cohort study. Retrospective data's of 176 patients who underwent conisation due to detection of dysplasia via colposcopic biopsy or cytology-histology discrepancy between 2012 and 2017 were collected. Colposcopy guided biopsies were performed according to HPV positivity and/or abnormal smear results in Izmir Katip Celebi University Ataturk Research and Training Hospital. RESULTS: Indications for colposcopic biopsies were HPV positivity in 51 patients (29.1%), abnormal smear results in 125 patients (70.9 %). Distribution of abnormal smear results were ASCUS, ASC-H, LSIL, HSIL in 6 (4.8 %), 21 (16.8 %), 24 (19.2%), 74 (59.2%) patients respectively. According to biopsy results, 8 patients (4.4 %) showed no dysplasia where two (1.1%) and 162 (91.5 %) patients were with LSIL and HSIL respectively. Only two were diagnosed with in situ carcinoma. Among 162 patients with HSIL in colposcopic biopsy, 45 showed no dysplasia where four were diagnosed with invasive carcinoma. CONCLUSIONS: To detect high grade cervical lesions colposcopy guided biopsy is gold standard. Although cone biopsy should be performed related to severity of dysplasia in order to sustain the diagnosis and treatment. Contradictory results between colposcopic and cone biopsies should be considered during decision-making process.

Is the increased risk of preterm birth following excision for cervical intraepithelial neoplasia restricted to the first birth post treatment?

OBJECTIVE: To explore whether the increased risk of preterm birth following treatment for cervical disease is limited to the first birth following colposcopy. DESIGN: Nested case-control study. SETTING: Twelve NHS hospitals in England. POPULATION: All nonmultiple births from women selected as cases or controls from a cohort of women with both colposcopy and a hospital birth. Cases had a preterm (20-36 weeks of gestation) birth. Controls had a term birth (38-42 weeks) and no preterm. METHODS: Obstetric, colposcopy and pathology details were obtained. MAIN OUTCOME MEASURES: Adjusted odds ratio of preterm birth in first and second or subsequent births following treatment for cervical disease. RESULTS: A total of 2798 births (1021 preterm) from 2001 women were included in the analysis. The risk of preterm birth increased with increasing depth of treatment among first births post treatment [trend per category increase in depth, categories <10 mm, 10-14 mm, 15-19 mm, ≥20 mm: odds ratio (OR) 1.23, 95% confidence interval (95% CI) 1.12-1.36, P < 0.001] and among second and subsequent births post treatment (trend OR 1.34, 95% CI 1.15-1.56, P < 0.001). No trend was observed among births before colposcopy (OR 0.98, 95% CI 0.83-1.16, P = 0.855). The absolute risk of a preterm birth following deep treatments (≥15 mm) was 6.5% among births before colposcopy, 18.9% among first births and 17.2% among second and subsequent births post treatment. Risk of preterm birth (once depth was accounted for) did not differ when comparing first births post colposcopy with second and subsequent births post colposcopy (adjusted OR 1.15, 95% CI 0.89-1.49). CONCLUSIONS: The increased risk of preterm birth following treatment for cervical disease is not restricted to the first birth post colposcopy; it remains for second and subsequent births. These results suggest that once a woman has a deep treatment she remains at higher risk of a preterm birth throughout her reproductive life.

Sequential cervical length screening in pregnancies after loop excision of the transformation zone conisation: a retrospective analysis.

OBJECTIVE: To review our experience with a screening programme that included four sequential cervical length (CL) measurements from 16 to 22( ) weeks of gestation. DESIGN: Historical cohort study. SETTING: Tertiary-care centre in a university hospital. POPULATION: There were 312 singleton pregnancies in 321 women with a previous large loop excision of the transformation zone (LLETZ), and 62 pregnancies after a second-trimester miscarriage in a previous pregnancy. METHODS: The CL measurements were performed by transvaginal ultrasound at 16, 18, 20, and 22 completed weeks of gestation. MAIN OUTCOME MEASURES: Early preterm delivery before 34 completed weeks of gestation. RESULTS: Early preterm delivery was found in 7.4%. The CL at 16 completed weeks of gestation was smaller in the LLETZ group (36 mm, interquartile range 30-40 mm) compared with the control group (38 mm, interquartile range 32-42 mm; P = 0.040). For the analysis of risk factors for early preterm delivery after LLETZ, only cases with a complete data set were included (n = 145). In a multivariate analysis, two parameters remained significantly predictive, with CL at 16 completed weeks of gestation being the most significant measure (P < 0.001, OR 0.90, 95% CI 0.83-0.98), followed by conception using IVF treatment (P = 0.031, OR 0.64, 95% CI 1.54-34.80). CONCLUSIONS: Even as early as 16 weeks of gestation, women with early preterm delivery reveal a significantly lower CL than those without. Dynamics in the CL do not add to this information.

A literature review of the current evidence for routine antibiotic prophylaxis after cervical tissue excisions.

Consistent data are available on supporting the routine use of prophylactic antibiotics for several obstetrical and gynaecological procedures. According to the Surgical Wounds Classification scheme, operations involving the vagina are included in the clean-contaminated category of procedures, and guidelines recommend the routine use of prophylactic antibiotics. The objective of this paper is to review the current evidence regarding prophylactic antibiotics for cervical tissue excisions. We performed a systematic search of medical databases to March 2014 and we found three randomised controlled trials reporting on the role of prophylactic antibiotics in 683 patients who underwent cervical excisions. When compared with controls, the prophylactic antibiotics group was similar in terms of postoperative bleeding, vaginal discharge, pain, incidence of adverse events, requirement of antibiotics and readmission rate secondary to bleeding. This systematic review based on three randomised controlled trials suggests that current evidence does not support the routine prophylactic antibiotics for cervical tissue excisions.

Outcome after loop electrosurgical excision procedure for cervical high-grade squamous intraepithelial lesion.

OBJECTIVE: The dilemma in treating cervical high-grade squamous intraepithelial lesion (HSIL) is how to achieve complete excision to minimize the risk of cervical cancer while sparing the anatomy of the cervix and its ability to function during pregnancy. The optimal management for positive margins after excisional treatment is still controversial. This study was conducted to determine the clinical and histologic predictors of residual/recurrent HSIL and assess the outcome of women with positive margin. MATERIALS AND METHODS: This retrospective cohort study included 386 women who had excisional treatment for HSIL during 1st January 2012 to 31st December 2015 in a university-affiliated hospital. RESULTS: Overall, 212 (54.9%) women had negative margins and 155 (40.2%) had positive margins. The cumulative rate of residual/recurrent HSIL at 2 and 5 years was 15.7% and 16.8% respectively in positive margins and 1.8% and 5.0% respectively in negative margins (p < 0.001). Of women who had residual/recurrent HSIL, significantly more women had positive margins compared to negative margins (74.1% vs 25.9%, p = 0.001). Positive margin was significantly associated with higher rate of subsequent abnormal cervical smear (48.2% vs 28.9%, p < 0.001), requiring further colposcopy (32.1% vs 14.4%, p < 0.001) and further treatment for SIL (7.5% vs 4.8%, p < 0.001) compared to negative margin. CONCLUSION: Most women (85%) with positive margin went without residual/recurrent HSIL, of which the option of close surveillance with cytology is reasonable. Repeat excision may be considered in selected women with positive margin, endocervical glandular involvement and those who are older or unable to comply with follow-up.

Obstetric outcomes after cervical loop electrosurgical excision procedure.

OBJECTIVES: This study aimed to investigate whether a history of loop electrosurgical excision procedure (i.e., conisation) affects obstetric and neonatal outcomes. METHODS: A retrospective cohort study was carried out in Västernorrland county, Sweden. 57 nulliparous women with singleton pregnancies and previous conisation were compared with 100 age-matched pregnant controls without history of conisation. RESULTS: There was significantly lower gestational age by delivery (p = 0.036), however, the premature delivery rate was not different. Caesarean section was also less frequent (OR: 0.29, 95% CI: 0.081-1.04, p = 0.047) in the conisation group than those in the control group. There were no differences in neonatal outcomes. CONCLUSIONS: Previous conisation does not affect the risk of prematurity or cervical dilatation during the first stage of labour. Women with history of conisation had a lower rate of caesarean section, and lower gestational age by delivery.

Increase of the T-reg-recruiting chemokine CCL22 expression in a progressive course of cervical dysplasia.

PURPOSE: An increasing infiltration of FoxP3-positive T-regs is associated with a higher grade of cervical intraepithelial neoplasia. The T-reg-recruiting chemokine CCL22 is expressed in various tumour entities. Aim of our study was to investigate the role of CCL22 in the progression and regression of cervical intraepithelial neoplasias, especially in patients with intermediate cervical intraepithelial neoplasias (CIN II). Furthermore, our aim was to characterize the CCL22-producing cells and explore the role of innate immunity in the process of cells recruitment. METHODS: CCL22 expression was analyzed immunohistochemically in 169 patient samples. The immunoreactive score as well as the median numbers of positive cells were calculated in each slide and correlated with the histological CIN grade and FoxP3 expression. Additionally, CD68/CCL22 as well as CD68/PPARγ and CD68/FoxP3 expression were examined by double immunofluorescence. Statistical analysis was performed by SPSS 26. RESULTS: A significantly higher expression of epithelial CCL22 in CIN II with progression in comparison to CIN II with regression (p = 0.006) could be detected. CCL22 was correlated with FoxP3 (Spearman's Rho: 0.308; p < 0.01). In 88%, CCL22-positive cells were positive for CD68, and 71% of CD68-positive macrophages expressed PPARγ. Colocalization of CD68 and FoxP3 was detected in 12%. CONCLUSION: We could demonstrate that increased expression of CCL22, mainly produced by macrophages, correlates with elevated potential of malignancy. CCL22 expression could act as a predictor for regression and progression in cervical intraepithelial neoplasia, and it may help in the decision process regarding surgical treatment versus watchful waiting strategy in order to prevent conisation-associated risks. Furthermore, our findings support the potential of CCL22-producing cells as a target for immune therapy in cervical cancer patients.

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.

Role of FoxP3-positive regulatory T-cells in regressive and progressive cervical dysplasia.

PURPOSE: Forkhead Box Protein 3 (FoxP3) is known as a key mediator in the immunosuppressive function of regulatory T-cells (Tregs). The aim of our study was to investigate whether FoxP3-positive Tregs have the potential to act as an independent predictor in progression as well as in regression of cervical intraepithelial neoplasia, especially in patients with intermediate cervical intraepithelial neoplasia (CIN II). METHODS: Nuclear FoxP3 expression was immunohistochemically analysed in 169 patient samples (CIN I, CIN II with regressive course, CIN II with progressive course, CIN III). The median numbers were calculated for each slide and correlated with the histological CIN grade. Statistical analysis was performed by SPSS 26 (Mann-Whitney U test, Spearman's rank correlation). RESULTS: An increased FoxP3 expression in CIN II with progression could be detected in comparison to CIN II with regression (p = 0.003). Total FoxP3 expression (epithelium and dysplasia-connected stroma) was higher in more advanced CIN grades (p < 0.001 for CIN I vs. CIN II; p = 0.227 for CIN II vs. CIN III). A positive correlation could be detected between FoxP3-positive cells in epithelium and total FoxP3 expression (Spearman's Rho: 0,565; p < 0.01). CONCLUSION: Expression of FoxP3 could be a helpful predictive factor to assess the risks of CIN II progression. As a prognosticator for regression and progression in cervical intraepithelial lesions it might thereby help in the decision process regarding surgical treatment vs. watchful waiting strategy to prevent conisation-associated risks for patients in child-bearing age. In addition, the findings support the potential of Tregs as a target for immune therapy in cervical cancer patients.

[Fertility preservation in cervical cancer, analysis of 30 years of practice and immersion in future developments]. / La préservation de fertilité en cas de cancer du col, analyse de 30 ans de pratique et immersion dans les évolutions à venir.

OBJECTIVES: The strategy of fertility preservation (FP) in cervical cancer has been challenged for several years and a therapeutic de-escalation seems to be necessary. In this context, we evaluated the oncological, fertility and obstetric outcomes of surgical techniques performed in our centre for FP. METHODS: This retrospective uni centric trial included 75 patients, managed at the Gustave Roussy Institute between 1995 and 2020, for cervical cancer (stage IB1 FIGO 2018) and having conducted a fertility preservation project after a complete pre-therapy work-up. The objective of this study was to understand our results on fertility and obstetrical outcomes and to correlate them with oncological data and finally to evaluate the evolution of our surgical practices. RESULTS: 54 patients benefited from an extended trachelectomy and no lymph node involvement was found. 1 patient received a complementary treatment postoperatively which did not allow to preserve her fertility. The recurrence rate was 4.8% (4/75) with one death described. 31 pregnancies were obtained, representing a pregnancy rate of 50%. 74% of pregnancies were obtained spontaneously and 60% of pregnancies were carried to term. CONCLUSION: Our results are similar to those in the literature. Despite a fertility preservation project, only half of the patients were able to achieve a pregnancy.

Conservative (non-radical) surgery for stage IB1 cervical cancer.

There has been lively debate in recent years following the publication of various retrospective case series and small cohort studies that suggest certain women presenting with International Federation of Gynecology and Obstetrics (FIGO) stage IB1 cervical cancer (pre-2018 revised classification) may be treated by non-radical surgery, either simple hysterectomy or cone biopsy, where fertility preservation is required. A strictly defined histological criterion is necessary for selecting such cases, incorporating tumour dimensions including estimated tumour volume, lympho-vascular space invasion and pelvic lymph node status. Meta-analyses of these studies show that the oncological outcomes are comparable to the excellent results achieved by radical hysterectomy and radical trachelectomy. In addition, the fertility and pregnancy outcomes for cases treated by conisation are superior to cases managed by radical trachelectomy. Multi-centre, ethically approved, prospective studies are currently on-going, which will provide better quality evidence in an attempt to contribute to this debate, with the intention of improving outcomes, including quality of life, in women presenting with small-volume stage IB1 cervical cancer.