Abstract Introduction There is an urgent need for biomarkers that can distinguish regressive from progressive cervical intraepithelial neoplasia (CIN) lesions to improve risk stratification in cervical cancer screening programs and avoid overtreatment. We aimed to evaluate the longitudinal performance of the S5 methylation classifier in predicting the clinical trajectory of untreated CIN grade 2 (CIN2) across different HPV genotype groups. Material and Methods This study included 122 women (aged 18–30) with histologically confirmed CIN2 enrolled in an active surveillance trial at Helsinki University Hospital, Finland (ISRCTN91953024). Patients were monitored every 6 months for up to 24 months with cytology, HPV genotyping, and colposcopy. S5 methylation levels (pyrosequencing) were compared between women who regressed to normal histology ( n = 89) and those who progressed to CIN3+ ( n = 22, including one microinvasive cancer) or had persistent CIN2 ( n = 11). Analysis was stratified based on baseline HPV genotypes. Results The baseline S5 classifier significantly predicted progression/persistence with an odds ratio (OR) of 1.15 (95%CI 1.05–1.25). When excluding HPV16/18, the S5 classifier demonstrated a similar, borderline predictive association (OR 1.19; 95%CI 1.00–1.41), whereas cytology and HPV genotyping did not. Longitudinal analysis showed that S5 methylation levels in progressors remained elevated throughout the 24‐month period, significantly predicting progression/persistence up to 18 months prior to histological diagnosis of progression. Conclusions In this active surveillance cohort, the S5 classifier showed potential as a prognostic triage biomarker for identifying progression in untreated CIN2, including cases with non‐HPV16/18 types. Our exploratory findings suggest that elevated methylation levels may precede histological progression by up to 18 months. As HPV16/18 prevalence declines, host‐viral methylation panels may offer improved risk stratification compared to standard triage, though larger prospective studies in vaccinated populations are needed to confirm these findings and establish clinical utility.
Abstract Introduction To assess the prevalence and ultrasonographic characteristics of newly detected findings suggestive of ovarian and deep endometriosis (DE) in postmenopausal women undergoing routine gynecological evaluation. Material and Methods This prospective observational study (NCT07503938) included consecutive postmenopausal participants attending two regional gynecology outpatient clinics for routine examination over 24 months. Transvaginal ultrasound was performed by a single operator according to International Deep Endometriosis Analysis (IDEA) group criteria. Findings suggestive of DE and/or ovarian cysts suggestive of endometriomas were recorded and characterized. Clinical data were collected using a structured questionnaire. Univariable and multivariable logistic regression identified factors associated with posterior compartment hypoechoic nodules. Results Four hundred ninety‐two participants were included (mean age 60.2 ± 6.1 years; median time since menopause 8.0 years). Ultrasound findings suggestive of endometriosis were identified in 40 participants (8.1%; 95% CI 5.9%–10.9%), including posterior compartment hypoechoic nodules in 36 (7.3%). Intestinal nodules ( n = 21; 4.3%) often showed plaque‐like morphology, thickness < 7 mm, regular margins, limited Doppler vascularity, and uncommon submucosal involvement. The prevalence of posterior nodules suggestive of DE decreased with increasing time since menopause (13.9% within ≤5 years vs. 4.3% >10 years; p for trend = 0.001). In multivariable analysis, ≤5 years since menopause was independently associated with posterior nodules (adjusted OR 3.25, 95% CI 1.35–7.83), as were a history of dysmenorrhea (adjusted OR 2.20, 95% CI 1.05–4.60) and chronic pelvic pain (adjusted OR 2.36, 95% CI 1.11–5.00). No independent association was observed with current pelvic pain, dyschezia, previous infertility, or systemic hormone replacement therapy. Six ovarian cysts with ultrasonographic features suggestive of endometriomas were identified (1.2%; 95% CI 0.45%–2.64%), five of which exhibited atypical features, including multilocularity, heterogeneous echoes, papillary excrescences, or wall thickening. Conclusions Ultrasound findings suggestive of DE may be detected after menopause and are associated with earlier postmenopausal timing and a history of reproductive‐age pain, but not with specific current pain symptoms or hormonal exposure. Their predominantly plaque‐like, poorly vascularized morphology may reflect fibrotic remodeling, although histological composition and biological activity cannot be established by ultrasound alone. Expert ultrasound remains important to distinguish benign‐appearing residual findings from clinically relevant or malignant pathology.
Abstract Introduction To evaluate postoperative urinary complications and their management in patients undergoing Bricker urinary diversion for gynecologic cancers, with a focus on identifying risk factors, especially uretero‐ileal strictures. Material and Methods We conducted a retrospective single‐center study of 77 patients who underwent Bricker urinary diversion for gynecologic cancers between 2000 and 2020. All surgeries were performed by the same gynecologic oncologic team. Results Primary tumor sites included the cervix and uterine body in 87% of patients, with others involving the vagina, vulva, and adnexa. Preoperative pelvic radiotherapy was performed in 71%, and para‐aortic/pelvic radiotherapy in 10%. Over a median follow‐up of 21 months, uretero‐ileal strictures occurred in 30%, and fistulas in 6%. Preoperative nephrostomy was significantly associated with a higher rate of strictures ( p = 0.001), while preoperative ureteral stenting was associated with a reduced risk ( p = 0.005). All patients with strictures or fistulas were initially managed with ureteral stenting; nephrostomy was subsequently required in 56% of stricture and 80% of fistula cases. Surgical treatment was eventually needed in 17% and 60%, respectively. Additional risk factors for strictures included preoperative chemotherapy ( p = 0.023) and intraoperative evidence of chronic enteritis ( p = 0.013). No significant differences were observed in overall or recurrence‐free survival between patients with and without strictures ( p > 0.05). Conclusions Uretero‐ileal strictures occurred in 30% and fistulas in 6% of patients undergoing Bricker urinary diversion. Preoperative ureteral stenting may help reduce stricture risk, and appropriate bowel segment selection is essential to minimize complications.
Abstract Introduction Globally, colposcopy is often performed by non‐experts with no certification or routine use of colposcopic scoring tools. A systematic colposcopic scoring tool, the Swedescore, has been developed to enhance the detection rate of cervical intraepithelial neoplasia grade 2 or worse (CIN2+). We aimed to compare the diagnostic accuracy of two colposcopy methods (systematic use of the Swedescore versus conventional colposcopy) for detecting CIN2+. Material and Methods This multicenter, non‐randomized clinical study included women (23–65 years) referred for colposcopy and with a visible transformation zone (type 1 and 2). Colposcopy was performed using the systematic scoring tool, Swedescore, or the conventional method. All women had four cervical biopsies collected. Colposcopists collected lesion‐directed biopsies (target biopsies) from abnormal areas with or without non‐lesion‐directed biopsies (random biopsies) from areas that appeared normal. The gold standard was the most severe diagnosis (CIN2+) based on all four biopsies. The primary outcome was CIN2+. We calculated sensitivity (SN), specificity (SP), positive predictive value (PPV), and negative predictive value (NPV) with 95% confidence intervals and compared results between the two methods. Results were stratified by age, body mass index (BMI), human papillomavirus (HPV) vaccination status, screening method, index cytology, index HPV type, and colposcopists. Clinical Trial Registration ClinicalTrials.gov NCT05870787. Results Among 929 women included (Swedescore: 534, conventional: 395), the diagnostic accuracy for the detection of CIN2+ was slightly higher with the Swedescore compared to the conventional method (SN: 84.7% vs. 77.8%, SP: 37.3% vs. 30.9%, PPV: 47.6% vs. 43.9%, NPV: 78.3% vs. 66.7%). Sensitivity for CIN2+ was significantly higher with the Swedescore compared to the conventional method in women ≥50 years (92.9% vs. 62.5%), those with high‐grade cytology (92.4% vs. 83.2%), and when colposcopy was performed by residents (91.8% vs. 70.6%). Regardless of HPV vaccination status and screening method, the Swedescore performed slightly better than the conventional method, although the differences were not statistically significant. Conclusions Our findings may suggest that, in a non‐expert setting, a systematic colposcopic examination using the Swedescore was associated with a slightly higher diagnostic accuracy for detecting CIN2+ compared to the conventional method. These findings should be interpreted considering baseline imbalances between the two methods.
