Ny forskning om jente- og kvinnehelse

BackgroundAccurate staging of cervical cancer is essential for treatment planning, with Magnetic Resonance Imaging (MRI) being the modality of choice. Cervical cancer is suspected to have variations in its presentation and etiology depending on the age of patients.PurposeTo explore the association between patient age and specific findings on contrast-enhanced MRI in women with newly diagnosed cervical cancer.Material and MethodsThis study included 146 consecutive patients with pathologically confirmed cervical cancer who underwent 3.0T contrast-enhanced MRI for initial staging. MRI scans were evaluated for tumor size, parametrium, uterine, bladder, and intestinal invasion, among other features. Ordinal, binary, and multinomial logistic regression models were used to assess age as a predictor for MRI stage and specific invasive findings. Receiver Operating Characteristic (ROC) curve analysis was performed for significant findings.ResultsThe mean patient age was 49.1 ± 12.2 years. Age was a significant predictor of a higher MRI stage (OR: 1.029, p = 0.025). Increasing age emerged as a significant predictor for uterine invasion (OR: 1.050, 95% CI: 1.022-1.085, p = 0.002), an association that remained significant even after controlling for disease stage. Age predicted higher odds of bladder mucosal (OR: 1.052, p = 0.011) and non-mucosal intestinal invasion (OR: 1.038, p = 0.041). ROC identified an age cutoff of 45.5 for uterine invasion (AUC: 65.2%).ConclusionRadiologists should maintain a heightened index of suspicion for more extensive local invasion when interpreting cervical cancer staging MRIs in older women.

Cervical cancer is common in French Guiana. Previous studies of the cancer registry have shown that the only prognostic factor was FIGO stage, with a 5-year survival rate of 58%. This study aimed to describe the management and survival rates prior to the establishment of the University Hospital. A multicenter retrospective study of 222 cases discussed in tumor board meetings between 2010 and 2021. Data collected included age, administrative status, comorbidities, place of residence, histology, FIGO stage, treatment modalities, and disease progression. Key findings were median age, 48 years; born abroad, 59%; residence on the Atlantic coast, 68%; FIGO stage III-IV, 54%; surgery, 47% of cases; radiotherapy, 46%; transfer outside French Guiana, 58%. Five-year overall survival was 65%, identical before and after 2016. In multivariate analysis, advanced FIGO stages (III, HR=3.22; IV, HR=3.65) and residence in remotes areas (HR=2.63) were independent prognostic factors for shorter survival. Difficulties in accessing care and mandatory transfers for radiotherapy impact patient outcomes. Recent decisions have been made within the framework of the new University Hospital (CHU), notably the establishment of a radiotherapy department and the strengthening of local healthcare infrastructure. These results provide a baseline for evaluating the impact of these decisions.

Over 660,000 women develop cervical cancer annually, caused by persistent infection with high-risk human papillomavirus (HPV). Published studies of mesenchymal stem/stromal cells (MSCs) as immunomodulatory agents are contradictory, with some reporting tumor suppression and others tumor promotion. The mechanism of these paradoxes has not been systematically investigated. This review aims to assess MSC-mediated immune evasion in HPV-related cervical cancer, quantify HPV stratification failure in the literature, and formulate a predictive stratification model linking MSC behavior to HPV oncogenic activity. A systematic review was performed in accordance with PRISMA 2020 guidelines across 8 databases. Studies were included if they reported an MSC intervention for cervical cancer with one or more immune-related outcomes. HPV stratification gap analysis was performed alongside data extraction and risk-of-bias evaluation. 14 studies were included: 13 completed preclinical and 1 ongoing clinical trial. MSC effects included immune evasion through adenosine, IL-10, and M2 macrophage polarization, and tumor suppression through STAT3, Wnt/β-Catenin, and epigenetic pathways. Of 13 completed studies, none measured HPV oncogenic activity as an experimental variable. Only two included an HPV-negative cohort. Differential effects of MSC exosomes on HPV16 and HPV18 cell lines were observed but not associated with HPV genotype. HPV oncogenic activity is an unmeasured and plausible modifier of MSC activity in cervical cancer. Stratification by HPV oncogenic status should be a methodological requirement for interpretable and translatable evidence, because E6/E7 signalling is linked to PDL-1, TGF-β, STAT-3 and NF-κB, all linked to MSC immunomodulatory pathways. A predictive stratification system and minimum reporting standards are suggested.

To evaluate the survival benefit of adding pelvic radiotherapy (RT) to chemotherapy and to identify patient subgroups most likely to benefit from pelvic RT. A multicentre retrospective study was conducted in Japan and included patients with newly diagnosed stage IVB (FIGO 2018) cervical cancer treated with chemotherapy alone or chemotherapy plus pelvic RT between 2016 and 2020. Patients were classified into the CT group (chemotherapy-alone) or PRT group (chemotherapy plus pelvic RT). Propensity score matching (PSM) was applied using age, histology, T stage, N stage, metastatic pattern, and number of metastatic lesions. Overall survival (OS) represented the primary endpoint; progression-free survival (PFS) and late adverse events constituted the secondary endpoints. Among 343 patients, the PRT group showed significantly longer OS than the CT group following PSM (median OS: 25.0 vs. 18.0 months; hazard ratio [HR], 0.58; 95% confidence intervals [CI], 0.42-0.79; p < 0.001). PFS was also significantly improved in the PRT group (HR, 0.65; 95% CI, 0.48-0.87; p = 0.002). The longer OS in the PRT group was seen across metastatic patterns, although this was less evident in early T stages (≤ T2). Brachytherapy was independently associated with improved OS in the PRT group. Grade ≥ 3 gastrointestinal toxicity was more frequent in the PRT group. In this nationwide, real-world study, definitive-dose pelvic RT combined with chemotherapy was associated with improved survival in selected patients with stage IVB cervical cancer. Prospective randomised trials are warranted to validate these findings.

Cervical cancer (CC) remains a leading cause of cancer-related mortality worldwide and cisplatin resistance poses a major challenge to effective treatment. MicroRNA-135 (miR-135) has been implicated in tumor progression and drug resistance, but its role in cisplatin-resistant CC remains unclear. To investigate whether miR-135 affects cisplatin resistance in CC cells by targeting CD44v6. Bioinformatic analysis (TargetScan) was performed to predict the miR-135 binding site in CD44v6, followed by a dual-luciferase reporter assay. RT-qPCR and Western blot were used to measure miR-135 and CD44v6 expression in cisplatin-resistant HeLa/DDP cells, HeLa cells and normal Ect1/E6E7 cells. HeLa/DDP cells were transfected with miR-135 mimic or NC mimic and cell proliferation (CCK-8, colony formation), apoptosis (flow cytometry) and CD44v6 expression were assessed. miR-135 directly bound to the CD44v6 3'-UTR, reducing luciferase activity by 58% (*p* < 0.001). miR-135 expression was decreased by 68% in HeLa/DDP cells compared to Ect1/E6E7 cells, while CD44v6 expression was increased 3.5-fold. miR-135 mimic transfection reduced CD44v6 protein expression by 62%, decreased cell viability by 57.3%, increased the apoptosis rate from 12.4% to 35.8% (absolute increase of 23.4%) and lowered the cisplatin IC50 from 22.36 to 8.47 μmol/L (2.64-fold reversal, *p* < 0.001). miR-135 overexpression was associated with reduced CD44v6 expression, decreased proliferation, increased apoptosis and enhanced sensitivity to cisplatin in HeLa/DDP cells. These findings demonstrate an inverse association between miR-135 and CD44v6 in cisplatin-resistant CC cells; however, causal mechanistic evidence (e.g., via CD44v6-specific knockdown or rescue experiments) is not provided. Further studies are required to establish whether CD44v6 directly mediates the chemosensitizing effects of miR-135.

Cervical cancer (CC) is one of the most common gynecological malignancies. Although E74-like factor 3 (ELF3) has been implicated as an oncogenic driver in multiple cancers, its expression pattern and functional role in CC remain unclear. An integrated analysis of transcriptome, proteome, and transcription-factor libraries was performed to identify the most significantly upregulated gene in CC, and GEPIA3.0 was used to confirm ELF3 overexpression. The expression levels of ELF3, guanosine monophosphate synthetase (GMPS), solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4), as well as the knockdown efficiencies of ELF3 and GMPS, were evaluated by RT-qPCR and Western blot. The effects of ELF3 or GMPS silencing on proliferation, migration, apoptosis, and ferroptosis were assessed by colony-formation, Transwell, and flow cytometry assays. Direct targeting of GMPS by ELF3 was verified by chromatin immunoprecipitation and dual-luciferase reporter assays, and a xenograft model in nude mice was established to demonstrate that ELF3 depletion suppresses CC growth. ELF3 was identified as the most significantly upregulated gene in CC. Silencing either ELF3 or GMPS inhibited proliferation and migration while inducing ferroptosis. Mechanistically, ELF3 transcriptionally regulated GMPS, and GMPS overexpression fully rescued the effects of ELF3 knockdown. In vivo, ELF3 depletion markedly restrained CC xenograft growth. These findings demonstrate that ELF3 functions as an oncogenic transcription factor in CC by upregulating GMPS, thereby enhancing proliferation and migration and restraining ferroptosis. Targeting the ELF3/GMPS axis represents a promising therapeutic strategy for CC.

Lymph node metastasis is an important prognostic factor in cervical cancer, but assessment of nodal response after concurrent chemoradiotherapy (CCRT) remains difficult. This study evaluated the diagnostic value of post-CCRT lymph node size for predicting pathological nodal involvement using a cohort treated with CCRT followed by planned surgery. This retrospective cohort study included 57 patients with cervical cancer who underwent CCRT followed by surgery including pelvic lymphadenectomy. The short- and long-axis diameters of the largest pelvic lymph node were measured on computed tomography before and after CCRT. Histopathological findings of resected lymph nodes were used as the reference standard. Receiver operating characteristic (ROC) analysis was performed to assess diagnostic performance. Pathological nodal metastasis was identified in 17 of 57 patients (29.8%). Post-CCRT lymph node diameters were significantly larger in the ypN1 group than in the ypN0 group. The short-axis diameter showed better diagnostic performance than the long-axis diameter, with an area under the curve of 0.859 (95% CI, 0.752-0.966) versus 0.802 (95% CI, 0.676-0.927). Among integer cutoff values, the short-axis diameter showed the highest Youden index at 5 mm and the highest F1 score at 7 mm. At a 7-mm cutoff, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 58.8%, 90.0%, 71.4%, 83.7%, and 80.7%, respectively. Post-CCRT pelvic lymph node size, especially the short-axis diameter, may be useful for estimating residual pathological nodal disease in cervical cancer.

Cervical cancer screening reduces cancer morbidity and mortality, but ineffective communication of test results and inadequate follow-up undermines these benefits. Variable knowledge about human papillomavirus (HPV), and the stigma, anxiety, and confusion associated with sexual transmission of HPV complicate communication about results. Our objective was to adapt and integrate evidence-based messages into a conversation guide to help clinicians discuss HPV-based cervical cancer screening results with patients. Iterative co-production process included patient engagement panels, semi-structured individual interviews with healthcare system users, preceded by an online questionnaire, and clinician engagement. Interview participants (n = 21) were female healthcare system users aged 21-65, with a cervical cancer screening test in the past 5 years. We consulted with a patient engagement panel to develop the study design and provide feedback on results. We invited interview participants to complete a questionnaire rating the helpfulness of 13 evidence-based messages, followed by a qualitative interview to better understand responses to the messages. Using results from rapid qualitative analysis, we refined messages and incorporated them into a draft conversation guide, reviewed with the patient engagement panel and women's health clinicians, and revised. Principal recommendations for conversations about test results were: (1) Recognize and respond to patient fear and anxiety, particularly fear of cancer; (2) Empower patients to navigate next steps in the screening continuum; and (3) Avoid using a sexually transmitted infection (STI) framework for HPV, which may focus patient reactions and concerns unhelpfully. Based on these recommendations, the conversation guide includes five primary messages, frequently asked questions with responses tailored to individual situations, and guidance for offering personalized follow-up instructions. Engaging with stakeholders and integrating end-user perspectives throughout the design process may lead to an increased ability to fulfill users' needs. As HPV-testing becomes the primary modality for cervical cancer screening, a conversation guide may help facilitate more effective communication about screening results.

To compare diffusion-relaxation correlation spectrum imaging (DR-CSI) and intravoxel incoherent motion (IVIM) for exploratory preoperative assessment of lymphovascular space invasion (LVSI) in cervical cancer. This exploratory retrospective study included 67 patients with pathology-confirmed cervical cancer, including 31 LVSI-positive and 36 LVSI-negative cases. Patients underwent preoperative 3.0 T magnetic resonance imaging (MRI) with DR-CSI and IVIM. DR-CSI-derived spectral fractions (f-A to f-F) and IVIM-derived parameters (D, D*, and f) were extracted from tumor volumes. Variables with P < .10 in univariable logistic regression were entered into separate DR-CSI and IVIM multivariable models. Receiver operating characteristic (ROC) analysis was performed in the same cohort, without internal or external validation; therefore, areas under the curve (AUCs) were interpreted as apparent performance estimates. In the final DR-CSI model, f-C (P < .001) and f-F (P = .001) were retained as LVSI predictors, yielding an apparent AUC of 0.866 (95% CI, 0.760-0.937). Among IVIM-derived parameters, D was retained in the final IVIM model (P = .029), with an apparent AUC of 0.630 (95% CI, 0.503-0.745). The DR-CSI model showed substantially higher apparent discrimination performance than the IVIM model (P = .004). DR-CSI-derived spectral fractions showed preliminary value for preoperative assessment of LVSI-related tumor aggressiveness in cervical cancer, with higher apparent discrimination than IVIM. Larger validated studies are needed to confirm clinical utility. DR-CSI-derived spectral fractions, particularly f-C and f-F, may represent candidate MRI biomarkers for preoperatively assessing LVSI-related tumor features in cervical cancer, with higher apparent discrimination than IVIM in this exploratory cohort, although further validation is required.

Recent randomized evidence suggesting that simple hysterectomy is non-inferior to radical hysterectomy in cervical cancer patients with low-risk disease has invigorated questions about the safety of a minimally invasive approach in this population. To determine whether the association between surgical approach and oncologic outcomes varied by disease risk group. Population-based retrospective cohort study of cervical cancer patients undergoing primary radical hysterectomy by a gynecologic oncologist from 2006 to 2017 in Ontario, Canada. Analyses were stratified by disease risk group, with patients classified as low-risk (depth of invasion <10 mm and maximum tumor diameter ≤20 mm) or high-risk (depth of invasion ≥10 mm or maximum tumor diameter >20 mm) according to pathologic Canadian Cancer Trials Group CX.5 Simple Hysterectomy and Pelvic Node Assessment (SHAPE) criteria. Overlap propensity score‑weighted survival models were used to examine the association between surgical approach and oncologic outcomes, adjusting for demographic, clinical, and pathologic factors. We identified 903 patients with median age 44 years (interquartile range, 38-53) and follow-up 10 years (interquartile range, 7-13). In low-risk patients (N=621), minimally invasive radical hysterectomy was not associated with all-cause death (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.39-2.01; P=.76), cervical cancer death (HR, 1.15; 95% CI, 0.27-4.87; P=.85), or recurrence (HR, 0.88; 95% CI, 0.4-1.91; P=.74) compared to open radical hysterectomy. In high-risk patients (N=282), minimally invasive radical hysterectomy was associated with significantly increased all-cause death (HR, 3.22; 95% CI, 1.37-7.58; P=.008), cervical cancer death (HR, 4.88; 95% CI, 1.50-15.83; P=.008), and recurrence (HR, 2.32; 95% CI, 1.01-5.34; P=.048) compared to open radical hysterectomy. The relationship between surgical approach and oncologic outcomes appeared to vary by disease risk group. Minimally invasive radical hysterectomy may not be associated with adverse oncologic outcomes in patients with low-risk disease, but recurrence and death were uncommon in this subgroup. Additional studies are needed to confirm whether minimally invasive surgery remains safe in a low-risk population defined by strict SHAPE criteria.

In this work, an intra-nanocomposite resonance energy transfer-based electrochemiluminescence (RET-ECL) biosensor was developed for detecting microRNA (miRNA-21), a cervical cancer relative biomarker. By means of the in-situ reduction method, silver nanoparticles (Ag NPs) were uniformly coated on the surface of Zirconium-based metal organic frameworks (UiO-66-NH 2 ) encapsulated with Ru(bpy) 3 2+ (Ru@UiO-66-NH 2 ), thus forming the Ru@UiO-66-NH 2 @Ag nanocomposite. Because of the incorporation of both ECL donor (Ru(bpy) 3 2+ ) and acceptor (Ag NPs) within a single nanostructure, Ru@UiO-66-NH 2 @Ag showed high RET efficiency, causing a significantly quenched ECL response. Afterward, the presence of miRNA-21 activated the upstream toehold-mediated strand displacement reactions (TSDR) to generate abundant S strands, which could further trigger the downstream catalytic hairpin assembly (CHA). Immobilizing glucose oxidase (GOD) on the surface of Ru@UiO-66-NH 2 @Ag enabled the catalysis of glucose oxidation and then the produced H 2 O 2 proceeded to etch Ag NPs to Ag + . As a result, a notably recovered ECL response was obtained for miRNA-21 assay with a low detection limit of 30 aM. Moreover, the biosensor successfully analyzed miRNA-21 expression levels in serum samples collected from cervical cancer patient and healthy volunteers, whose results were consistent with those of the standard methods. Therefore, this biosensor held huge potential in analysis of cervical cancer-related miRNA.

Cervical cancer remains a major cause of cancer-related morbidity and mortality in women, particularly among patients diagnosed with locally advanced, recurrent, or metastatic disease. Here, we investigated the role of transcriptional repressor GATA-binding 1 (TRPS1) in cervical cancer progression and defined its downstream regulatory mechanism. Bioinformatics analysis revealed differential expression of TRPS1 between cervical cancer and normal cervical tissues. To further explore its functional role, TRPS1 was overexpressed in cervical cancer cell lines via lentiviral infection. In vitro and in vivo experiments confirmed that TRPS1 expression was downregulated in cervical cancer, and its overexpression inhibited cervical cancer cell proliferation, migration, invasion, and stemness, as well as tumor growth in xenograft models. Mechanistically, ORC6 was identified as a candidate downstream effector of TRPS1. TRPS1 bound to the ORC6 promoter and repressed ORC6 transcription, leading to reduced ORC6 expression. Functional rescue experiments showed that ORC6 restoration partially reversed TRPS1-mediated inhibition of cell-cycle progression, apoptosis resistance, stemness-marker expression, EMT-associated marker expression, and tumor growth. Notably, low TRPS1 expression and high ORC6 expression were associated with lymphovascular invasion and lymph node metastasis in cervical cancer patients. Together, these findings identify a TRPS1-ORC6 regulatory axis that restrains cervical cancer stemness and progression.

Cervical cancer is the leading cause of cancer deaths among women in Botswana, yet uptake of cervical screening remains suboptimal. Understanding knowledge and barriers to screening is essential to inform strategies to achieve cervical cancer elimination. We conducted high-risk human papillomavirus (hrHPV) testing and an accompanying cross-sectional survey at health clinics and in the community in South East District, Botswana (February 2022-July 2023). Eligible participants were women aged ≥25 years with an intact cervix and no prior diagnosis of cervical cancer. Interviewer-administered structured questionnaires assessed demographics, prior screening attendance, knowledge of cervical cancer, and perceived barriers to screening. Open-ended responses were thematically categorized. Logistic regression was used to examine factors associated with knowledge and screening barriers. Of 3000 women screened, 2994 (99.8%) had known HIV status and were included. Median age was 43 years (interquartile range [IQR] 36-51), and 1500 (50.1%) were women with HIV (WWH). Overall, 67.2% (2005/2994) reported prior cervical cancer screening, with substantially higher uptake among WWH than women without HIV (80.0% vs 54.5%, P < 0.001). Knowledge of cervical cancer etiology was limited, with only 27.1% (788/2905) correctly identifying hrHPV as the cause. Younger age, HIV-positive status, higher education, formal employment, and prior screening attendance were independently associated with better knowledge. Among women who had never been screened, the most commonly reported barriers were lack of prioritization (38.3%; 376/981), fear (17.0%; 167/981), lack of awareness (17.0%; 167/981) and service provision issues (12.0%). Despite relatively high screening uptake, important gaps in knowledge and persistent individual- and system-level barriers remain. Strengthening cervical screening delivery through HPV self-collection alongside targeted education, would address current barriers to cervical screening in Botswana.

Advances in radiation (RT) treatment planning enhance the need for uniform quality oversight on clinical trials. NRG GY-017 was a randomized trial of the anti-program ligand death 1 (PD-L1) antibody, atezolizumab, before and concurrent (arm A) or concurrent with chemoradiaton (arm B) for locally advanced cervical cancer. We describe the prospectively collected pretreatment RT quality and workflow. Forty patients were consented and randomized. Thirty-seven patients submitted pretreatment RT plans for central review, and 36 patients ultimately received protocol therapy. Intensity modulated radiation therapy (IMRT) contouring guidelines and dose specifics were outlined in the protocol, with volume and dose deviations specified as per protocol, minor and major variation. Each site had to pass a standardized IMRT credentialing process. Sites were required to submit an IMRT plan for physician expert contour target and organ-at-risk review in a rapid pretreatment manner. An expert physician then scored the contours and plan as per protocol or as a deviation. For major deviations, the sites were required to revise and resubmit the plans, which were then re-reviewed prior to protocol start. The median follow-up time was 20 months. Thirty-seven participants had a central expert review of the pretreatment external beam radiation therapy plan. Thirteen plans (35%) were scored as a major deviation requiring revision: 11 secondary to contours (5 bowel and 6 nodal volumes) and 2 secondary to incorrect expansion on the volume or the dose distribution. The major deviation plans were resubmitted; however, 2 of them required revisions for a total of 3 plans. Because of the quality review, all patients had per-protocol scores prior to the treatment administration. Our data indicate that 35% of the baseline submitted advanced technology IMRT plans required revision and resubmission in order to meet protocol standards. RT plan quality workflow continues to evolve with advanced techniques and has implications in clinical trial review. Pretreatment plan review is an important quality measure for cervical cancer clinical trials.

Perineural invasion (PNI) is an adverse feature in cervical cancer and may influence nerve-sparing surgery. We compared conventional radiomics and VGG-SAM deep-learning strategies for MRI-based preoperative prediction of PNI. A retrospective cohort of 103 patients with cervical cancer, including 82 PNI-negative and 21 PNI-positive patients, was analyzed. PyRadiomics features were extracted from raw DICOM MRI and paired tumor masks. Four deep variants were evaluated: VGG only, SAM only, VGG + SAM naive fusion, and VGG + SAM learnable fusion. Patient-level stratified five-fold cross-validation was used. Primary metrics were sensitivity, specificity, balanced accuracy, F1-score, ROC-AUC, and PR-AUC. Uncertainty for the naive-versus-learnable comparison was assessed with 10,000 paired bootstrap resamples and exact McNemar tests. The strongest radiomics baseline, PyRadiomics + XGBoost, achieved balanced accuracy 0.6057, F1-score 0.3684, ROC-AUC 0.6731, and PR-AUC 0.4460. Naive VGG + SAM fusion achieved the best sensitivity (0.5714), balanced accuracy (0.7491), F1-score (0.6154), ROC-AUC (0.7854), and PR-AUC (0.6231). Learnable fusion achieved the highest specificity (0.9634) and precision (0.7500) while matching the highest accuracy (0.8544). Paired bootstrap comparisons showed wide confidence intervals across clinically relevant metrics. Hybrid VGG-SAM modeling outperformed conventional radiomics alone, but greater fusion complexity did not yield uniform benefit. Naive fusion favored sensitivity-oriented discrimination, whereas learnable fusion mainly shifted the operating point toward higher specificity. Larger multi-institutional cohorts and clinical comparators are needed.

Cervical cancer (CC) is a major global health problem, and distant metastasis is a critical determinant of prognosis and survival. However, comprehensive data on the incidence and distribution of non-lymphatic distant organ metastases are limited. This systematic review and meta-analysis aimed to quantify the incidence of non-lymphatic distant organ metastasis in patients with CC and to identify the most commonly reported organ sites. A systematic search was conducted across PubMed/Medline, Web of Science, Scopus, and Embase from inception to March 1, 2025. To supplement the database searches and minimize publication bias, we also searched Google Scholar to identify potentially relevant studies. Reference lists of included studies were screened for additional eligible articles. Observational studies reporting the incidence or distribution of non-lymphatic distant organ metastases (bone, brain, liver, and lung) in CC cohorts were included. Case reports, reviews, and studies restricted exclusively to patients with established stage IVB/M1 disease at presentation were excluded, to avoid overrepresenting patients with already documented metastatic disease. Data were extracted using a standardized form. Pooled incidence rates per 100 patients with 95% confidence intervals (CIs) were calculated using a random-effects model. Heterogeneity was assessed using the I 2 statistic. A total of 42 studies, comprising 238 387 patients, were included in the analysis. The pooled incidence rate of metastasis was 2.91 per 100 CC patients (95% CI: 2.84-2.97). Regional analysis showed that the Western Pacific region had the highest pooled incidence at 4.66 per 100 patients (95% CI: 4.52-4.79), followed by the European region at 2.50 per 100 patients (95% CI: 2.09-2.97) and the Americas at 1.68 per 100 patients (95% CI: 1.61-1.75). Among site-specific non-lymphatic distant organ metastases, bone was the most common, with a pooled incidence of 3.67 per 100 patients (95% CI: 2.37-5.06), followed by lung metastases (3.00 per 100 patients, 95% CI: 2.13-4.21), brain metastases (1.83 per 100 patients, 95% CI: 0.91-2.75), and liver metastases (1.70 per 100 patients, 95% CI: 0.45-2.95). Our findings indicate that the incidence of distant metastasis varies substantially by anatomic site, with bone and lung being the most common locations. However, due to large heterogeneity, these findings should be interpreted as descriptive trends rather than precise estimates. The predominance of bone and lung metastases emphasizes the need for enhanced clinical awareness regarding these organs and underscores the importance of standardized prospective studies to validate these patterns and guide surveillance strategies.

Radiation-induced vaginal stenosis (RIVS) is a common late toxicity of cervical cancer radiation therapy, yet its incidence, assessment, and reporting in low- and middle-income countries (LMICs) are poorly characterized. This scoping review synthesizes existing evidence on the incidence, assessment methods, and management of RIVS in LMIC settings. A scoping review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines. PubMed, Scopus, and Web of Science were searched for available literature through December 2024 for studies reporting RIVS among women with cervical cancer treated with radiation therapy in LMICs. Data were extracted on study characteristics, incidence, assessment methods, and management. Nonparametric tests and Spearman correlations were used to explore associations between reported incidence and study-level variables. Twenty-four studies met the inclusion criteria, representing nine LMICs as defined by the World Bank; no studies originated from low-income countries. The median publication year was 2020, and half of the studies were retrospective. Among studies reporting extractable incidence data, the median (IQR) overall incidence of RIVS was 48.8% (33.5-75.9). Studies that identified RIVS as a primary outcome reported significantly higher incidence than those in which it was not a primary focus (P < .001). Incidence was also higher in studies published after 2014 (P = .02). No significant differences were observed across countries, regions, or income groups. Reporting of management strategies was limited, with only 6 studies describing toxicity management. RIVS is common among patients with cervical cancer treated in LMICs, yet assessment and reporting remain inconsistent, and management practices are poorly described. The absence of data from low-income countries and the limited use of standardized toxicity assessment hinder accurate estimation of survivorship burden. Improved documentation, standardized assessment, and culturally informed interventions are needed to address late vaginal morbidity in LMICs.

Uninsured or underinsured Hispanic women in Minnesota use the state's free cervical cancer screening program, Sage. Although the rate of screening program use is high, incidence of and mortality from cervical cancer persist in this group. We examined systemic barriers to follow-up cervical cancer care despite access to the free program. From fall 2020 through spring 2021, we conducted virtual focus groups with 23 Hispanic women in Minnesota who previously received Sage services. We interviewed 7 key informants, including service providers, clinic administrators, and Sage team members. Three bilingual researchers independently used inductive approaches to identify themes from transcripts, refined categories, and finalized analysis through feedback sessions. We used the social-ecological model framework to reveal barriers to follow-up care after an abnormal cervical cancer screening result. Exploratory inductive analyses of data from focus groups and key informants identified 4 interconnected barriers: (1) reliance on community clinics and patient navigators, often causing navigator burnout; (2) scheduling and attending follow-up appointments at clinics outside of familiar community clinics, particularly in rural areas; (3) negative health care experiences and interpreter misuse that discouraged further care; and (4) confusion and anxiety from unexpected billing, despite Sage being a free program. To address the identified barriers, we recommend expanding and compensating patient navigator roles, strengthening interpreter use, and training hospital staff to reduce billing errors. Even with free screening available through Sage, structural failures (billing confusion, rural access gaps, navigator workload) undermined equitable care. Addressing these systemic issues is essential if programs like Sage are to realize their potential in reducing disparities in incidence of cervical cancer among Hispanic women.

To assess the feasibility, early outcomes, and toxicity of single-implant image-guided adaptive brachytherapy (IGABT) for locally advanced cervical cancer in a multicenter French cohort; a pragmatic strategy to address limited and uneven access to utero-vaginal IGABT while preserving disease control and treatment safety. We retrospectively analyzed 363 consecutive patients (Fédération Internationale de Gynécologie Obstétrique 2009 IB-IVA) treated with concurrent chemoradiation consisting of pelvic ± paraortic intensity modulated radiation therapy /volumetric modulated arc therapy (45 Gy in 25 fractions) with nodal boost to involved lymph nodes when indicated, followed by 1 applicator insertion delivering 4 high-dose-rate fractions. Planning was magnetic resonance imaging (MRI) guided with the applicator in place when available, otherwise computed tomography-guided with rigid fusion to an MRI performed a few days before. Composite doses were converted to equivalent doses per 2 Gy fractions, as per the linear-quadratic model. Outcomes (local control [LC], nodal and distant control, overall survival, and disease-free survival) were estimated by Kaplan-Meier from the end of radiation therapy. Late toxicity was graded according to the NCI-CTCAE version 5.0, with severe events defined as grade >= 3. T2b was the predominant T stage (59.5%), with nodal involvement in 47.9% of patients. The median overall treatment time (OTT) was 56 days (interquartile range, 50-61). Median D90-CTV HR (minimum dose delivered to 90% of the high-risk clinical target volume) was 85.9 Gy EQD2 (IQR, 80.4-91.6 Gy EQD2 ). At a median follow-up of 20.2 months (range, 1.6-121 months), the Kaplan-Meier-estimated 3-year LC rate was 83.1% (95% CI, 76.4-88.0). At 36 months, LC was higher with MRI-centered than computed tomography-MRI fusion planning (93.5% [85.7-97.2] vs 78.5% [70.4-84.6]) on unadjusted Kaplan-Meier. LC rates were 94% for patients with an OTT <50 days, 89% for those with an OTT of 50 to 55 days, and 81% for patients with an OTT >55 days. Overall, grade ≥3 toxicity events occurred in 14.0% of the cohort. In this multicenter real-world cohort, LC was high overall, particularly among patients treated with MRI-centered, applicator-in-place brachytherapy planning. Single-implant high-dose-rate IGABT for locally advanced cervical cancer was feasible, providing outcomes broadly consistent with historical multi-insertion series in terms of side effects. Longer follow-up and expanded accrual will refine durability and prognostic analyses.

The percentage of eligible women screened for breast cancer varies among National Breast and Cervical Cancer Early Detection Program (NBCCEDP) awardees. We assessed the effect of awardee- and state-level factors on the percentage of eligible women screened for breast cancer among NBCCEDP awardees. We focused on primary care-health professional shortage areas (PC-HPSAs) and nurse practitioner scope of practice. First, we calculated the study outcome, defined as the percentage of eligible women screened among NBCCEDP state awardees during July 2022-June 2024. Next, we gathered data on awardee- and state-level predictors from multiple sources and estimated 2 general linear multilevel models. Models differed only by the inclusion of an interaction term between PC-HPSA and nurse practitioner autonomy. Finally, we calculated marginal and partial R 2 to determine combined and individual contributions of predictors on variability in the study outcome. The average percentage of eligible women screened for breast cancer among awardees was 9.6% (range, 0.5%-78.0%). Awardees in states with (1) full nurse practitioner autonomy or (2) a larger percentage of their population living in PC-HPSAs screened larger percentages of eligible women as compared with awardees in states without full autonomy or with smaller PC-HPSA populations. Awardees in states with full nurse practitioner autonomy and larger PC-HPSA populations screened even higher percentages of eligible women (β = 0.46; P = .02). Interaction model predictors explained 59% (marginal R 2 = 0.59) of the variability in the percentage of eligible women screened among awardees, with PC-HPSA being the largest contributor, explaining 27% of the variability (partial R 2 = 0.27). NBCCEDP awardees can encourage their clinical partners to reach women in PC-HPSAs and encourage strategic partnerships with nurse practitioners to address differences in screening.

Use of image-guided brachytherapy (IGBT) in cervical cancer improves patient outcomes. However, implementation in resource-limited settings is challenging due to limited capacity upscale, absence of workflow enhancement strategies, and financial barriers. Optimizing workflows is essential, yet the relationship between workflow efficiency and IGBT uptake remains unclear. This cross-sectional study examined brachytherapy (BT) workflows across 14 nationally representative centers. Standardized forms collected data on infrastructure, treatment workflows ((A): Conventional two-dimensional (2D) X-Ray-Guided BT, with point-A-based fractions planned using 2D X-ray imaging, (B): Standard intracavitary (IC) three-dimensional (3D) IGBT, with fractions planned using computed tomography (CT)- or magnetic resonance (MR)-based imaging with volume-based prescriptions, (C): Advanced 3D IGBT, with fractions delivered using advanced IC or intracavitary-interstitial (IC-IS) techniques and planned using CT- or MR-based imaging with volume-based prescriptions.)), procedural times, anesthesia, imaging, and treatment planning. National BT resource data was also collected. Recommendations were developed to optimize workflows and facilitate IGBT transition. A total of 365 workflows were analyzed, wherein workflow B was most common (51%). Median procedure times were 2 hours 08 minutes (Interquartile range (IQR) 1 hour and 7 minutes), 2 hours 35 minutes (IQR 1 hour and 51 minutes), and 4 hours 16 minutes (IQR 2 hours and 33 minutes) for workflows A, B, and C, respectively. Using sedation instead of full anesthesia shortened workflows by a median of 35 minutes. BT machine demand, based on national cervical cancer incidence, ranged from 0.2 to 9.5; four countries had low (< 0.5), two moderate (0.5 - 1.0), and eight high demand (>1.0). Resource- and context-specific recommendations for IGBT transition were provided. BT workflows varied widely. Substantially increased procedure times and resource use were observed with advanced workflows. Findings highlight opportunities to improve efficiency through anesthesia choice, imaging strategy, and planning workflow optimization. Implementing context-specific strategies will be crucial for IGBT transition. Funding from the XXXX, in collaboration with XXXX and participating sites.

Radiotherapy is integral to cervical cancer management, but can cause iatrogenic premature ovarian insufficiency (POI) or early menopause, leading to vasomotor symptoms, sexual dysfunction, mood changes, and long-term health risks. Systemic menopausal hormone therapy (MHT) is recommended to mitigate these effects in women with POI. Its role is physiologic hormone replacement, termed menopausal replacement therapy (MRT). This study assessed systemic MHT use and prescribing patterns in premenopausal patients treated with radiotherapy for cervical cancer in British Columbia. We conducted a retrospective cohort study of women aged 18-45 years, diagnosed with cervical cancer, and treated with curative intent primary or adjuvant radiotherapy between January 1 and December 31, 2022. Data was obtained from the BC Cancer Registry and extracted through chart review. Descriptive statistics and Fisher's exact test were used for analysis. Fifty-one patients met inclusion criteria (median age 38 years). Most received primary chemoradiotherapy (86.3%), while 13.7% received adjuvant radiotherapy. Overall, 74.5% (n = 38/51) were prescribed MHT after treatment. The proportion of patients receiving MHT was higher among those treated with adjuvant radiotherapy compared to those who received primary chemoradiotherapy (85.7% vs. 72.7%, P = 0.66). Median time to first MHT prescription was 3.47 months after completing radiotherapy (range 2 weeks-2 years). All MHT prescriptions were provided following completion of radiotherapy. Among those prescribed MHT, 63.2% required dose escalation, 78.9% had formulation changes, 18.4% had dose reductions, and 18.4% discontinued therapy. Three quarters of patients were prescribed MHT. Initiation was delayed until after radiotherapy completion. Frequent dose and formulation adjustments highlight the complexity of survivorship care and the need for standardized counseling and management pathways to improve quality of life.

Concurrent chemoradiotherapy (CRT) followed by brachytherapy is the standard of care for locally advanced cervical cancer. However, post-treatment management remains challenging. Accurate response assessment is essential because it informs subsequent management, particularly the indication for completion surgery. Radiation-induced tissue changes may impair the reliability of clinical examination and conventional imaging, while the respective roles of advanced imaging modalities and completion surgery remain debated. Functional lumbopelvic MRI incorporating diffusion-weighted and perfusion sequences is the reference imaging modality for response assessment and provides greater diagnostic performance than clinical examination alone. FDG PET-CT offers complementary information, particularly regarding nodal disease and early metabolic response, but the routine combination of FDG PET-CT with MRI has not been shown to improve diagnostic accuracy. MRI performed early during CRT may help differentiate responders from nonresponders based on changes in the apparent diffusion coefficient. However, the optimal timing of MRI after treatment completion remains uncertain. Available evidence does not support the routine use of conization for response assessment. Completion surgery provides no prognostic benefit and increases morbidity in patients with squamous cell carcinoma who achieve a complete response after CRT and brachytherapy. Evidence remains insufficient to establish its role in adenocarcinoma. When completion surgery is indicated, delaying the procedure until at least 6-8 weeks after CRT may reduce postoperative morbidity. Simple hysterectomy should be favored over radical hysterectomy, which increases morbidity without improving survival. Current evidence demonstrates no superiority of minimally invasive surgery or laparotomy in terms of oncologic outcomes or overall morbidity.

Sevoflurane, a commonly used inhaled anesthetic, has been implicated in modulating tumor biology and perioperative immune responses, yet the underlying molecular mechanisms remain poorly understood. This study aims to investigate whether sevoflurane regulates key immune-related genes in cervical cancer patients undergoing laparoscopic radical hysterectomy (LRH) and to explore the clinical relevance of such regulation. Based on prior RNA-seq screening, we established a two-step validation framework to identify sevoflurane-regulated genes in a clinical cohort. A total of 116 cervical cancer patients undergoing LRH were enrolled, including 70 who received sevoflurane anesthesia and 46 who received propofol anesthesia. Peripheral blood samples were collected at five perioperative time points. mRNA expression levels of candidate genes were measured by qRT-PCR, lymphocyte subsets were analyzed by flow cytometry, and VAMP5 protein expression was assessed by intracellular staining. Bioinformatics analyses were performed using TCGA data to evaluate associations between candidate genes and tumor immune infiltration. MAP3K7 and VAMP5 were validated as sevoflurane-downregulated targets, showing sustained suppression postoperatively compared to the propofol group. VAMP5 expression correlated significantly with tumor progression and immune cell infiltration in cervical cancer, particularly CD8 + T-cells, B-cells, and macrophages. Among sevoflurane-treated patients, those with lower VAMP5 expression exhibited delayed postoperative recovery of CD8 + T-cell counts at 48 and 72 h after surgery, whereas no such difference was observed for other lymphocyte subsets. This study identify VAMP5 as a novel molecular link between anesthetic choice and immune modulation, suggesting that sevoflurane may influence perioperative immune recovery through vesicle-associated mechanisms, with potential implications for optimizing anesthesia strategies to improve oncologic outcomes.

To summarize the available evidence on the management of cervical cancer in older women across early and advanced disease stages, with particular attention to treatment selection, feasibility, tolerance, and specific clinical situations, including cervical cancer associated with pelvic organ prolapse. A narrative review was conducted using PubMed/MEDLINE, Embase, and the Cochrane Library. Studies addressing surgery, radiotherapy, concurrent chemoradiotherapy, brachytherapy, para-aortic lymphadenectomy, cervical cancer associated with pelvic organ prolapse, and pre-treatment geriatric assessment were considered. The evidence was synthesized qualitatively according to six predefined clinical questions. In early-stage disease, radical hysterectomy is feasible in selected fit elderly patients but is associated with increased perioperative morbidity, with advancing age. The available evidence does not establish whether surgery or definitive radiotherapy provides superior oncological outcomes in this population. In locally advanced cervical cancer, concurrent chemoradiotherapy appears to improve survival compared with radiotherapy alone in selected older patients, but with increased toxicity. Brachytherapy is associated with improved local control and survival, yet its use decreased with advancing age. No age-specific evidence demonstrated a survival benefit form pretreatment para-aortic lymphadenectomy. Data on cervical cancer associated with pelvic organ prolapse are limited to heterogeneous case reports and small retrospective studies. Pretreatment geriatric assessment influences treatment decisions in mixed cancer populations, but cervical cancer-specific outcome data are lacking. Age-specific evidence remains limited and largely retrospective, and chronological age alone should not determine access to standard treatment. Treatment selection requires integration of tumor characteristics, frailty, comorbidities, functional status, expected treatment tolerance, quality of life, and patient preferences.

To review the available evidence on post-treatment follow-up and recurrence management after cervical cancer. We conducted a narrative review of the literature on surveillance modalities, and the management of pelvic and nodal recurrences. Most recurrences occur within three years of treatment, but the survival benefit of detection before symptom onset remains unproven. After fertility-sparing surgery, HPV testing is sensitive for detecting asymptomatic pelvic recurrence. After hysterectomy, most recurrences are symptomatic, and clinical examination has a higher diagnostic yield than HPV testing or vaginal vault cytology. After concurrent chemoradiotherapy (CRT), persistent HPV infection is associated with an increased recurrence risk, but its limited specificity and the absence of a validated HPV-based surveillance strategy restrict its clinical utility. MRI and FDG PET/CT are useful for response assessment and investigation of suspected recurrence, but evidence supporting routine imaging of asymptomatic patients is lacking. Intensive follow-up schedules have not improved recurrence detection or survival. Evidence on recurrence management is predominantly retrospective. Pelvic recurrences after primary surgery have been treated with CRT, supplemented by brachytherapy for vaginal involvement. In selected patients with central pelvic recurrence after CRT, complete surgical resection may provide prolonged survival, but carries substantial morbidity. Nodal recurrences outside previously irradiated fields have been treated with CRT. Available evidence supports a predominantly clinical, treatment-adapted follow-up. The survival benefit of intensive surveillance, routine imaging, or detecting asymptomatic recurrence remains uncertain. Recurrence management requires individualized multidisciplinary assessment based on disease extent, disease-free interval, and previous treatments.

ObjectivesTo estimate cervical screening coverage and inequities among Peruvian women aged 30-49 years and evaluate lifetime cost-utility and 5-year budget impact of scaling up HPV DNA testing, including self-sampling.SettingPeru, using national ENDES (Demographic and Family Health Survey) data and public sources.MethodsWe linked a cross-sectional ENDES 2015-2024 analysis to a public-payer decision model. Up-to-date screening was Pap or visual inspection with acetic acid within 3 years, or molecular HPV testing within 5 years. A screening decision tree and lifetime state-transition (Markov) model compared current practice with HPV self-sampling, clinician-collected testing, and hybrid expansion. We estimated costs, quality-adjusted life-years (QALYs), sequential incremental cost-effectiveness ratios (ICERs), probabilistic optimality, and budget impact at S/ 25,007 (Peruvian soles) / QALY.ResultsIn 2024, 63.6% were up to date, 36.4% underscreened, 15.0% never screened, and 12.9% reported recent molecular HPV testing. The efficiency frontier was current practice, hybrid expansion to 90%, and clinician-collected HPV testing at 90%; sequential ICERs were S/ 5434 and S/ 10,982/QALY. In 5000 simulations, clinician-collected 90%, self-sampling 90%, and hybrid 90% had optimal-strategy probabilities of 69.46%, 15.46%, and 13.38%. Annualized budget impact was S/ 24.44 million for hybrid 90% and S/ 67.17 million for clinician-collected 90%.ConclusionsClinician-collected HPV testing at 90% maximized expected net monetary benefit under modeled assumptions, while hybrid expansion required less short-term expenditure. Policy should balance lifetime efficiency, feasibility, affordability, and linkage to diagnosis and treatment.