Ny forskning om jente- og kvinnehelse

Gynecological cancers, including cervical, endometrial, and ovarian cancers, represent a growing global health burden with increasing incidence and mortality. The vaginal microbiome has emerged as a promising target for early cancer diagnosis and therapeutic intervention. Therefore, this review summarizes the composition and dynamics of the vaginal microbiome, emphasizing its association with the pathogenesis of gynecological cancers through chronic inflammation, immune modulation, and hormonal interactions. Advances in technologies such as 16S rRNA sequencing, metagenomics, and multi-omics have enabled the identification of potential microbial biomarkers. Probiotics, antibiotics, and vaginal microbiota transplantation are treatment technologies of gynecological cancers demonstrating considerable potential in restoring microbial balance and improving clinical outcomes. Furthermore, significant challenges persist in standardizing microbial biomarkers and translating research findings into precision therapies. Future studies should prioritize large-scale clinical validation and develop integrative strategies to harness the potential of the vaginal microbiome for cancer prevention and personalized treatment.

Senile vaginitis is a common clinical condition with limited treatment options. Estrogen deficiency leads to atrophy of the vaginal walls and thinning of the mucosa. It is noteworthy that although vaginal atrophy is an almost universal consequence of menopause, many postmenopausal women do not develop genitourinary symptoms. These observations collectively indicate that estrogen-independent pathogenic mechanisms are involved. In our preliminary study, through metabolomic screening, we identified three functionally relevant metabolites, namely guggulsterone (GS), umbelliprenin, and inosinic acid. This study seeks to elucidate the pathogenic mechanism of GS in senile vaginitis and to unveil novel therapeutic avenues for this condition. Cellular and animal experiments confirm that GS elevates intracellular ferrous iron (Fe 2+ ), malondialdehyde, and reactive oxygen species levels in vaginal epithelial cells, thereby inducing ferroptosis and upregulating the expression of inflammatory factors in vaginal tissues. Consequently, these processes compromise vaginal mucosal integrity, thereby exacerbating epithelial atrophy and the progression of inflammation. Treatment with the ferroptosis inhibitor ferrostatin-1 partially reversed the accumulation of Fe 2+ , lipid peroxides, and cellular oxidative stress. By utilizing a combination of lipidomic mass spectrometry, molecular docking, and surface plasmon resonance, it was collectively demonstrated that GS directly binds to heme oxygenase 1 (HMOX1). Utilizing VK2/E6E7 cell models with lentivirus-mediated HMOX1 knockdown and overexpression, this study demonstrates that GS might contribute to ferroptosis in vaginal epithelial cells by upregulating HMOX1 expression. Notably, treatment with MG132 potentiated the GS-induced upregulation of HMOX1, whereas the autophagy-lysosome inhibitor bafilomycin A1 had no significant effect. These findings suggest that GS may upregulate HMOX1 levels by inhibiting its degradation through the proteasome pathway. Collectively, these findings establish GS as a critical regulator of vaginal epithelial cell ferroptosis through HMOX1 targeting, revealing new therapeutic avenues for senile vaginitis. Antioxid. Redox Signal. 45, 618-635.

Reproductive efficiency is a key determinant of sustainability and profitability in sheep farming systems; however, the role of the vaginal microbiome in shaping pregnancy outcomes remains insufficiently understood. This study aimed to characterise the vaginal microbial communities of Central Anatolian Merino sheep using 16S rRNA gene amplicon sequencing and to explore their potential association with reproductive success. Vaginal samples were collected from 20 healthy ewes (10 non-pregnant (G1), that failed to conceive and returned to oestrus and 10 pregnant (G2), conceived at first service) with comparable physiological characteristics before breeding, followed by high-throughput amplicon sequencing to comprehensively profile the bacterial community structure. Comparative analyses were conducted between pregnant and non-pregnant animals to identify microbial patterns linked to pregnancy outcomes. The vaginal microbiome exhibited a diverse yet structured taxonomic composition across both groups, dominated by members of Bacillota (44.8% in G1 and 45.6% in G2), Actinomycetota (12.0% in G1 and 9.3% in G2), Pseudomonadota (6.6% in G1 and 6.2% in G2) and Bacteroidota (5.6% in G1 and 5.9% in G2). Alpha diversity did not differ significantly between groups (Wilcoxon rank-sum test, p > 0.05 across all indices), and beta diversity showed no significant separation (PERMANOVA, R 2 = 0.055, p = 0.38), indicating substantial community overlap. Differential abundance analysis (edgeR) identified 23 taxa that differed between groups (FDR < 0.05), suggesting that reproductive outcomes may be influenced by subtle ecological shifts rather than large-scale microbial restructuring. Collectively, these findings provide novel insights into the vaginal microbial ecology of Central Anatolian Merino sheep and identify candidate microbial signatures that may warrant further investigation as potential correlates of fertility. Given the observational design and limited sample size, these associations should be interpreted as preliminary and hypothesis-generating. By advancing our understanding of host-microbiome interactions within the reproductive tract, this study establishes a foundation for microbiome-informed strategies aimed at improving reproductive performance and supporting sustainable sheep production.

To evaluate whether reducing overall treatment time (OTT) by shortening interventional radiotherapy (IRT; brachytherapy) duration affects outcomes in patients with locally advanced cervical cancer undergoing definitive chemoradiation. In this randomized clinical trial, conducted in 2016-2017, 75 patients with stage IB2-IVA cervical cancer were enrolled. The intervention group (n = 41) completed high-dose-rate IRT within 1 week, whereas the control group (n = 34) received the conventional 3-week schedule. The primary endpoint was treatment-related complications. At 5-year follow-up, 7 patients were lost to follow-up, leaving 68 patients for analysis. Median OTT was significantly shorter in the intervention group (59 vs. 64.5 days; p = 0.01), and the complete response rate was higher (53.1% vs. 31.3%; p = 0.041). No significant differences were observed in overall survival (p = 0.962) or disease-free survival (p = 0.128). Multivariate analysis identified treatment response as a significant predictor of survival, with complete response associated with improved outcomes (p < 0.001). Acute and late adverse events, including proctitis, cystitis, and vaginal hemorrhage, were comparable between groups (all p > 0.05). Shortening IRT duration reduced OTT and improved complete response without increasing treatment-related toxicity, although no significant survival benefit was observed.

This study aims to develop the functional nanocomposites (Au-MoS 2 ) for biomedical applications potentially for anticancer activity. The nanocomposite was synthesized via chemical method by integrating gold nanoparticle onto exfoliated MoS 2 nanosheets. Scanning electron microscopy analysis revealed irregular, aggregated MoS 2 nanosheets with a porous and rough morphology, decorated by uniformly distributed spherical shaped Au particles. Energy-dispersive X-ray analysis confirmed the presence of Mo, S, and Au, indicating the successful formation of the high purity hetero-structured nanocomposite. Fourier transform infrared spectroscopy confirmed the key functional groups and interfacial interactions between the components, while X-ray diffraction pattern showed the crystalline nature of both MoS 2 and Au nanoparticles. The biological evaluation indicates moderate cytotoxic activity with an IC 50 of 181.7 µg/mL. Morphological observations and fluorescence staining confirmed apoptotic features including chromatin condensation, membrane blebbing, and nuclear fragmentation. Further, the gene expression analysis revealed upregulation of pro-apoptotic markers (Bad and caspases), and downregulation of anti-apoptotic Bcl-2, highlighting the activation of mitochondrial-mediated apoptosis. The Au-MoS 2 nanocomposite demonstrated combined effects, structural stability, and controlled cytotoxicity, highlighting its potential as an effective platform for targeted cancer therapy and other biomedical applications.

Cervical cancer disproportionately impacts women in low- and middle-income countries (LMICs), where over 90% of global cervical cancer deaths occur. Lay health workers, such as community health promoters (CHPs), with appropriate training and support, can play a pivotal role in cervical cancer prevention. Our team developed a multi-level intervention, Elimisha-HPV, to support CHP-delivered human papillomavirus (HPV) testing in Kenya. The present analysis evaluates impact of Elimisha-HPV on the following CHP outcomes: i ) knowledge of screening delivery and privacy, confidentiality, and professionalism; ii ) stigma associated with cervical cancer, human immunodeficiency virus (HIV), and HPV; and iii ) confidence to counsel in screening delivery. We used descriptive statistics and linear mixed effects regression models to evaluate intervention effects (intervention group, n = 64; control group, n = 60). For knowledge and privacy, no statistically significant effects were observed (knowledge: β= -0.08 [95% CI, -0.22 to 0.07]; privacy: β= 0.04 [95% CI, -0.05 to 0.13]). No statistically significant intervention effects were observed for stigma associated with cervical cancer, HIV, or HPV (cervical cancer: β= 0.02 [95% CI, -0.13 to 0.16]; HIV: β= 0.01 [95% CI, -0.11 to 0.13]; HPV: β= 0.02 [95% CI, -0.11 to 0.14]). For the confidence to counsel Likert scale-style questions, evaluated using descriptive and regression approaches, proportional increases were observed across both arms, but the main effect was not statistically significant ( β= 0.01 [95% CI, -0.09 to 0.11]). Our findings align with previous work demonstrating that stigma surrounding cervical cancer in LMICs is difficult to effectively influence, and provide a foundation for shaping future stigma-reduction campaigns. ClinicalTrials.gov identifier: NCT05736588.

To identify predictive biomarkers for immunotherapy response in advanced/recurrent cervical cancer by evaluating peripheral blood indicators including T-cell subsets and serum biomarkers. This prospective study (June 2022-July 2024) enrolled 50 patients with stage III-IVa or recurrent cervical cancer receiving first-line immunotherapy combined with chemo/radiotherapy from Qingdao Central Hospital network. We analyzed baseline CD4 + /CD8 + T-cell percentages and post-treatment (after one course) levels of CA125, SCCA, T-cell subsets, and PD-1 expression on T-cells using logistic regression (treatment efficacy，comparing 36 responders vs. 14 non-responders) and Cox regression (prognosis, with disease progression or death events occurring in 26 patients). Treatment response was significantly associated with: (1) baseline CD4 + T-cell percentage and (2) post-treatment CA125/SCCA levels, CD8 + T-cell percentage, and PD-1 expression on both CD4+/CD8+ T-cells (all p < .05). Prognostic factors identified by Cox regression included these same markers plus post-treatment CD4 + T-cell percentage. Optimal responders showed: high baseline CD4 + T-cells, low post-treatment CA125/SCCA, elevated CD4 + /CD8 + T-cells, and reduced PD-1 expression. Peripheral T-cell subsets and serum biomarkers show significant associations with predicted immunotherapy outcomes. High baseline CD4 + T-cells with post-treatment normalization of immune markers (increased T-cells, decreased PD-1+ cells, and tumor antigens) are associated with a higher likelihood of benefiting from immunotherapy. It should be noted that this study has limitations, including a modest sample size and the assessment of biomarkers at only a single post-treatment time point, which may affect the generalizability of the findings. These peripheral blood biomarkers may represent a minimally invasive approach for exploring treatment dynamics and are considered worthy of further investigation as potential adjuncts in the context of personalized immunotherapy for advanced cervical cancer. However, their predictive performance and clinical utility remain to be validated in larger, independent cohorts before any clinical application can be considered.

The objectives of this cross-sectional survey were to assess the knowledge, attitudes, and practices toward cervical cancer screening among female university students in Italy and to identify the associated determinants. The survey was conducted in July and September 2025 in Caserta and Naples, involving 1003 respondents. The average knowledge score regarding human papillomavirus (HPV) infection and cervical cancer was 12.6 out of 20, with only 2% achieving the maximum score. Knowledge was significantly higher among participants who were older, those in the medical field, those vaccinated against HPV, those who had oral sex, and those who received information from healthcare workers (HCWs). Only 12.7% perceived themselves at high risk for HPV-related cancer, with higher concern among those not in the medical field and those who had acquired information from HCWs. More than half (56.9%) considered Pap test useful, and this was more likely among older participants, those with a higher knowledge score, those who had received HPV vaccination, and those who had acquired information from HCWs. Among screening-eligible students aged ≥25 y, 65.1% had undergone cervical cancer screening, and 72.7% adhered to the recommended intervals. Screening uptake was higher among those older and those who had engaged in sexual intercourse. These findings highlight the urgent need for targeted health education interventions, optimized HCW communication, and the dissemination of information to improve awareness, risk perception, and cervical cancer screening uptake.

The prognosis for patients with recurrent or metastatic cervical cancer (r/mCC) remains challenging, with a 5-y survival rate of approximately 17%. Although first-line treatment has evolved from traditional single-agent chemotherapy to combination regimens that incorporate targeted therapy and immunotherapy-showing improved initial response rates - therapeutic options after disease progression remain limited and often yield suboptimal outcomes. Ivonescimab, the first tetravalent bispecific monoclonal antibody capable of simultaneously targeting programmed death receptor-1 (PD-1) and vascular endothelial growth factor A (VEGF-A), demonstrates robust anti-tumor activity and a manageable safety profile across various solid tumors through synergistic blockade of both immune checkpoint pathways and tumor angiogenesis. This case report describes a patient diagnosed with cervical squamous cell carcinoma accompanied by hepatic metastases who received first-line therapy with platinum-based chemotherapy in combination with cadonilimab and bevacizumab. According to RECIST 1.1 criteria, a partial response (PR) was achieved after four treatment cycles, with a PFS of 11 months. Subsequent to disease progression, second-line treatment was initiated with ivonescimab combined with single-agent albumin-bound paclitaxel. After two treatment cycles, PR was achieved, and the patient continues to derive clinical benefits. Throughout the treatment course, the patient experienced only low-grade adverse events (CTCAE grade 1 or below) and maintained a satisfactory quality of life. To our knowledge, this is the first reported case demonstrating a significant response to ivonescimab in recurrent or metastatic cervical cancer following failure of first-line immunotherapy combined with anti-angiogenic therapy. This case preliminarily validates its anti-tumor activity and safety characteristics, and presents a novel therapeutic strategy for later-line management.

The hypothesis-generating case study aimed at identifying those who are sensitive to anti-PD-L1 and TGF-β bifunctional fusion proteins and exploring potential mechanisms in the treatment of recurrent cervical cancer. We report that recurrent cervical cancer treated with anti-PD-L1 and TGF-β bifunctional fusion proteins in Qilu Hospital of Shandong University show distinct clinical therapeutic outcomes. We describe the clinical course, characteristics, and genetic characteristics of the patients and analyzed the differentially expressed genes (DEGs) following treatment. The elevation of peripheral blood lymphocytes after treatment may predict response to anti-PD-L1 and TGF-β bifunctional fusion proteins, since partial response (PR) and progressive disease (PD) exhibit different trends. A total of 4,844 DEGs were selected between PR and PD patients during the anti-PD-L1 and TGF-β bifunctional fusion protein treatments, which are believed to be involved in the regulation of the immune response. We demonstrated that changing-fate genes continuously change during treatment fostering the IL 17 signaling pathway and TGF-β signaling pathways. Finally, we identified the prognostic genes and validated that high expression levels of PMEPA1, FSTL3, SERPINE1, CXCL1, CXCL8, and low expression levels of JUND，MAP2K2 were significantly associated with poor prognosis of cervical cancer patients using the TCGA database. Anti-PD-L1 and TGF-β bifunctional fusion proteins are feasible and effective for recurrent cervical cancer through the IL 17 signaling pathway and TGF-β signaling pathways. A novel immune infiltration-based gene signature consisting of PMEPA1, FSTL3, SERPINE1, CXCL1, CXCL8, JUND, and MAP2K2 plays a crucial role in recurrent cervical cancer patients with anti-PD-L1 and TGF-β bifunctional fusion proteins.

Human papillomaviruses (HPVs) cause diverse cutaneous and mucosal diseases, with several genotypes strongly associated with cervical cancer. Beyond the well-established role of cellular microRNAs (miRNAs) in gene regulation, increasing evidence shows that HPV also encodes its own viral miRNAs (v-miRNAs). These v-miRNAs modulate both viral and host gene expression, influencing key pathways involved in oncogenesis, including cell cycle control, apoptosis, immune evasion, and epithelial - mesenchymal transition. By shaping these regulatory networks, HPV-derived miRNAs promote viral persistence and contribute to malignant transformation. Their stability and specificity also make them promising biomarkers for cervical cancer diagnosis and prognosis, although clinical translation remains challenging. This review provides an updated overview of HPV-encoded miRNAs, their validated molecular targets, and their roles in tumour development. It also highlights emerging therapeutic strategies and future perspectives for integrating miRNA-based approaches into precision oncology for HPV-related cervical cancer.

To develop a machine learning-based risk prediction model for acute radiation enteritis (ARE) in patients with cervical cancer, providing a new method for early and accurate prediction of ARE during radiotherapy. This prospective study enrolled patients with cervical cancer undergoing radiotherapy from March 2024 to March 2025. The patients were randomly divided into training and test sets at a 7:3 ratio. Prediction models were constructed using Logistic Regression (LR), Decision Tree (DT), and Random Forest (RF) algorithms. Model performance was evaluated based on the area under the receiver operating characteristic curve (AUC), accuracy, precision, sensitivity, specificity, and F1-score. The incidence of ARE was 52.85% (204/386). Among the three models, the Random Forest model demonstrated the best performance, with an AUC of 0.961, sensitivity of 0.934, and F1-score of 0.905. These performance metrics were consistently higher than those of the LR (AUC, 0.860; sensitivity, 0.739; F1-score, 0.736) and DT (AUC, 0.910; sensitivity, 0.887; F1-score, 0.873) models. The RF model showed good clinical utility in effectively identifying high-risk patients for early intervention. Feature importance ranking derived from the RF model identified the parametrial dose, radiotherapy time, clinical stage, rectal V40, age, Platelet-to-Lymphocyte Ratio (PLR), concurrent chemotherapy, and hypertension as the most influential predictors, in descending order of importance. The RF-based risk prediction model exhibited excellent performance in assessing the risk of ARE among patients with cervical cancer undergoing radiotherapy, thereby enabling individualized risk assessment and facilitating early preventive strategies.

Objective : Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has recently emerged as a promising therapeutic strategy for cervical cancer, particularly in tumors resistant to conventional radiotherapy and chemotherapy. This review aims to systematically summarize the current understanding of ferroptosis mechanisms in cervical cancer and its potential therapeutic implications. Methods : We comprehensively reviewed the literature focusing on key regulators of ferroptosis in cervical cancer, including system Xc- (SLC7A11), glutathione peroxidase 4 (GPX4), iron metabolism, and lipid peroxidation pathways. The interactions between ferroptotic processes and cervical cancer-specific cellular redox homeostasis and metabolic adaptations were analyzed. Additionally, the crosstalk between ferroptosis and oncogenic signaling pathways such as p53 and NRF2 was examined. Results : Accumulating preclinical evidence indicates that induction of ferroptosis sensitizes resistant cervical cancer cells to standard therapies by disrupting cellular redox balance and metabolic mechanisms. The intricate interplay between ferroptotic pathways and established tumorigenic signaling networks highlights the complexity of ferroptosis regulation in cervical cancer progression. Nonetheless, translational challenges remain, including the lack of robust ferroptosis-specific biomarkers for clinical application, potential off-target toxicity, and the need for optimized combination regimens. Conclusion : Future research should prioritize elucidating ferroptosis modulators within the tumor microenvironment, refining combinatorial therapeutic strategies, and developing targeted delivery systems. Integrating ferroptosis-based approaches with existing treatments holds significant potential to overcome therapeutic resistance and improve outcomes in advanced or recurrent cervical cancer. This review provides new insights and strategic directions for leveraging ferroptosis as a novel and actionable vulnerability in cervical cancer therapy.

Immunotherapy offers potential benefits for recurrent or metastatic cervical cancer (R/M CC), yet personalized predictive tools are essential for optimizing treatment. This study aims to develop a nomogram integrating nutritional-inflammatory biomarkers and clinical features to predict survival in R/M CC patients undergoing immune checkpoint inhibitor (ICI) therapy. We retrospectively analyzed 98 R/M CC patients treated with ICIs. Overall survival (OS) was the primary endpoint. Demographic characteristics and peripheral blood biomarkers before and after ICI treatment were collected. Univariate analysis screened potential variables, followed by LASSO regression to select key biomarkers and compute the Risk-Score. Prediction models combining clinical features and the Risk-Score were evaluated using ROC curves and decision curve analysis (DCA). The optimal nomogram model was developed and validated with ROC curves, calibration plots, and DCA. Three models were established: (i) a clinical model based on age and squamous cell carcinoma antigen (SCC-Ag), (ii) a Risk-Score model, and (iii) a combined model integrating age, SCC-Ag, and Risk-Score. The combined model showed superior predictive performance. A nomogram incorporating age, stage, SCC-Ag, and Risk-Score predicted 6-month, 1-year, and 2-year survival probability, with respective AUC values of 0.892, 0.868, and 0.846. Calibration curves and DCA affirmed high predictive accuracy and clinical utility. The nomogram integrating nutritional-inflammatory biomarkers and clinical parameters may serve as a promising tool for predicting survival in R/M CC patients undergoing ICI therapyand may help guide individualized treatment strategies following further validation. This study established a comprehensive model that integrates clinical features and five nutritional-inflammatory biomarkers, effectively predicting OS in patients with R/M CC undergoing ICI therapy, with an AUC of 0.897.The results indicate that a high-risk score is strongly correlated with a poorer prognosis. Kaplan-Meier survival curve analysis further underscores the pivotal role of cancer-related inflammation in driving metastasis and deteriorating prognosis.By integrating clinical features and an immune-inflammatory score into a visual nomogram, this model offers clinicians a simplified and intuitive tool for personalized assessment of patients’ immune status and treatment response, ultimately enhancing the clinical application of immunotherapy.

Understanding motivators for cervical cancer screening among young women is critical for improving participation rates and reducing the incidence of cervical cancer. Young women have low participation rates in the CervicalScreen Norway. In 2022, the first cohort of school-based human papilloma virus vaccinated women entered the screening programme at the age of 25 years. This paper investigates reflections regarding cervical cancer screening and factors that influence attendance among first or second-time invitees in the CervicalScreen Norway. The study comprises 18 qualitative semi-structured individual interviews with Norwegian women aged 25-29 years of which 14 had attended screening. We used reflexive thematic analysis with a critical approach and identified three main themes related to trust, social expectations, and perceived vulnerability. The three main themes were 'trusting health authorities but wishing for a clearer message'; 'normalisation of screening participation driven by social expectations'; and 'efforts to avoid vulnerability during the test procedure'. Trusting the authorities to provide beneficial health initiatives, the women would follow advice about screening. Social expectations led to consider screening participation as the right thing to do. These young women felt vulnerable and inexperienced with gynaecological examinations and opted for screeners that reduced their feeling of vulnerability. Providing clear information on the screening procedure and expectations during gynaecological examinations is essential to reduce vulnerability and enhance participation among young women. Communication should highlight that screening is readily accessible in primary healthcare and be shared through media platforms popular with younger women.

Cervical cancer is the fourth common gynecological malignancy. To explore new therapeutic targets, we found that the transcriptional and translational levels of ELAVL1 were markedly increased in SiHa and HeLa cells as well as cervical cancer specimens. Knockdown of ELAVL1 substantially suppressed the proliferation, invasion, and migration of cervical cancer cells, while inducing apoptosis. Conversely, overexpression of ELAVL1 resulted in a substantial increase in the proliferative, invasive, and migratory capacities of SiHa cells. Bioinformatics predictions, RIP-qPCR and dual-luciferase reporter assays indicated that ELAVL1 might interact with the 3'UTR of ACVRL1 , and upregulate ACVRL1 and CASP14 expression. Co-transfection experiments and functional assays revealed that ELAVL1 might modulate malignant phenotypes of cervical cancer cells via the ACVRL1/CASP14 pathway. Furthermore, in vivo si-ELAVL1 administration significantly inhibited tumor growth in nude mouse xenograft models. ELAVL1 may promote cervical cancer progression, potentially through regulating the ACVRL1/CASP14 pathway, rendering ELAVL1 a potential candidate for therapeutic intervention.

Cervical cancer remains one of the most commonly diagnosed malignancies among women worldwide. Although USP22 is known to be involved in tumor progression, its specific function in cervical cancer remains unclear. This study explored the biological significance of USP22 and the mechanism by which it regulates cervical cancer progression. Through bioinformatic analysis, we identified that USP22 expression was significantly upregulated in cervical cancer tissues and was associated with proliferative potential. Single-cell RNA sequencing analysis revealed high USP22 expression in malignant epithelial cells, and USP22 expression was associated with the differentiation potential of cervical cancer cells. Moreover, USP22 deficiency suppressed cervical cancer cell proliferation, triggered cell cycle arrest in G0/G1, accelerated apoptosis, and inhibited migration and invasion. Mechanistically, USP22 bound to and deubiquitinated IRAK1, thereby preventing its proteasomal degradation and maintaining NF-κB pathway activation. USP22 deficiency significantly suppressed xenograft tumor growth and inhibited expression of the proliferation marker Ki67. Furthermore, IRAK1 overexpression abolished the suppressive effects of USP22 deficiency on cervical cancer cell growth and stemness. Collectively, this study provides evidence that USP22 regulates NF-κB signaling pathway by deubiquitinating and stabilizing IRAK1, suggesting that the USP22/IRAK1/NF-κB axis is a promising target for developing novel therapeutic strategies in cervical cancer.

Environmental microplastic exposure has been increasingly implicated in cervical carcinogenesis, yet the underlying biological mechanisms of microplastic-associated disease progression remain largely unexplored. Therefore, this study combined transcriptomic analysis, chemical-gene interaction data, machine learning, and molecular docking to investigate the molecular impact of microplastics exposure associated with disease progression. Transcriptomic data from GEO database was retrieved and differential expression analysis was performed, yielding a consensus core of 330 common genes across disease conditions. Microplastic candidates including Polystyrene, Polyethylene, Polypropylene, Nylon 612, Polymethyl Methacrylate, and Polyvinyl Chloride were selected based on established in vitro and in vivo evidence of carcinogenic potential in cervical tissues. Cross-referencing with chemical-gene interaction data identified 15 candidate genes linked to microplastic exposure and cervical cancer. The combinatorial feature selection across all 15-gene combinations (n = 32,570) using Support Vector Machine and Multinomial Logistic Regression algorithms yielded an optimized 5-gene diagnostic signature (FN1, HTR4, KIF14, PTP4A3, SLC7A2) for multiclass classification of Normal, CIN, and Cervical Cancer samples. The optimized SVM model achieved multiclass AUC values of 0.937, 0.889, and 0.925 for the Normal, cervical intraepithelial neoplasia (CIN), and Cancer classes, respectively, with further validation in independent GSE27678 validation cohort, demonstrating its robustness and generalizability. Molecular docking using AutoDock Vina demonstrated that polystyrene exhibited the highest binding affinities across all five target proteins, with peak scores of -6.681 kcal/mol, with KIF14. Collectively, these findings highlight potential molecular interactions between microplastics, particularly polystyrene, and key genes involved in cervical cancer progression. Thus, the proposed five-gene provides a promising framework for multiclass diagnosis and future studies of microplastics-associated carcinogenesis.

Cervical cancer (CC) remains a leading cause of cancer-related death among women, and the outlook for patients with advanced, recurrent or persistent disease is poor. Molecular markers that track disease progression and expose pharmacologically tractable vulnerabilities are therefore needed. GSE63514 and GSE138080 were used for exploratory candidate generation and cohort-specific disease-stage and discrimination analyses; random forest analysis was restricted to candidate prioritization. Prognostic relevance was assessed in TCGA-CESC (n = 304). Two independent siRNAs silenced RSRC1 in SiHa and CaSki cells, followed by viability, DNA synthesis, migration, cell-cycle and p53/CDK2 analyses. CDK2 overexpression, treatment with the p53 inhibitor pifithrin-α and a stable shRNA xenograft model evaluated pathway involvement and in vivo effects. RSRC1 expression increased across cervical disease stages. In GSE138080, RSRC1 discriminated cervical squamous cell carcinoma from non-carcinoma samples (area under the curve = 0.972, 95% confidence interval 0.925-1.000). High RSRC1 expression was associated with shorter overall survival (hazard ratio = 2.45, 95% confidence interval 1.55-3.87; P < 0.001) and remained independently associated after multivariable adjustment. In both cell lines, either siRNA reduced viability, DNA synthesis and migration, induced G2/M accumulation, increased p53 and decreased CDK2. CDK2 overexpression or pifithrin-α partially reversed these phenotypes. Stable RSRC1 depletion slowed xenograft growth, reduced Ki-67 and CDK2, and increased p53. RSRC1 is a candidate progression-associated biomarker that supports CC cell proliferation and migration. The findings support partial involvement of p53/CDK2-associated signaling, while independent clinical validation and direct characterization of RSRC1-regulated splicing remain necessary.

Although dexamethasone (DEX) is essential for preventing chemotherapy-induced nausea and vomiting during concurrent chemoradiotherapy (CCRT) for cervical cancer, prolonged administration carries risks of adverse events. Therefore, we evaluated the effect of a shortened DEX duration (steroid-sparing therapy) on the total control (TC) of nausea and vomiting in patients with cervical cancer undergoing CCRT comprising cisplatin 40 mg/m 2 to avoid the risk of adverse effects associated with DEX administration. This multicenter, retrospective study included 579 patients with cervical cancer who underwent CCRT between January 2016 and March 2024. Patients were classified into the steroid- sparing (DEX day 1; N=80) and non-steroid-sparing (DEX days 1-3; N=499) groups. TC was defined as the absence of vomiting and nausea without rescue medication during the entire CCRT period. A multivariate logistic regression analysis was used for between-group comparisons to adjust for potential confounders. The baseline rate of olanzapine use was significantly higher in the steroid-sparing group [28.8% vs . 10.6% (non-steroid-sparing group); p <0.001]. TC rates during the entire CCRT period were 30.0% and 36.5% in the steroid and non-steroid-sparing groups, respectively. No statistically significant difference in the overall TC period [odds ratio (OR)=0.826; 95% confidence interval (CI)=0.480-1.420; p =0.490] was observed. Furthermore, propensity score matching analysis adjusted for olanzapine use, radiation dose, and other covariates confirmed these findings (OR=0.736; 95% CI=0.370-1.460; p =0.381). However, the TC rate during the delayed phase in the non-steroid-sparing group (71.7%) was higher than that in the steroid-sparing group (60.0%), indicating an increased risk of treatment failure (OR=0.591; p =0.035). This difference was not statistically significant after Bonferroni correction (significance threshold: p <0.0125). Furthermore, propensity score-matched univariate analysis confirmed no significant difference in the delayed phase between the two groups ( p =0.243). Steroid-sparing therapy did not compromise TC rates, suggesting that it may be a clinically acceptable option for patients undergoing CCRT. However, individualized risk assessment and appropriate antiemetic use remain essential.

The clinical role of local therapy for advanced uterine cervical cancer remains unclear. While systemic chemotherapy is the standard treatment, pelvic radiotherapy may contribute to local control and potentially improve outcomes in selected patients. This study aimed to evaluate the clinical significance of pelvic irradiation in patients with advanced cervical cancer with para-aortic lymph node (PAN) and/or distant metastases. We retrospectively reviewed 35 patients with cervical cancer with PAN and/or distant metastases who underwent radiotherapy including whole-pelvic irradiation between 2009 and 2019. Patients were classified into a distant metastasis (DM) group and a PAN group. The DM group was further subdivided into patients with lymph node-only metastases (LY group) and those with organ metastases (OR group). Overall survival (OS) was estimated using the Kaplan-Meier method and compared using the log-rank test and Cox proportional hazards model. The median OS for all patients was 2.22 years. The median OS was 1.76 years in the DM group and 3.02 years in the PAN group, with no statistically significant difference between the groups ( p =0.838). Within the DM group, the median OS was 1.18 years in the OR group and 2.01 years in the LY group, with no significant difference ( p =0.590). Treatment was generally well tolerated, with limited severe adverse events. In Cox proportional hazards analysis using the PAN group as the reference, neither the OR nor the LY group showed a statistically significant difference in OS. Although limited by its retrospective design and small sample size, this study suggests that semi-definitive pelvic radiotherapy may be a reasonable treatment option for selected patients with cervical cancer with distant metastases.

To evaluate healthcare professionals' knowledge, attitudes, communication confidence and practices within an organised human papillomavirus (HPV)-based cervical cancer screening programme and identify factors associated with communication practices. A cross-sectional survey was conducted among 470 general practitioners and nurses involved in organised cervical cancer screening in Portugal's Central Region, January-March 2024. Participants completed a 28-item questionnaire. Exploratory factor analysis identified communication domains, and generalised linear models examined factors associated with communication practices. Knowledge of HPV infection and screening was relatively high, with gaps in HPV test interpretation and clinical management. General practitioners reported greater communication confidence than nurses. HPV infection- and screening-related information was communicated more frequently than information concerning HPV transmission and oncogenic risk. Professional group, knowledge of HPV infection and screening guidelines, communication confidence and communication of HPV test results were independently associated with the HPV infection and screening-related communication domain. No significant associations were identified for communication of HPV transmission and oncogenic risk. Despite relatively high knowledge, gaps remained in knowledge and communication practices, particularly regarding HPV transmission and oncogenic risk. Professional training integrating clinical knowledge with communication about HPV, cervical cancer screening and cancer risk may strengthen healthcare professionals' preparedness for HPV-based screening.

Cervical cancer is a preventable cancer through the use of screening and the human papillomavirus (HPV) vaccine. Even with the availability of screening and the HPV vaccine, disparities exist by geographic area (rural versus urban) and sexual orientation and gender identity. Due to stigma the lesbian, gay, bisexual, transgender, queer, and other sexual and gender minorities (LGBTQ+) encounter in healthcare, they are less likely to engage in routine healthcare. This is compounded in the rural LGBTQ+ population because of additional barriers such as lack of access to care, lack of competent providers, and financial constraints. A recent study in LGBTQ+ individuals in rural central and Southern Illinois revealed that only 50% of individuals were compliant with cervical cancer screening. Barriers to screening included poor prior experiences, financial burden, and gender dysphoria. There are strategies that could be utilized to address the disparities that exist among rural LGBTQ+ individuals. These include enhancing medical and clinical education, enhancing workforce diversity, enhancing the clinical environment to promote health equity, and enhancing regulatory pressure to enhance LGBTQ+-specific education opportunities. These efforts will be critical in reducing the health disparities that exist in cervical cancer screening among the LGBTQ+ population.

To evaluate 2-year late gastrointestinal (GI) toxicity, oncologic outcomes, and cost-effectiveness of hypofractionated concurrent chemoradiation with 44 Gy in 20 fractions (44 Gy/20F; HYPO) versus conventional fractionation (45 Gy/25F; CVRT + EMB) for locally advanced cervical cancer (LACC). The primary analysis was the randomized HYPOCx-iRex comparison (HYPO n = 21 vs. CVRT n = 19). A pre-planned pooled analysis additionally incorporated a concurrent, nonrandomized single-institute EMBRACE-II cohort (EMB n = 28; total n = 68). Late GI toxicity was graded by CTCAEv5.0. Dose-toxicity analysis used Cox and Probit regression to identify the effective dose associated with 10% toxicity probability (ED10). The indirect ratio of excess dose volume at 60 Gy EQD2 (iRex60) was evaluated as a brachytherapy (BT) conformity index. Locoregional control (LRC) and overall survival (OS) were estimated by Kaplan-Meier. Incremental cost-effectiveness ratios (ICERs) were calculated from provider and societal perspectives. Median overall treatment time was 39 versus 46 days in HYPO versus CVRT+EMB (p < 0.001). Late GI toxicity was numerically higher in HYPO (2-year Gr ≥2: 23.8% vs. 10.8%, pLR = 0.168; Gr ≥3: 19.1% vs. 5.3%, pLR = 0.066); iRex60 was identified as an independent predictor in multivariable regression (ED10 = 1.6 and 1.85 for Gr ≥2/Gr ≥3; proposed cut-off iRex60 <1.7). Favorable but nonsignificant trends in LRC (95.2% vs. 77.5%; HR = 0.43, pLR = 0.260) and OS (100% vs. 76.8%; HR = 0.22, pLR = 0.107) were observed. The 44Gy/20F regimen demonstrated dominant cost-effectiveness. Hypofractionated chemoradiation achieved LRC and OS comparable to conventional fractionation with shorter treatment time and lower cost. The higher late GI toxicity observed with hypofractionation is clinically meaningful without statistical significance. Further optimization of brachytherapy conformity and low-to-intermediate dose constraints is proposed before clinical adoption. The iRex60 threshold and the cost-effectiveness findings are hypothesis-generating and need further validation.

Cisplatin resistance remains a major limitation in the treatment of cervical cancer, with enhanced DNA damage repair contributing to reduced therapeutic sensitivity. The role of STAT5A in coordinating DNA double-strand break repair under therapeutic stress remains unclear. Here, we investigated the role of STAT5A in cisplatin responsiveness using clinical tissue analysis, CRISPR/Cas9-based genetic models, DNA repair assays, and xenograft models. STAT5A depletion sensitized cervical cancer cells to cisplatin, whereas STAT5A overexpression reduced cisplatin sensitivity. Mechanistically, STAT5A showed increased spatial association with γH2AX-positive nuclear regions following cisplatin exposure and transcriptionally promoted RNF8 expression. STAT5A enhanced HR-associated repair through an RNF8-mediated mechanism, as supported by reciprocal genetic experiments and residual DNA damage analysis. STAT5A loss was accompanied by reduced ATM/CHK2 activation, decreased expression of MRN complex components, RNF8 and RAD51, and increased persistence of cisplatin-associated DNA damage. Importantly, pharmacological inhibition of STAT5 reduced RNF8 expression, increased DNA damage, and enhanced the antitumor activity of cisplatin in cellular and xenograft models. Together, these findings identify STAT5A-RNF8 signaling as a regulator of HR-associated DNA repair and cisplatin responsiveness in cervical cancer and support further evaluation of this pathway as a therapeutic target.

Radiotherapy is central to cervical cancer (CC) treatment, yet radiosensitivity remains a key determinant of prognosis. Although adaptive immune response (AIR) influences tumor progression, its role in modulating CC radiosensitivity and the underlying molecular mechanisms remain largely unexplored. This study aims to elucidate the link between AIR and radiosensitivity, and to identify novel therapeutic targets. Multi-omics data were integrated to identify AIR-related prognostic genes via differential expression, weighted gene co-expression network analysis (WGCNA), univariate Cox, and least absolute shrinkage and selection operator (LASSO) analyses. A risk model was constructed and validated. Functional enrichment, immune infiltration, and drug sensitivity were assessed. Clinical validation used immunohistochemistry, and a radioresistant cell line was established. The expression levels of the key genes were measured by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting; colony formation assays evaluated radiosensitivity following their knockdown. Two genes (ITM2A and TCL1A) were identified to construct a prognostic risk model. High-risk groups exhibited distinct immune pathways, reduced immune infiltration, and altered drug sensitivity. Both genes correlated with mast cell differentiation. Notably, ITM2A and TCL1A were downregulated in radioresistant phenotypes, and their knockdown significantly enhanced post-irradiation colony formation versus controls, indicating a radiosensitizing role. ITM2A and TCL1A are identified as novel AIR-related radiosensitivity genes. Our risk model may serve as a potential prognostic stratification tool for CC, offering insights into combinatorial immunotherapy and radiosensitization strategies.

Treatment options remain limited for patients with recurrent cervical cancer following prior platinum-based systemic chemotherapy. Despite the activity of nedaplatin plus irinotecan in recurrent cervical cancer, its clinical value as a platinum rechallenge regimen following prior platinum-based systemic chemotherapy remains unclear. This study examined the efficacy and safety of this combination therapy in this setting. Patients with recurrent cervical cancer who received at least 1 cycle of nedaplatin plus irinotecan after recurrence or progression following prior platinum-based systemic chemotherapy at Jichi Medical University Hospital between January 2018 and December 2025 were retrospectively analyzed. Treatment efficacy and safety were evaluated, and survival outcomes were estimated using the Kaplan-Meier method. This study included 26 patients. The median platinum-free interval was 3 months, and 21 patients received nedaplatin plus irinotecan as a second-line platinum-containing systemic chemotherapy. The objective response rate among patients with measurable disease was 23.8%, whereas the disease control rate among all evaluable patients was 53.8%. The median progression-free survival was 5.0 months, whereas the median overall survival was 22.5 months. Grade ≥ 3 hematologic adverse events included neutropenia in 15 patients, anemia in 9, and thrombocytopenia in 5. No treatment-related death occurred. Nedaplatin plus irinotecan demonstrated clinically meaningful activity with manageable toxicity in selected patients with recurrent cervical cancer following prior platinum-based systemic chemotherapy. Platinum rechallenge may be a potential treatment option in this setting, although further studies are warranted to identify patients most likely to benefit.