ObjectivesThis study evaluates artificial intelligence (AI) reasoning capabilities in gynecologic cancer genetic counseling, comparing the performance of ChatGPT and DeepSeek models to guide patient-centered AI implementation in clinical genetics.MethodsUsing 40 National Comprehensive Cancer Network-aligned counseling scenarios, we conducted blinded dual-oncologist evaluations of two large language models. Methodological rigor included model anonymization, a pre-calibrated scoring framework, and validated metrics (Global Quality Scale and Patient Education Materials Assessment Tool) assessing informational coherence, understandability, and actionability.ResultsDeepSeek demonstrated superior informational breadth (mean character difference: -609.0, p < .0001) and visual communication (diagram integration, p < .01), with 49-fold greater probability in recommending clear and actionable actions (p < .01, OR = 49.0). ChatGPT excelled in concise summarization (22% faster response generation, p = .013).ConclusionStrategic AI model selection-leveraging DeepSeek's visually-rich, structured educational approach for complex information, and ChatGPT's concise, rapid summarization for efficient communication-enhances patient-centered genetic education when combined with clinician oversight. This framework supports healthcare's digital transformation by optimizing human-AI collaboration in hereditary cancer care.

The post-treatment recurrence after chemoradiotherapy remains a major clinical challenge in cervical cancer, and the underlying mechanisms remain incompletely understood. In this study, single-cell RNA sequencing analysis of human cervical cancer tissues before and after concurrent chemoradiotherapy (CCRT) revealed that cervical cancer tumor cells exhibited enhanced stemness along with upregulated expression of CD24 and MUC16 following CCRT. Meanwhile, tumor-associated macrophages exhibited upregulated expression of Siglec-10 and Siglec-9 after CCRT. Siglec-10+/Siglec-9+ macrophages could interact with CD24+/MUC16+ tumor cells, thereby potentially suppressing their ability to eliminate tumor cells. IL-4 strongly induces PD-L2 expression in Siglec-10+/Siglec-9+macrophages. Furthermore, these Siglec-10+/Siglec-9+ macrophages inhibited T cell function via PD-L2/PD-1 interactions, thereby facilitating tumor immune evasion. In summary, in cervical cancer following CCRT, CD24+/MUC16+ tumor cells might interact with Siglec-10+/Siglec-9+ macrophages to suppress tumor cell elimination and upregulate PD-L2 expression, thereby promoting T cell dysfunction, tumor immune evasion, disease recurrence, and ultimately poorer patient prognosis. CCRT-resistant CD24+/MUC16+ tumor cells drive M2-like macrophage polarization, which might subsequently suppress T cell function.

Fibrosis, angiogenesis and chronic inflammation are the intrinsic characteristics of endometriosis. It is accompanied by significant changes in the cell composition of both ectopic and eutopic endometrial tissues, occurring both before and after treatment with a gonadotropin-releasing hormone agonist (GnRHa). To further understand the pathological characteristics of fibrosis associated with endometriosis, it is worthwhile to explore the cellular heterogeneity of both ectopic and eutopic endometrium, as well as the changes before and after GnRHa treatment, using single-cell RNA sequencing (scRNA-seq). We performed scRNA-seq on a total of six samples (eutopic endometrium and ectopic lesions) from three patients with confirmed endometriosis. The patients comprised two untreated groups and one group that had undergone three months of GnRHa treatment. We profiled the transcriptomes of approximately 73,531 single cells from these samples. To this end, we aimed to characterize the changes in both the eutopic endometrium and the ectopic lesions during treatment. We observed a significant difference in the cellular composition between ectopic and eutopic endometrium in endometriosis patients. We divided stromal cells into five main subgroups, named ACTA2 + cluster, ECM1 + cluster, PDGFRB + cluster, Stromal cluster 4, and Stromal cluster 5 respectively. The ACTA2 + cluster is found predominantly in ectopic tissues and ECM1 + cluster mainly exists in eutopic endometrial tissues. In samples from GnRHa-treated patients, we observed a significant reduction in the number of cells within the ECM1 + cluster compared to untreated patients. This cluster represents the most critical cell subpopulation susceptible to hormonal influence, and the initiation of fibrosis may be triggered by decreased ECM1 expression in stromal cells. Analysis of immune cell composition revealed that CD8 + T-cells were significantly increased in ectopic endometrium compared to both eutopic endometrium and, furthermore, to post-GnRHa treatment tissues. The ratio of NK1 cells was significantly decreased, and the percentage of macrophages was increased in ectopic lesions compared to eutopic endometrium. Furthermore, GnRHa treatment induced a marked elevation in the percentage of neutrophils in ectopic endometrium. Cellular heterogeneity exists between ectopic and eutopic endometrium in ovarian endometriosis. Our analysis revealed significant stromal cell differences between these tissues and identified an ECM1-high subpopulation as the key cellular group in the non-fibrotic state. Furthermore, reduced ECM1 protein expression appears to initiate the fibrotic process in endometriosis.

BackgroundWhile human papillomavirus testing has become the primary screening modality for cervical cancer prevention, its implementation necessitates supplementary triage strategies. The viral oncoproteins E6 and E7, serving as primary mediators of high-risk HPV (hrHPV)-induced carcinogenesis, emerge as viable candidates for this risk stratification. We aimed to examine the clinical diagnostic performance of HPV E6/E7 immunocytochemical (ICC) assay in exfoliated cervical cells samples, to investigate the feasibility of using it as a potential biomarker in clinical triage algorithms for hrHPV-positive populations.MethodsWe prospectively collected and analyzed 1,005 hrHPV-positive cases from Beijing Obstetrics and Gynecology Hospital, Capital Medical University during September 2023 and March 2025. The diagnostic and triaging performance of HPV E6/E7 ICC assay were evaluated by sensitivity, specificity, positive predictive values, negative predictive values and operating characteristic curve.ResultsWhen used to detect CIN2+, the sensitivity of HPV E6/E7 ICC detection is (0.88, 95% CI: 0.82–0.92), which is better than that of cytological detection (0.609, 95% CI: 0.53–0.67), χ2 = 26.23, p < 0.05; the NPV of. HPV E6/E7 ICC detection is (0.95, 95% CI: 0.92–0.97), which is better than that of cytological detection (0.85, 95% CI: 0.82–0.88), χ2 = 38.14, p < 0.05. When the HPV typing test result is 16/18+,the sensitivity of HPV E6/E7 ICC detection is (0.93, 95% CI:0.86–0.96), which is better than that of cytological detection (0.61, 95% CI:0.52–0.70), χ2 = 33.47, p < 0.05; the NPV of HPV E6/E7 ICC detection is (0.940, 95% CI:0.89–0.97), which is better than that of cytological detection (0.81, 95% CI:0.75–0.85), χ2 = 13.84, p < 0.05. When the HPV typing test result is other hrHPV type, the sensitivity of HPV E6/E7 ICC detection is (0.81, 95% CI:0.71–0.89), which is better than that of cytological detection (0.75, 95% CI:0.64–0.84), χ2 = 0.914, p = 0.339; the NPV of HPV E6/E7 ICC detection is (0.95, 95% CI:0.92–0.97), which is better than that of cytological detection (0.91, 95% CI:0.86–0.94), χ2 = 4.29, p = 0.038.ConclusionHPV E6/E7 ICC assay with high-sensitivity feature may be potential new biomarkers for hrHPV positive women. In addition, its triaging performance is better than that of cytology.

3003 Background: T-Bren is a HER2-directed antibody-drug conjugate (ADC) consisting of an anti-HER2 monoclonal antibody linked to a potent topoisomerase I inhibitor (Ed-04). In phase I studies, T-Bren demonstrated encouraging anti-tumor activity with a manageable safety profile in patients (pts) with solid tumors. Results of safety/efficacy from two phase II studies in pts with R/M ovarian cancer (OC) are presented. Methods: Two studies evaluated T-Bren as monotherapy in pts with R/M platinum-resistant (disease progression within 6 months of the last dose of platinum-based chemotherapy) and platinum-sensitive OC. Pts with R/M OC were treated at 3.8mg/kg or 4.4mg/kg D1 Q3W. Primary endpoints include ORR and RP2D. Pts were selected for HER2 expression (ultra-low/1+/2+/3+). Results: As of Nov 30, 2025, a total of 65 pts were enrolled at 3.8 (N = 51), or 4.4mg/kg (N = 14) D1Q3W. Of all pts, 28 (43.1%) pts previously received ≥3 lines of therapy. The most common grade 3 and above hematologic TRAEs were thrombocytopenia (41.5%), leukopenia (35.4%), neutropenia (35.4%), and anemia (29.2%); the most common grade 3 and above non-hematologic TRAEs were asthenia (6.2%), lymphocyte count decrease (6.2%). Grade 3 and above TRAEs, which were predominantly hematologic in nature, were able to be effectively managed with standard supportive measure including dose reductions, as demonstrated by the TRAE leading to discontinuation rate of 3.1%. No ILD was observed. No new safety signals were identified. Median follow-up was 7.8 mo. Among pts at 3.8mg/kg D1 Q3W, confirmed ORR (cORR) was 88.9% in platinum-sensitive OC and 47.5% in platinum-resistant OC. mPFS had not reached and 9-mo PFS rate was 85.7% in platinum-sensitive OC and 61.2% in platinum-resistant OC. Efficacy results are summarized in the table below. Conclusions: T-Bren has demonstrated promising anti-tumor activity with a manageable safety profile in heavily pre-treated pts with R/M OC. Dose 3.8mg/kg D1 Q3W was chosen as the RP3D. Phase III study of platinum-resistant OC is in preparation. Clinical trial information: NCT06031584; NCT06131450 . Total (N=63) 3.8mg/kgTotal (N=49) 3.8mg/kgPlatinum-sensitive (N=9) 3.8mg/kgPlatinum-resistant(N = 40) Median prior LoT (range) 2 (1-8) 2 (1-6) 2 (1-4) 2 (1-6) ORR, % (95% CI) 57.1 (44.0, 69.5) 59.2 (44.2, 73.0) 88.9 (51.8, 99.7) 52.5 (36.1, 68.5) cORR, % (95% CI) 49.2 (36.4, 62.1) 55.1 (40.2, 69.3) 88.9 (51.8, 99.7) 47.5 (31.5, 63.9) DCR, % (95% CI) 88.9 (78.4, 95.4) 89.8 (77.8, 96.6) 100 (66.4, 100) 87.5 (73.2, 95.8) mPFS (mo) (95% CI) 9.3 (7.0, NR) NR (7.0, NR) NR (5.6, NR) NR (7.0, NR) 9-mo PFS rate, % (95% CI) 50.1 (24.0, 71.6) 67.5 (46.0, 81.9) 85.7 (33.4, 97.9) 61.2 (34.5, 79.7) *All pts who received at least one dose of T-Bren, excluding those still ongoing with insufficient follow up were used for efficacy analysis.

Ferroptosis, an iron-dependent form of programmed cell death, has recently garnered significant attention for its intricate involvement in the tumor immune microenvironment (TIME) and its implications in tumor immunotherapy. This review comprehensively explores the molecular mechanisms underlying ferroptosis and its regulation within tumor cells, highlighting the complex dual effects of ferroptosis on immune cell functions in TIME. While ferroptosis enhances cancer cell immunogenicity and promotes antitumor immunity through immune cell activation, it may also impair immune responses by disrupting T/B/NK cell functions and macrophage polarization. Critically, ferroptotic cells release damage-associated molecular patterns (DAMPs) such as high-mobility group box 1 (HMGB1) and oxidized phospholipids, triggering inflammation via receptors like Toll-like receptor 4 (TLR4) and activating inflammasomes. This review explores how this ferroptosis-driven inflammatory cascade reshapes TIME components, highlighting its potential to sensitize tumors to immunotherapy. Targeting ferroptosis pathways may overcome resistance to immune checkpoint blockade. However, cancer cells develop ferroptosis resistance through metabolic adaptations and antioxidant systems, complicating therapeutic strategies. Future studies should unravel context-specific regulatory networks linking ferroptosis, inflammation, and immunity to optimize immunotherapy efficacy.

Background and aims:Cervical cancer remains a significant threat to women's health, with pregnant women representing a particularly vulnerable population. This study aimed to investigate the impact of cervical intraepithelial neoplasia (CIN) on pregnancy outcomes using longitudinal biological sample analysis. Methods:We conducted a retrospective study of 125 pregnant women who underwent vaginal examination following abnormal cervical cytology and/or positive human papillomavirus (HPV) testing. Suspected cases underwent colposcopy-directed cervical biopsy performed by experienced clinicians (10 year of work experience) during pregnancy. Postpartum follow-up included repeat cervical cytology, HPV testing, and colposcopic biopsy when indicated. Results:Among the 125 patients, 34 underwent colposcopic biopsy during pregnancy, with histopathological results demonstrating strong concordance with colposcopic findings (kappa = 0.82, *p < 0.001). Postpartum follow-up within one year of delivery included colposcopy and cervical biopsy in 98 patients. Multivariate logistic regression analysis revealed that persistent cervical cytological abnormalities (OR 9.838; 95% CI 3.851-25.135; *p < 0.001) were significantly associated with abnormal colposcopic findings. Conclusion:For pregnant women declining cervical biopsy during pregnancy, colposcopy represents a safe and clinically valuable diagnostic tool. Persistent cervical cytological abnormalities, but not HPV positivity, were identified as a significant risk factor for CIN2 + persistence.

Fibrosis constitutes the principal pathophysiological mediator of pain and infertility manifestations in endometriosis, and the inhibitory factor of the TGF-β pathway, MADH7, makes a vital impact on the progression of fibrosis. Ovarian tumor domain-containing protein 1 (OTUD1) deubiquitinase binds to the MADH7 protein, although its specific role in endometriosis needs to be investigated. This study is the first to explore the role of OTUD1 in endometriosis and to investigate its impact on the growth of endometriosis lesions in vitro and in vivo, using C57BL/6N female mice and human primary stromal endometriosis cells (HEMCs). Moreover, the obtained results demonstrated that OTUD1 inhibited the expression of fibrosis-related proteins in HEMCs in vitro, and the mechanistic execution of this phenotype was achieved via coordinated deubiquitination coupled with MADH7-mediated transcriptional reprogramming. These events stopped the growth of lesions in vivo and reduced abdominal inflammation. The study demonstrated the critical role of the deubiquitinating enzyme OTUD1 in endometriosis, indicating its potential therapeutic effect on endometriosis.

BackgroundHuman papillomavirus (HPV) self-sampling may be an accurate and effective alternative sampling method to conventional cervical cancer screening methods. This systematic review compares the accuracy and acceptance of self-sampling to clinician sampling for HPV testing in Asia.MethodsThe PubMed, Cochrane Library, Cumulative Index to Nursing and Allied Health, and Web of Science databases were searched for publications published from the establishment of the database to 2023. The risk of bias was assessed using the QUADAS-2 tool for studies included in this review. All studies evaluating the accuracy and acceptance of HPV self-sampling, and agreement of self- and clinician-collected samples in Asia were included. The accuracy of each study was demonstrated through the sensitivity and specificity in diagnosing cervical intraepithelial neoplasia or cancer, as well as the detection rate of HPV. The agreement between the two sampling methods was assessed based on the detection outcomes of HPV. Acceptance was indicated by women’s preferences for HPV self-sampling.ResultsSixty-seven studies including 117,279 adult, female participants were included in this review. The type of HPV screening, other intervention components, study design, sample size, follow-up period, analysis method, numerical outcomes, results, and limitations were extracted from each study. The sensitivity and specificity of HPV self-sampling in detecting cervical intraepithelial neoplasia were higher than 80% and 70%, consistent with the results of HPV clinician sampling. The consistency between self-sampling and clinician-sampling was high in most studies, and the kappa value was more than 0.7. Women had high acceptance of self-sampling but expressed some concerns.ConclusionSelf-sampling for HPV testing can significantly improve cervical cancer screening coverage, especially in areas with limited medical resources or reluctance to accept physician sampling. In most studies, the accuracy and acceptance of HPV self-sampling was comparable to clinician sampling. However, the diagnostic criteria and HPV detection methods still need to be adjusted due to the low sensitivity of HPV self-sampling in some studies in China and India. Targeted health education should be carried out to improve the acceptance of HPV self-sampling in women.Systematic review registrationhttps://inplasy.com/?s=INPLASY202520107, INPLASY202520107.

High-grade serous ovarian cancer (HGSOC) is a highly aggressive and deadly gynecological cancer, with metastasis being a key factor in its poor prognosis. Historically, HGSOC was thought to spread primarily through the peritoneal cavity, but recent research has revealed additional routes of metastasis, including the blood and lymphatic systems. This review discusses the complex processes of HGSOC metastasis, focusing on peritoneal immune suppression, stromal reprogramming, and the role of circulating tumor cells in blood-based spread. We also explore the clinical significance of lymphatic metastasis, particularly its impact on patient outcomes. Gaining insight into molecular and genetic drivers, such as BRCA mutations and interactions within the immune microenvironment, is essential for developing targeted treatments. Future studies should aim to enhance experimental models, identify early detection markers, and investigate novel therapeutic approaches to effectively address HGSOC metastasis and improve patient survival.

BACKGROUND:Functional CAR-T cell exhaustion in the immunosuppressive tumour microenvironment remains the main barrier to the success of CAR-T cell therapy for treating solid tumours. Mesothelin (MSLN) has emerged as an attractive target for CAR-T cell therapy for several solid malignancies, including ovarian cancer. In this study, we aimed to investigate the role and mechanism of lipid metabolites in anti-MSLN CAR-T cell exhaustion in ovarian cancer cells. METHODS:We engineered anti-MSLN CAR-T cells targeting ovarian cancer cells with high MSLN expression as a pivotal tool for in vitro and in vivo experiments. Moreover, liquid chromatography-tandem mass spectrometry (LC-MS/MS) revealed the critical role of oxylipin 12-HETE in the exhaustion of CAR-T cells. By employing structure-based high-throughput virtual screening (HTVS), we identified the inhibitor targeting B7-H3. FINDINGS:We demonstrated that GPR31-dependent 12-HETE accumulation in the ovarian cancer microenvironment drives CAR-T cell exhaustion via lipid peroxidation, impairing their antitumour efficacy. Genetic or pharmacological inhibition of the 12-HETE/GPR31 axis restored CAR-T cell cytotoxicity and proliferation, leading to significant tumour regression in murine models. Silencing B7-H3 relieved repression of FOXO3, leading to reduced 12-LOX expression and lower 12-HETE levels, which places B7-H3 upstream of this metabolic checkpoint. Through structure-based screening, we identified HI-TOPK-032 as a potent B7-H3 inhibitor that synergised with CAR-T cell therapy by reversing exhaustion markers (e.g., PD-1, TIM-3) and enhancing cytokine polyfunctionality. Combined HI-TOPK-032 and anti-PD-1 treatment achieved superior tumour control compared to monotherapies, particularly in B7-H3/12-LOX-high patient-derived xenografts, underscoring its precision therapeutic potential. INTERPRETATION:CAR-T cell therapy combined with HI-TOPK-032 is a promising novel strategy for treating MSLN-expressing solid tumours. FUNDING:This study was funded by the National Natural Science Foundation of China (Grant number: 82503173), Beijing Hospitals Authority's Ascent Plan (Grant number: DFL20221201), Beijing Hospitals Authority Clinical Medicine Development of Special Funding Support (Grant number: ZYLX202120), Beijing Natural Science Foundation (Grant number: 7162063), Capital Medical University Laboratory for Clinical Medicine and Gynecological Tumour Precise Diagnosis and Treatment Innovation Studio.

PURPOSE:To compare camrelizumab (an anti-PD-1 monoclonal antibody) plus famitinib (a multitarget receptor tyrosine kinase inhibitor) versus camrelizumab and chemotherapy in recurrent or metastatic cervical cancer (R/M CC). METHODS:Patients with pretreated R/M CC were randomly assigned to receive camrelizumab (200 mg intravenously once every 3 weeks) plus famitinib (20 mg orally once daily), camrelizumab, or investigator's choice of chemotherapy. The primary end point was comparison of objective response rate (ORR) per blinded independent central review (BICR) for camrelizumab-famitinib versus camrelizumab in the intention-to-treat population. RESULTS:Overall, 105, 54, and 35 patients received camrelizumab-famitinib, camrelizumab, and chemotherapy, respectively. As of April 21, 2023, ORR per BICR was significantly improved with camrelizumab-famitinib compared with camrelizumab (41.0% [95% CI, 31.5 to 51.0] v 24.1% [95% CI, 13.5 to 37.6]; difference, 16.9% [95% CI, 2.1 to 31.7]; one-sided P = .0181). Per investigator, ORR with camrelizumab-famitinib was 42.9% (95% CI, 33.2 to 52.9), notably higher than 22.2% (95% CI, 12.0 to 35.6) with camrelizumab and 14.3% (95% CI, 4.8 to 30.3) with chemotherapy. Median progression-free survival per investigator was prolonged with camrelizumab-famitinib than camrelizumab and chemotherapy (8.1 months [95% CI, 6.2 to 12.4] vs 4.1 months [95% CI, 2.1 to 5.1] and 2.9 months [95% CI, 2.0 to 6.2]). Median overall survival with camrelizumab-famitinib, camrelizumab, and chemotherapy, as of October 19, 2023, was 20.2 months (95% CI, 15.3 to not reached [NR]), 14.9 months (95% CI, 12.6 to NR), and 13.9 months (95% CI, 7.4 to 20.0), respectively. Eighty-nine (84.8%), eight (15.1%), and 18 (60.0%) patients who received camrelizumab-famitinib, camrelizumab, and chemotherapy, respectively, experienced grade ≥3 treatment-related adverse events. CONCLUSION:Camrelizumab plus famitinib improved antitumor activity while exhibiting a manageable safety profile in patients with pretreated R/M CC, potentially offering a novel treatment option.

Background:The triglyceride-glucose (TyG) index, a promising biomarker for insulin resistance, is linked to the risk of various metabolic-related cancers. However, to date, data on the association of TyG index with different subtypes of endometrial cancers and the potential mediating role of clinical factors remain limited. Methodology:Data was collected from the Beijing Obstetrics and Gynecology Hospital, Capital Medical University spanning from 2014 to 2024. Female participants with complete data on the TyG index were included in the analysis. Multivariate logistic regression analyses were used to assess the association of TyG index with endometrial cancer risk, adjusted by series of confounders. Mediation effects were evaluated using Valeri and VanderWeele's method. Results:A total of 1,194 eligible participants were enrolled, with 597 (50%) women diagnosed with endometrial cancer. The fully adjusted multivariate logistic regression model revealed a significant association between the TyG index and the risk of endometrial cancer (odds ratio [OR]Tertile 3 versus Tertile 1: 1.93, 95% confidence interval [CI]: 1.37-2.73; P for trend=0.028). Notably, BMI exhibited significant mediation effects on this association, even after adjusted by potential confounders (P for trend<0.001). The proportion of the effect mediated by BMI was 25% in the crude analysis (95% CI: 0.15, 0.37; P<0.001) and increased to 41% in the adjusted analysis (95% CI: 0.24, 0.76; P<0.001). However, no correlation was found between TyG index and the clinical characteristics of endometrial cancer (P>0.05). Moreover, BMI is associated with the risk of different endometrial cancers. Conclusion:This cross-sectional study demonstrated that a higher TyG index, representing higher level of insulin resistance, was associated with a higher risk of endometrial cancer. Importantly, we found that BMI acted as a significant mediator in this relationship. Prospective studies are needed to further validate these findings.