International Journal of Gynecological Cancer最新文献

Objective: This multicenter retrospective cohort study aimed to compare survival outcomes and adverse events between early and late initiation of niraparib maintenance therapy in patients with newly diagnosed advanced ovarian cancer.

Methods: We included patients with stage III-IV ovarian cancer who showed a complete or partial response to frontline platinum-based chemotherapy and received niraparib maintenance therapy between October 2019 and December 2022. The primary endpoint was the HR for progression-free survival based on the median initiation interval, which was defined as the duration between the completion of chemotherapy and commencement of maintenance therapy. The secondary endpoint was the comparison of progression-free survival at another time point that determined the interval that maximized the difference between the survival curves of the two groups using the Contal and O'Quigley method.

Results: This analysis included 146 patients who received niraparib maintenance therapy. The median age was 58 years (IQR 50-63.3). The median initiation interval was 8.4 (IQR 5.7-8.9) weeks. After adjusting for prognostic factors for progression-free survival identified through multivariable analysis, early initiation (≤8 weeks) of niraparib was associated with significantly better progression-free survival (HR=0.57; 95% CI 0.33 to 0.99; p=0.047). Furthermore, the initiation interval that maximized the difference in progression-free survival was 6 weeks. Multivariable analysis revealed that early initiation (≤6 weeks) of niraparib significantly increased progression-free survival (HR=0.37; 95% CI 0.18 to 0.76; p=0.007). The rate of treatment discontinuation due to treatment-emergent adverse events was higher (12.5% versus. 2.8%; p=0.036) in patients receiving niraparib within 6 weeks than those treated later, with no significant effect in those initiating treatment within 8 weeks.

Conclusion: Early initiation of niraparib maintenance therapy within 8 weeks of chemotherapy completion improved progression-free survival, with further benefits observed with treatment within 6 weeks in patients with newly diagnosed advanced ovarian cancer.

Objective: Volatile organic compounds profiling has emerged as a promising approach for cancer detection. Electronic noses are portable sensor-based devices capable of recognizing volatile organic compound patterns in various biological matrices, offering a rapid, non-invasive, and cost-effective diagnostic alternative. The aim of this systematic review was to evaluate the diagnostic performance of electronic noses in gynecologic oncology and to delineate their technical characteristics.

Methods: This review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and was registered in International Prospective Register of Systematic Reviews (CRD420251122293). PubMed, Scopus, and Google Scholar were searched up to August 2025. Eligible studies included prospective investigations evaluating volatile organic compound analysis through electronic noses in ovarian, cervical, endometrial, and vulvar cancers, as well as high-grade squamous intraepithelial lesions, using histopathology as the reference standard. Diagnostic performance parameters were extracted, and the risk of bias was assessed with Quality Assessment of Diagnostic Accuracy Studies 2. No meta-analysis was performed due to study heterogeneity.

Results: Fifteen studies with a total of 1224 patients were included. Among them, 562 (45.9%) had gynecologic malignancies, and 662 (54.1%) served as controls. Ten studies (66.7%) investigated ovarian cancer, 4 (26.7%) cervical cancer, and 1 (6.7%) high-grade squamous intraepithelial lesions of the cervix; no studies evaluated endometrial or vulvar cancers. Biological matrices analyzed included breath (33.3%), urine (20%), tissue (20%), plasma (6.7%), genitourinary secretions (6.7%), or combined samples (6.7%). Reported diagnostic performance ranged from 71% to 97.7% for sensitivity, from 63% to 100% for specificity, and from 71% to 95% for accuracy across all cancer types. In ovarian cancer studies, sensitivity ranged from 71% to 97.7%, specificity from 63% to 91.4%, and accuracy from 71% to 87%. In cervical cancer studies, sensitivity ranged from 88% to 93%, and specificity from 85% to 100%.

Conclusions: Electronic nose technologies show encouraging diagnostic accuracy in gynecologic oncology, particularly for cervical cancer, whereas performance in ovarian cancer remains more variable depending on the biological matrix and comparator group. Despite promising results, the lack of standardized protocols and the heterogeneity of current evidence limit immediate clinical translation. Larger, multicenter, and standardized studies are needed to validate their integration into diagnostic workflows.

Objective: Squamous cell carcinoma and adenocarcinoma in early-stage cervical cancer differ in biology and prognosis, yet current guidelines recommend uniform management. This study aimed to develop and internally validate histology-specific prognostic models for squamous cell carcinoma and adenocarcinoma to predict disease-free survival and overall survival, thereby supporting individualized adjuvant therapy for intermediate-risk cervical cancer.

Methods: A multi-center retrospective analysis was conducted on patients with early-stage cervical cancer who underwent radical surgery without pathologic high-risk features. Patients were stratified into squamous cell carcinoma and adenocarcinoma cohorts. Histology-specific nomograms for disease-free survival and overall survival were developed using Cox regression and internally validated via 5-fold cross-validation. Model discrimination was assessed using the concordance index (C-index), and prognostic stratification using Kaplan-Meier analysis.

Results: A total of 1053 patients with stage IB to IIA cervical cancer (911 squamous cell carcinoma, 142 adenocarcinoma) treated at 3 tertiary hospitals from 2005 to 2017 were included. Nomograms incorporating lymphovascular space involvement, stromal invasion, tumor size, and adjuvant therapy showed superior accuracy over Sedlis models (C-indices: 0.81/0.80 for disease-free survival/overall survival in squamous cell carcinoma; 0.91/0.96 for disease-free survival/overall survival in adenocarcinoma). Risk scores stratified patients into distinct prognostic sub-groups. In squamous cell carcinoma, high-risk patients had higher recurrence and mortality rates than low-risk patients (5-year recurrence rate: 11.7% vs 1.6%; mortality rate: 7.7% vs 0.6%). In adenocarcinoma, high-risk patients showed worse outcomes (5-year recurrence rate: 13.3% vs 0.0%; mortality rate: 6.1% vs 0.0%). Kaplan-Meier analysis confirmed significant survival differences across risk groups in both sub-types (all p < .05).

Conclusions: Histology-specific nomograms incorporating intermediate-risk factors and adjuvant therapy effectively stratified prognostic sub-groups in early-stage cervical cancer, and may help inform risk-adapted post-operative management. Prospective external validation is needed for broader application.

Objective: This study aimed to evaluate p16 expression and its clinical utility in cervical biopsies from women who tested positive for high-risk human papillomavirus (HPV) in a real-world screening program, assessing its correlation with HPV genotype, lesion grade, clinical management, and diagnostic upgrading.

Methods: We conducted a diagnostic test study nested within the first round (2017-2022) of a population-based HPV DNA screening program in a Brazilian municipality. Women who tested positive for HPV were referred for colposcopy, and those who underwent cervical biopsy with p16(INK4a) immunohistochemistry were included. We analyzed age, HPV results, biopsy diagnoses, p16 status, procedures, and clinical outcomes using the χ² test or Fisher exact test and logistic regression (p < .05).

Results: Among 696 biopsies, 48.4% were p16-positive. Positivity increased with lesion severity, from 14.3% in negative biopsies to 80.0% in cervical intra-epithelial neoplasia grade 2 and 95.1% in cervical intra-epithelial neoplasia grade 3/adenocarcinoma in situ (p < .001). No significant association was found between p16 and specific HPV genotypes (43·4%-60%), although 73% of p16-positive carcinomas were linked to HPV16/18. Excisional treatment was performed in 61.7% of p16-positive cases versus 7.5% of p16-negative cases (p < .001). Cervical intra-epithelial neoplasia grade 2 or worse was diagnosed in 69.4% of p16-positive cases (p < .001), with diagnostic upgrading 7 times more frequent than in p16-negative cases (19.9% vs 2.8%; p < .001). p16 showed a positive predictive value of 69% and a negative predictive value of 90% for cervical intra-epithelial neoplasia grade 2 or worse detection, reaching 91.6% in the non-HPV16/18 sub-group. The regression analysis confirmed p16 expression with 20-fold higher odds for significative cervical lesions (odds ratio 20.2, 95% confidence interval 13.3 to 30.6, p < .001).

Conclusions: Systematic p16 assessment in population-based screening improves risk stratification, diagnostic accuracy, and treatment allocation. These findings support integrating p16 into cervical cancer prevention strategies, particularly, in resource-limited settings where optimizing diagnostic precision and treatment balance is crucial.

Objective: We aimed to describe the association between molecular sub-groups and outcomes in patients with advanced/metastatic endometrial carcinoma amenable to maintenance/active surveillance after carboplatin-based chemotherapy.

Methods: Patients treated in the GINECO trial UTOLA (NCT03745950, randomly allocating patients 2:1 to olaparib/placebo after tumor control under carboplatin-based chemotherapy), with prospective centralized targeted next-generation sequencing, and mismatch repair and p53 immunostainings were included. Next-generation sequencing (667.5 kb) included POLE (exo-nuclease domain), TP53, PIK3CA, PIK3R1, PTEN, KRAS, and CTNNB1. Tumors were categorized following the 2022 European Society of Gynaecological Oncology/European Society for Radiotherapy and Oncology/European Society of Pathology guidelines as POLE-mutated, mismatch repair-deficient, p53-abnormal (immunostaining or TP53 mutation), and with no specific molecular profile. Exploratory analyses categorized non-p53-abnormal tumors based on literature (mismatch repair-deficient: mutational burden; no specificity: PIK3R1/PTEN wild-type tumors, CTNNB1/KRAS-mutated tumors, others).

Results: Among 145 patients in the intention to treat population (median follow-up 31 months), 1, 21 (15%), 76 (53%), and 45 (32%) had POLE, mismatch repair-deficient, p53-abnormal, and non-specific tumors (2 missing mismatch repair), respectively. Molecular characterization was associated with progression-free (log-rank, p = .017) and overall survival (p < .001). Patients with p53abn tumors had a hazard ratio for death of 2.43, 95% confidence interval 1.50 to 3.93 (adjusted on age, stage IV, measurable lesions after chemotherapy). Exploratory analyses showed high mutational burden mismatch repair-deficient tumors with prognostic similar to p53abn tumors, whereas tumors with lower mutational burden had better progression-free survival. PIK3R1/PTEN wild-type and CTNNB1/KRAS-mutated non-specific tumors had better outcomes than p53abn tumors. Other non-specific tumors have survival similar to p53abn tumors.

Conclusions: Integration of molecular sub-group as a stratification parameter might be considered for randomized trials in advanced/metastatic endometrial carcinoma after carboplatin-based chemotherapy. Deeper characterization of mismatch repair-proficient tumors might enhance prognostication.