Search Results (1,804)

Environmental exposure to pesticides is considered a risk factor for gynecological cancers, contributing to their onset and progression through various mechanisms. This narrative review investigates the role of different pesticides in the development and progression of ovarian, endometrial, and cervical cancers, and provides a comprehensive synthesis of epidemiological findings along with molecular mechanisms, highlighting carcinogenic pathways, conflicting findings, and potential therapeutic implications. Relevant epidemiological and experimental studies published between 2000 and 2025 were identified through searches of major scientific databases. Various pesticides, particularly organochlorines, contribute to gynecological cancers through mechanisms such as estrogen mimicry, DNA damage, oxidative stress, increased pro-inflammatory cytokines, and disruption of cellular signaling pathways. However, most studies found no significant association between certain pesticides, such as Triazines and Atrazine, and gynecological cancers. Furthermore, some pesticides, like Carbendazim, exhibit a dual role; while carcinogenic, they can also serve therapeutic purposes in cancer treatment when utilized with nanotechnology. Overall, pesticide exposure is a significant factor in the development and progression of women’s cancers, although the strength of the evidence varies across pesticide classes. Despite numerous studies, contradictory findings necessitate further research to clarify causal relationships. Full article

Cervical cancer remains a major global health challenge and a leading cause of gynecological cancer-related mortality, particularly in developing countries. Although persistent human papillomavirus infection is the primary driver of cervical carcinogenesis, host factors such as immune dysregulation and microbiome dysbiosis may contribute to disease progression. Corisin is a microbiota-derived peptide implicated in epithelial injury and fibrosis, but its role in cervical neoplasia is unknown. To investigate its potential involvement, circulating corisin levels were measured in 27 women with cervical intraepithelial neoplasia (CIN) or cervical cancer and compared with those in 15 healthy women. Corisin localization in cervical carcinoma tissues was examined by immunohistochemistry, and its biological effects were evaluated in HeLa cells. Circulating corisin levels were significantly elevated in patients with CIN and cervical cancer, with the highest levels observed in CIN3 and cervical squamous cell carcinoma. Corisin was detected within cervical carcinoma tissues in intracellular and extracellular compartments adjacent to tumor cells. In HeLa cells, corisin accumulated in mitochondria, impaired cell-cycle progression, induced apoptosis, increased p21 expression, and promoted epithelial–mesenchymal transition-like morphological changes. These findings suggest that corisin is elevated from the early stages of cervical neoplasia, is present within the cervical tumor microenvironment, and may contribute to pathogenic cellular processes associated with cervical cancer progression. Full article

Background: Waiting-room time is an important and neglected element of the outpatient experience in the field of oncology, which carries far-reaching consequences for overall patient satisfaction, perceptions of quality, and healthcare experience. Methods: We carried out a cross-sectional, mixed-methods study, conducted at the Juravinski Cancer Centre in Hamilton, Canada, from October to December 2024. Results: We studied 418 patients with a mean age of 61.6 years. Overall, 59.6% of respondents had spent less than 30 min in the waiting room, while 56.2% accepted a delay of 15–30 min. Waiting for more than 30–45 min was perceived as long by 61% of participants. In regards to physician choice, 59.8% of respondents preferred to be seen by their known provider, while 30.9% were ready to meet another one, particularly in terms of scheduled regular follow-up and urgent appointments followed by consultations. Interestingly, chemotherapy visits were the least common type of appointment where patients agreed to see different providers. A significant association was identified between appointment types and readiness to change physicians (p < 0.05). Although 78.7% agreed that delays were caused by complex conditions, only 29.2% received sufficient information about delays. Conclusions: Most gynecologic oncology patients want continuity of care, yet many are flexible with consultations, follow-up, and urgent visits. In outpatient clinics, patient-centered scheduling, balancing efficiency and patient satisfaction with better communication is an objective for system improvements. Full article

Gynecological malignancies and breast cancer impose substantial health and economic burdens. This review examines how local and systemic microbiota may affect epithelial integrity, inflammation, estrogen metabolism, and immunity. The vaginal ecosystem is the most extensively studied female microbial niche. Cervical cancer serves as the most illustrative clinical example: loss of stable Lactobacillus crispatus dominance and increased prevalence of anaerobic bacteria (anaerobic dysbiosis) are associated with persistent HPV infection, which directly elevates the risk of cervical precancerous lesions. The estrobolome is particularly relevant in endometrial cancer, where intestinal bacterial beta-glucuronidase activity may increase estrogen reabsorption, particularly in obesity and metabolic disease. In ovarian cancer, microbiota is being studied as a possible risk modifier in BRCA1 carriers, but the evidence remains exploratory. In breast cancer, intratumoral bacteria may shape the immune microenvironment, particularly in triple-negative disease. The primary limitation of current research is methodological heterogeneity. Low-biomass samples, such as those from the ovary or endometrium, are highly susceptible to technical contamination. Most studies are cross-sectional and cannot establish causality. Current evidence supports microbiota as a modifier, not a standalone marker or a substitute for standard diagnosis and treatment. Its most plausible near-term role is in multiparameter risk or response models, pending standardized prospective validation. Full article

Peritoneal carcinomatosis (PC) is a common, prognostically unfavorable manifestation of advanced gastrointestinal and gynecological malignancies whose treatment is constrained by the blood-peritoneal barrier, which limits drug penetration even when cytoreductive surgery is combined with systemic chemotherapy. This review evaluates current intraperitoneal treatment modalities and emerging technologies for overcoming this limitation, based on recent clinical trials and meta-analyses identified through Scopus and PubMed. We sequentially examine conventional intraperitoneal chemotherapy (IPC); hyperthermic intraperitoneal chemotherapy (HIPEC) in ovarian, gastric, and colorectal cancers, with attention to patient selection and the peritoneal cancer index as determinants of survival benefit; pressurized intraperitoneal aerosol chemotherapy (PIPAC) and its electrostatic precipitation variant (ePIPAC); and photodynamic and photothermal therapy for tumor treatment. Novel strategies are also discussed, including IPC combined with immune checkpoint inhibitors, optical dosimetry, and nanomedicine-based drug delivery as tools for improving treatment precision. Overall, management of PC is transitioning toward a personalized, multimodal approach: HIPEC and PIPAC provide standardized platforms for regional therapy, but future progress depends on integrating advanced drug delivery systems, immunotherapy, and real-time intraoperative monitoring, with standardization of protocols through large multicenter trials remaining a priority for translating these modalities into clinical practice. Full article

Assisted reproductive technology (ART) is increasingly utilized worldwide, yet concerns remain regarding its potential association with breast and gynecological malignancies and the safety of fertility-preservation strategies in cancer survivors. Ovarian stimulation exposes women to supraphysiologic hormone levels, raising questions about cancer risk, particularly for hormone-sensitive tumors. Current evidence, however, is largely reassuring. Registry-based studies and meta-analyses demonstrate no consistent increase in breast or endometrial cancer following ART, although endometrial cancer risk remains inconclusive despite large new cohorts. Cervical cancer has not been linked to ART exposure. For ovarian cancer, risk appears primarily driven by underlying infertility, parity, and endometriosis rather than ART itself, and no excess risk is observed among BRCA mutation carriers. In parallel, fertility preservation (FP) has become an integral component of gynecologic oncology care for reproductive-aged women. Strategies including cryopreservation of oocytes, embryos, or ovarian tissue, as well as fertility-sparing surgery or hormonal therapy, can be safely pursued in carefully selected early-stage cancers. Pregnancy and livebirth rates vary by diagnosis: outcomes are favorable after breast and cervical cancers, more limited in endometrial cancer due to endometrial receptivity challenges, and possible but less predictable in ovarian cancer, where stage and histology guide feasibility. Available observational evidence does not suggest a clear increase in recurrence risk among carefully selected patients, although evidence remains limited and long-term follow-up is needed. Overall, current data suggest ART is safe when individualized to patient and tumor characteristics, highlighting the importance of proactive fertility counseling, modified stimulation protocols, and multidisciplinary care to optimize oncologic and reproductive outcomes. Full article

Background: Cervical cancer screening uptake in Romania remains below 20%, with invasive sampling cited as a major participation barrier. Urinary HPV testing is a non-invasive alternative, but data from Eastern European populations are scarce and reporting stratified by histological grade is inconsistent. Objectives: To evaluate the agreement between paired urinary and clinician-collected cervico-vaginal HPV testing, and to assess the diagnostic performance of urinary HPV testing for biopsy-confirmed cervical intraepithelial neoplasia grade 2 or worse (CIN2+). Methods: Prospective cross-sectional study in three outpatient obstetrics and gynecology clinics (May 2025–May 2026). A total of 230 women aged 25–70 years provided paired cervico-vaginal (PreservCyt^®) and first-void urine (Colli-Pee^®) specimens. To capture the full spectrum of disease probability, participants were recruited across three clinical scenarios: primary screening, cytology triage and HPV-positive triage. A multiplex RT-PCR assay targeted a total of 14 high-risk HPV genotypes, providing separate identification for HPV16 and HPV18, alongside a pooled detection for the remaining 12 high-risk strains. Colposcopy-guided cervical biopsy served as the reference standard. Results: Paired hrHPV testing achieved substantial agreement (κ = 0.696, 95% CI 0.604–0.788), with higher genotype-specific concordance for HPV16 (κ = 0.755) and HPV18 (κ = 0.789). Discordance was directionally asymmetric (30 cervical-positive/urine-negative versus 4 urine-positive/cervical-negative; McNemar p < 0.001). For biopsy-confirmed CIN2+ (59 of 230; 25.7%), urinary hrHPV showed a sensitivity of 86.4% (95% CI 75.5–93.0), specificity 56.7%, positive predictive value 40.8% and negative predictive value 92.4%, compared with 91.5%, 43.3%, 35.8% and 93.7% for cervico-vaginal testing. Urinary HPV positivity increased monotonically with histological severity (25.0% no-lesion, 69.0% CIN1, 86.4% CIN2+; linear-by-linear p < 0.001). Conclusions: Urinary HPV testing demonstrates substantial agreement with clinician-collected sampling, near-equivalent negative predictive value, and a robust dose–response with histological severity. It is a clinically credible non-invasive entry point for a triage cascade in settings such as Romania, where low participation rather than analytical performance is the principal screening barrier. Full article

Endometriosis is a chronic gynecological disease affecting approximately 10% of women of reproductive age and up to 40% of women with infertility, with a significant impact on quality of life due to pain and reproductive impairment. Its etiology remains unclear, although several mechanisms have been proposed, including retrograde menstruation and immune dysfunction. Increasing evidence highlights similarities between endometriosis and cancer, particularly regarding selected hallmarks such as sustained cell proliferation, angiogenesis, inflammation, invasion, and immune dysregulation. Notably, alterations in glucose metabolism have been identified, suggesting a metabolic reprogramming resembling the Warburg effect in cancer. This review examines clinical aspects, therapeutic challenges, and emerging evidence for Warburg-like glycolytic metabolism in endometriotic lesions, which favors aerobic glycolysis over oxidative phosphorylation to evade apoptosis and promote survival in hypoxic microenvironments. These cancer-like hallmarks—shared with malignancies—suggest repurposing glycolytic inhibitors as targeted therapies to disrupt disease progression beyond symptom palliation. However, most evidence remains preclinical, and important challenges regarding disease heterogeneity, target validation, and safety still need to be addressed. Full article

Objectives: Assessment of the impact on survival of endometrial carcinoma according to the 2009 FIGO (International Federation of Gynecology and Obstetrics) classification and the new FIGO 2023 classification highlighting the worse prognosis of the aggressive subtypes. Methods: This multicenter retrospective study included 1181 patients with endometrial cancer. Comprehensive clinical, pathological and treatment-related variables were collected. Primary outcomes included overall survival assessed through five-year follow-ups. Statistical analysis included comparative tests, Kaplan–Meier survival estimation, Cox proportional hazards models and ROC curves analysis to review prognostic accuracy. Results: Aggressive endometrial carcinoma (n = 353) showed significant worse overall survival compared with non-aggressive cases (35.7 versus 60 months). A novel classification based on FIGO 2023 was developed, integrating histological aggressiveness into a different stage and combining early non-aggressive stages in only one stage. While FIGO 2009 and 2023 classifications showed prognostic value, the new model improved risk stratification, clearly distinguishing high-risk groups. Multivariate analysis identified aggressive subtype, stage, age, diabetes, myometrial invasion and lymphovascular invasion as independent predictors. Conclusions: Aggressive histological subtype in endometrial cancer should carry greater prognostic weight in terms of survival and clinical management. Our findings support a potential shift in the current paradigm for these relatively rare but high-risk cases. Full article

Immune checkpoint inhibitors and antibody–drug conjugates have rapidly expanded treatment options for gynecologic malignancies, although the magnitude of benefit varies substantially across tumor types and biomarker-defined populations. This narrative review summarizes the biologic rationale, predictive biomarkers, pivotal clinical trials, regulatory approvals, guideline-supported strategies, and emerging directions for immune checkpoint blockade and antibody–drug conjugates in endometrial, cervical, and ovarian cancers. In endometrial cancer, molecular classification and mismatch repair status have transformed treatment selection, with PD-1 or PD-L1 blockade now integrated into first-line chemoimmunotherapy and recurrent disease management. HER2-directed and TROP-2-directed antibody–drug conjugates are also emerging as biomarker-directed strategies. In cervical cancer, human papillomavirus-driven tumor biology, PD-L1 expression, and tissue factor expression support the use of checkpoint inhibitors, antibody–drug conjugates, and therapeutic vaccine approaches across locally advanced and recurrent or metastatic settings. In ovarian cancer, single-agent checkpoint blockade has shown limited activity in unselected populations, but recent advances include biomarker-selected chemoimmunotherapy in platinum-resistant disease and clinically meaningful activity of folate receptor alpha-directed and HER2-directed antibody–drug conjugates. Across gynecologic cancers, key challenges include refining predictive biomarkers, optimizing sequencing after prior immunotherapy exposure, managing overlapping toxicities, and designing trials that enrich for biologically responsive subgroups. Future progress will depend on integrating molecular classification, immune contexture, ADC target expression, and patient-specific clinical factors into treatment selection. Full article

Vulvar cancer is a rare gynecologic malignancy with a bimodal age distribution, predominantly affecting older women while demonstrating increasing HPV-related incidence in younger populations. Accurate staging is essential for individualized treatment strategies to optimize outcomes while minimizing morbidity. Positron Emission Tomography (PET) has emerged as an important imaging modality in oncology; however, its precise role in vulvar cancer requires critical evaluation given the limited prospective evidence. This review focuses on the role of ¹⁸F-FDG PET/CT in vulvar cancer based on the literature published to date. Current evidence suggests that PET/CT provides high sensitivity for primary tumor detection and is particularly valuable for nodal and distant staging in locally advanced disease, where it may significantly influence management. However, its limited spatial resolution precludes detection of micrometastases, and it cannot replace sentinel lymph node biopsy for groin staging. PET/CT also contributes to radiotherapy planning through improved target delineation and demonstrates utility in detecting recurrence, although false positives remain a limitation. MRI remains superior for local staging, supporting a complementary multimodality imaging approach. Emerging tracers, including Fibroblast Activation Protein Inhibitor (FAPI), along with artificial intelligence-based radiomics, represent promising but still investigational directions. In conclusion, ¹⁸F-FDG PET/CT is a useful adjunct in vulvar cancer, especially for advanced disease, but its interpretation should be integrated within a multimodal framework due to limited supporting evidence. Full article

Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein kinase kinase kinase (MAP3K) involved in stress-induced apoptosis. Increasing evidence indicates that ASK1 activation contributes to the anticancer activity of numerous compounds, particularly those that induce oxidative or endoplasmic reticulum stress. This review summarizes studies demonstrating ASK1-dependent apoptosis in models of lung, breast and gynecologic, or gastrointestinal cancers following treatment with natural products, phytochemicals, and synthetic agents, focusing on mechanistic evidence linking ASK1 to downstream activation of the JNK and p38 MAPK pathways, mitochondrial dysfunction, and caspase-dependent cell death. Studies were selected based on direct experimental validation of ASK1 activation and involvement in the observed anticancer effects. Overall, this review supports ASK1 as a promising molecular target for the development of novel cancer treatment strategies. Full article

Background/Objectives: Metastases from cutaneous malignancies to the female genital tract and pelvic lymph nodes are rare clinical entities that frequently masquerade as primary gynecologic tumors, leading to significant diagnostic challenges. The distinction between primary and metastatic disease is critical, yet complex, given the varying patterns of spread exhibited by different skin cancers. This study aims to provide a tumor-specific overview of these metastatic patterns to guide diagnosis and therapy. Methods: We conducted a narrative review informed by a systematic literature search of MEDLINE/PubMed, Embase, Scopus, and Web of Science for records regarding primary cutaneous melanoma, cutaneous squamous cell carcinoma (cSCC), basal cell carcinoma (BCC), Merkel cell carcinoma (MCC), and cutaneous lymphomas metastasizing to the female genital tract (FGT) or pelvic lymph nodes. Data were synthesized qualitatively to identify organotropic patterns, diagnostic pitfalls, and management outcomes across these distinct malignancies. Results: The analysis reveals distinct metastatic niches: cutaneous melanoma shows a predilection for the ovary, often mimicking epithelial ovarian carcinoma, whereas cSCC and MCC typically involve pelvic lymph nodes via contiguous spread from inguinal basins. Histologic evaluation with broad immunohistochemical panels is mandatory to confirm the diagnosis, as imaging alone lacks specificity. Crucially, the introduction of immune checkpoint inhibitors and targeted therapies has significantly improved survival in advanced melanoma, cSCC, and MCC, altering the role of pelvic surgery. Conclusions: Management of cutaneous malignancies metastatic to the pelvis is shifting from a focus on radical surgery to a systemic-first approach. Pelvic metastasectomy should be reserved for selected oligometastatic cases or symptom control within a multidisciplinary framework. Clinicians must maintain a high index of suspicion in patients with a history of skin cancer to avoid overtreatment and optimize quality of life. Full article

Background: Tertiary lymphoid structures (TLSs) are spatial immune niches in solid tumors, but their relationship to mature regulatory dendritic-cell (mregDC) states in ovarian cancer remains incompletely resolved. Methods: We integrated public gynecological-tumor single-cell RNA sequencing, representative CD11C/HLA-DRA/LAMP3/CCR7 multiplex immunofluorescence, public Xenium and multi-sample spatial transcriptomics, TCGA-OV immune deconvolution and exploratory prognostic modeling, scTenifoldKnk and CellOracle perturbation analyses, and supplementary computational drug prioritization. Results: A $LAMP{3}^{+}CCR{7}^{+}$ dendritic-cell state showed mature migratory, antigen-presentation, checkpoint, and NF-$\kappa$B/TNF-associated programs. Spatial analyses linked TLS-score-defined regions to mregDC, antigen-presentation/MHC-II proxy, and interferon-associated signals, with distance-gradient analyses supporting TLS-proximal enrichment. Immune deconvolution associated the TLS/mregDC axis with an immune-infiltrated TCGA-OV contexture, whereas adjusted analyses emphasized dependence on broader immune-program richness. Perturbation analyses nominated candidate regulatory axes for experimental testing, and the supplementary drug-prioritization layer was retained only as target-class hypothesis support. Conclusions: These data support a hypothesis-generating model of a TLS-associated $LAMP{3}^{+}CCR{7}^{+}$ mregDC antigen-presentation program in ovarian cancer, while requiring raw-channel tissue validation, functional perturbation, and independent clinical testing. Full article