Search Results (88)

Female cancers such as breast and gynaecological cancers contribute to a significant global health burden and are a leading cause of fatality among women. With current treatment options often limited by resistance to cytotoxic drugs, side effects and lack of specificity to the cancer, there is a pressing need for alternative treatments. Recent research has highlighted the promising role of non-coding RNAs (ncRNA) in regulating these issues and providing more targeted approaches to suppressing key cancer pathways. This review explores the involvement of the various types of non-coding RNAs in regulating key oncogenic pathways, namely, the MAPK, PI3K/Akt/mTOR, Wnt/β-catenin and p53 pathways, in a range of female cancers such as breast, cervical, ovarian and endometrial cancers. Evidence from a multitude of studies suggests that non-coding RNAs function as double-edged swords, serving as both oncogenes and tumour suppressors, depending on their expression and cellular interactions. By mapping and investigating these regulatory interactions, this review demonstrates the complexity and dual functionality of ncRNAs in cancer. Understanding these complex mechanisms is essential for the development of new and effective ncRNA-based diagnostic methods and targeted therapies in female cancer treatment. Full article

Objective: This study aims to explore the benefit of adjuvant chemoradiotherapy compared with radiotherapy alone following a radical hysterectomy with pelvic lymphadenectomy. The study focuses on patients with clinically early-stage squamous cervical cancer who have a single high-risk factor postoperatively. Methods: This retrospective study included women diagnosed between 2001 and 2018, with: (1) clinical tumour (cT) stage 1A2–2A2, (2) cervical squamous carcinoma, (3) treated with radical hysterectomy and pelvic lymphadenectomy (4) followed by adjuvant (chemo)radiotherapy, and with (5) one high-risk factor (i.e., positive resection margins, parametrial involvement, or pelvic lymph node metastases). Recurrence-free and overall survival were estimated using Kaplan−Meier and Cox proportional hazards analyses. Inverse probability treatment weighting was used to adjust for confounding. Results: Of the 122 patients with squamous cell carcinoma and one high-risk factor, 76 (62%) received adjuvant chemoradiotherapy and 46 (38%) received adjuvant radiotherapy alone. Larger tumour size, tumour grade 3, and pathological parametrial invasion were more common in the radiotherapy group, while patients who received chemoradiotherapy were more likely to have multiple lymph node metastases. The unadjusted and for confounding adjusted 5-year survival rates were comparable between the adjuvant chemoradiotherapy and radiotherapy groups for both recurrence-free survival (85% versus 87%; p = 0.58, and 84% versus 91%; p = 0.49) and overall survival (84% versus 87%; p = 0.51, and 84% versus 91%; p = 0.49). Conclusions: Adding chemotherapy to radiotherapy may not improve survival of patients with early squamous cervical cancer treated with radical hysterectomy and pelvic lymphadenectomy, and with a single postoperative high-risk factor. Full article

Standard of Care (SOC) for locally advanced cervical cancer is represented by external beam radiation therapy concurrent with platinum-based chemotherapy and immunotherapy (cCIRT) followed by brachytherapy boost and immunotherapy maintenance. In some instances, it is impossible to perform brachytherapy due to patient and/or cancer issues. In these circumstances, an external beam boost could be delivered. Using a robotic arm LINAC, it is mandatory to use intramucosal implanted fiducials which are needed for tumour tracking. To avoid invasive procedures, we developed an original intravaginal 3D-printed universal device containing gold fiducials embedded within it. In this paper, we describe the step-by-step procedure that allowed us to obtain the utility model patent, including the in vivo test (feasibility, reproducibility, device compliance) on seven patients within the study protocol “STereotActic Radiotherapy Boost in locally Advanced Cervical carcinoma patientS” (STARBACS). Full article

The aberrant DNA methylation of tumour suppressor genes, including CADM1, MAL, and PAX1, is implicated in cervical carcinogenesis. Objectives: This pilot study aimed to evaluate the methylation levels of these genes in HPV-positive women and assess their diagnostic performance for detecting histologic high-grade squamous intraepithelial lesions (HSILs) and carcinoma. Methods: Cervical samples from 73 HPV-positive women were analyzed using droplet digital PCR (ddPCR) to quantify methylation levels of CADM1, MAL, and PAX1. The methylation levels were further compared across cytological and histological classifications. A control group of 26 HPV-negative women with negative cytology was also included. The diagnostic performance was assessed through receiver operating characteristic (ROC) analysis, as well as sensitivity and specificity calculations for individual genes and gene panels. Results: MAL methylation was absent in NILM, LSIL, and HSIL samples but was significantly elevated in carcinoma. PAX1 methylation was observed in both high-grade and some low-grade lesions. CADM1 methylation remained low or undetectable in the NILM, LSIL, and HSIL groups, with a significant increase observed in carcinoma cases. The CADM1/MAL panel demonstrated the highest diagnostic accuracy, with an area under the curve (AUC) of 0.912, 70% sensitivity, and 100% specificity. ddPCR exhibited superior analytical sensitivity compared to real-time PCR. Conclusions: The CADM1/MAL methylation panel, assessed by ddPCR, may serve as a specific biomarker for the triage of HPV-positive women at risk of HSIL and carcinoma. However, this study’s limited sample size and single-centre design necessitate cautious interpretation. Further validation in larger, population-based cohorts is necessary to confirm its clinical utility. Full article

Background: Tumour-associated neutrophils play an important role in tumour progression and immunomodulation. However, the prognostic significance and immunological implications of neutrophil-associated genes (NAGS) in cervical cancer remain poorly defined. Methods: We analyzed neutrophil infiltration and its correlation with gene expression in TCGA cervical cancer data using immune deconvolution. NAGS were identified via correlation and enrichment analysis. A prognostic model was constructed using Cox and LASSO regression and validated in the GSE30759 cohort. Kaplan–Meier analysis, ROC curves, and multivariate Cox regression were used to assess prognostic performance. The model’s association with the tumor immune microenvironment and immunotherapy response was further analyzed. The expression pattern of SEMA6B was explored using cell lines, clinical subgroups, and human protein profiles, and its immunological relevance was evaluated using multiple immune infiltration algorithms. Results: Twelve genes were identified as significantly correlated with neutrophil infiltration and enriched in immune-related pathways such as chemotaxis, neutrophil degranulation, and PI3K-AKT signaling. Further NAGS models were developed based on key genes. High-risk patients exhibited an immunosuppressive tumor microenvironment, elevated TIDE scores, and lower predicted responsiveness to immunotherapy. SEMA6B was significantly downregulated in the tumour group but may be reactivated during metastasis. High expression of SEMA6B was associated with poorer prognostic features and immune evasion. Conclusions: We developed a NAGS signature that may inform prognosis and immune microenvironment status in cervical cancer. These findings suggest the potential clinical utility of NAGs-based models in guiding immunotherapy strategies. Moreover, SEMA6B may serve as a promising immunological and prognostic biomarker, pending further mechanistic validation. Full article

Background: Reconstructive surgery with free flaps is a fundamental component in head and neck surgery, but flap failure remains a significant concern. The hemoglobin, albumin, lymphocyte, and platelet (HALP) score is a prognostic factor commonly applied in the evaluation of patients suffering from malignant tumours. This score has emerged as a potential preoperative risk assessment tool; however, its predictive accuracy for free flap failure has not been fully evaluated. The potential of this formula, in the cervical–facial reconstructive area, has not yet been well studied in the international literature. Methods: This retrospective study included patients who had undergone free flap reconstruction in the maxillofacial surgery departments of Perugia and Ancona over the past ten years. To optimize the HALP formula, advanced machine learning technologies, mainly the Julius AI platform, were applied. The HALP formula was refined through three phases: the original formula, a weighted version, and the final “Modified HALP.” Predictive performance was assessed using ROC curve analysis, multivariate logistic regression, and internal validation. Results: The final version of the HALP score, created in the present study, achieved an AUC-ROC of 0.95 (95% CI: 0.91–0.99), outperforming the original and weighted versions. At the optimal cut-off, the final “Modified” HALP score demonstrated 90.91% sensitivity and 92.36% specificity, remaining an independent predictor of flap failure after adjusting for confounders. Conclusions: The aim of the study was to optimize the HALP score by integrating clinical information with the aim of making significant progress in the prediction of failure in reconstructive flaps. The Modified HALP score emerges as a powerful tool for preoperative risk stratification in free flap surgery, potentially improving patient outcomes through targeted interventions. Future research should focus on external validation and exploring the underlying biological mechanisms. Full article

Gynaecological cancers, including endometrial, ovarian, and cervical cancers as well as breast cancer, despite numerous studies, still constitute a challenge for modern oncology. For this reason, research aimed at the application of modern diagnostic methods that are useful in early detection, prognosis, and treatment monitoring deserves special attention, Great hopes are currently being placed on the use of liquid biopsy (LB), which examines various tumour components, including cell-free RNA (cfRNA), circulating tumour cells (CTCs), circulating tumour DNA (ctDNA), exosomes, and tumour-educated platelets (TEPs). LB has shown promise as a minimally invasive means of early diagnosis of cancers, detection of recurrence, prediction of therapy response, treatment monitoring, and drug selection. The integration of this test into clinical practice in modern oncology is challenging, but offers many benefits, including reducing the risks associated with invasive procedures, improving diagnostic and therapeutic efficacy, and improving the quality of life of oncology patients. The aim of this review is to present recent reports on the use of ctDNA in diagnosing, predicting the outcome of, and monitoring the treatment of gynaecological and breast cancers. Full article

Background: The advent of artificial intelligence (AI) has revolutionised many fields in healthcare. More recently, it has garnered interest in terms of its potential applications in histopathology, where algorithms are increasingly being explored as adjunct technologies that can support pathologists in diagnosis, molecular typing and prognostication. While many research endeavours have focused on solid tumours, gynaecological malignancies have nevertheless been relatively overlooked. The aim of this review was therefore to provide a summary of the status quo in the field of AI in gynaecological pathology by encompassing malignancies throughout the entirety of the female reproductive tract rather than focusing on individual cancers. Methods: This narrative/scoping review explores the potential application of AI in whole slide image analysis in gynaecological histopathology, drawing on both findings from the research setting (where such technologies largely remain confined), and highlights any findings and/or applications identified and developed in other cancers that could be translated to this arena. Results: A particular focus is given to ovarian, endometrial, cervical and vulval/vaginal tumours. This review discusses different algorithms, their performance and potential applications. Conclusions: The effective application of AI tools is only possible through multidisciplinary co-operation and training. Full article

The aim of this work was a detailed radiological and histopathological evaluation of a solid tumour that was diagnosed in a 2-year-old goose (Anser domesticus). The radiograph examination showed an osseous change involving the cervical vertebrae. The tumour measuring 15 cm × 10 cm × 9 cm was dense and had well-defined borders, suggesting the presence of calcified bone tissue. Histopathology revealed a well-defined benign neoplasm derived from bone that consisted largely of irregular, disorganized bone trabeculae surrounded by a layer of osteoblasts. The tumour has been classified as an osteoma, which originates from the body of the vertebrae. Osteoma is a benign, well-differentiated tumour with a structure that resembles bone tissue. It presents as a well-demarcated, hard, single tumour that can grow to a considerable size. The aetiology of osteomas in birds remains unclear because of the small number of cases described. Therefore, the influence of factors such as age, breed or sex, trauma, embryonic malformation, infection, developmental disorders, and genetic factors on the development of this type of tumour has not been established. Trauma seems to be the most obvious cause of growth in this case. This work provides valuable information about osteomas in birds, which is important for understanding such neoplasms. Full article

In recent years, anthraquinones have been widening their therapeutic opportunities given their numerous health benefits. The search for adequate delivery platforms to improve their pharmacokinetics leads us to propose herein folate-capped gold nanoparticles with an anthraquinone derivative attached onto their surface. Through a straightforward, two-step procedure, we obtained stable nanoparticles that can deliver anthraquinones selectively to cells overexpressing folate receptors. The new conjugates were highly toxic against two tumour cell lines, lung carcinoma A549 and cervical carcinoma HeLa, and showed significant in vitro targeting effects for FR+ HeLa cells. We anticipate that the convenience of this synthetic procedure could enable the future development of folate-targeted conjugates bearing highly active anthraquinone-derived drugs. Full article

Background/Objectives: Cervical cancer primarily disseminates through the lymphatic system, with the metastatic involvement of pelvic and para-aortic lymph nodes significantly impacting prognosis and treatment decisions. Sentinel lymph node (SLN) mapping is critical in guiding surgical management. However, resource-limited settings often lack advanced detection tools like indocyanine green (ICG). This study evaluated the feasibility and effectiveness of SLN biopsy using alternative techniques in a high-risk population with a high prevalence of large tumours. Methods: This prospective, observational study included 42 patients with FIGO 2018 stage IA1–IIA1 cervical cancer treated between November 2019 and April 2024. SLN mapping was performed using methylene blue alone or combined with a technetium-99m radiotracer. Detection rates, sensitivity, and false-negative rates were analysed. Additional endpoints included tracer technique comparisons, SLN localization patterns, and factors influencing detection success. Results: SLNs were identified in 78.6% of cases, with bilateral detection in 57.1%. The combined technique yielded higher detection rates (93.3% overall, 80% bilateral) compared to methylene blue alone (70.4% overall, 40.7% bilateral, p < 0.05). The sensitivity and negative predictive values were 70% and 93.87%, respectively. Larger tumours (>4 cm), deep stromal invasion, and prior conization negatively impacted detection rates. False-negative SLNs were associated with larger tumours and positive lymphovascular space invasion. Conclusions: SLN biopsy is feasible in resource-limited settings, with improved detection rates using combined tracer techniques. However, sensitivity remains suboptimal due to a steep learning curve and challenges in high-risk patients. Until a high detection accuracy is achieved, SLN mapping should complement, rather than replace, pelvic lymphadenectomy in high-risk cases. Full article

Background/Objectives: Uterine carcinosarcoma (UCS) refers to a rare high-grade aggressive epithelial non-endometrioid endometrial carcinoma, with tumour cells demonstrating epithelial–mesenchymal metaplastic transition and composed of both carcinomatous epithelial and sarcomatous (homologous or heterologous) components. Methods: The aim of this study was to evaluate the epidemiology, management approach, outcomes and survival patterns of patients with UCS. Seventy-seven cases of UCS treated with primary surgery in a single tertiary centre underwent retrospective cohort analysis across a ten-year period. Observational data on clinicopathological variables and treatment pathways were reviewed and independent risk factors for relapse and mortality were analysed. Results: The 5-year disease-free and overall survival rates were 52.10% and 46.6%, respectively. Cervical stromal involvement was independently related to disease-free survival (HR = 6.26; 95%CI 1.82–21.59; p = 0.004) and overall survival (HR = 3.64; 95%CI 1.42–9.38; p = 0.007), whilst sarcomatous component type was independently related to recurrence only (HR = 3.62; 95%CI 1.38–9.51; p = 0.009) after adjusting for other pathological and treatment variables. No significant difference in recurrence or mortality was found when comparing the performance of pelvic lymph node dissection (p = 0.803 and p = 0.192 respectively) or the administration of adjuvant treatment (p = 0.546 and p = 0.627 respectively). Conclusions: Whilst our data suggests an encouraging similarity in overall survival rates compared with the literature, UCS continues to represent significant treatment challenges—with a paucity of guidelines available. Data regarding molecular analysis was not systemically available in our cohort, the more recent introduction of which (alongside the revision of endometrial cancer staging) will undoubtedly provide UCS patients with improved therapeutic options in the future. Full article

Background: Although grade is a well-recognised prognostic factor for endometrioid endometrial cancer (EEC), in more studies grade 1 (G1) and grade 2 (G2) EEC are combined and compared together with grade 3 (G3) tumours. The aim of our study is to separately investigate the outcomes, prognostic factors and recurrence patterns of G2 EEC and whether the differentiation between G1 and G2 EEC is clinically useful. Methods: we retrospectively reviewed 523 patients with EEC treated with primary surgery over a decade (March 2010–January 2020) at Oxford University Hospitals NHS Trust, focusing on those with G2 disease. Results: Patients with G2 EEC had worse 5-year cancer-specific survival (93.3% vs. 98.5%, p < 0.01) compared to patients with G1 EEC, but a favourable prognosis compared to G3 EEG, both in terms of disease-free survival (91.6 vs. 83.8%, p = 0.04) and cancer-specific survival (93.3% vs. 78.5%, p < 0.01). Both stage and grade are independent risk factors for cancer-specific mortality in EEC. Cervical stromal involvement, parametrial involvement and distant metastatic disease are all independent risk factors for cancer-related mortality in G2 ECC. Only 12.5% of recurrences of G2 EEC were diagnosed with examination in routine follow up in asymptomatic patients. Conclusions: our results suggest that the grading system should continue to differentiate G1 EEC and G2 EEC for better prognosis interpretation. Full article

Background/Objectives: Cervical mesonephric adenocarcinomas (MNACs) are among the rarest neoplasms of the female genital tract. Unlike the majority of cervical cancers, which are predominantly squamous in origin and strongly associated with HPV seropositivity, MNACs are distinct in both histology and pathophysiology. Despite their unique characteristics, MNACs have historically been managed in parallel with squamous cell carcinomas, resulting in a lack of optimised, evidence-based treatment protocols. In this systematic review, we aim to evaluate the current management strategies for MNACs and their associated clinical outcomes. Additionally, we critically appraise existing surgical and adjuvant therapies and propose embryologically oriented surgical techniques to achieve optimal tumour resection. Methods: We performed a systematic search across the MEDLINE, CENTRAL, EMBASE, and ClinicalTrials.gov databases from 1960 to June 2024. The search strategy employed a combination of keywords and MeSH terms, including “Uterine Cervical Neoplasms” [MeSH], “mesonephric tumour”, “mesonephric neoplasm”, and “mesonephric cancer”. All relevant publications, including case reports and case series, were considered. Results: A total of 49 publications were finally included in the analysis, involving a thorough description of 91 MNAC cases. Most patients had stage I disease (70.8%) (n = 51). Hysterectomy was performed in 77 patients. The median follow-up was 29 months (range 1–199 months). Disease recurrence was observed in 35.2% (n = 25) of the cases, with the median disease-free survival (DFS) being 24 months (range 1–199). At the follow-up, 64.8% (n = 46) of patients remained in remission irrespective of the treatment modality, while 27.4% (n = 20) died due to disease progression. Conclusions: Mesonephric neoplasms of the uterine cervix are rare and clinically aggressive cancers that signify poor prognosis. Accurate identification and effective management can be challenging due to their particular anatomic and immunohistochemical characteristics. Therefore, a more tailored embryological-based approach should be considered for an optimal oncologic outcome. Full article

Cervical cancer is a global health problem; therapies focused on eliminating tumour cells and strengthening different immunotherapies are in development. However, it has been observed that cervical tumour cells can evade cell death mechanisms and generate immune system molecules to promote their proliferation and metastasis. In this context, we analysed the role of the IL-2 and CD95 pathways, essential molecules in activating the immune system and eliminating tumour cells. However, it is important to analyse their role in cervical tumour cells because these cells could be using these pathways to proliferate. In this study, we found that SiHa and HeLa cells respond to treatment, with 10 IU/mL of IL-2 inducing their proliferation and 100 IU/mL of IL-2 decreasing their proliferation. We also observed that they express a high percentage of the CD95 receptor and its ligand (CD95L) and that treatment with CD95 agonist antibodies at low doses increases cell proliferation. Furthermore, simultaneous treatment with high doses of IL-2 plus CD95 agonist antibody positively regulates LC3B accumulation. We did not observe apoptosis under any of the treatments carried out. In conclusion, cervical tumour cells can use the IL-2 and CD95 pathways to induce their proliferation and potentially activate cytoprotective mechanisms for survival. Full article