Search Results (1,346)

Background/Objectives: Cervical cancer treatment relies heavily on high-dose-rate (HDR) ¹⁹²Ir brachytherapy; however, therapeutic efficacy remains limited by tumor radioresistance and the inability to escalate dose without increasing toxicity to surrounding healthy tissues. The present study investigates the potential of gold nanoparticles (AuNPs) to enhance radiosensitivity under clinically relevant ¹⁹²Ir brachytherapy conditions through the combined action of physical dose amplification and radiobiological modulation. Particular emphasis is placed on the unique radiophysical interactions generated by the mixed gamma and secondary beta emissions of ¹⁹²Ir, which, in the presence of high atomic number nanoparticles, promote localized photoelectric absorption and the emission of low-range secondary electrons, including Auger electrons. The study further aims to determine how AuNPs size and post-irradiation temporal evolution influence radiation-induced cytotoxicity and apoptosis in cervical cancer cell lines, thereby providing a biologically representative model of nanoparticle-assisted brachytherapy. Methods: Clonogenic survival, dose enhancement factor (DEF), and apoptosis were evaluated following irradiation in the presence of 10 nm and 50 nm AuNPs in two independent biological experiments (n = 2). Results: A clear dose-dependent reduction in survival fraction and increase in apoptosis were observed in nanoparticle-treated groups compared with irradiation alone. Radiosensitization demonstrated strong size dependence, with 50 nm AuNPs producing the greatest enhancement, a finding that may reflect size-dependent differences in cellular internalization, intracellular distribution, and nanoscale energy deposition previously established in AuNP studies. Importantly, biological effects intensified at later post-irradiation intervals, demonstrating a sustained temporal evolution of the radiobiological response beyond the initial irradiation event, potentially involving oxidative and other delayed cellular stress mechanisms described in AuNP radiosensitization. Conclusions: These findings demonstrate the capacity of AuNPs to enhance the radiobiological response of cervical cancer cells to ¹⁹²Ir brachytherapy and identify nanoparticle size and post-irradiation time as important determinants of this effect. They therefore support AuNP-assisted brachytherapy as a promising strategy for further development toward biologically optimized radiotherapy capable of improving tumor response without escalation of the prescribed radiation dose. Full article

Cervical cancer is a leading cause of cancer-related death among women, and acquired resistance to paclitaxel (PTX) frequently results in treatment failure. Dehydrocavidine (DHC), the principal bioactive alkaloid from the traditional Chinese herb Corydalis saxicola, has shown antitumor activity, but its potential in cervical cancer and synergism with PTX remain unknown. We investigated the combined effect of low-dose PTX and DHC in HeLa and SiHa cells and a HeLa xenograft model. ZIP (zero interaction potency) synergy analysis revealed strong synergy in inhibiting proliferation, colony formation, and migration. In vivo, the combination significantly suppressed xenograft tumor growth. Network pharmacology, molecular docking, and experimental validation identified fatty acid synthase (FASN) and stearoyl-CoA desaturase 1 (SCD1) as key targets; the combination downregulated their expression, reducing lipid droplets and triglyceride accumulation. Public single-cell transcriptomic analysis showed elevated FASN/SCD1 in tumor cells and cancer-associated fibroblasts, correlating with poor overall survival. These findings demonstrate that low-dose PTX plus DHC synergistically suppresses cervical cancer by inhibiting FASN/SCD1-mediated lipid metabolism reprogramming, providing a promising strategy to overcome PTX resistance and reduce toxicity. Full article

Basophil extracellular traps (BETs) represent a recently recognized extracellular effector mechanism whose biology remains far less defined than that of neutrophil extracellular traps. This review critically examines the terminology, molecular composition, signaling requirements, and disease relevance of BET formation. Current evidence supports a rapid, predominantly non-lytic process in which mitochondrial reactive oxygen species promote the externalization of mitochondrial DNA, particularly after IL-3 priming followed by FcεRI or C5a receptor activation. The resulting networks contain mtDNA associated with basophil granule proteins, including basogranulin in humans and mMCP-8 in mice, although their complete proteomic composition and route of cellular export remain unresolved. Functional studies indicate that BETs can immobilize Escherichia coli and Staphylococcus aureus and contribute to extracellular bacterial killing, while in vivo observations place BET release in helminth-associated inflammation and several inflammatory dermatoses. A small cervical cancer study reported circulating BET-like structures during anticancer treatment, although their basophil origin and molecular composition were not comprehensively confirmed and their biological significance remains unknown. By separating direct basophil evidence from mechanisms inferred from other trap-forming cells, this review defines the current experimental boundaries of the field and highlights priorities for mechanistic and translational investigation. Full article

Background: Endothelial activation and thromboinflammation play an important role in cancer-associated thrombosis. An imbalance between von Willebrand factor (vWF) and its physiological regulator ADAMTS13 may reflect the development of a prothrombotic endothelial state in patients with malignancies. However, the dynamics of the vWF-ADAMTS13 axis during chemotherapy and thromboprophylaxis remain insufficiently characterized. Objectives: To characterize the vWF-ADAMTS13 axis as a potential laboratory marker of endotheliopathy in patients with gynecologic malignancies and to assess its dynamics during chemotherapy and thromboprophylaxis with low-molecular-weight heparin (LMWH). Materials and Methods: This prospective comparative study included 74 patients with stage I–III gynecologic malignancies undergoing chemotherapy after surgical treatment. Group I comprised 34 patients with a history of thrombotic complications (VTE), including 23 patients with ovarian cancer and 11 with cervical adenocarcinoma. Group II included 40 patients without previous VTE, including 20 patients with ovarian cancer and 20 with cervical adenocarcinoma. The control group consisted of 25 healthy women. Plasma vWF levels, ADAMTS13 antigen and functional activity, ADAMTS13 inhibitor levels, and the vWF/ADAMTS13 ratio were assessed before chemotherapy and after 1–2 chemotherapy cycles. Patients in Group I additionally received thromboprophylaxis with nadroparin calcium. Results: Before chemotherapy, an imbalance of the vWF-ADAMTS13 axis was observed in patients with malignancies compared with healthy controls and was most pronounced in patients with a history of thrombosis. The vWF/ADAMTS13 ratio was 0.65 in controls, 1.02 and 0.84 in patients without previous VTE with ovarian and cervical cancer, respectively, and 1.59 and 1.34 in the corresponding subgroups with a history of thrombosis (p < 0.05). After 1–2 chemotherapy cycles, the vWF–ADAMTS13 axis showed a further shift toward imbalance, characterized by increased vWF levels, decreased ADAMTS13 antigen levels and functional activity, and increased ADAMTS13 inhibitor concentrations. The vWF/ADAMTS13 ratio increased to 2.04 in patients with ovarian cancer and to 1.65 in those with cervical cancer and a history of thrombosis. In Group I, the subsequent assessment following chemotherapy and LMWH thromboprophylaxis demonstrated partial reversal of these changes: ADAMTS13 antigen levels increased, while vWF levels and ADAMTS13 inhibitor concentrations decreased, and the vWF/ADAMTS13 ratio declined from 2.04 to 1.30 in ovarian cancer and from 1.65 to 1.14 in cervical cancer. Conclusions: The vWF-ADAMTS13 axis is markedly altered in patients with gynecologic malignancies, including those without previous VTE, with the most pronounced imbalance observed in patients with a history of thrombosis. The post-chemotherapy assessment demonstrated a further shift toward imbalance, whereas the subsequent assessment following chemotherapy and LMWH thromboprophylaxis in Group I showed partial reversal of these changes. The vWF/ADAMTS13 ratio may represent a potential integrative and dynamic marker of endothelial–hemostatic imbalance in patients with gynecologic malignancies. Full article

Background: Concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced cervical cancer, but resistance and recurrence remain major clinical challenges. Tumor immune–metabolic reprogramming profoundly affects treatment response and immune evasion; however, the molecular mechanisms of lipid metabolism remodeling and its interaction with T cells after CCRT in cervical cancer are still unclear. This study aimed to investigate how CCRT-induced metabolic changes in cervical cancer cells influence T cell function and immune evasion. Methods: We performed metabolic pathway activity analysis, cell–cell communication prediction, and transcriptomic analysis on paired single-cell transcriptomic data from three cervical cancer patients before and after CCRT (n = 3 paired). Validation was conducted using multiple independent GEO cohorts, in vitro cell culture experiments, and multi-sample immunofluorescence staining. Results: CCRT was associated with upregulation of FABP4/5 in malignant epithelial cells and activation of the PPAR and adipocytokine signaling pathways, leading to lipid metabolic reprogramming. Epithelial cells with high FABP4/5 expression showed enhanced predicted intercellular communication with T cells via the computationally inferred ligand–receptor axes PTGER4 and CXCR4. T cells with high communication intensity exhibited an immunosuppressive phenotype signature, accompanied by metabolic alterations in lipid and carbohydrate pathways and enrichment of regulatory T cell subsets. Validation experiments confirmed the association between FABP4/5 and inhibitory T cells. Conclusions: This study suggests that FABP4/5-mediated lipid metabolism reprogramming may represent a key mechanism contributing to the immunosuppressive crosstalk between cervical cancer epithelial cells and T cells after CCRT. Targeting this axis may reverse T cell dysfunction and provide a potential immunometabolic strategy to reduce post-CCRT recurrence. Full article

Advanced cervical cancer remains a major cause of mortality in women worldwide as it has limited treatment options and recurrence is very common. This highlights the necessity to develop patient-derived organoids (PDOs) as preclinical models that can recapitulate the clinical heterogeneity of the cancer in terms of molecular features and genetic background. The PDOs have potential for guiding personalized treatment in clinical practice. In this study, we have established patient-derived cervical cancer organoids from biopsy samples of five patients with two different histological subtypes (squamous cell carcinoma and adenocarcinoma) using a modified protocol. The organoids were characterized to assess their genetic and phenotypic similarity to the parental tumor tissue. The organoids developed in vitro preserved several characteristics of the parental tumors, including histological features, HPV status and a subset of genomic alterations. The expression of cervical cancer-related genes, including PIK3CA, MET, and LRP1B, was found to be comparable between the organoids and the parental tumor tissue. Moreover, characterization of the PDOs after cryopreservation showed the histopathological features of the parental tumor tissue. This study demonstrates that the CERvical Cancer OrganoidS (CERCOS) established using the current protocol hold potential to serve as a platform for personalized medicine. Full article

Background/Objectives: Management of locally advanced cervical cancer (LACC) and other gynecological malignancies aims to achieve locoregional control while avoiding morbid surgical salvage. This exploratory, hypothesis-generating study described the treatment pathways of three protocol groups and examined whether clinical, sociodemographic, and treatment-deviation variables are associated with any oncological surgery. Methods: Sixty-nine adult patients with gynecological or urogenital cancers (89.9% cervical carcinoma) treated with platinum-based chemotherapy at a Romanian tertiary center between April 2024 and April 2025 were stratified into INTERLACE-type dose-dense induction chemotherapy followed by chemoradiotherapy (Group A, n = 27), classic three-weekly neoadjuvant chemotherapy followed by chemoradiotherapy (Group B, n = 7), and no induction chemotherapy (Group C, n = 35). Associations with any oncological surgery (upfront, completion, or salvage) were explored by multivariable logistic regression with bootstrap internal validation, Firth penalized regression, and restricted sensitivity analyses. Results: Twenty-five patients (36.2%) underwent surgery (14 upfront, 8 completion, 3 salvage), and none of them were from Group A, whose median follow-up was only 8.6 months and whose allocation was confounded by diagnosis and stage. The model showed an apparent area under the curve of 0.717 (optimism-corrected 0.672), accuracy of 73.9% against a no-information rate of 63.8% (p = 0.049), sensitivity of 0.480, and specificity of 0.886. Urban provenience (OR 0.343, 95% CI 0.113–1.039, p = 0.059), Delta Target Dose (OR 1.109 per Gy, p = 0.076), and number of chemotherapy cycles (OR 1.298 per cycle, p = 0.076) showed non-significant trends whose direction was unchanged in all sensitivity analyses. Conclusions: The absence of surgery after induction chemotherapy is hypothesis-generating rather than confirmatory, and the exploratory model is not a clinical prediction tool. Geographic provenience and planning-to-delivery treatment deviation are candidate variables for prospective evaluation in a homogeneous LACC population with standardized radiotherapy parameters and mature oncological endpoints. Full article

Persistent infection with high-risk human papillomavirus (hrHPV) is the principal cause of cervical cancer and initiates a complex process of immune evasion that enables malignant progression despite continuous expression of the viral oncoproteins E6 and E7. Effective antitumor immunity depends on coordinated antigen presentation through human leukocyte antigen class I (HLA-I) molecules, activation of CD8⁺ cytotoxic T lymphocytes, and balanced regulation of immune responses. During cervical carcinogenesis, these mechanisms are progressively disrupted through HLA-I downregulation, CD8⁺ T-cell exhaustion, expansion of FOXP3⁺ regulatory T cells, and activation of the PD-1/PD-L1 and CTLA-4 immune checkpoint pathways, ultimately establishing an immunosuppressive tumor microenvironment that promotes immune escape. This narrative review integrates current evidence on HLA-I-mediated antigen presentation, CD8⁺ cytotoxic T-cell function, FOXP3⁺ regulatory T cells, and immune checkpoint signaling into a unified model of immune escape during cervical carcinogenesis. In addition, it discusses the clinical implications of these interconnected mechanisms, including immune checkpoint inhibition, emerging therapeutic strategies, integrated immune profiling, and future directions in personalized immunotherapy. A comprehensive understanding of the interactions between antigen presentation, immune-cell function, and immune checkpoint regulation provides the biological foundation for current and future immunotherapeutic approaches. Integrating molecular, cellular, and spatial immune characteristics may improve patient stratification, optimize treatment selection, and facilitate the implementation of precision immuno-oncology in cervical cancer. Full article

Cervical cancer remains a major cause of cancer-related mortality worldwide, highlighting the need for strategies that may improve responses to conventional chemotherapeutics. Epigallocatechin gallate (EGCG), a green-tea polyphenol with diverse biological activities, has been investigated as a potential chemosensitizing agent. This study evaluated the interaction between EGCG and doxorubicin (DOX) in HeLa cervical cancer cells, with HaCaT keratinocytes included as a non-malignant comparator. Cell viability and drug interactions were assessed using the CCK-8 assay and Chou–Talalay combination index (CI) analysis. Complementary assays evaluated membrane integrity, wound closure, apoptosis, cell-cycle distribution, intracellular DCF-associated fluorescence with or without N-acetylcysteine (NAC) pretreatment, caspase-3 immunoreactivity, and EGFR, FOXP3, CASP3, and CASP7 mRNA expression. Network-based analyses were additionally used to identify candidate molecular associations and pathways. CI analysis demonstrated synergistic EGCG–DOX interactions in HeLa cells under the tested conditions, whereas additive or antagonistic interactions predominated in HaCaT cells. Combined treatment produced the greatest reduction in viable cells, increased apoptosis, altered cell-cycle distribution, and reduced wound closure. It also produced the highest viability-normalized DCF-associated fluorescence, which was attenuated by NAC pretreatment, indicating an antioxidant-sensitive change in intracellular oxidative status without establishing a causal role in cytotoxicity. Combined treatment was further associated with increased total caspase-3 immunoreactivity and altered EGFR, FOXP3, CASP3, and CASP7 transcript levels. Overall, EGCG and DOX exhibited synergistic interactions and multiple treatment-associated cellular and transcriptional responses in HeLa cells under the present in vitro conditions. These findings do not establish cancer-specific selectivity or a definitive molecular mechanism but provide a basis for validation in additional cervical cancer models and at clinically relevant exposures. Full article

Attenuated Salmonella strains are a promising gene delivery vector in the development of vaccines targeting various human diseases. For example, the Ty21a vaccine is a Salmonella-based vaccine that elicits a robust local, cellular, and systemic immune response against Salmonella typhi infection. Human immunodeficiency virus (HIV) is responsible for the AIDS pandemic and requires lifelong treatment to manage. Human papillomavirus (HPV) is the cause of the vast majority of cervical cancer cases in the global population. Influenza is a seasonal, pandemic virus that can lead to high death tolls in humans and livestock and considerable financial losses. In this review, we outline current methods of protection and treatment for HIV, HPV, and influenza, as well as how a versatile Salmonella-based gene delivery vector’s mechanism of action can lead to immunity. We also describe several studies that utilize many of these Salmonella-based vector vaccines to provide protection against infection with these viruses, as many of these Salmonella-based vectors exhibit different factors that may enhance their gene delivery, immune responses, and post-delivery clearance out of host cells. Finally, we discuss the benefits and drawbacks of using Salmonella-based vaccines and future directions for these vaccine candidates, as well as the implications of introducing these vaccines into the current landscape. Full article

Background/Objectives: Cervical cancer cells evade chemotherapy by upregulating antioxidant defenses (e.g., glutathione (GSH)). A platform that simultaneously amplifies ROS and suppresses antioxidant defense is a low toxicity strategy. This study presents a local nanoplatform that combines chemodynamic therapy (CDT) with chemotherapy for the localized treatment of cervical cancer. Methods: Diallyl trisulfide (DATS) was loaded into the echinacoside (ECH)-copper metal–phenolic networks (MPNs) nanoparticles (ECD NPs) through a one-step coordination assembly method. The nanoparticles were incorporated into a poloxamer/HPMC thermosensitive hydrogel for vaginal delivery. The formulation was characterized for size, drug loading, sol–gel transition, and pH-responsive release. Antitumor activity was evaluated in SiHa and HeLa cells via Cu²⁺ uptake, GSH depletion, ROS accumulation, apoptosis markers, and viability. In vivo efficacy and biosafety were assessed in an orthotopic cervical cancer model. Results: ECD NPs showed uniform size (~135 nm), high DATS loading (~27.6%). The ECD NPs-loaded hydrogel exhibited a sol–gel transition at 36.7 °C. The ECD NPs-loaded hydrogel released 16.4% of DATS at pH 7.4, 32.4% at pH 4.5, 64.8% at pH 6.5, and 80.9% at pH 5.6 over 24 h. Release was minimal at vaginal pH, clearly triggered at tumor pH, and fastest at lysosomal pH, confirming pH-responsive behavior. The ECD NPs-loaded hydrogel enhanced Cu²⁺ uptake, depleted GSH, elevated ROS, and reduced cell viability to <50% at 80 μg/mL. In the orthotopic model, the ECD NPs hydrogel achieved a tumor inhibition rate of 87.81%, significantly outperforming free DATS (65.3%) and blank MPN (55.62%) hydrogels, with no evident systemic toxicity. Conclusions: The ECD NPs hydrogel triggers a Cu²⁺-driven ROS/GSH cascade that combines copper-mediated oxidative stress with DATS-induced apoptosis for enhanced antitumor activity. Its vaginal localization, pH-responsive release, and biosafety profile support further evaluation for cervical cancer therapy. Full article

Background: Organized cervical cancer screening aims to reduce the burden of advanced disease through earlier detection. However, a substantial proportion of women continue to present with locally advanced cervical cancer (LACC) requiring definitive chemoradiation. This study evaluated temporal changes in the demographic and clinicopathological characteristics of women with LACC treated with definitive chemoradiation before and after implementation of the organized cervical cancer screening program in Serbia. Methods: This retrospective single-center cohort study included 200 consecutive women with histologically confirmed LACC treated with definitive chemoradiation at the Institute of Oncology and Radiology of Serbia. Two cohorts were analyzed: a pre-screening cohort (2010–2011, n = 100) and a post-screening cohort (2022–2023, n = 100). Demographic and clinicopathological characteristics, including age, histopathology, FIGO stage, lymph node involvement, and geographic distribution, were compared. For study purposes, all patients were retrospectively restaged according to the FIGO 2018 classification using the best available clinical, radiological, and pathological data. Results: Women in the post-screening cohort were significantly older at diagnosis than those in the pre-screening cohort (mean age 54.9 vs. 49.7 years, p = 0.0046), with a substantially higher proportion of patients older than 64 years (28% vs. 2%, p < 0.0001). Although the overall distribution of FIGO stages II–IV did not differ significantly, a marked redistribution of FIGO 2018 substages was observed (p < 0.0001), characterized by an increased proportion of stage IIIC disease and significantly more frequent lymph node involvement (63% vs. 41%, p = 0.0018). Geographic distribution remained stable, with most patients referred from the Belgrade administrative district. Conclusions: This study demonstrated clinically relevant temporal changes in the demographic and clinicopathological characteristics of women requiring definitive chemoradiation for LACC in Serbia. More than a decade after implementation of organized cervical cancer screening, tertiary referral centers continue to manage a substantial burden of patients with locally advanced disease requiring complex, resource-intensive treatment. These findings should not be interpreted as a direct evaluation of the national screening program but may provide valuable insights for healthcare planning in Serbia and other countries with similarly resource-constrained healthcare systems. Strengthening participation in organized screening, ensuring timely diagnostic evaluation, and improving HPV vaccination uptake remain essential to reduce the burden of advanced cervical cancer. Full article

Cervical cancer remains the leading cause of cancer-related mortality among women in Nepal, where national screening coverage is approximately 16%. This study evaluated the feasibility of a community-based, door-to-door self-sampling strategy for high-risk human papillomavirus (hrHPV) detection in an urban municipality of central Nepal and assessed hrHPV prevalence, genotype distribution, screening outcomes, and associated demographic factors. A cross-sectional study was conducted between September 2023 and May 2024 in Ward No. 3 of Lalitpur Metropolitan City. Women aged 30–60 years were recruited through trained community health workers, provided education and home-based self-sampling kits, and completed a demographic questionnaire. Dry cervical swabs from 418 participants were tested for hrHPV. Women with positive results underwent visual inspection with acetic acid (VIA), followed by colposcopy, biopsy when indicated, and thermal ablation for confirmed precancerous lesions. Overall participation was 64.1%, and hrHPV prevalence was 10.3%. Non-16/18 hrHPV genotypes predominated (55.8%), followed by HPV16 (20.9%). Women aged > 50 years were more likely to be hrHPV- and VIA-positive (OR = 7.39, p = 0.02). Six pre-cancer cases were identified: five cervical intraepithelial neoplasia (CIN1) and one CIN3 case. Community-based hrHPV self-sampling was found to be feasible and achieved effective linkage to triage and treatment, supporting its consideration for strengthening cervical cancer screening in Nepal. Full article

Background: Romania has one of the highest cervical cancer incidence and mortality rates in the European Union (EU) and one of the lowest levels of screening participation. We examined eight years of screening activity at an accredited centre in Bihor County, north-western Romania, encompassing the pre-pandemic period (2018–2019), the COVID-19 pandemic (2020–2021), the post-pandemic recovery (2022–2023) and the transition from primary cytology to primary human papillomavirus (HPV) DNA screening (2024–2025). Methods: This retrospective, single-centre study included 17,807 de-identified screening-episode records collected between 2018 and 2025 at Pelican Clinical Hospital, Oradea. Cytology was the primary screening test in the cytology era (2018–2023), whereas high-risk HPV (HR-HPV) DNA testing (cobas HPV Test, Roche, Pleasanton, CA, USA) with reflex cytology was used in the HPV-primary era (2024–2025). Screening activity was expressed relative to the provider’s registered administrative catchment of 65,978 women. Because quarterly counts were markedly overdispersed, changes in screening volume were analysed using negative-binomial incidence-rate ratios (IRRs) and a segmented negative-binomial interrupted time-series; cytological positivity was evaluated using age-adjusted logistic regression and the Cochran–Armitage trend test. Results: The number of screening episodes recorded over eight years corresponded to 27.0% (95% confidence interval [CI] 26.6–27.3) of the registered catchment, while annual throughput never exceeded 5.2%. Mean monthly screening volume declined from 264.5 tests in the pre-pandemic period (2018–2019) to 88.6 during the pandemic (2020–2021; IRR 0.335, 95% CI 0.177–0.634; 66.5% reduction; p < 0.001), corresponding to an estimated deficit of approximately 3700 tests; the interrupted time-series estimated an immediate 86% reduction at lockdown onset. Activity recovered to 61% of the pre-pandemic rate during the post-pandemic recovery (2022–2023; IRR 0.614, 95% CI 0.482–0.783) and to 90% in the HPV-primary era (2024–2025; IRR 0.898, 95% CI 0.733–1.100), coinciding with the transition to primary HPV screening. All primary HPV tests produced valid results, compared with an annual unsatisfactory-sample rate of 2.9–4.2% during primary cytology. Cytological positivity remained stable during 2018–2023, and the cytological high-grade squamous intraepithelial lesion (HSIL) detection rate per 1000 screened did not change significantly during the pandemic, although absolute HSIL detections declined with screening volume. In 2024–2025, HR-HPV positivity was 22.8% (1301/5700; 95% CI 21.8–23.9), and 47.9% of HPV-positive women had abnormal reflex cytology. Conclusions: The pandemic substantially reduced screening activity at a provider already operating with low throughput relative to its registered catchment. Activity subsequently returned to near pre-pandemic levels during the period coinciding with the introduction of primary HPV screening, which also improved primary-sample adequacy. However, the absence of persistent patient linkage and of follow-up data from colposcopy, histology and treatment precluded estimation of population-based coverage, screening intervals and detection of histologically confirmed cervical intraepithelial neoplasia grade 3 or worse (CIN3+). The findings support population-based invitation and recall, clearly defined age-specific screening and follow-up algorithms, self-sampling, targeted catch-up after pandemic-related delays and longitudinal evaluation using histologically confirmed CIN3+ as the principal clinical endpoint. Full article

Background: The fibrous tumor extracellular matrix (ECM), driven by cancer-associated fibroblasts (CAFs), forms a physical barrier against drugs and immune cells, yet direct CAF elimination risks promoting metastasis. Methods: In this study, we developed a locally injectable hydrogel based on synergistic dynamic covalent crosslinking (imine and boronate ester bonds), enabling instant gelation, shear thinning, and dual-pH/ROS-responsive degradation. Two types of drug-loaded nanoparticles (NPs), coated with homotypic cell membranes, were incorporated into this hydrogel. In the acidic, reactive oxygen species (ROS)-rich tumor microenvironment (TME), the system responsively releases the antifibrotic drug SIS3 to reprogram CAFs while simultaneously delivering doxorubicin (DOX) specifically to tumor cells. Biological effects were evaluated in vitro using cell cultures and in vivo in mouse models. Results: This dynamic hydrogel-based co-delivery system effectively reprograms CAFs, reduces tumor mechanical stress, breaks the fibrotic barrier, and promotes the deep infiltration of chemotherapeutics and immune cells, thereby enhancing the efficacy of chemotherapy. Conclusions: This injectable pH/ROS-responsive dynamic covalent hydrogel, loaded with CAF- and cancer cell-targeting NPs, remodels the TME, enhances drug and immune cell penetration, and offers a promising biomaterial-based strategy for cervical cancer treatment. Full article