Original research publications

Cervical cancer is one of the most common cancers in women around the globe and death from such cancer is largely due to late or insufficient diagnosis. Traditional forms of screening like Pap smears and HPV testing, though common with extensive use, have limitations in sensitivity, false negative and require repeated clinical follow-ups. To overcome these diagnostic gaps, we have presented a supportive layout of a Bisected Circular-Resonator and Axial Line Refractive Index Biosensor (BCALRIB) with a machine learning-driven approach that can help to detect cervical cancerous cells in the early stage. The recommended layout of geometry has emerged as especially valuable because cancer-related cells present greater nuclei and changed nuclear-to-cytoplasmic ratios, which produce distinctive optical signals. Additionally, an acceptable tolerance analysis has been evaluated to check and enhance the device's robustness against deviations in biological components. The optimum impressive sensitivity values of 1000.00 nm/RIU, 933.33 nm/RIU, and impressive detection limit values of 0.008289 RIU, 0.006935 RIU have been obtained for cervical cancerous nucleus (CCNu), and cervical cancerous cytoplasm (CCCy), respectively, with reference to healthy nucleus (HeNu), and healthy cytoplasm (HeCy). The impressive value of 175.81 quality factor has been obtained. The impressive machine learning parameter, resulting in a 0.996351 R-squared score with 6.057260 × 10 -05 of mean square error score. The current biosensors with SPR provide rapid, specific, and real-time detection of cervical cancer biomarkers by utilizing the variation of refractive indices on the sensor interface.

HPV vaccine hesitancy remains a critical barrier to cervical cancer prevention in China despite a series of strategic policy initiatives. Our study conducted two large-scale online cross-sectional surveys in 2022 and 2025 among nationally representative samples of female university students, applying propensity score matching to enhance comparability. HPV vaccine hesitancy, assessed on a 0-10 scale (including graded hesitancy and refusal), increased significantly over time, with prevalence rising from 8.8% to 21.6%, and mean hesitancy scores also increasing. Although HPV knowledge improved and exposure to negative information declined, the perceived necessity of vaccination fell markedly, and trust eroded across several domains, including trust in health professionals' advice and in both domestic and imported vaccines. Multivariable analyses identified perceived necessity, healthcare professional recommendation, and trust in professionals and domestic vaccines as protective factors, while prior self-payment for other vaccines was also associated with lower hesitancy. These determinants remained stable over time, underscoring the need for targeted strategies to counter rising hesitancy.

We assessed whether rectal retractor use was associated with dose parameters, organ volumes, treatment-related adverse events, and oncological outcomes in patients who underwent cervical cancer brachytherapy. This retrospective study included 148 patients treated with intracavitary brachytherapy between June 2020 and June 2025. Patients treated with and without a rectal retractor were compared regarding dosimetric, volumetric, adverse event, and survival outcomes. Adverse events were graded via RTOG criteria. Cumulative dose parameters were calculated using EQD2. ROC analysis and multivariable logistic regression were performed to evaluate factors associated with grade ≥ 2 adverse events. Rectal retractor use occurred in 58 patients (39.2%). Baseline demographic characteristics and tumour size were comparable between groups, although rectal retractor use differed according to applicator type. Rectal retractor use was associated with lower rectal D2cc (no retractor vs. retractor: 65.70 Gy vs. 60.79 Gy, p = 0.002) but higher bladder D2cc (no retractor vs. retractor: 75.59 Gy vs. 80.08 Gy, p < 0.001) values. Prescribed EQD2, HR-CTV coverage, sigmoid D2cc, and volumetric parameters were similar. Grade ≥ 2 vaginal adverse events were less frequent in the retractor group than in the no-retractor group (32.8% vs. 56.7%, p = 0.004). No significant difference was observed in grade ≥ 2 rectal ( p = 0.380) or urinary adverse events ( p = 0.083). ROC analysis showed that first-fraction volumetric parameters had limited discriminatory ability for grade ≥ 2 adverse events (AUC range: 0.417-0.613). In multivariable analysis, rectal retractor use was associated with lower odds of grade ≥ 2 vaginal adverse events (OR 0.29; 95% CI, 0.13-0.63; p = 0.002). Rectal retractor use was associated with rectal dose sparing and lower odds of grade ≥ 2 vaginal adverse events without compromising target coverage. However, this finding should be interpreted cautiously because rectal retractor placement was not randomised and was influenced by applicator compatibility.

Cervical cancer (CC) remains a public health challenge in developing countries. Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase highly expressed in CC. Studies showed that PGE2 may transactivate EGFR in some models. However, understanding the interaction between the EGFR and PGE2 signaling pathways in CC is a key area for investigation. The Cancer Genome Atlas (TCGA) was used to evaluate gene expression correlation and clinical outcomes. Panitumumab and aspirin were employed to inhibit EGFR and COX-1/2, respectively. Cell migration was evaluated using Boyden chamber. MTT and clonogenic assays determined cell viability and clonogenicity. Western Blotting analyzed protein expression. PGE2 was measured in the supernatants of cell lines using ELISA. Flow cytometry was used for cell death assays. TCGA analysis revealed a significant positive correlation between EGFR and COX-1, COX-2, and microsomal prostaglandin E synthase-1 (mPGES-1). CC patients showed decreased overall survival upon overexpression of EGFR or COX-2. CASKI and HeLa cells were cisplatin-resistant, whereas C33A cells were chemosensitive. CASKI cells exhibited the highest EGFR levels, while HeLa cells showed highest levels of COX-2 and mPGES-1. HeLa cells showed marked upregulation of COX-2 and mPGES-1 and increased PGE2 secretion upon EGF stimulation. Moreover, PGE2 activated ERK signaling and promoted cell migration through an EGFR-dependent mechanism. Panitumumab plus aspirin impaired cell viability, clonogenicity and chemoresistance. Simultaneous stimulation with EGF and PGE2 mitigated cisplatin-induced apoptosis in CASKI cells. The interactions between EGFR and PGE2 signaling pathways link inflammation and oncogenic signaling, promoting tumor aggressive behavior.

Immune checkpoint inhibitors (ICIs) are first-line therapy for cervical cancer (CC), yet their efficacy is limited to a subset of patients owing to low tumor immunogenicity. Single-cell RNA sequencing revealed that CC patients exhibiting robust immune responses following radiotherapy (RT) showed upregulation of necroptosis along with lower baseline RIPK1 expression. In vitro and in vivo experiments further illustrated that RT alone upregulates RIPK1 expression. Inspired by these findings, we developed a hafnium (Hf)-based nanoscale metal-organic framework loaded with LD4172, a RIPK1 degrader (LD4172/Hf). The combination of RT and LD4172/Hf effectively induced necroptosis, and elicited a potent immune response via triggering necroptosis-mediated immunogenic cell death (NICD). This effect was characterized by enhanced macrophage infiltration and phagocytosis, increased M1 polarization, reduced M2 polarization, and improved antigen presentation capacity in macrophages. Furthermore, combined RT + LD4172/Hf with PD‑1 blockade amplified the anti‑tumor immunity driven by NICD. This combined treatment nearly doubled the production of tumor-killing cytokines (IFNγ and GZMB) in CD8 + T cells and promoted the expansion of CD44⁺ effector memory T cells upon tumor rechallenge, compared with RT plus PD-1 blockade alone, thereby enabling efficient tumor elimination and conferring protection against tumor relapse. Collectively, these findings position LD4172/Hf in combination with radio-immunotherapy as a promising therapeutic strategy for CC patients.

Phosphatidylinositol 3-kinase (PI3K) and histone deacetylase (HDAC) inhibition is a potential tumor treatment strategy, including for cervical cancer. Herein, a novel series of thienopyrimidine derivatives was rationally designed, synthesized, and biologically evaluated as dual PI3K/HDAC inhibitors targeting cervical cancer. Compound B7 was evaluated for its inhibitory effects across the entire PI3K and HDAC families, and exhibited strong PI3Kα (IC 50 = 25.41 ± 5.23 nM), PI3Kδ (IC 50 = 41.58 ± 4.54 nM), HDAC6 (IC 50 = 29.35 ± 3.41 nM), and moderate HDAC8 inhibition (IC 50 = 157.27 ± 6.18 nM). In cellular assays, B7 suppressed the proliferation of four cervical cancer cell lines (HeLa, SiHa, Ca-Ski, and ME-180) with IC 50 values below 5 μM. And B7 showed moderate selectivity in normal L-O2 and HEK-293T cell viability with IC 50 values around 15 μM. Mechanistically, B7 induced HeLa cell S-phase arrest and apoptosis. Notably, it blocked the PI3K/AKT pathway and upregulated α-tubulin and SMC3 acetylation without altering Ac-H3/H4 levels, consistent with its enzymatic selectivity for HDAC6/8 over Class I HDACs. Molecular dynamics simulations revealed that B7 formed stable binding modes with PI3Kα and HDAC6/8. Although rapid systemic clearance currently limits its in vivo application, the potent cellular efficacy of B7 highlights its utility as a dual PI3K/HDAC lead compound, providing a distinct chemical scaffold for further structural optimization.

MicroRNA (miRNA) dysregulation may provide complementary molecular information for cervical lesion assessment and triage. This prospective observational study evaluated six candidate miRNAs in paired plasma and liquid-based cytology (LBC) specimens and their associations with cytological severity, high-risk human papillomavirus (hrHPV), and p16 expression. Among 328 women, cytology was classified as normal (n = 52), atypical squamous cells of undetermined significance (ASC-US; n = 44), low-grade squamous intraepithelial lesion (LSIL; n = 42), high-grade squamous intraepithelial lesion (HSIL; n = 82), or squamous cell carcinoma (SCC; n = 108). hrHPV positivity increased from 0% in normal cytology to 93.5% in SCC and p16 positivity from 0% to 95.4% (both P < 0.001). In paired plasma and LBC specimens, miR-21-5p, miR-155-5p, miR-9-5p, and miR-15b-5p progressively increased with cytological severity, whereas miR-375-3p and miR-145-5p decreased (all p < 0.001). For discrimination of HSIL/SCC from normal/ASC-US/LSIL, individual-miRNA areas under the curve (AUCs) ranged from 0.970 to 0.993. After stratified 10-fold cross-validation, AUCs were 0.818 (95% CI, 0.765-0.869) for hrHPV, 0.807 (0.751-0.860) for p16, and 0.840 (0.789-0.888) for hrHPV + p16. The six-miRNA LBC panel achieved an AUC of 0.9999 (0.9996-1.000), 99.5% sensitivity, 100.0% specificity, and a Brier score of 0.006. These findings demonstrate strong internal discrimination by LBC-derived miRNAs; however, validation against histologically confirmed endpoints in independent, clinically representative populations is required before clinical application.

Cervical cancer is a prevalent form of cancer that affects women on a global scale. MicroRNA-155 (miR-155) has been identified as a key player in cervical cancer, with its over-expression signifying a promising target for therapeutic interventions. However, the molecular mechanisms by which miR-155 contributes to the invasive progression of cervical cancer, as well as miRNA-based therapeutic approaches, remain to be elucidated. To address the issues, we initially investigated the functional role of miR-155 in cervical cancer progression. In vitro and in vivo results demonstrated that miR-155 was closely associated with the malignant progression of cervical cancer through regulation of the epithelial-mesenchymal transition (EMT) process, specifically by directly targeting ZFPM2 protein, thereby exerting oncogenic effects. Based on these findings, we designed manganese-based composite agents, namely MnO 2 @PDA-DNAzyme-substrate-methotrexate nanoparticles (MPDM NPs), for simultaneous miRNA imaging and chemotherapy toward cervical cancer. The MPDM NPs exhibited favorable biocompatibility and tumor microenvironment (TME) responsive release behavior, allowing controlled release of Mn 2+ , methotrexate (MTX), and DNAzyme probes for miR-155 detection and therapeutic intervention. In vivo studies with tumor-bearing mice indicated that the MPDM NPs could effectively target tumors. The Mn 2+ -activate miRNA imaging achieved a detection limit for miR-155 of 0.3 nM. Moreover, the drug MTX enabled tumor chemotherapy by regulating the EMT process. This, in turn, has resulted in an impressive tumor inhibition rate of 86.2%. This proposed strategy indicated significant potential for the advancement of precision theranostics in the context of cervical cancer.

To determine whether a patient-centered, digitally enabled smart speculum reduces discomfort and improves cervical visualization compared with the traditional bivalve speculum during routine pelvic examination. In a paired comparative clinical evaluation, 81 women undergoing routine gynecologic examination in 5 facilities in Cameroon's Centre Region, from June 1, 2024, to September 30, 2024, were examined with both a traditional and a smart speculum. The primary outcome was insertion discomfort on a 10-point visual analog scale; secondary outcomes were discomfort at opening and removal, percentage cervical visualization, and complete visualization of the transformation zone and external cervical os. Comparisons used the Sign test, Wilcoxon signed-rank test, and McNemar test ( P <.05). Discomfort was significantly lower with the smart speculum at every stage ( P <.001 for insertion, opening, and removal). Percentage visualization clustered near 100% (Wilcoxon P <.001). Full visualization increased from 53 of 81 (65%) to 73 of 81 (90%) for the transformation zone and from 60 of 81 (74%) to 80 of 81 (99%) for the external cervical os ( P <.001). A patient-centered, digitally enabled speculum substantially improves comfort and cervical visualization during pelvic examination. Locally manufactured and integrated into artificial intelligence-supported telemedicine workflows, it could reshape cervical cancer screening and reproductive health services in Africa and beyond. Within the Africa Health Security and Sovereignty agenda, it shows digitalization and local manufacturing converging: an instrument designed, built, and serviced on the continent, carrying its own imaging and working channel. Comparable devices in Colombia and Ghana, and automated visual evaluation now tested across 5 African countries, suggest a workable route to equitable, sovereign screening.

Managing inter- and intrafraction motion remains a major challenge in cervical cancer radiotherapy. This study reports a two-year, single-centre experience with daily CBCT-guided cervical online adaptive radiotherapy (oART), evaluating the workflow feasibility of a radiation therapist (RTT)-led adaptive workflow, including treatment session duration and target coverage. Thirty patients with cervical cancer were treated with CBCT-guided oART between October 2023 and December 2025. After initial supervised sessions, treatment delivery transitioned to an RTT-led workflow supported by a traffic-light protocol with on-call multidisciplinary backup. Cervical oART was introduced in phases, progressing from single-isocentre cases to more complex treatments including two isocentres and para-aortic lymph nodes. Workflow evaluation was based on retrospective analysis of session logs, process timing and oART workflow-related interventions. A total of 744 adaptive sessions were analysed. Median total session duration was 33.0 min (interquartile range 13.0). Imaging and beam delivery times were stable, whereas decision-intensive steps showed greater variability, requiring corrections to AI-generated contours in all patients. Median total session duration was comparable between the first five supervised sessions and the subsequent RTT-led sessions (32.5 vs. 32.0 min). Contour review showed the strongest correlation with total session duration (ρ = 0.73). Uterus displacement outside the PTV due to intrafraction motion was observed in approximately 11% of all post-treatment CBCT-verifications and was typically limited to small fundal regions. Daily CBCT-guided cervical oART can be efficiently implemented within an RTT-led workflow, demonstrating workflow feasibility while maintaining target coverage despite intra-fraction anatomical variability.

Evidence regarding repeated remimazolam administration remains limited. We hypothesized that remimazolam would be associated with fewer adverse events than propofol while maintaining stable sedative requirements across three repeated sedation sessions. Patients with cervical cancer undergoing three fractions of interstitial brachytherapy were randomized to propofol or remimazolam. The primary outcome was the proportion of sedation episodes with at least one prespecified intraoperative adverse event across three sessions. Secondary outcomes included sedative dose, hemodynamics, and sleep quality assessed using the Pittsburgh Sleep Quality Index (PSQI) and Athens Insomnia Scale (AIS). A total of 100 participants were randomized, of whom 91 completed all three prespecified sedation sessions and were included in the primary per-protocol analysis (46 in the propofol group and 45 in the remimazolam group). Across 138 propofol and 135 remimazolam episodes, overall adverse events were less frequent with remimazolam (17.78% vs. 59.42%; RR, 0.30; 95% CI, 0.18-0.49; p < 0.001). Respiratory depression (3.70% vs. 26.09%; RR, 0.14; 95% CI, 0.04-0.53; p = 0.004) and hypotension (8.15% vs. 41.30%; RR, 0.20; 95% CI, 0.09-0.42; p < 0.001) were also lower with remimazolam. Remimazolam requirements remained stable across sessions (third vs. first: mean difference, 0.19 mg; 95% CI, -0.78 to 1.15; p = 0.846). No significant between-group differences were observed in PSQI or AIS scores. Across three consecutive sedation sessions for interstitial brachytherapy, remimazolam was associated with fewer respiratory and hemodynamic adverse events than propofol, while sedative requirements remained stable across the three sessions. Chinese Clinical Trial Registry (identifier: ChiCTR2500108294).

To map community-based health-promotion strategies used to improve cervical cancer screening uptake and to identify intervention components, delivery models, equity targets and implementation gaps. Scoping review. The review followed PRISMA-ScR and JBI population-concept-context guidance. PubMed/MEDLINE, PubMed Central, publisher pages, ClinicalTrials.gov-linked records and DOI records were searched from inception through 3 June 2026, with backward and forward citation chasing. English-language original intervention or implementation studies with a community-facing screening-promotion component were eligible. One reviewer screened all full texts, and two coauthors validated the final inclusion decisions. Data were charted and synthesized descriptively across intervention, outcome, implementation and equity variables. Twenty-one original intervention or implementation studies were included in the evidence map. Nine contextual sources informed the background and five methodological sources informed review conduct but were not counted as included original evidence. Six recurring strategy families were observed: lay or peer workforce models, culturally tailored education, navigation and barrier reduction, HPV self-sampling, mHealth reminders and integrated outreach. Across heterogeneous designs, multicomponent approaches commonly linked trusted messengers, tailored communication, convenient screening access and active follow-up; no comparative effectiveness ranking was undertaken. Community-based cervical screening promotion can be designed and evaluated as a prevention cascade rather than as a one-time awareness activity. Future programmes should measure movement from engagement and access through screening completion, result delivery, triage and treatment linkage.

To determine whether Magnetic Resonance Imaging (MRI) findings reflect pathological risk factors in early-stage cervical cancer and whether its clinical significance differs by histological subtype. This multicenter retrospective study included patients with FIGO 2009 stage ≤ IB1 cervical cancer who underwent preoperative MRI. Maximal tumor diameter (MRI(L)) and perpendicular short diameter (MRI(D)) were categorized at 10-mm intervals. Associations with pathological low-risk criteria (tumor length ≤ 20 mm, invasion depth ≤ 10 mm, and their combination [S-criteria]) and lymphovascular space invasion (LVSI) were analyzed for squamous cell carcinoma (SCC) and HPV-associated adenocarcinoma (HPVA-adenocarcinoma) using the Cochran-Armitage trend test, with interobserver agreement assessed using weighted kappa statistics. The study included 246 SCC and 93 HPVA-adeno cases. MRI categorization showed substantial interobserver agreement (κ = 0.87-0.97). The S-criteria threshold differed by subtype: in SCC, the proportion meeting S-criteria fell to 58.6 % in the MRI(L) 10-20 mm category, versus 83.3 % in HPVA-adeno. LVSI positivity also increased significantly with MRI category in both subtypes (p < 0.0001 and p = 0.006), with distinct patterns: in SCC, LVSI rose sharply once MRI(L) reached 10 mm (14.8 % vs. 56.5 %); in HPVA-adeno, LVSI was rare among MRI-invisible tumors (2.7 %) but present in 33.3 % of visible tumors < 10 mm. This histology-specific pattern was confirmed by a formal interaction test for LVSI (p = 0.024). The clinical significance of MRI findings differs by histological subtype in early-stage cervical cancer: MRI size categories reliably reflect pathological risk in SCC, whereas MRI size alone is insufficient for risk stratification in early-stage HPVA-adenocarcinoma.

Cervical cancer can be prevented and treated if detected early through regular screening. However, 88% of women aged 30 to 49 have never been screened in Tanzania. This study explored facilitators and barriers to cervical cancer screening among women and healthcare providers in rural Kilimanjaro, Tanzania, using the Theoretical Domains Framework and the Capability, Opportunity, Motivation-Behavior model. An exploratory qualitative design was employed; data were collected from March to October 2024. Six focus group discussions were conducted with 54 women aged 30-50 years, and twelve in-depth individual interviews with healthcare providers. Data were transcribed, coded, and thematically analyzed using QDA Miner Lite v2.0.8. Four main themes emerged, each with sub-themes: (1) knowledge about cervical cancer and screening (disparities in knowledge between screened and non-screened women; healthcare providers' knowledge and training needs; age and parity as knowledge mediators); (2) power of social influence (social facilitation; social barriers); (3) emotional and structural influences on cervical cancer screening (emotional barriers and coping; structural and logistical barriers); and (4) enhancing cervical cancer screening uptake (targeted community education and outreach; improving service accessibility). Barriers include limited knowledge, misconceptions, fear of pain and positive results, limited access to services, and a shortage of trained healthcare providers. Social support from families, peers, community leaders, and healthcare providers was identified as a strong facilitator. Increasing cervical cancer screening uptake in rural communities requires targeted, theory-informed interventions that incorporate education to enhance awareness, strengthen social support, and improve health services. Main findings : Four themes with eight sub-themes were identified. Barriers include limited knowledge and misconceptions, fear of pain and positive results, and limited access and staff. Facilitators include social support from families, peers, and community leaders, and targeted community education and outreach. Added knowledge : Highlights the need for context-specific, theory-informed interventions integrating community education, social support, and health system strengthening to improve CC screening in low-resource settings. Global health impact for policy and action : Provides baseline evidence from low-resource settings to inform targeted strategies for increasing CC screening coverage toward the WHO 70% screening target.

In most countries, breast and cervical cancer screening invitations are sent only to those legally registered as women. In the Netherlands, since 2022, self-registration for receiving invitations enables transgender and non-binary (TNB) individuals to be screened. This study aims to explore their awareness, barriers, experiences, and preferences regarding breast and cervical cancer screening. A cross-sectional survey was co-created with and administered to TNB individuals. Attitudes were measured using the Attitude Scale for Cancer Screening. Respondents were recruited through TNB advocacy and support organizations. Differences across gender identity groups were assessed using Chi-square tests, and open-text responses were analyzed thematically. Analyses were conducted based on the number of participants who completed each section. Among participants who changed their gender registration (n = 219), most (n = 179; 81.7%) were aware this could affect screening invitations, while just over half (n = 110; 50.2%) knew about the option to self-register. The main barriers were discomfort and the intimate nature of exams, distress about body parts inconsistent with gender identity, and missed invitations due to gender registration. Communication preferences varied across gender identities. Non-binary individuals and transgender men placed the highest importance on healthcare professionals acknowledging their transgender history, whereas transgender women considered this less important. Overall, respectful treatment by healthcare professionals was perceived as more important than the screening location itself, and a majority of participants (n = 77; 64.7%) expressed a preference for human papillomavirus (HPV) self-sampling over a Pap smear at the General Practitioner. While many barriers are shared with cisgender populations, challenges specific to gender identity, such as gender dysphoria and missed invitations due to gender registration, require targeted interventions. Increasing awareness of self-registration, providing affirming and accessible information, and training healthcare professionals in gender-sensitive care are essential to ensure respectful, supportive, and inclusive screening experiences.

WD repeat and SOCS box containing protein 1 (WSB1) promotes tumor progression and metastasis; however, its role in the response to hyperthermia combined with chemoradiotherapy in cervical cancer remains unclear. Therefore, this study investigated the involvement of WSB1 and the c-Myc/Wnt/β-catenin axis in the antitumor effects of this combined treatment. WSB1 expression was examined in multiple cervical cancer cell lines, and its functional roles were evaluated using the cell counting kit-8, colony formation, wound healing, Transwell migration/invasion, and apoptosis assays. The c-Myc-mediated transcriptional regulation of WSB1 was analyzed using chromatin immunoprecipitation and dual-luciferase reporter assays. Wnt/β-catenin signaling activity and DNA damage were assessed via western blotting and immunofluorescence. Antitumor efficacy was further evaluated in a cervical cancer xenograft model treated with hyperthermia, chemoradiotherapy, or both. WSB1 was highly expressed in both HeLa and SiHa cells and promoted proliferation, migration, and invasion, while inhibiting apoptosis. c-Myc directly transcriptionally activated WSB1 , and WSB1 was required for c-Myc-driven activation of Wnt/β-catenin signaling, thereby forming a positive feedback loop. Combined hyperthermia and chemoradiotherapy markedly suppressed malignant phenotypes in vitro and tumor growth in vivo , increased DNA damage, and downregulated c-Myc, WSB1, and Wnt/β-catenin pathway components, with minimal systemic toxicity. WSB1 acts as an oncogenic driver in cervical cancer by sustaining c-Myc/Wnt/β-catenin signaling across different histological subtypes. Axis disruption via combined hyperthermia and chemoradiotherapy effectively inhibits tumor progression. This presents WSB1 and its signaling network as potential therapeutic targets for a broad range of patients with cervical cancer.

Cervical cancer is a health issue in the Amazon region. Human papillomavirus (HPV) is the primary cause of cervical cancer. Oxidative stress has been shown to play a role in the HPV-associated carcinogenesis process. To evaluate the prevalence of HPV infection and its correlation with oxidative stress biomarkers in women from Belém, Pará. This was a cross-sectional pilot study involving 71 women conducted between March 2021 and March 2022. Endocervical samples were analyzed for HPV DNA using PCR, and the oxidative stress biomarkers malondialdehyde (MDA) and glutathione (GSH) were measured in blood samples. Statistical analyses were performed using SPSS software, version 21.0. The prevalence of HPV was 28.2% (20/71). Participants aged 39 to 48 years showed significantly higher levels of MDA (≥3.54 nmol/mL), with 34% exhibiting elevated levels (p-value = 0.036). HPV-positive women tended to have lower levels of GSH (p-value = 0.090). There is likely an imbalance between oxidative damage and antioxidant defense mechanisms in HPV pathogenesis; furthermore, low levels of the antioxidant GSH indicate that the studied population may be exposed to the harmful effects of reactive oxygen species (ROS). Oxidative stress may play a role in HPV persistence and cervical carcinogenesis. The high prevalence of sexually transmitted HPV infection and the presence of oxidative stress among women in the Brazilian Amazon may indicate a limited impact of cervical cancer prevention measures. Oxidative stress biomarkers (MDA and GSH) could potentially serve as low-cost diagnostic options, offering an alternative for resource-poor areas in the Brazilian Amazon.

Cervical cancer remains a major cause of cancer-related morbidity and mortality in women worldwide. Although HPV18-positive tumors are frequently associated with aggressive clinicopathological behavior, the redox-linked mechanisms by which HPV18 drives cervical cancer progression remain incompletely defined. Here, integrated clinical, multi-omics, biochemical, and in vivo analyses were performed to delineate the role of HPV18-E7 in ferroptosis regulation. In the TCGA-CESC cohort, HPV18 positivity was associated with inferior progression-free survival and disease-free survival and was enriched in adenocarcinoma-related histology. Functionally, HPV18-E7 promoted cervical cancer cell proliferation and suppressed RSL3-induced ferroptotic death, lipid peroxidation, ferrous iron accumulation, and clonogenic loss. Integrated transcriptomic, proteomic, and metabolomic profiling identified ferroptosis defense, oxidative phosphorylation, glutathione/redox homeostasis, sulfur amino acid metabolism, and lipid remodeling as convergent pathways downstream of HPV18-E7. A lipid-focused re-analysis identified 41 features that met VIP > 1 and P < 0.05 in both knockdown comparisons and changed concordantly, of which 20 also met q < 0.05 in both comparisons. Reciprocal co-immunoprecipitation confirmed associations of HPV18-E7 with HSPA5 and of HSPA5 with GPX4. HPV18-E7 stabilized HSPA5 protein by attenuating K48-linked ubiquitination and proteasomal turnover, and thereby maintained GPX4 abundance. MG132, but not chloroquine under the tested condition, attenuated the loss of the HSPA5/GPX4 module after HPV18-E7 depletion, supporting a predominant proteasomal contribution in this setting. Gain- and loss-of-function rescue experiments established HSPA5 as a required downstream effector of HPV18-E7-mediated GPX4 maintenance and ferroptosis resistance. In a HeLa xenograft model, HPV18-E7 depletion markedly enhanced the antitumor efficacy of the ferroptosis inducer RSL3, accompanied by increased MDA and 4-HNE signals and reduced Ki67 and SCD1 expression. Collectively, these findings identify an HPV18-E7/HSPA5/GPX4 axis that promotes cervical cancer progression by preserving ferroptosis resistance, while lipid remodeling provides a complementary metabolic component of the phenotype.

Cervical cancer represents the second most prevalent malignancy among women in India and is etiologically linked to persistent infection with high-risk human papillomavirus (HPV) strains. Mesua ferrea Linn, a medicinal tree species distributed across the Eastern Himalayan region, Eastern Indian states, and the Western Ghats, has demonstrated anticancer potential in several preclinical investigations; however, its mechanistic basis in cervical cancer remains insufficiently elucidated. In this study, a network pharmacology-based workflow was employed to identify the phytochemicals of Mesua ferrea, predict key targets, analyse protein-protein interactions and construct a compound-target pathway network along with network enrichment analysis. ADMET analysis, molecular docking, and molecular dynamics simulation were used to assess the stability of key compounds relative to potential targets. 16 phytochemicals, based on drug-likeness criteria, were identified, yielding 60 common targets, including AKT1, KDR, PIK3CA, MTOR, and EGFR, which are involved in Ras, PI3K-Akt, Jak-Stat, and HPV-associated pathways. Molecular docking and molecular dynamics simulations verified the stable binding of key phytochemicals to core cervical cancer-associated proteins. Collectively, these findings indicate that Mesua ferrea Linn exerts multi-target, multi-pathway regulatory effects in cervical cancer, supporting its potential as a source of phytotherapeutic agents. The study provides a mechanistic foundation for future in vitro and in vivo validation, contributing to the rational development of plant-derived interventions for cervical cancer management.

Although neuromodulation has emerged as a critical factor in cancer biology, its involvement in cervical cancer remains largely unexplored. In this study, we identified the serotonin transporter (SERT), a marker of serotonergic neurons, as a potential tumor suppressor in cervical cancer. SERT expression was progressively reduced with increasing severity of cervical lesions and was negatively associated with patient survival. Functionally, SERT overexpression significantly inhibited cervical cancer cell viability and xenograft tumor growth in the presence of serotonin (5-Hydroxytryptamine, 5-HT), both in vitro and in vivo. Mechanistically, SERT promoted mitochondrial-mediated tumor cell apoptosis through upregulation of Bax and cleaved caspase-3, without affecting cell proliferation. This proapoptotic effect may be associated with inhibition of STAT3 pathway activation. Notably, these tumor-suppressive effects could be largely abolished by fluoxetine (FLX), a selective serotonin reuptake inhibitor (SSRI) widely used as a first-line antidepressant. Collectively, our findings reveal a direct suppressive function of the SERT-5-HT axis in cervical cancer cells and suggest a potential risk that FLX may interfere with this antitumor activity, warranting further investigation to assess its impact on cervical cancer progression.

Automated segmentation of acetowhite lesions in Visual Inspection with Acetic Acid (VIA) cervicography is critical for colposcopy-guided biopsy targeting in low-resource cervical cancer screening programs. Standard transformer architectures compute attention solely from feature content, neglecting spatial proximity between tokens, while unified decoder designs conflate semantic and boundary channels-leaving boundary accuracy at the squamocolumnar junction unresolved. We propose SegFormer-HF-CSG , a parameter-efficient framework that addresses these limitations through two targeted modifications to the SegFormer backbone (as Illustrated in Figure 1):• Hausdorff Distance-based Spatial Bias (HF): injects pairwise spatial proximity information into the self-attention mechanism across all encoder stages, improving geometric coherence of acetowhite boundary predictions without adding trainable parameters.• Conceptual Split Gate (CSG): decouples the decoder into independent semantic and boundary pathways with adaptive soft gating, adding only 59,712 parameters (+2.3%).Evaluated on 545 VIA cervicography images, SegFormer-HF-CSG achieves DSC of 96.91%, HD95 of 3.46 mm, and Normalized Surface Distance of 98.82%, outperforming eight reference architectures spanning convolutional, hybrid, and transformer families ( p < 0.01, Bonferroni-corrected) at a total of 2.62 M parameters-the smallest footprint in the evaluated set.

The immunomodulatory factor translationally controlled tumor protein (TCTP) drives tumor progression by inducing an immunosuppressive microenvironment; however, its specific role and underlying mechanisms in cervical cancer (CC) remain uncharacterized. To address this gap, in this study, we analyzed the expression of TCTP, non-canonical nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), zinc finger E-box-binding homeobox 1 (ZEB1), C-X-C motif chemokine ligand 12 (CXCL12), and C-X-C chemokine receptor type 4 (CXCR4) in CC tissues from patients and compared them with that in paired no cervical epithelial lesion tissues. TCTP, ZEB1, non-canonical NF-κB pathway molecules, and CXCL12 exhibited marked upregulation at the mRNA and protein levels in CC tissues. TCTP knockdown reduced ZEB1, p100/p52, and CXCL12 expression in CC cells. Treating CC cells with non-canonical NF-κB activation cascade agonist CD40L and inhibitor B022 increased and decreased ZEB1 and CXCL12 expression, respectively. Dual luciferase reporter assays in both SiHa and HeLa cells confirmed that ZEB1 has a transcriptional activating effect on CXCL12 expression, suggesting that TCTP may interact with NF-κB/ZEB1 to regulate CXCL12 secretion. Additionally, CC tissues exhibited elevated infiltration of immunosuppressive cell populations, including M2-polarized tumor-associated macrophages, regulatory T cells, myeloid-derived suppressor cells, and exhausted CD4 + PD-1 + T cells. Furthermore, these cells showed increased surface expression of CXCR4, the specific receptor for CXCL12. In summary, our findings indicate that high TCTP expression potentiates NF-κB/ZEB1-mediated signaling in CC, increases CXCL12 secretion, and recruits the infiltration of immunosuppressive cells in CC tissues, thereby providing a potential molecular target for improving the tumor-suppressive microenvironment.

Cancer immunotherapy based on nanovaccines aims to elicit specific anti-tumor immune responses, demonstrating significant therapeutic potential. However, its clinical translation remains hindered by two major challenges: inadequate immunogenicity of the vaccine itself and limited antigen presentation efficiency in dendritic cells (DCs). To overcome these bottlenecks, we have developed a biomimetic nanovaccine for cervical cancer treatment. This vaccine employs a sophisticated biomimetic design: its core consists of iron oxide nanoparticles that serve as both an immune adjuvant and a carrier for the STING agonist DMXAA; the core is enveloped by a hybrid membrane formed by fusing cancer cell membranes (carrying a complete set of tumor-associated antigens) with bacterial membranes (rich in natural immune adjuvants); and the outermost layer is further functionalized with mannose ligands for specific targeting of DCs in the lymph nodes. This multi-layered architecture achieves exceptional synergistic immune activation: the hybrid membrane not only provides a personalized antigen repertoire but also, through its bacterial components, acts as a natural adjuvant to robustly activate innate immunity; upon external stimulation, the core synchronously releases the STING agonist, efficiently activating the cytosolic STING pathway and significantly amplifying the production of type I interferons and related cytokines, thereby shaping a potent anti-tumor immune microenvironment; meanwhile, the mannose-mediated active targeting ensures efficient uptake of the vaccine by DCs in the lymph node sinuses, ultimately greatly promoting antigen cross-presentation and the activation and proliferation of cytotoxic T lymphocytes. In vivo experimental results demonstrate that this nanovaccine can significantly inhibit tumor progression in mouse models of cervical cancer and effectively prevent tumor recurrence. This study provides a novel and translationally promising strategy for the development of highly effective and personalized cancer immunotherapy platforms.

Extensive evidence confirms the high effectiveness of human papillomavirus (HPV) vaccines in young girls; however, real-world data on vaccine effectiveness (VE) among women vaccinated at ages 18-45 remain limited, particularly in China, where HPV status at vaccination is often unknown. We conducted a population-based matched test-negative design study using linked cervical cancer screening and immunization records in Shenzhen, China. Cases positive for vaccine-type high-risk HPV (hrHPV) DNA were matched 1:1 with negative controls by age, screening date, household registration, and screening type. VE for at least one dose was estimated using conditional logistic regression and stratified by time since vaccination, vaccine valency, and age at vaccination. Among 7,060 matched pairs, overall VE increased significantly with time since vaccination: 6.4% (95% CI: -3.9% to 15.7%) at <1y, 17.9% (5.5% to 28.7%) at 1-<2y, and 40.2% (29.6% to 49.2%) at ≥2y. Among women vaccinated ≥2y earlier, VE against HPV16/18 was 48.4% (33.7% to 59.8%) for 2-/4-valent vaccines and 54.4% (26.5% to 71.7%) for the 9-valent vaccine. Significant protection at≥2y was observed across all age-at-vaccination groups: 45.7% (25.0% to 60.7%) for ages 18-26, 39.6% (23.5% to 52.4%) for ages 27-35, and 35.5% (12.6% to 52.4%) for ages 36-45. In conclusion, HPV vaccination confers moderate protection against vaccine-type hrHPV DNA positivity among Chinese women vaccinated at ages 18-45. However, as this outcome reflects a single-time-point surrogate virologic endpoint rather than persistent infection or clinical disease, adult women should continue regular cervical cancer screening.

Studies have reported inconsistent findings regarding the potential effects of polycystic ovary syndrome (PCOS) on neurocognitive function. This study aimed to investigate whether cognitive function, particularly spatial learning and memory, and hippocampal tissue are impaired in middle-aged rats with a history of PCOS. Spatial learning and memory, hippocampal histopathology, and the expression of genes including beta-secretase 1 (bace1), microtubule-associated protein tau (mapt), amyloid-beta precursor protein (app), nestin (nes), and doublecortin (dcx) in hippocampal tissue were compared between middle-aged PCOS rats and controls (n = 7/group). During training (learning), middle-aged PCOS rats had significantly higher mean latency (22.04 (1.86, 42.22); P = 0.03) and duration (5.62 (1.41, 9.84); P = 0.009) than controls. However, memory performance did not differ significantly between PCOS rats and controls. PCOS rats had a significantly higher number of damaged neurons in the CA1 (24.25 ± 2.68 vs. 9.50 ± 0.64), CA2 (20.75 ± 1.03 vs. 8.25 ± 1.10), CA3 (20.50 ± 1.65 vs. 8.50 ± 1.04), and DG (28.25 ± 1.88 vs. 13.00 ± 1.29) regions of the hippocampus than controls (P < 0.05), and they showed mild hippocampal damage. In PCOS rats, bace1 gene expression was significantly increased in hippocampal tissue, whereas mapt gene expression was decreased compared with controls. The expression levels of the other genes did not differ significantly between the two groups. A history of PCOS during reproductive age may increase the risk of cognitive dysfunction, particularly impaired spatial learning, as well as hippocampal damage later in life.

Mitochondrial dysfunction has been implicated in various female reproductive disorders, but the underlying molecular links remain poorly understood. Here, we systematically investigated the genetic associations between mitochondrial-related genes and 14 female reproductive disorders through an integrative analysis of multi-omics datasets. Summary-level data on mitochondrial gene expression, DNA methylation, and protein abundance were obtained from multiple quantitative trait loci (QTL) resources and jointly analyzed in relation to 14 common female reproductive disorders. By integrating genetic association signals across molecular layers, we identified multiple mitochondrial-related genes showing nominal candidate associations with reproductive outcomes. Notably, genetically predicted NEU4 expression was nominally associated with lower risks of ovarian dysfunction and polycystic ovary syndrome. At the methylation level, NEU4 was represented by 25 probe-trait associations across six reproductive phenotypes. At the proteomic level, higher genetically predicted NUDT9 abundance was associated with abnormal uterine bleeding. Overall, 12 associations survived false discovery rate (FDR) correction, of which 10 also satisfied the heterogeneity in dependent instruments (HEIDI) threshold. ALDH2 remained a recurrent nominal and pharmacologically annotated candidate. These findings provide an exploratory molecular landscape and prioritize a smaller set of FDR-supported signals for independent replication and mechanistic investigation.

Polycystic ovary syndrome (PCOS) is one of the most prevalent disorders affecting women. The status of PCOS research in sub-Saharan Africa is unknown, where non-communicable diseases are prevalent but often underrecognized. To assess current knowledge about PCOS in sub-Saharan Africa and identify gaps in the literature. A systematic search was conducted across PubMed, Embase, Cochrane, and African Journals Online through 9 August 2026 to identify original studies on PCOS in sub-Saharan Africa. Original research studies involving sub-Saharan African populations, without age-related constraints, were eligible. We excluded non-original studies and studies that did not focus on PCOS. Three independent reviewers (S.H., M.A., and C.C.M.) performed the searches. Of 1973 retrieved records, 40 studies met the inclusion criteria, predominantly from Nigeria, with additional contributions from South Africa, Cameroon, the Democratic Republic of Congo, Tanzania, Benin, Kenya, and Ethiopia. Most studies were observational and primarily focused on PCOS in the context of infertility. No population-based prevalence studies were identified; however, 13 studies reported PCOS prevalence, mostly in clinically selected populations. PCOS remains understudied in sub-Saharan Africa, with substantial gaps in population-based epidemiology, diagnostic practices, phenotype distribution, management, and metabolic outcomes. Addressing these gaps through larger, well-designed studies is critical to accurately assess the disease burden, inform clinical guidelines, and optimize management strategies. Additionally, overcoming barriers such as cultural attitudes, cost, and limited accessibility to diagnostic tools and treatment options remains essential to improving PCOS care and research across the region.PROSPERO registration ID CRD420250649730 - 13 March 2025.

Hyperandrogenemia (HA) and low sex hormone-binding globulin (SHBG) are core features of polycystic ovary syndrome. The creatinine-to-albumin ratio (CAR), a simple renal-nutritional marker linked to female infertility, has not been studied in relation to HA or low SHBG. To examine the association of CAR with low SHBG and HA, defined by the free androgen index (FAI), in U.S. women of reproductive age. In this cross-sectional analysis of NHANES 2013-2016, we included 683 women aged 18-49 years. CAR (serum creatinine/albumin) was categorized into tertiles; low SHBG was defined as < 30 nmol/L and HA as FAI ≥ 75th percentile. Survey-weighted multivariable logistic regression was used, with multiple imputation (m = 5) as a sensitivity analysis. In Model 1 (age, race/ethnicity, education, income), the highest CAR tertile was associated with low SHBG (OR 2.93, 95% CI 1.49-5.75; P = 0.003; P for trend = 0.004) and FAI-defined HA (OR 1.87, 95% CI 1.05-3.34; P = 0.036; P for trend = 0.044). In Model 2 (plus smoking, BMI, low HDL-C), associations attenuated (OR 1.95, 95% CI 1.05-3.64 for low SHBG; 1.24, 95% CI 0.65-2.34 for HA-FAI). HA defined by total testosterone was not associated with CAR. Higher CAR was associated with low SHBG and FAI-defined HA after demographic adjustment, with attenuation after metabolic adjustment, suggesting confounding by shared metabolic factors. As CAR derives from routine laboratory tests, it may be a practical marker of reproductive metabolic risk; the cross-sectional design precludes causal inference.