Search Results (23,833)

Pancreatic cancer (PC) remains one of the malignancies with the most unfavorable prognosis and limited treatment options. The lack of biomarkers for early diagnosis and the asymptomatic nature of the disease contribute to delays in diagnosis and high mortality rates. In recent years, the role of the human microbiota in cancer biology has become increasingly significant, and the oral microbiota in particular has been found to be involved in the pathogenesis and prognosis of several neoplasms. This review summarizes the current evidence relating the salivary microbiota to PC in three key areas: screening and diagnostic potential, pathophysiology and tumor progression, as well as presenting prognostic implications and potential influence on therapy. With regard to early diagnosis, it has been reported that patients with PC have reduced levels of Neisseria elongata (N. elongata) and Streptococcus mitis (S. mitis) and elevated levels of Granulicatella adiacens. Several studies have shown that bacteria present in the saliva can migrate from the oral cavity to pancreatic tissue via hematogenous or enteric routes, where they may actively contribute to tumor development and progression. In particular, it has been shown that Porphyromonas gingivalis (P. gingivalis) and Veillonella atypica (V. atypica) translocate from the mouth to pancreatic tumors, promoting carcinogenesis by inducing a pro-inflammatory tumor microenvironment. Furthermore, some studies have identified certain species associated with prognosis and response to PC treatment. Despite the encouraging results, differences in study methodology, the lack of standardized methods and the scarcity of longitudinal data currently hinder clinical application. Large-scale, multi-omics prospective studies are needed to clarify causality and validate their clinical utility. Overall, the salivary microbiota represents a promising and non-invasive tool for improving early diagnosis, understanding prognosis and enhancing the management of PC. Full article

Background: Appropriateness of diagnostic test prescriptions represents a critical component of quality care in pediatric allergology, directly influencing diagnostic accuracy, therapeutic decisions, healthcare resource utilization, and patient outcomes. A multidisciplinary expert panel was convened to develop evidence-based clinical recommendations addressing the appropriate use of specialist consultations and diagnostic investigations in children with asthma, allergic rhinoconjunctivitis, and vernal keratoconjunctivitis (VKC). Methods: Clinical questions were formulated using the PICO framework and prioritized through structured expert consensus. Systematic literature reviews were conducted across major databases, and the certainty of evidence was assessed using the GRADE methodology. Results: Specialist evaluation emerged as a key determinant of improved diagnostic precision, optimization of treatment strategies, and reduction of inappropriate therapies. In asthma, spirometry, FeNO measurement, and allergy testing contributed to enhanced diagnostic accuracy and better control. In allergic rhinoconjunctivitis, allergological assessment supported diagnosis and the selection of immunotherapy, with demonstrated benefits on symptoms and quality of life. For VKC, multidisciplinary specialist involvement facilitated early diagnosis, personalized management, and prevention of complications. Conclusions: Although the overall certainty of evidence ranged from moderate to low, consistent clinical benefits supported consensus-based recommendations. Implementation of these recommendations may improve care quality, promote equitable access to diagnostic resources, and reduce unnecessary healthcare utilization. Full article

p53, miR-34a, and SIRT-1 are involved in cellular stress responses, senescence, and inflammation—processes central to the pathophysiology of atrial fibrillation (AF). In this study, circulating TP53 and SIRT-1 serum miR-34a expression were determined in patients with and without AF, in order to assess their associations with AF. We also checked their potential diagnostic utility as systemic biomarkers associated with AF. The study included 189 adults, 94 AF+, 95 AF−. Clinical, anthropometric, and biochemical data were collected. Whole-blood TP53 and SIRT-1 mRNA expression and serum miR-34a expression were quantified by RT-qPCR. ROC analysis and Youden-derived odds ratios assessed exploratory diagnostic performance. AF patients had significantly higher expression of TP53 (0.0352 vs. 0.0253; p < 0.001) and miR-34a (0.0215 vs. 0.0099; p < 0.001), but significantly lower expression of SIRT-1 (0.0079 vs. 0.0145; p < 0.001). The level of SIRT-1 expression showed the highest discriminatory performance (exploratory AUC = 0.6987; p < 0.0001). TP53 expression levels exceeding 0.0295 were associated with nearly threefold higher odds of AF (OR = 2.92, 95% CI: 1.61–5.28, p = 0.0006), whereas the expression levels of SIRT-1 and miR-34a were not significantly associated with AF in cut-off analysis. In the AF group, a positive correlation was found between the expression of TP53 and SIRT-1 (Rho = 0.3609, p < 0.001); however, it was not consistent with a canonical model of miR-34a-mediated SIRT-1 suppression. In turn, the expression of miR-34a correlated positively with age and C-reactive protein level and negatively with estimated glomerular filtration rate (eGFR). The obtained results suggest that AF is associated with altered expression of circulating TP53, SIRT-1, and miR-34a. However, due to the fact that the expression levels were measured in peripheral compartments, and not in atrial tissue, the obtained results should not be interpreted as direct evidence of AF-related atrial remodeling. For these reasons, further investigations involving simultaneous measurements of the TP53/miR-34a/SIRT-1 regulatory axis, both in the circulating compartment and atrial tissue, should be performed. Full article

Background and Objectives: This study investigated the prognostic value of two simple blood urea nitrogen (BUN)-based ratios, BUN/hemoglobin (Hb) and BUN/Albumin, for predicting in-hospital mortality and prolonged hospitalization in patients with acute upper gastrointestinal bleeding (UGIB). Their performance was compared with established risk scores, including the Glasgow–Blatchford score (GBS), AIMS-65, ABC and Rockall scores. Materials and Methods: This retrospective cohort study included 486 patients evaluated for acute UGIB between March 2023 and February 2026. The diagnostic performance of BUN/Hb and BUN/Albumin ratios was assessed using receiver operating characteristic (ROC) analysis and compared with established risk scores. Associations with clinical outcomes were evaluated using logistic regression analyses. Results: The median age was 67 years, and 292 patients (60.1%) were male. In-hospital mortality occurred in 17 patients (3.5%), while prolonged hospitalization was observed in 207 patients (42.6%). AIMS-65 showed the highest Area Under the Curve (AUC) for mortality prediction (0.799; 95% CI 0.696–0.902), followed by the ABC score (0.731) and the BUN/Albumin ratio (0.711). For prolonged hospitalization, BUN/Hb showed the highest AUC (0.706; 95% CI 0.660–0.752), although differences from established scores were not statistically significant. In multivariable analysis, BUN/Albumin remained associated with mortality, whereas BUN/Hb did not reach statistical significance for prolonged hospitalization. However, mortality-related findings should be interpreted with caution because only 17 in-hospital deaths occurred in the study cohort. Conclusions: Simple BUN-based ratios may provide complementary prognostic information in acute UGIB. BUN/Albumin was associated with in-hospital mortality and showed modest discriminatory ability, but it did not demonstrate statistically significant superiority over established risk scores. BUN/Hb showed the numerically best discrimination for prolonged hospitalization, but without statistically significant superiority or persistent significance in multivariable analysis. Overall, these ratios may serve as supportive tools for early risk assessment rather than replacements for established risk scoring systems. Full article

Background and Clinical Significance: Carcinoid heart disease (CHD) is an uncommon valvular manifestation of neuroendocrine tumours, usually affecting right-sided cardiac valves. Left-sided involvement is rare and is generally associated with bronchopulmonary carcinoid, right-to-left shunting, or markedly elevated circulating vasoactive substances. Therapeutic decision-making is particularly challenging in advanced disease when severe tricuspid regurgitation occurs in patients at prohibitive surgical risk. Case Presentation: We report the case of a 61-year-old male patient with progressive dyspnoea, abdominal distension, lower-limb oedema, facial flushing, and 15 kg of unintentional weight loss. Transthoracic and transoesophageal echocardiography demonstrated torrential tricuspid regurgitation caused by thickened, retracted, and immobile leaflets, with additional mitral and aortic valve involvement, raising strong suspicion of CHD. An agitated-saline contrast study demonstrated delayed right-to-left shunting without patent foramen ovale, suggesting an extracardiac, likely intrapulmonary, shunt. Somatostatin receptor PET/CT identified a pancreatic lesion with metastatic disease, and bone marrow biopsy confirmed neuroendocrine tumour infiltration. Owing to prohibitive surgical risk, as reflected by a Tricuspid Regurgitation Impact Score (TRI-SCORE) with an estimated in-hospital mortality of 65%, unfavourable tricuspid anatomy for repair, and refractory venous congestion, heterotopic bicaval valve implantation was performed (TricValve system -P&F). Discussion: This case highlights the role of echocardiography in recognising the characteristic phenotype of CHD, detecting occult right-to-left shunting, and supporting selection of a palliative transcatheter intervention. It also illustrates the value of a multimodality diagnostic strategy integrating echocardiography, functional oncological imaging, and histopathology in tumour-related cardiac disease. Conclusions: In selected inoperable patients with advanced carcinoid-related tricuspid regurgitation, heterotopic bicaval valve implantation may represent a feasible strategy for reducing venous congestion and improving functional status. Full article

Background: The diagnostic value of surface electromyography (sEMG) for identifying muscles affected by myofascial trigger points (TrPs) remains controversial. However, advances in pain neurophysiology and discussions regarding TrPs within the International Classification of Diseases (ICD-11) have renewed interest in objective diagnostic approaches. Objective: To synthesize current evidence on the diagnostic utility of sEMG for detecting TrP-related muscle alterations across different electromyographic signal analysis domains. Methods: A scoping review was conducted following JBI guidance and PRISMA-ScR guidelines. PubMed, Scopus, Web of Science, CINAHL and Cochrane were searched for studies involving adults with symptomatic or asymptomatic TrPs, myofascial pain syndrome, or TrP-related referred pain. Fifteen studies met the inclusion criteria. Analyses included amplitude-, frequency-, time–frequency-, and spatial-domain sEMG parameters. Results: Muscles affected by TrPs showed increased resting electromyographic activity and reduced activation during maximal voluntary contraction in several studies. Frequency domain analyses indicated changes in median frequency and muscle fatigue index, whereas time–frequency analyses suggested redistribution of sEMG signal energy toward lower-frequency components or altered spectral power during experimentally provoked referred pain. Spatial analyses revealed altered activation patterns, although these findings did not consistently correspond with TrP anatomical locations. Overall, the limited number of studies assessing diagnostic sensitivity and specificity prevents firm conclusions. Conclusions: sEMG may be useful as a non-invasive complementary tool for functional assessment and monitoring of TrP-related muscle dysfunction. However, current evidence does not support its use as a standalone diagnostic method. Time–frequency, machine learning-supported and spatial analyses appear promising for future clinical research, but standardized protocols and external validation are required before clinical diagnostic criteria can be proposed. Full article

Background/Objectives: Spontaneous intracranial hypotension (SIH) is caused by spinal cerebrospinal fluid (CSF) leakage and is typically diagnosed by clinical presentation and characteristic MRI signs; however, objective tools for monitoring physiological changes and treatment response remain limited. Cine phase-contrast MRI (PC-MRI) enables noninvasive quantification of aqueductal CSF dynamics, yet reliable analysis is challenging since the cerebral aqueduct is extremely small and susceptible to low contrast, partial volume effects, and ROI-dependent measurement variability—particularly in SIH where CSF pulsatility is often reduced. Methods: We propose an end-to-end automated framework that integrates (1) a cascade localization–segmentation strategy, consisting of Tiny YOLOv4 detection followed by MultiResUNet segmentation on a YOLOv4-derived cropped ROI; (2) physiology-informed pulsatility-based segmentation (PUBS) to refine anatomical masks into functional flow ROIs; and (3) one-dimensional convolutional neural networks (1D-CNNs) to extract exploratory waveform morphology features from 32-phase cardiac-cycle velocity waveforms. The study includes 39 participants, yielding 59 cine PC-MRI examinations: 11 controls, 28 Pre-treatment SIH scans and 20 Post-treatment Recovery scans. Results: The cascade model significantly improves segmentation robustness compared with a full-image baseline, achieving higher Dice scores and markedly lower boundary errors across cohorts (e.g., Pre-treatment SIH HD95: 1.66 ± 0.74 px vs. 15.37 ± 44.98 px). PUBS refinement reduces quantification deviation from expert manual references in SIH (mean relative error: 7.4% to 5.6%) and improves diagnostic performance for multiple hemodynamic parameters (e.g., downward mean flow AUC: 0.747 to 0.792). For waveform morphology analysis, the end-to-end 1D-CNN classifier was evaluated using repeated-seed participant-level grouped LOOCV. The repeated-seed ensemble prediction showed modest out-of-sample discrimination between Normal controls and Pre-treatment SIH scans, with an AUC of 0.646, a bootstrap 95% confidence interval of 0.455–0.826, and a permutation-test p-value of 0.072. Separately, exploratory analysis of the final baseline-trained 1D-CNN latent space showed marked, apparent Normal-versus-SIH separability and an intermediate recovery distribution in PCA space, suggesting that aqueductal waveform morphology may encode SIH-related physiological information. Conclusions: These findings suggest that SIH-related information may be reflected not only in flow magnitude but also in aqueductal CSF waveform morphology. However, the modest and statistically non-significant out-of-sample performance of the end-to-end 1D-CNN classifier indicates that morphology-based AI features should currently be regarded as exploratory biomarker candidates rather than validated stand-alone diagnostic tools. Larger independent cohorts are required to confirm their reproducibility, physiological meaning, and clinical utility. Full article

Shear wave elastography (SWE) is an increasingly investigated ultrasound-based technique in musculoskeletal imaging that provides quantitative information on tissue stiffness and biomechanical properties. This narrative review aims to summarize the basic principles, technical considerations, current clinical applications, limitations, and future perspectives of SWE in musculoskeletal imaging. Unlike conventional grayscale and Doppler ultrasonography, which mainly assess morphology and vascularity, SWE may provide additional functional information in major musculoskeletal tissues, including tendons and ligaments, skeletal muscles, peripheral nerves, fibrocartilaginous structures, plantar fascia, and selected soft tissue lesions. Current evidence suggests potential roles for SWE in detecting early biomechanical alterations, assessing disease severity, differentiating symptomatic from asymptomatic tissues, and monitoring response to treatment or rehabilitation. However, musculoskeletal tissues are anisotropic, viscoelastic, and position-dependent; as a result, SWE measurements are influenced by acquisition-related factors, tissue biomechanics, positioning and loading conditions, region of interest (ROI) placement, tissue depth, and device-related variability. For this reason, SWE findings should not be interpreted as standalone diagnostic criteria but should be considered together with clinical findings, conventional ultrasonography, MRI, electrophysiology, histopathology, and patient-centered outcomes when appropriate. This review highlights the need for tissue-specific measurement protocols, standardized reporting, normative reference data, inter-vendor harmonization, and longitudinal validation against clinically meaningful outcomes before SWE can be more reliably integrated into routine musculoskeletal imaging and rehabilitation practice. Full article

The coronary arteries are a pair of arteries that branch off from the aorta and encircle the heart, providing oxygenated blood to the myocardium. Although coronary artery atherosclerosis remains a main cause of morbidity and mortality worldwide, coronary artery anomalies (CAAs) are increasingly recognized as a clinically relevant cause of ischemic events and can be subdivided into origin, course, or termination anomalies. The aim of this narrative review is to summarize the cross-sectional diagnostic imaging and clinical background of CAAs. Full article

Background/Objectives: The aim of the present investigation was to validate the diagnostic performance of the AI-based dental cloud software Diagnocat^® AIS (Version 1.0 (UDI: 860010268018), DGNCT LLC, Miami, FL, USA) regarding the detection possibilities of seven different endodontic findings on cone-beam computed tomography (CBCT) against a multi-rater consensus reference standard, and to characterize its calibration, threshold-optimized performance and clinical utility. Methods: 358 root-canal-treated teeth from 167 CBCT scans (167 patients) were retrospectively evaluated at a single private dental practice. From initially included 383 root-canal-treated teeth from 177 patients, 358 (93.5%) were recognized by the AI tool and entered the primary analysis. Two experienced dentists with a clinical focus on endodontics independently graded each tooth and disagreements were adjudicated by a senior expert. Seven different endodontic findings were evaluated: (i) apical (periapical) lesion; (ii) short root-canal filling (apical filling end >2 mm short of the radiographic apex); (iii) voids/lacunae in the root-canal filling; (iv) missed (un-instrumented/un-filled) canal; (v) overfilled root-canal filling (apical extrusion); (vi) apicoectomy (resected root apex with or without retrograde filling); and (vii) coronal restoration with a full-coverage crown. Diagnocat^® output was binarized at the manufacturer-fixed 0.50 probability threshold; sensitivity, specificity, predictive values, accuracy, area under the curve AUC (ROC), Cohen κ and Gwet AC1 were computed with 95% cluster-bootstrap confidence intervals (cluster = scan). Threshold optimization, probability calibration, GEE-based subgroup analyses, and decision-curve analysis were pre-specified. Results: Diagnostic performance varied by finding. AUCs were 0.984 for missed canal, 0.917 for overfilled root canal, 0.902 for short root filling, 0.893 for crown, 0.864 for apical lesion, 0.857 for apicoectomy and 0.761 for voids in the root filling. Apical-lesion sensitivity rose from 33.6% for sub-millimeter lesions to ≥80% for lesion measuring 1–5 mm. Re-tuning the decision threshold raised missed-canal sensitivity from 69.6% to 97.5%. Decision-curve analysis confirmed positive benefits for missed canal and root-filling-quality findings. Conclusions: The AI tool Diagnocat^® can be recommended as a focused screening adjunct in CBCT-based endodontic interpretation for missed canals, crowns, and gross root-filling-quality flaws. Sub-millimeter apical lesions and several less common findings (resorption, instrument fragment, retrograde filling) remain outside the reliable performance envelope of the current platform. Full article

Maternal psychoactive substance use during pregnancy represents a major threat to placental integrity and fetal development. As the central interface for maternal–fetal exchange, the placenta is highly susceptible to psychoactive substances, including alcohol, tobacco, cannabis, cocaine, opioids, and synthetic drugs, which can cross the placental barrier and induce structural and functional alterations. This review synthesizes current evidence on the biological mechanisms, diagnostic approaches, and forensic relevance of psychoactive substances-induced placental pathology. We summarize how different substances disrupt placental vascularization, oxidative balance, epigenetic regulation, and cellular viability, leading to impaired nutrient and oxygen transfer and increasing the risk of adverse outcomes such as intrauterine growth restriction, preterm birth, congenital anomalies, and long-term neurodevelopmental impairment. We further discuss the role of placental tissue in identifying prenatal drug exposure and reconstructing exposure timelines. Beyond its clinical relevance, placental examination provides objective evidence with potential forensic value in cases of suspected maternal substance use, while also informing non-punitive, evidence-based interventions. Overall, integrating placental pathology into reproductive health research and prenatal care offers a multidisciplinary framework to improve maternal–fetal outcomes and guide public health strategies addressing substance use during pregnancy. Full article

Background/Objectives: Pes planus and pes cavus are common foot deformities, which may lead to pain, functional limitations, and impairment of foot biomechanics. While calcaneal pitch, talar declination, and Meary angles, commonly used in diagnosis, provide objective information, their lack of a gold standard and the observer’s dependence on manual measurements limit their reliability. Therefore, in this study, these angles obtained from weight-bearing lateral foot radiographs were evaluated according to literature references, and the aim was to determine the model that provides the most accurate prediction in the diagnosis of pes planus using machine learning algorithms. It should be emphasized that, because the diagnostic labels were derived from literature-based thresholds of these same angles, the machine-learning task addressed here is the automated reproduction and standardization of expert, angle-threshold-based classification, rather than an independent clinical diagnosis from raw images. Methods: This retrospective study was conducted using weight-bearing lateral foot radiographs of 697 male patients obtained from the archives of public hospitals in Gaziantep. Calcaneal pitch, Meary angle, and talar declination angles were evaluated in both feet, and the data were labeled as normal, pes planus, and pes cavus. The dataset, consisting of a total of 1394 feet, was divided into training and test groups and analyzed using Random Forest, XGBoost, Logistic Regression, Support Vector Machine (SVM), and K-Nearest Neighbors (KNN) algorithms; the diagnostic performance of the models was compared using measures such as accuracy, F1 score, sensitivity, and specificity. Results: A total of 1394 feet from 697 male patients (mean age 24.8 ± 5.57 years) were analyzed using five machine learning algorithms with calcaneal pitch angle (CPA), Meary angle (MA), and talar declination angle (TDA) as reference labels. Ensemble-based methods showed superior performance, with XGBoost achieving perfect classification (Accuracy = 1.000) under all three labels for the left foot and 0.996–1.000 for the right foot, while Random Forest reached 0.986–1.000 across all experiments. Logistic Regression and SVM yielded moderate accuracies (0.905–0.973), whereas KNN consistently performed the weakest (0.905–0.964), particularly in the pes cavus subgroup. The near-perfect accuracy obtained when the labeling angle was itself included among the predictors reflects, at least in part, the algebraic reconstruction of the threshold rule from a same-source variable rather than genuine diagnostic generalization; results should therefore be interpreted with this in mind. Conclusions: This study demonstrates that machine learning, particularly ensemble methods such as XGBoost and Random Forest, provides high accuracy and consistency in diagnosing foot arch deformities based on radiographic angle measurements. Traditional models, such as Logistic Regression, still hold value in terms of clinical interpretability despite their lower performance. The findings suggest that machine learning-based approaches can offer objective, rapid, and reliable decision support tools for diagnosing pes planus and pes cavus, but external validation studies are necessary for clinical generalizability. Full article

Background/Objectives: Homologous recombination deficiency (HRD) is a predictive biomarker in high-grade serous ovarian carcinoma for platinum-based chemotherapy and PARP inhibitors. The implementation of HRD testing in routine diagnostics has generated multiple commercial assays that differ in genomic targets, bioinformatic analysis, and HRD scoring strategies. We aimed to assess the analytical performance and feasibility of a locally semi-automated workflow based on the Agilent SureSelect CD HRR17 panel with SeqOne/SomaHRD analysis, and to compare it with established commercial HRD assays currently used in routine clinical practice: Myriad MyChoice CDx and SOPHiA DDM Dx HRD Solution. Methods: Thirty high-grade serous ovarian carcinoma cases diagnosed between 2019 and 2023 were retrospectively analyzed. HRD status was assessed with the Agilent-SeqOne workflow and compared with Myriad (n = 12) and SOPHiA (n = 18). Concordance and correlation between genomic instability metrics were evaluated. Results: The Agilent/SeqOne workflow showed high concordance with both comparison workflows. Genomic instability metrics strongly correlated across assays (R² up to 0.96). A lower proportion of inconclusive classifications was observed with the Agilent/SeqOne workflow. Discordances were mainly observed in borderline cases near classification thresholds. Variant detection was highly concordant within shared genomic regions. Conclusions: The locally semi-automated HRD workflow demonstrated high analytical concordance with established commercial assays in evaluable cases. Operational advantages related to workflow flexibility and local reanalysis support its potential implementation in routine molecular diagnostics. Full article

Background/Objectives: Patient experience is increasingly recognised as a key dimension of healthcare quality, yet most tools fail to capture its temporal and processual nature, limiting its contribution to system improvement. This study aimed to demonstrate how a biographical approach to patient experience can generate actionable insights for improving care pathways. Specifically, we sought to: (i) identify and characterise distinct types of prehospital care pathways among patients hospitalised for COVID-19; (ii) identify patient-perceived significant events and safety issues; and (iii) generate structured variables to inform a subsequent quantitative phase. Methods: We conducted semi-structured biographical interviews with 31 patients hospitalised for COVID-19 in two French university hospitals. Data were collected using a life-events calendar (LEC), enabling day-by-day reconstruction of symptoms, healthcare contacts, and decision-making processes. Thematic analysis was performed with multidisciplinary triangulation. The qualitative phase identified three pathway types and the key mechanisms underlying each; these patterns were subsequently confirmed in a separate quantitative follow-up study (n = 312) using state sequence analysis. Results: Three distinct pathway types emerged: short (≤3 days), intermediate (4–9 days), and long (≥10 days). Delayed pathways were associated with repeated false-negative tests, underestimation of severity, and silent hypoxaemia. Across all pathways, patient experience suggested critical system-level failures, including diagnostic delays and inadequate escalation of care. Notably, in many cases, hospitalisation was triggered by a relative rather than a healthcare professional. These findings highlight the role of patient and social context as key components of care pathways. Conclusions: When captured longitudinally, patient experience may provide actionable insights into healthcare system functioning, suggesting structural mismatches between clinical trajectories and care responses. The life-events calendar method offers a replicable framework for transforming patient experience data into clinically and organisationally relevant knowledge. Integrating such approaches into healthcare evaluation could enhance patient safety, improve care coordination, and support more responsive care systems beyond COVID-19. Full article

Human papillomavirus (HPV) infection remains the principal etiological factor in cervical cancer development worldwide, with Eastern Europe continuing to demonstrate disproportionately high cervical cancer incidence and mortality rates. Regional disparities in screening implementation, vaccination coverage, and HPV genotype distribution contribute substantially to the persistent burden of HPV-related disease. In recent years, increasing attention has focused on molecular biomarkers and the vaginal microbiome as complementary approaches for improving cervical cancer prevention strategies. This systematic review aimed to evaluate recent evidence regarding HPV genotype distribution, molecular biomarkers, vaginal microbiome composition, and their implications for cervical cancer prevention in Eastern Europe. A systematic literature search was conducted in PubMed/MEDLINE, Scopus, Web of Science, Embase, and the Cochrane Library for studies published between January 2020 and May 2026. This systematic review was conducted in accordance with the PRISMA 2020 guidelines and prospectively registered in PROSPERO (CRD420261391136). Studies from Eastern European populations reporting data on HPV genotype distribution, screening strategies, vaccination, molecular biomarkers, or vaginal microbiome composition were included. HPV prevalence in screening populations ranged from approximately 12% to over 20%, with HPV16 consistently identified as the predominant genotype across all included studies. However, non-16/18 high-risk genotypes, particularly HPV31, HPV51, HPV52, HPV66, and HPV68, represented a substantial proportion of infections in several Eastern European cohorts. Studies evaluating CINtec PLUS cytology and HPV E6/E7 mRNA testing demonstrated improved specificity for identifying clinically significant cervical lesions compared with HPV DNA testing alone. Emerging evidence also suggested associations between vaginal dysbiosis, increased microbial diversity, persistent high-risk HPV infection, and progression to cervical intraepithelial neoplasia. Although the 9-valent HPV vaccine provides coverage for most circulating high-risk genotypes identified in the region, vaccination uptake remains inconsistent throughout Eastern Europe. The findings of this systematic review support the growing importance of extended HPV genotyping, molecular biomarkers, and microbiome-related approaches in cervical cancer prevention strategies in Eastern Europe. Strengthening organized screening programs, expanding vaccination coverage, and improving access to molecular diagnostic technologies remain essential priorities for reducing the regional burden of HPV-related disease. Full article