Search Results (1,172)

Background: Familial hypercholesterolemia (FH) is a monogenic disorder causing markedly elevated low-density lipoprotein cholesterol (LDL-C) and premature atherosclerosis. Glucose-6-phosphate dehydrogenase (G6PD) is a key enzyme in antioxidant defense via NADPH production. G6PD deficiency, an X-linked disorder impairing redox homeostasis, may contribute to cardiovascular disease (CVD) risk. This study examined whether G6PD deficiency increases CVD risk in FH patients. Methods: We retrospectively analyzed 217 FH patients. Clinical data included demographics, lipid profiles, G6PD status, and atherosclerotic CVD outcomes (coronary, cerebrovascular, or peripheral arterial disease). In a subset, FH was confirmed by LDLR gene sequencing, and G6PD Mediterranean and Seattle variants were genotyped. Cumulative CVD prevalence was compared between G6PD-deficient and G6PD-normal FH patients. Multivariable logistic regression was adjusted for age, sex, body mass index, high blood pressure, and smoking. Results: Participants (mean age 47 years, 60% female) had markedly elevated LDL-C (mean 292 mg/dL at diagnosis). Atherosclerotic CVD was present in 119 (55%) patients. G6PD-deficient FH patients had a significantly higher CVD prevalence than those with normal G6PD activity (77.4% vs. 39.8%, p < 0.0001). LDL-C levels were higher in the G6PD-deficient group than in the non-deficient group, and this difference reached statistical significance in the univariate analysis. In the multivariable analysis, G6PD deficiency remained an independent CVD predictor (adjusted OR 3.57, 95% CI 1.30–9.83) after controlling for conventional risk factors. Conclusions: In FH, hereditary G6PD deficiency is associated with a markedly increased risk of atherosclerotic CVD. A pro-oxidative state in G6PD-deficient FH patients may play a role in premature atherogenesis. G6PD status may represent a cardiovascular risk modifier in FH, warranting further research into underlying mechanisms and targeted management. Full article

Background: Severe hypertriglyceridemia (SHTG) is associated with acute pancreatitis, metabolic dysfunction, and increased cardiovascular risk. Its genetic architecture ranges from rare biallelic variants causing familial chylomicronemia syndrome (FCS) to more prevalent polygenic or multifactorial chylomicronemia syndromes (MCS). Methods: We systematically reviewed scientific literature up to 2025 for studies reporting genetic data, clinical features, or therapeutic outcomes in adults with triglycerides (TG) ≥ 500 mg/dL. Extracted data were synthesized for genotype, polygenic risk score (PRS), TG levels, metabolic comorbidities, hepatic steatosis, pancreatitis, and treatment response. Results: Ten studies (n = 2521) were included. FCS due to biallelic LPL, APOC2, GPIHBP1, or LMF1 variants accounted for <5% of cases and showed extreme TG elevations (>2800 mg/dL) with pancreatitis prevalence (>70%). APOA5, APOC3, and APOB variants were associated with intermediate TG levels and high rates of metabolic dysfunction-associated steatotic liver disease (MASLD). Polygenic hypertriglyceridemia represented ~70–80% of cases, with TG ≈ 2200 mg/dL and pancreatitis prevalence 15–20%, largely modulated by metabolic triggers. MASLD was present in >70% of polygenic cases, supporting a “two-hit” model where hepatic overproduction of TG-rich lipoproteins amplifies TG excess. Interventional trials demonstrated TG reductions with APOC3 antisense therapy (70–80%) and ANGPTL3 inhibition (50–55%), while GLP-1RA significantly reduced hepatic fat (30–35%) and resolved NASH in up to 59% of patients. Conclusions: SHTG displays a genotype–phenotype gradient: FCS is linked to recurrent pancreatitis, whereas polygenic/MCS forms are closely associated with MASLD and metabolic dysfunction. These findings support a precision-medicine approach integrating genetic testing and PRS-guided strategies—prioritizing APOC3/ANGPTL3 inhibitors for FCS and combined TG-lowering plus metabolic therapies for MCS—to reduce pancreatitis recurrence and liver disease. Full article

Atherogenic dyslipidemia (AD) is a high-risk phenotype for cardiovascular disease, characterized by elevated triglycerides, increased small dense low-density lipoprotein cholesterol (sdLDL-C), and frequently coexisting hypertension. Although FTO gene variants have been implicated in lipid dysregulation, their role in AD among Latin American women remains poorly defined. We conducted a case–control study in 219 working perimenopausal women (97 AD cases and 122 controls). Sociodemographic, clinical, and biochemical variables were assessed. Three FTO SNPs (rs9939609, rs9940128, and rs8050136) were genotyped. Associations were evaluated using logistic regression models adjusted for age and BMI, with gene–environment interactions tested for smoking. Linkage disequilibrium (LD) and haplotype analyses were also performed. Women with AD exhibited significantly higher triglycerides, LDL-C, and sdLDL-C, along with increased hypertension prevalence, but no differences in BMI or glycemia. Multivariable models identified LDL-C (aOR ≈ 8), triglycerides, sdLDL-C, and systolic blood pressure as the strongest determinants of AD. The rs8050136 AA genotype was associated with a fourfold higher risk (aOR = 4.12; 95% CI: 1.49–11.95, p = 0.007). Smoking independently doubled AD risk (aOR = 2.33) and amplified the effect of rs8050136. Adjusted haplotype analysis revealed that the A-A-A (aOR = 5.33; 95% CI: 1.42–20.00) and A-G-A combinations (aOR = 2.54; 95% CI: 1.01–6.38) were significantly associated with AD. FTO polymorphisms, particularly rs8050136 and the A-A-A and A-G-A haplotypes, contribute independently and supra-additively to AD risk. The observed gene–environment interaction with smoking emphasizes the multifactorial nature of AD and supports genotype-based risk stratification and targeted preventive strategies in precision cardiovascular medicine. Full article

Background/Objectives: Cervical cancer is one of the most frequent malignancies among women in Kazakhstan, where human papillomavirus (HPV) vaccination was initiated in 2024. Despite the implementation of vaccination and cytology-based screening programs, diagnostic limitations remain, and local evidence linking HPV infection to clinical outcomes is scarce. This study aimed to evaluate the correlation between HPV status, cervical cytology results, colposcopic impression, and biopsy results in a non-vaccinated female population. Methods: A cross-sectional study was conducted at the University Medical Center, Astana, between November 2024 and March 2025. A total of 396 women of reproductive age were enrolled. Cervical samples underwent liquid-based cytology and high-risk HPV testing with the RealBest assay. Colposcopy was performed following abnormal cervical cytology results, and colposcopy-guided biopsies were obtained where indicated. Sociodemographic characteristics were assessed, and associations between HPV genotype and clinical outcomes were analyzed using descriptive and inferential statistics. Results: HPV infection was detected in 140 women (35.4%). HPV-16 was the most common genotype (11.4%), followed by HPV-52 (6.6%) and HPV-33 (5.3%). Among 198 women evaluated by colposcopy, abnormal findings were observed in 72.2%, with HPV-16 showing a significant association with higher-grade abnormalities (p < 0.001). Biopsies were available for 40 participants: 12 had CIN I, 12 had CIN II, 10 had CIN III, and 4 had carcinoma in situ. HPV-16 was the only genotype significantly linked to CIN II/III lesions. Conclusions: HPV-16 was strongly associated with abnormal colposcopic findings and high-grade histology, underscoring its oncogenic importance. The prevalence of HPV-52 and HPV-33 further supports the need for HPV nonavalent vaccination. These findings highlight the importance of HPV-based screening, genotype-specific triage, and expanded vaccination to reduce cervical cancer incidence in Kazakhstan. Full article

Background: Men who have sex with men (MSM) are at high risk for anal human papillomavirus (HPV) infection, with HIV-positive MSM bearing the highest disease burden. Longitudinal data on anal HPV infection among HIV-negative and HIV-positive MSM are limited. We assessed and compared the prevalence, incidence, and clearance of anal HPV infection among HIV-negative and HIV-positive MSM in Xinjiang, China. Methods: Sexually active HIV-positive and HIV-negative MSM aged 18 years and older have been enrolled in an ongoing observational cohort study of HPV since 1 September 2016, in Xinjiang, China. Participants were followed up on every 6 months with anal HPV testing and questionnaires regarding sexual behaviors. We compared HPV prevalence, incidence, and clearance between HIV-positive and HIV-negative MSM. Prevalence ratios (PRs), incidence rate ratios (IRRs), and clearance rate ratios (CRRs) for HIV-negative and HIV-positive MSM were calculated. Results: A total of 1425 MSM, including 131 HIV-positive and 1294 HIV-negative individuals, with a median age of 29 years (interquartile range [IQR]: 24 to 36), were included in our analysis. Compared with HIV-negative MSM, HIV-positive MSM demonstrated significantly higher prevalence across both individual and grouped HPV genotypes. Specifically, the prevalence of grouped HPV genotypes (any, high-risk, low-risk, 9v, 4v, HPV16/18, and HPV 6/11) was consistently elevated in HIV-positive individuals. PRs for individual HPV types 31, 45, 34, 44, 53, and 81 were 2.47 (95% CI: 1.16–5.25), 2.47 (1.10–5.54), 4.94 (1.25–19.52), 3.29 (1.08–10.06), 2.02 (1.01–4.04), and 2.66 (1.18–6.01), respectively. Furthermore, the incidence of most individual HPV genotypes were higher, while the clearance rates were lower among HIV-positive MSM. Specifically, IRRs for HPV types 31, 33, 45, 55, and 66 were 2.12 (1.19–3.75), 2.19 (1.24–3.90), 2.32 (1.17–4.59), 3.02 (1.15–7.93), and 2.44 (1.18–5.05), respectively. CRRs for HPV types 51 and 58 were 0.33 (0.21–0.52) and 0.60 (0.45–0.79), respectively. Conclusions: HPV prevalence, incidence, and clearance of anal HPV exhibited heterogeneity between HIV-positive and HIV-negative MSM. HPV vaccination and condom promotion programs should be recommended for HIV-positive MSM to mitigate the burden of HPV infection in this vulnerable population. Full article

Background: KRAS mutations are detected in ~40% of colorectal cancer (CRC), yet their prognostic value is heterogeneous across specific substitutions; the impact of uncommon variants, particularly in non-metastatic disease, remains uncertain. Methods: We evaluated the prognostic role of the relatively infrequent KRAS G12A substitution in two independent retrospective cohorts of stage II–III CRC treated with surgical resection without neoadjuvant therapy: an institutional series (FMU; n = 299) and a public dataset (AC-ICAM; n = 178). Tumors were genotyped for KRAS (and BRAF in AC-ICAM), and relapse-free survival (RFS) and overall survival (OS) were investigated. Results: KRAS G12A comprised 3.0% (FMU) and 3.4% (AC-ICAM). Across genotypes, G12A showed the highest univariable hazards compared to wild-type (WT) references for both RFS and OS in each cohort. Notably, RFS events among G12A clustered within 12 months of surgery. In multivariable Cox models, G12A remained independently associated with worse RFS and OS in each cohort, whereas non-G12A KRAS mutations did not differ significantly from the WT references. Conclusions: Across two cohorts, KRAS G12A identified a small but clinically meaningful high-risk subset of stage II–III CRC characterized by early recurrence and inferior survival. Recognition of this variant may inform postoperative risk stratification in the adjuvant setting. Full article

Chronic hepatitis B virus (HBV) and Occult HBV infection (OBI) remain a health burden in sub-Saharan Africa. This study investigated HBV prevalence, circulating genotypes, and associated risk factors with HBV exposure among HIV-positive adults on antiretroviral therapy and pregnant women in southwestern Cameroon. A total of 233 HIV patients and 190 third-trimester pregnant women were screened for HBV DNA, viral load, serological markers (HBsAg, anti-HBc, and anti-HBs), and HBV genotypes were determined by partial sequencing of the S gene. HBV DNA was detected in 10% of HIV-positive patients and 4% of pregnant women, with an overall prevalence of 7%. OBI accounted for 9% and 3%, respectively. Anti-HBc seroprevalence was high (75% in HIV, 46% in pregnant women), while self-reported vaccination coverage was low (1% and 11%). Genotypes A, B, D, and E were identified, with genotype B reported for the first time in Cameroon. Immune escape mutations and the adefovir resistance mutation rtA181V were detected. Self-reported alcohol use was associated with HBV exposure in HIV patients (aOR = 2.08; p = 0.028) and inversely associated with tertiary education in pregnant women (aOR = 0.18; p = 0.038). This study highlights a significant burden of HBV and OBI among vulnerable populations in Cameroon. Full article

Congenital heart defects (CHDs) occur in 50–75% of patients with 22q11.2 deletion syndrome (22q11.2DS), ranging from mild to severe manifestations. The genetic and environmental factors contributing to variable CHD phenotypes in 22q11.2DS are largely unknown. In this study, we used a mouse model of 22q11.2DS, termed Df1/+, to evaluate the effect of maternal vitamin A (VitA) dietary imbalance (supplementation or deficiency) on the incidence of aortic arch defects (AADs), which is a common type of CHD observed in both 22q11.2DS patients and Df1/+ mouse embryos. While most groups showed a previously observed 30% AAD incidence, two groups exhibited significantly higher rates: (1) Df1/+ embryos from WT mothers on a VitA-Supl diet (51% AADs) and (2) Df1/+ embryos from Df1/+ mothers on a VitA-Def diet (45% AADs). Thus, a low or high maternal VitA diet can increase the frequency of AADs in embryos depending on the maternal genotype. Transcriptomic analysis of the hearts of these high-risk embryos at embryonic day (E)18.5 revealed downregulation of key genes (Hdac3, Ptgds, Sirt5, Pfkm, and Lclat1) associated with energy metabolism pathways, such as oxidative phosphorylation and glycolysis, suggesting impaired cardiac recovery mechanisms. In conclusion, our findings demonstrate that altered VitA exposure can exacerbate AAD incidence in a maternal-genotype-dependent manner, highlighting the complex interplay between embryonic and maternal genetic background and environmental factors in CHDs associated with 22q11.2DS. Full article

Background/Objectives: Cardiac surgery, particularly procedures performed with cardiopulmonary bypass (CPB), carries a high risk of neurological complications, including postoperative delirium (POD), which affects 16–73% of patients and increases the likelihood of long-term cognitive impairment. Brain-derived neurotrophic factor (BDNF), a neurotrophin involved in neuronal function, synaptic plasticity, and inflammatory regulation processes, including its Val66Met polymorphism, has been implicated as a potential predictor of POD. This study aimed to evaluate the relationship between perioperative plasma BDNF levels, the BDNF Val66Met polymorphism, and the incidence of POD in patients undergoing elective cardiac surgery with CPB. Methods: This prospective observational single-center study enrolled 287 adults scheduled for elective isolated coronary artery bypass grafting (CABG) with CPB, of whom 107 met all inclusion criteria for final analysis. Exclusion criteria included urgent surgery and pre-existing cognitive or psychiatric disorders. Preoperative evaluation included cognitive testing (MoCA), laboratory and biochemical analysis, and genotyping for BDNF Val66Met. Postoperatively, patients were assessed for POD using the CAM-ICU scale for the first three consecutive days. Cognitive function (using MoCA) and other neurological complications were evaluated during hospitalization, at 30-day and 12-month follow-up. Associations between biomarkers, genetic factors, and clinical outcomes were analyzed. Results: POD occurred in 19.6% of patients who were older, had higher EuroSCORE II, greater coronary disease burden, more frequent prior stroke and chronic kidney disease, and lower neutrophil counts. POD was significantly associated with prolonged hospital stay, need for continuous renal replacement therapy, and reoperation. The BDNF Val66Met polymorphism was present in 31.8% of patients but was not associated with POD, although carriers exhibited higher plasma BDNF concentrations across all time points. Conclusions: Perioperative plasma BDNF concentrations and the BDNF Val66Met polymorphism were not independently associated with the occurrence of POD in elective CABG patients. However, POD was significantly linked to prolonged hospitalization and reoperations. Neurological complications remain an important challenge in cardiac surgery, emphasizing the need for further research and early identification strategies to improve postoperative outcomes. Full article

Background and Objectives: Thrombophilia is a prothrombotic disorder that increases the risk of blood clotting and can pose serious health problems. It is considered a condition of gene–gene or gene–environment interactions. Variation in the prevalence of thrombophilia mutations and their interaction among populations necessitates localized genetic assessments. However, population-based genetic data remains limited for developing effective preventive strategies. Materials and Methods: This cross-sectional observational study was conducted over five years (2020–2024) at a tertiary university hospital in Northern Greece. A total of 2961 individuals aged 18–85 years (mean: 50.5) were registered based on family or medical history of venous thromboembolism (VTE) or clinical symptoms of VTE. The final analysis included 2078 participants comprising 1143 males (55%) and 935 females (45%), who met all the inclusion criteria. Inclusion criteria were absence of acute illness or malignancy, informed consent, and an adequate DNA quantity for genotyping, whereas excluded criteria included incomplete laboratory data, active inflammatory or malignant disease, and cognitive or psychiatric conditions. Peripheral blood samples were collected in 2 mL K₃-EDTA tubes, and genomic DNA was analyzed using real-time polymerase chain reaction (PCR) with melting curve analysis and hybridization probes (LightMix^® in vitro diagnostics, TIB MolBiol, Berlin, Germany). Five thrombophilia-related polymorphisms, Factor V Leiden (F5 G1691A), prothrombin (F2 G20210A), methylenetetrahydrofolate reductase (MTHFR C677T and MTHFR A1298C), and Plasminogen Activator Inhibitor-1 (PAI-1) 4G/5G, were examined for allele and genotype frequencies, Hardy–Weinberg equilibrium testing, pairwise linkage disequilibrium (D′ and r²), and power analysis. For subjects tested for Factor V Leiden (n = 1476), the activated protein C resistance (APC) ratio was additionally evaluated using the ACL TOP 750 analyzer. Results: Allele frequencies were 7.3% for FV Leiden and 3.7% for FII. The PAI-1 allele was distributed at 44%, while the MTHFR (C677T and A1298C) alleles were each present at 33%. Significant linkage disequilibrium was identified between MTHFR (C677T and A1298C) and between MTHFR A1298C and PAI-1. No evolutionary pressure or demographic bias was found in the Hardy–Weinberg equilibrium. The APC ratio demonstrated a high sensitivity (99.2%) and specificity (96.6%), indicating that it may serve as a reliable screening method. Conclusions: Our findings highlight informative patterns in the genetic predisposition to thrombophilia, which may help develop rule-based strategies for implementing thromboprophylaxis guidelines and personalized medical interventions. Full article

Glaucoma is a major ocular neurodegenerative disease and a leading cause of irreversible blindness worldwide, with prevalence projected to exceed 110 million by 2040. Although lowering intraocular pressure (IOP) remains the only proven treatment, glaucoma arises from a complex interplay of genetic, local, and systemic factors—including oxidative stress, vascular dysregulation, mitochondrial dysfunction, and neuroinflammation. Emerging evidence suggests that modifiable lifestyle factors may influence these pathogenic pathways. In this review, higher dietary nitrate from leafy greens is consistently associated with lower primary open-angle glaucoma risk, aligning with nitric-oxide-mediated endothelial support and more stable ocular perfusion pressure. Flavonoids (anthocyanins and flavanols), carotenoids (lutein/zeaxanthin), and B vitamins have strong biological rationale for glaucoma prevention but have limited support from long-term, large population-based studies. The effect of polyunsaturated fats on glaucoma remains inconsistent and warrants source-(plant vs. animal) and substitution-based analyses. Consistent protective effects of aerobic exercise and high-quality sleep may be associated with favorable metabolic profiles and ocular perfusion, potentially mitigating retinal ganglion cell loss. Conversely, smoking and alcohol use are frequently coupled with poorer diet quality (e.g., lower vegetable intake) and heightened oxidative stress, which may exacerbate glaucomatous neurodegeneration. However, much of the current literature is constrained by cross-sectional designs, reliance on self-reported food frequency questionnaires, and insufficient use of structural endpoints such as retinal nerve fiber layer imaging. This review focuses on the potential of lifestyle modification and future directions in prevention and treatment strategies for glaucoma, highlighting the need for large-scale, multi-ethnic, genotype-stratified longitudinal studies and randomized controlled trials to establish causality and define optimal intervention strategies. Full article

Genetic background is a critical determinant of disease expression, arrhythmic vulnerability, and therapeutic response in inherited cardiomyopathies. Implantable cardioverter-defibrillators (ICD) remain the cornerstone for primary prevention of sudden cardiac death, yet conventional selection based on left ventricular ejection fraction does not adequately reflect the heterogeneity of genetic substrates. Increasing evidence demonstrates that pathogenic variants differ not only in prevalence across cardiomyopathy subtypes but also in prognostic impact. Truncating variants, particularly in genes encoding structural proteins, are often associated with severe remodeling, progressive dysfunction, and high arrhythmic risk, whereas missense variants may confer variable expressivity, ranging from aggressive arrhythmogenic phenotypes to milder or late-onset disease. This variability underscores the importance of distinguishing variant classes in clinical decision-making. Integrating genetic information with advanced imaging markers, such as late gadolinium enhancement, allows refinement of arrhythmic risk stratification beyond static thresholds and supports more tailored ICD allocation. Nevertheless, translation into routine practice is limited by challenges in variant interpretation, phenotypic overlap between cardiomyopathy subtypes, and the lack of prospective validation of genotype-based models. In the precision medicine era, evolving strategies should move toward dynamic, multimodal approaches that combine genotype, phenotype, and imaging biomarkers, enabling more accurate prediction of arrhythmic risk and more cost-effective use of ICD therapy. Full article

Secondary peritonitis (SP) remains a major clinical challenge due to its high complication rates and it often results in sepsis and multi-organ dysfunction. This study investigated the association between four nitric oxide synthase (NOS) single-nucleotide polymorphisms (SNPs)—NOS3 c.-786T>C (rs2070744), NOS3 c.894G>T (rs1799983), NOS3 27 bp variable number tandem repeat (VNTR) (rs61722009), and NOS2 (rs2297518)—and sepsis-related complications in 202 patients with SP. Demographic and baseline clinical characteristics, Acute Physiology and Chronic Health Evaluation (APACHE) II scores, Mannheim Peritonitis Index, and complications (multiple organ dysfunction syndrome (MODS), multiple organ failure (MOF), acute respiratory distress syndrome (ARDS), and sepsis) were analyzed for associations with the NOS gene variants. Haplotype analysis was also performed. No SNP showed an association with in-hospital mortality. However, the NOS3 c.-786T>C TT genotype was significantly associated with an increased risk of MOF (p = 0.008), and remained independently associated after multivariate adjustment (p_MOF = 0.006). The T4bG haplotype was significantly more frequent among patients with MODS (p = 0.026), MOF (p = 0.048), and sepsis (p = 0.018). These findings suggest that NOS gene variants, particularly NOS3 c.-786T>C and the T4bG haplotype, may potentially serve as biomarkers for risk stratification in critically ill patients. Full article

Hepatitis E virus (HEV) is an emerging cause of viral hepatitis in Europe, with increasing recognition in immunocompromised patients. While genotype 3 (HEV-3) is most prevalent in the region, molecular epidemiology data from Hungary have been limited. HEV strains from 118 RNA-positive patients diagnosed between 2018 and 2025 were genotyped. Next-generation sequencing yielded near-complete HEV genomes for 76 samples. HEV-3 was dominant (98.3%). Subtype 3a was the most common (34.7%), followed by 3c, 3f, and 3e. Rare subtypes (3g, 3h, 3i, 3m, 3ra) and HEV-4b were detected for the first time in Hungary. Among immunocompromised patients, 41.6% developed chronic infection. Ribavirin resistance-associated mutations G1634R and V1479I were frequently detected. In silico analysis of potential multiple infections indicated the presence of at least two HEV strains of distinct origin in six patients. Our surveillance revealed extensive genetic diversity of HEV in Hungary. The detection of rare HEV-3 subtypes and the first documented occurrence of HEV-4b in the country highlight likely viral introductions linked to the increasing international trade. Ongoing surveillance is essential in protecting high-risk groups and limiting HEV transmission in a globalized food system. Full article

Human papillomavirus (HPV) represents the most common sexually transmitted infection worldwide and a major public health challenge. Nearly all sexually active individuals will acquire HPV during their lifetime, with the highest prevalence observed in adolescents and young adults shortly after sexual debut. More than 200 genotypes have been described, ranging from low-risk types, mainly responsible for benign lesions, to high-risk types, which are associated with cervical, anogenital, and head and neck cancers. While most infections are transient and spontaneously cleared by the immune system, persistent high-risk HPV can lead to precancerous lesions and malignant transformation, often in synergy with other sexually transmitted pathogens or in the context of microbiome imbalance. The introduction of vaccines and advanced screening technologies has substantially modified prevention strategies. Vaccination coverage remains heterogeneous, with persistent gaps particularly among males due to cultural, social, and educational barriers. Schools are increasingly recognized as strategic environments to promote awareness, sex education, and gender-neutral vaccination. Innovative approaches such as microbiome modulation, therapeutic vaccines, and liquid biopsy biomarkers are emerging as promising perspectives. This review aims to provide an updated overview of HPV epidemiology, clinical impact, prevention strategies, and future frontiers, with special attention to adolescents as a priority target group. Full article