Search Results (374)

Mucopolysaccharidosis type I (MPS I) results in the accumulation of glycosaminoglycans (GAG) and, for the purposes of newborn screening, is differentiated into two forms: severe (Hurler syndrome) versus attenuated (encompassing Scheie and Hurler-Scheie syndromes). MPS I was added to the federal Recommended Uniform Screening Panel for newborn screening (NBS) in 2016, and as of December 2025, 45 of 54 programs in the United States (US) screen for MPS I. Within the newborn screening program, a second-tier analysis of GAG is thought to reduce false-positive rates, particularly through mitigating the detection of pseudodeficiency. However, there have been some concerns that the use of second-tier GAG analysis might inadvertently result in missed detection of attenuated cases. A survey of all US NBS programs was conducted requesting data on the total number of screen-positive NBS results for MPS I as well as the final diagnostic outcome from these results. Diagnostic outcomes after screening were classified as false-positive, pseudodeficiency, severe MPS I, attenuated MPS I, and MPS I of undetermined phenotype. Additionally, information on testing methodologies and dates of MPS I NBS implementation was collected. Responses were obtained from 32 NBS programs. The cohort of screening programs utilizing second-tier blood spot GAG determinations detected a higher proportion of severe cases than those not using this second-tier test (48% vs. 29%). The proportion of attenuated cases remained consistent between both groups (13% vs. 14%). The proportion of pseudodeficiency detection was only slightly lower in the cohort using second-tier GAG analysis (85% vs. 91%). Second-tier GAG analysis appears to reduce the detection of false-positive cases and improves the resolution of severe MPS I cases, though the proportion of pseudodeficiency was only slightly lower compared to the programs that do not use second-tier GAG analysis. Currently, the proportion of attenuated cases is comparable between the two cohorts, but the higher number of “undetermined phenotype” cases may eventually shift the balance toward states not using GAG analysis once the type is determined. Full article

In 2023, the Russian Federation expanded its national newborn screening (NBS) program from 5 to 36 conditions, 29 of which are inherited metabolic diseases (IMDs). This study presents the first nationwide results and outcomes of the expanded NBS program. Between January 2023 and December 2024, dried blood spots from 2,466,615 newborns (98.53% of the birth cohort) were analyzed for IMDs using MS/MS. Screen-positive cases were referred to the national reference center for confirmatory testing, which included biochemical (MS/MS and GC-MS) and genetic analyses (NGS). A total of 41,728 neonates (1.69%) screened positive, of whom 37,733 underwent confirmatory testing. It resulted in 834 confirmed diagnoses of IMDs (1 in 2900 live births). Phenylketonuria was the most prevalent IMD (n = 538; 1 in 4600), followed by MCADD (n = 99; 1 in 25,000). Distinct regional and ethnic variations were observed, including a high prevalence of tyrosinemia type 1 in the Chechen Republic and MCADD in North Ossetia. The integration of NGS was essential for resolving complex cases, such as identifying heterozygous carriers and dual diagnoses. These findings underscore the program’s clinical utility, highlight unique epidemiological patterns, and identify challenges such as false positives and diagnostic complexities, which will guide future refinements. Full article

Background: Rift Valley fever virus (RVFV) is a significant mosquito-borne zoonotic virus with high public health and veterinary importance in Africa and the Middle East. Reliable diagnostic assays for detecting antibodies and assessing their functional neutralizing capacity are essential for surveillance programs, vaccine monitoring, and outbreak preparedness. Objective: This study evaluates and compares the analytical performance of a competitive enzyme-linked immunosorbent assay (cELISA) and a virus neutralization test (VNT) for detecting RVFV antibodies in vaccinated sheep sera, establishing an integrated laboratory workflow for virus titration, serological detection, and functional neutralization. Methods: Twenty serum samples were collected from sheep pre-vaccination and one month post-vaccination with Smithburn live attenuated RVFV vaccine. Sera were tested using a commercial multispecies RVFV competitive ELISA to detect antibodies specific to the viral nucleocapsid protein. Viral titration was conducted in Vero cells, and 50% tissue culture infective dose (TCID₅₀/0.1 mL) was calculated using the Reed and Muench method. VNT was performed at 24, 48, 72, and 96 h after infection with different viral doses (10² to 10⁵ TCID₅₀/0.1 mL), and the neutralizing ability of serial serum dilutions (1:2 to 1:1024) was tested. Compared with the control, protection was determined by cytopathic effect (CPE) inhibition. Results: ELISA revealed robust antibody signals up to a 1:32 dilution, with signal-to-noise (S/N) < 40%, whereas for higher dilutions, antibody detection became inconclusive or negative. Virus titration was performed to verify a stock concentration of 10^6.5 TCID₅₀/0.1 mL. The VNT exhibited time- and dose-dependent kinetics; high protection rates (≥97) were observed at 1:2–1:8 dilutions against 10²–10³ TCID₅₀/0.1 mL challenge doses; however, neutralizing efficacy decreased significantly at higher viral loads and higher serum dilutions. While cELISA and VNT results correlated strongly at low serum dilutions, the cELISA showed decreased sensitivity at dilutions ≥ 1:64, where the VNT remained capable of detecting functional neutralizing activity. Conclusions/Discussion: The results demonstrate that while both assays correlate well at high antibody concentrations, they diverge at lower concentrations. This discrepancy highlights the functional difference between binding antibodies (N-protein) and neutralizing antibodies (Gn/Gc glycoproteins). Consequently, the cELISA is ideal for rapid screening, whereas the VNT is indispensable for confirming functional immunity. Integrating both assays provides a more accurate immunological profile for RVFV surveillance and vaccine evaluation. Full article

Lung cancer remains one of the most formidable health challenges globally, with significant morbidity and mortality rates. Despite advancements in diagnostic and treatment technologies, the disease’s high prevalence, late-stage detection, and complex variations continue to hinder effective management. Early detection and accurate diagnosis play a pivotal role in improving survival rates. Crucially, the clinical and translational relevance of AI-based prediction lies in its potential to significantly reduce the incidence of late-stage diagnoses, thus increasing the chance of successful intervention. Lung cancer was first identified by medical professionals in the mid-19th century. Today, cancer remains a significant global health challenge, affecting an estimated 14 million individuals annually and causing 8.2 million fatalities worldwide. Lung cancer ranks among the leading causes of death associated with cancer. This research aims to bridge gaps in lung cancer diagnosis by exploring various learning methodologies. By focusing on studies from the last 10 years, this survey provides a contemporary understanding of the field, emphasizing the importance of automated diagnostic systems in reducing human error and improving efficiency. The selection of relevant research is based on a rigorous methodology, including specific inclusion and exclusion criteria, which are later discussed in detail with supporting figures and comparative data. Ultimately, this work underscores the critical need for innovative diagnostic solutions and comprehensive screening programs to combat lung cancer, save lives, and advance the field of medical research. Full article

Background: Low-dose computed tomography (LDCT) screening reduces lung cancer mortality; however, the effectiveness of screening programs depends not only on detection, but also on completion of downstream diagnostic pathways following a positive screening result. Refusal of recommended invasive diagnostic procedures represents a critical but understudied form of post-screening attrition. Methods: This retrospective observational study was conducted within an organized multicenter LDCT lung cancer screening program in Vojvodina, Serbia. Consecutive participants screened between September 2020 and October 2025 were included. Positive screening was defined as Lung-RADS 4A, 4B, or 4X. Refusal was defined as the absence of any invasive diagnostic procedure within six months following multidisciplinary team recommendation. Demographic, clinical, smoking-related, and perceptual factors were analyzed. Time to invasive diagnostic procedures was assessed for bronchoscopy and surgical treatment. Multivariable logistic regression was used to identify factors independently associated with refusal. Results: Among 10,261 screened individuals, 479 (4.7%) had positive LDCT findings. Of these, 60 participants (12.5%) refused invasive diagnostic evaluation. In multivariable analysis, multimorbidity (OR 3.45, 95% CI 1.61–7.38), previous malignancy (OR 2.92, 95% CI 1.16–7.35), higher cumulative smoking exposure (OR 1.02 per pack-year, 95% CI 1.00–1.03), and screening center (Subotica vs. Novi Sad: OR 2.40, 95% CI 1.21–4.78) were independently associated with refusal of invasive diagnostic procedures. Greater concern about personal lung cancer risk was associated with a lower likelihood of refusal (OR 0.54, 95% CI 0.29–0.99). Time to bronchoscopy differed significantly across screening centers and screening years, whereas time to surgical treatment was comparable across centers and years. Conclusions: Refusal of invasive diagnostic procedures following positive LDCT screening represents a meaningful implementation challenge influenced by both patient vulnerability and system-level factors. Addressing modifiable barriers through improved risk communication and optimization of post-screening diagnostic pathways may enhance diagnostic continuity and strengthen the real-world effectiveness of lung cancer screening programs. Full article

Introduction: Early detection and timely treatment (Tx) initiation are critical to improving lung cancer (LC) outcomes. This study assessed the natural language processing (NLP)-assisted incidental pulmonary nodule (IPN) evaluation program, which employs chest computer tomography (CT) report analysis as an LC diagnostic screening (LCS) tool to identify suspicious lung findings (SLF) necessitating further investigation, and evaluated its impact on prognosis and diagnostic work-up and Tx timelines for patients with LC. Materials and Methods: Consecutive LC patients (n = 200) diagnosed at Assuta Medical Centers (AMC) between January 2019 and December 2022 were retrieved from the AMC electronic database using the MDClone big data platform, and divided into two groups: group A (NLP-assisted IPN evaluation, n = 100) and group B (traditional referral for evaluation of SLF by the community physician, n = 100). Stage at diagnosis, different diagnostic work-up and Tx timelines, and overall survival (OS) were assessed. Results: The NLP-assisted IPN evaluation program led to a significant stage shift (stage I disease: 48% vs. 27% in groups A and B, respectively, p = 0.013). Although the time from imaging to Tx initiation was similar (2.1 ± 5.3 months vs. 2.6 ± 5.9 months in groups A and B, respectively, p = 0.654), the time to systemic Tx (p = 0.035) and the time to radiotherapy (p = 0.044) were significantly shorter in group A. Conclusions: Implementing an NLP-assisted IPN evaluation program may enable earlier LC detection, driving a stage shift towards earlier diagnosis, improved diagnostic efficiency, and expedited time-critical interventions. Full article

Persistent infection with hepatitis D virus (HDV), also known as hepatitis delta, is considered the most severe form of chronic viral hepatitis. HDV is a defective RNA virus that depends on hepatitis B virus (HBV) for propagation. Despite its global distribution, HDV stays a neglected part of the viral hepatitis agenda, often overlooked in surveillance systems and public health policy. This oversight is particularly concerning given HDV’s aggressive clinical course, characterized by more rapid progression to cirrhosis, liver failure, and hepatocellular carcinoma (HCC) compared to HBV mono-infection. Mongolia has the highest incidence and mortality rates of HCC worldwide, with approximately 47% of cases estimated to be attributable to chronic HDV infection. Globally, an estimated 12–25 million people are co-infected with HBV and HDV, although the true prevalence is higher due to insufficient screening and incomplete data collection. Because HDV infection is entirely dependent on HBV, prevention of HBV infection through effective vaccination stands for an indirect yet highly effective strategy to curb HDV transmission. The World Health Organization (WHO), together with the global health community, has established ambitious targets to eliminate viral hepatitis as a public health threat by 2030. However, achieving HDV elimination remains particularly challenging due to limited diagnostic capacity, low awareness, and minimal inclusion of HDV in national hepatitis programs. This review explores the intersection of HDV and HBV, focusing on how expanded and optimized HBV vaccination coverage can serve as a cornerstone of global HDV prevention efforts. We examine epidemiological evidence, scientific rationale, policy developments, and key implementation challenges, with particular attention to high-burden settings such as Mongolia. Finally, we propose strategic recommendations to bridge policy and practice gaps in HDV elimination. Full article

Background and Objectives: Colorectal cancer (CRC) is the most common gastrointestinal malignancy in Oman and among the top three cancers nationally, with an increasing burden of early-onset CRC (EOCRC) diagnosed before age 50. Despite national CRC guidelines, the lack of an organized screening program means most cases are detected symptomatically and at advanced stages. This study evaluated age-related differences in colonoscopic findings and advanced neoplasia risk in symptomatic adults to inform early detection and screening strategy development. Materials and Methods: A cross-sectional analysis of 2041 colonoscopies performed at two national tertiary referral centers, Sultan Qaboos University Hospital and Royal Hospital, was conducted (2018–2021). Patients were categorized by age (<50 vs. ≥50 years). Outcomes included adenoma detection rate (ADR), advanced premalignant lesions (APL), colorectal cancer (CRC), and advanced colorectal neoplasia (ACRN; APL and/or CRC). Associations between presenting symptoms and ACRN were analyzed using univariable logistic regression, and diagnostic yield was estimated via number needed to scope (NNS). The cohort was predominantly symptomatic (71.9%), with 15.8% screening and 12.3% surveillance procedures. Results: Of 2041 procedures, 742 (36.3%) were in patients <50 years. ADR, APL, CRC, and ACRN were significantly higher in those ≥50 years (14.9%, 7.5%, 5.8%, and 13.3%) than in younger adults (8.5%, 3.2%, 2.7%, and 5.9%; all p < 0.01). Among younger adults, rectal bleeding (OR 2.17, 95% CI 1.15–4.08, p = 0.026) and abdominal pain (OR 2.14, 95% CI 1.15–3.98, p = 0.022) were significantly associated with ACRN. Diagnostic efficiency (NNS) was highest for loss of appetite in both age groups (4.7 in <50 vs. 2.8 in ≥50 years). Despite lower overall rates, a substantial burden of advanced neoplasia was observed in symptomatic adults <50 years (5.9% ACRN, 2.7% CRC). Conclusions: This bicenter study demonstrates clear age-related disparities in colorectal neoplasia, with a clinically important burden of advanced disease in symptomatic adults under 50 years. These findings highlight the importance of prompt colonoscopic evaluation for younger adults presenting with alarm symptoms, particularly rectal bleeding and abdominal pain, and provide evidence supporting risk-stratified diagnostic approaches. While age-related differences suggest potential value in earlier screening initiation, our predominantly symptomatic tertiary care cohort cannot directly determine optimal screening age thresholds. Prospective screening trials and cost-effectiveness analyses are needed to establish population-based detection rates and inform evidence-based screening policy development in Oman. Full article

Background/Objectives: The Speech-Language Pathologists (SLP) are an integral part of the multidisciplinary team approach to rehabilitation of persons with aphasia (PWA). However, the efficacy of treatment provided by SLPs can vary due to several factors related to clinicians, patients, and the availability of services. The present study was conducted with the aim of investigating current practices in aphasia rehabilitation, key challenges, and future directions as perceived by the SLPs in the Indian context. Methods: The study was conducted using a web-based survey comprising a 32-item questionnaire to gather information related to demographic and professional details, knowledge and use of aphasia rehabilitation approaches, patient education, counselling, bilingual & multilingual contexts, and challenges faced by SLPs. A total of 142 responses were analyzed after initial screening to assess the knowledge, use, and confidence of aphasia rehabilitation along with challenges faced by SLPs in the Indian context. Results: The results indicated significant challenges in the assessment of aphasia due to a lack of formal screening and diagnostic languages in several languages. Further, the results also indicated variations in the knowledge level and confidence in the use of various approaches to aphasia rehabilitation, which warrants the urgent need for organizing short-term training programs for SLPs. The participants also self-reported significant challenges in managing bilingual and multilingual patients with aphasia due to differences in their knowledge and confidence in the selection of language for treatment. On the other side, major patient-related challenges include inadequate logistics, lack of funding, unavailability of speech and language therapy services, social acceptance, and support from family members. The participants also reported the necessity of improving tele-rehabilitation services and developing materials and mobile apps for rehabilitation in Indian languages as future directions for aphasia rehabilitation. Conclusions: The present study through a self-reported questionnaire identified key challenges in aphasia rehabilitation related to the clinician and PWA in the Indian context. The results of the study warrant the need for immediate action to overcome the challenges to enhance the rehabilitation services to PWAs. Full article

Background: Breast cancer remains a leading cause of morbidity and mortality among women in Latin America. Mammography is the most effective population-based tool for early detection; however, its impact is limited by persistent social, geographic, and structural inequities. Evidence from the region indicates that ethnicity, rural residence, and health system organization play a central role in shaping unequal access to screening services. Methods: We conducted a narrative review informed by a systematic search strategy, following PRISMA 2020 recommendations. Searches were performed in 17 international and regional databases in English and Spanish, covering publications from 2015 to 2025. Eligible studies included non-interventional quantitative designs reporting mammography access, utilization, or coverage among women residing in Latin American countries. Three reviewers independently screened records, extracted data, and classified determinants of inequality into sociodemographic, geographic, and health-system domains. Results: Of 532 records identified, 12 studies met the inclusion criteria, primarily from Mexico, Brazil, Peru, and Chile. Most analyses were based on nationally representative surveys. Mammography coverage ranged from approximately 20% to 60%, with consistently lower uptake among Indigenous women, rural populations, and women without health insurance. Reduced screening was associated with low educational attainment, socioeconomic disadvantages, rural residence, ethnic self-identification, and fragmented health system affiliation. Structural barriers, including concentration of diagnostic infrastructure in urban areas, reliance on opportunistic screening models, and limited capacity for systematic follow-up, were recurrent across countries. Conclusions: Inequities in mammography access and utilization in Latin America reflect deeply rooted social and structural determinants rather than a lack of screening technology alone. Reducing preventable breast cancer mortality requires strengthening organized, population-based screening programs, decentralizing diagnostic services, improving continuity of care, and implementing culturally appropriate strategies tailored to Indigenous, rural, and uninsured populations. Full article

Background: Diabetic retinopathy (DR) poses a significant global health challenge that needs scalable and efficient screening pathways beyond the current limitations of teleophthalmology. This study retrospectively evaluated the diagnostic performance of an artificial intelligence (AI) DRISTi system (Version 2.1) against ophthalmologist grading for more-than-mild diabetic retinopathy (mtmDR), vision-threatening diabetic retinopathy (vtDR), and diabetic macular edema (DME). Methods: The methods involved a retrospective, observational, non-interventional validation comparing the AI DRISTi system’s output to ophthalmologist grading on 739 colour fundus images acquired using Topcon NWC 400, CrystalVue NFC 600/700, Canon CR2/CR2 AF, and Zeiss VISUCAM 500 cameras. Results: Primary outcomes included sensitivity and specificity, with statistical analyses utilizing 2 × 2 contingency tables and 95% confidence intervals. The AI system achieved an accuracy of 93.36% (sensitivity 95.03%; specificity 92.90%) for mtmDR, 98.64% (sensitivity 96.92%; specificity 99.01%) for vtDR, and 97.97% (sensitivity 92.85%; specificity 98.88%) for DME. Performance was robust and consistent across all evaluated camera types. Conclusions: In conclusion, the AI DRISTi system (Version 2.1) demonstrates strong diagnostic performance for mtmDR, vtDR, and DME, comparable to leading commercial AI systems, from fundus photographs acquired across multiple camera platforms. This system holds significant promise as an adjunctive screening tool for large-scale DR screening programs, contributing to early detection, appropriate triage, and the prevention of vision loss in at-risk populations. Full article

Background/Objectives: Increasing scientific evidence supports the importance of early diagnosis of autism spectrum disorder (ASD), followed by timely intervention, in optimizing developmental trajectories. Despite these advances, achieving an early diagnosis remains challenging, and substantial delays in the diagnostic process continue to be reported worldwide. This study aimed to describe the clinical and sociodemographic characteristics associated with early referral to a telehealth parent-mediated intervention program for infants at high likelihood for ASD, under 18 months of age, with the broader goal of informing clinical services in the field of neurodevelopmental disorders. Methods: Infants were evaluated by a multidisciplinary team using standardized measures to assess autism risk, developmental functioning, adaptive behavior, and parental stress. Potential differences in age at access to the program were examined by comparing families who were referred before versus after 12 months of age. Results: Of the 78 families who expressed interest in the program, 69 consented and 60 met eligibility criteria (male/female ratio = 40/20; mean age = 10.0 months). Families were evenly distributed across Italy, and 66% of parents held a university degree. Self-referral accounted for 62% of cases. Higher parental concern was associated with earlier referral and children referred after 12 months of age showed significantly lower developmental and adaptive functioning scores. Conclusions: These findings support the feasibility of identifying prodromes of autism within the first year of life and highlight gaps in specialized services for infants at elevated likelihood in Italy. Maternal concern and self-referral drove early consultation, underscoring the need for improved pediatric training. Future studies should assess longitudinal population-based screening and the feasibility and long-term impact of timely interventions in routine care. Full article

Background and Objectives: Celiac disease (CD) is a major global public health problem that can occur at any age. Pediatric CD can be typical, atypical, or even asymptomatic. Early diagnosis and early initiation of treatment are essential for improving patients’ quality of life and preventing serious complications later in life. However, it is impossible to identify asymptomatic children and adolescents without screening. In this systematic review, we attempted to identify different mass screening programs that have been reported for CD in apparently healthy children and adolescents across the world, to highlight the advantages and disadvantages of such strategies, and to collect and synthesize data from these studies reporting the prevalence of CD. In addition, where data were available, we also attempted to evaluate the diagnostic accuracy of the tests used, their cost-effectiveness, the reported clinical benefits, and follow-up data from individuals identified through screening. Materials and Methods: Electronic databases, including PubMed and Scopus, were systematically searched. Initially, a total of 316 studies were retrieved. Finally, 55 studies met all inclusion criteria and were included in this review. The included studies were published between 1996 and 2023. Results: The reported age of participants ranged from 6 months to 23 years. Confirmation of CD by biopsy was reported in all but six studies. According to the studies that provided data, the (tTG IgA) seroprevalence of CD in apparently healthy children and adolescents, detected through different mass screening methods around the world, ranged from 0.20% (Turkey) to 3.11% (Italy). In addition, the prevalence of biopsy-confirmed CD ranged from 0.036% (Vietnam) to 3% (Sweden and Spain). Studies from 17 countries reported mass screening strategies based on finger-prick rapid tests. All rapid tests detected CD antibodies, except two, which detected HLA DQ2/DQ8 haplotypes. Rapid tests appeared to be no less sensitive and specific than other screening tests for CD and were probably less expensive, but further studies are needed for more reliable conclusions. Of the 55 studies in the review, only 10 reported follow-up data. After 3 months of a gluten-free diet, the general condition of the patients improved; after 6 months, tTG IgA and EMA IgA levels decreased and hemoglobin values increased; while after 1 year, tTG IgG levels also decreased, symptoms subsided, the children’s weight and height increased, school performance improved, episodes of upper respiratory tract infections decreased, and thyreoperoxidase antibodies that were positive at screening became negative. Conclusions: Mass screening for CD in asymptomatic children and adolescents is a challenge. Future research should provide more answers regarding the most appropriate target age, the frequency of screening, the optimal screening method, the cost-effectiveness, the clinical utility, and the long-term impact of mass screening on patients’ quality of life. Full article

In recent years, the development of new diagnostic technologies, such as tandem mass spectrometry (MS/MS) and next-generation sequencing (NGS), has caused a veritable revolution in the diagnosis of genetic diseases, reducing time, cost, and invasiveness associated with prior diagnostic techniques. While MS/MS laid the foundation for the development of numerous, usually institutionally based, neonatal screening programs, NGS has gained traction in newborn screening (NBS), primarily through pilot projects and private funding across different countries. As a result, the traditional Wilson and Jungner criteria have been supplemented by additional criteria, including considerations of equity and access, in response to emerging technologies. This review aims to provide an up-to-date overview of the global landscape of metabolic screening panels, highlight the major ongoing genomic screening projects, and outline the current models for integrating these two screening systems. Substantial differences exist across countries in the numbers and types of diseases included in national NBS programmes. In this context, Italy represents a prominent case, as its neonatal screening framework has seen significant expansion and development in recent years, reaching a particularly comprehensive metabolic screening panel. Nonetheless, a number of initiatives to incorporate genomic technologies into the NBS pathway are currently underway, primarily involving high-income countries. Nonetheless, unlike metabolomic-based NBS programs, no country has a government-mandated NGS program as first-tier testing for newborns. New evidence is emerging from ongoing models of integration of multi-omics approaches into NBS, including the use of AI and machine learning. Identifying the most appropriate system for this integration to reduce the false-positive and false-negative rates associated with both screening types, ensure more equitable access to screening, and facilitate faster access to treatment may represent a useful and foresightful way to conceptualize NBS in the future. This transitional phase should promote rigorous improvements before full-scale adoption. Full article

Cervical cancer remains a major global public health concern, with persistent infection by high-risk human papillomavirus (hrHPV) types recognized as the primary etiological factor. This review explores the multifactorial nature of the disease, focusing on the complex interplay between host genetic susceptibility and epigenetic alterations that drive cervical carcinogenesis. Evidence from genome-wide association studies (GWAS) is discussed, highlighting the contribution of specific genetic loci, predominantly within the HLA region, to susceptibility to HPV infection and disease progression. In parallel, the review examines the molecular mechanisms by which the viral oncoproteins E6 and E7 promote genetic instability and epigenetic reprogramming, including histone modifications and dysregulation of non-coding RNAs. Particular emphasis is placed on DNA methylation, affecting both the viral genome and host genes such as FAM19A4, CADM1, PAX1, and MAL, as a promising biomarker for triage and detection of high-grade intraepithelial lesions (CIN2+). Finally, the review evaluates currently available methylation-based assays and self-sampling devices, highlighting their potential to enhance diagnostic accuracy and increase participation in cervical cancer screening programs. Full article