Expert Review Of Molecular Diagnostics[JOURNAL]
Sun
200 papers
Bacterial respiratory infections: advances in diagnostic strategies.
Gentili C, Meyer Sauteur PM, Buonsenso D
Expert Rev Mol Diagn · 2026 Jul · PMID 42400293 · Publisher ↗
INTRODUCTION: Respiratory tract infections (RTIs) are among the most common causes of medical consultation in children. Although the majority of upper respiratory tract infections are viral and self-limiting, bacterial p...
INTRODUCTION: Respiratory tract infections (RTIs) are among the most common causes of medical consultation in children. Although the majority of upper respiratory tract infections are viral and self-limiting, bacterial pathogens remain responsible for a relevant proportion of cases and may require targeted antimicrobial therapy. Accurate microbiological diagnosis is therefore essential to guide clinical management and support antimicrobial stewardship. AREAS COVERED: This review discusses the etiology and clinical presentation of pediatric respiratory infections and examines current diagnostic approaches, including traditional culture-based methods and nucleic acid amplification tests (NAATs). The advantages of molecular diagnostics - such as rapid turnaround time, high sensitivity, and improved pathogen detection - are highlighted alongside their role in antimicrobial stewardship and public health surveillance. At the same time, important limitations are explored, including difficulties in distinguishing colonization from active infection, challenges in polymicrobial detection, absence of host-response information, and barriers related to cost and accessibility. Emerging technologies and future perspectives in pediatric molecular diagnostics are also addressed. EXPERT OPINION: While molecular diagnostics have transformed pathogen detection, their clinical interpretation remains complex. Future diagnostic strategies should integrate molecular data with quantitative pathogen measurements, host-response biomarkers, and clinical phenotyping to better distinguish infection from colonization. Interdisciplinary research, real-world implementation studies, and cost-effectiveness evaluations will be essential to translate technological advances into meaningful improvements in pediatric infectious disease care.
Artificial intelligence in molecular diagnostics for pandemic preparedness.
Sagar K, Mukherjee D, Savareh BA … +7 more , Talibouya Toure C, Ceruti A, Ghosh P, Weidmann M, Truyen U, Abd El Wahed A, Kobialka RM
Expert Rev Mol Diagn · 2026 Jul · PMID 42396845 · Publisher ↗
INTRODUCTION: Molecular diagnostics focusing on the detection and analysis of nucleic acids, are indispensable tools for early pathogen identification, transmission monitoring, and genomic surveillance during pandemics....
INTRODUCTION: Molecular diagnostics focusing on the detection and analysis of nucleic acids, are indispensable tools for early pathogen identification, transmission monitoring, and genomic surveillance during pandemics. Recent technological advances have broadened the diagnostic landscape, incorporating PCR-based methods, isothermal amplification, high- CRISPR-based amplification detection and sequencing. Despite their diagnostic potential, widespread implementation remains limited by high validation costs, time and logistical constraints, the need for specialized professional knowledge and a lack of adaptability in resource-limited settings. Artificial Intelligence (AI) is increasingly recognized as a promising but challenging approach, offering tools that streamline assay development, automate data interpretation, and optimize real-time diagnostic performance. AREAS COVERED: This review introduces recently published AI tools with potential to enhance the in-silico design validation process of oligonucleotides for molecular assays. These cover tools for initial assay design and optimization to validation and continuous assay updates. The limitations, including concerns regarding data accuracy, the lack of transparency in data processing ('black box' models), and unresolved licensing and regulatory issues are highlighted for each tool and as expert opinion. EXPERT OPINION: Collectively, these challenges currently confine most AI-based approaches to research settings and prevent their routine implementation in clinical molecular diagnostics. Their widespread adoption depends on addressing remaining technical, regulatory, and practical challenges.
Navigating PD-L1 testing in immuno-oncology: analytical robustness, clinical validation, and the role of the VENTANA SP263 assay.
D'Abbronzo G, Lucà S, Cioce A … +6 more , Diluvio A, Cretella P, Sibillo MC, Salzillo C, Masola V, Franco R
Expert Rev Mol Diagn · 2026 Jun · PMID 42347817 · Publisher ↗
INTRODUCTION: PD-L1 expression today represents a crucial biomarker in the selection of patients eligible for immune checkpoint inhibitor therapies (PD-1/PD-L1), particularly in tumors such as NSCLC, urothelial carcinoma...
INTRODUCTION: PD-L1 expression today represents a crucial biomarker in the selection of patients eligible for immune checkpoint inhibitor therapies (PD-1/PD-L1), particularly in tumors such as NSCLC, urothelial carcinoma, and TNBC. Its role in modulating immune response and the tumor microenvironment makes this topic of growing relevance in clinical oncological practice. AREAS COVERED: This review examines the most recent literature on histological and plasma PD-L1 expression, comparative studies between antibodies and IHC cutoffs, integration of liquid biopsy and new biomarkers (e.g. CPS, ctDNA). A targeted literature search was conducted using PubMed/MEDLINE, Scopus, and Web of Science, covering publications from January 2010 to March 2025. Meta-analyses and clinical studies related to TNBC, NSCLC, and urothelial carcinoma are included, with insights into therapeutic resistance and combination strategies. EXPERT OPINION: While SP263 demonstrates strong analytical performance and reproducibility, analytical concordance does not equate to clinical interchangeability. PD-L1 testing should remain assay-, tissue-, and indication-specific, supported by regulatory approval and clinical outcome data. Future integration of digital tools and multimodal biomarkers may improve standardization and predictive accuracy.
Extracellular vesicles as diagnostic and prognostic biomarkers in non-small cell lung cancer.
Akbar S, Fernandes Q, Khaja Mohamed Yoosuf ZS … +9 more , Elasad R, Assami L, Makni-Maalej K, Inchakalody V, Al-Muftah M, Uddin S, Merhi M, Ahmad A, Dermime S
Expert Rev Mol Diagn · 2026 Jun · PMID 42323710 · Publisher ↗
INTRODUCTION: Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related mortality worldwide, largely due to late-stage diagnosis and limited availability of reliable biomarkers. Extracellular vesicle...
INTRODUCTION: Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related mortality worldwide, largely due to late-stage diagnosis and limited availability of reliable biomarkers. Extracellular vesicles (EVs) are membrane-bound nanoparticles released by cells that carry nucleic acids, proteins, and lipids reflective of their cellular origin. Their stability and accessibility through minimally invasive sampling make them promising liquid biopsy biomarkers. AREAS COVERED: This review summarizes current evidence supporting EVs as diagnostic and prognostic biomarkers in NSCLC. We discuss the clinical relevance of EV-associated molecular signatures, including miRNAs, other non-coding RNAs, and proteins, in early detection, disease stratification, and outcome prediction. Recent advances in EV isolation and characterization technologies, particularly microfluidic and high-throughput platforms, are highlighted. We also examine key barriers to clinical translation, including biological heterogeneity, methodological variability, and the lack of standardized protocols. EXPERT OPINION: EVs have the potential to transform NSCLC management by enabling minimally invasive diagnosis, real-time disease monitoring, and personalized treatment strategies. However, widespread clinical implementation requires standardized methodologies, improved tumor-specific EV enrichment, and large-scale validation studies. Future integration of multi-omics, artificial intelligence, and advanced detection technologies is expected to enhance biomarker performance and facilitate the incorporation of EV-based liquid biopsy approaches into precision oncology.
Explainable epigenetic aging clocks: an overview of existing AI models and approaches.
Johnson AA, Shokhirev MN
Expert Rev Mol Diagn · 2026 Jun · PMID 42318857 · Publisher ↗
INTRODUCTION: There is a growing demand to make epigenetic aging clocks that are interpretable and actionable. Here, we identify and describe explainable artificial intelligence (XAI) epigenetic clocks that convert CpGs...
INTRODUCTION: There is a growing demand to make epigenetic aging clocks that are interpretable and actionable. Here, we identify and describe explainable artificial intelligence (XAI) epigenetic clocks that convert CpGs into higher-level abstractions using deep learning. AREAS COVERED: By combing through PubMed, this narrative review identifies six different XAI clocks: XAI-AGE, DL-XAI, EpInflammAge, PathwayAge, EXP.REACTOME, and EXP.TFT. XAI-AGE, DL-XAI, PathwayAge, EXP.REACTOME, and EXP.TFT provide explainability by leveraging the fact that a subset of DNA methylation sites are annotated to genes. From here, genes are converted into biological pathways or a protein-protein interaction network. Conversely, the XAI clock EpInflammAge works by taking methylation-based predictors of circulating chemokines and cytokines - referred to as synthetic proxies - and feeding these as inputs into a deep learning model. EXPERT OPINION: By evaluating and comparing extant XAI clocks, it is clear that explainability is compatible with the ability to make accurate age predictions that are associated with meaningful health signals. The pathway- or network-level models are, however, more difficult to interpret and less actionable than the XAI clock based on synthetic proxies. Explainability and actionability could be improved by only incorporating robust estimators of well-understood biomarkers or by exclusively including tangible, easy-to-understand biological pathways.
Neuro-axonal injury biomarker serum neurofilament light chain is associated with osteoarthritis: a dual-cohort study from NHANES and UK Biobank.
Liu M, Ma H, Zhou H … +6 more , Xie K, Luo C, He Z, Ning Z, Wei J, Yu D
Expert Rev Mol Diagn · 2026 Jul · PMID 42296085 · Publisher ↗
BACKGROUND: Osteoarthritis (OA) affects over half a billion people globally, representing a major public health burden. Serum neurofilament light chain (sNFL) has recently been implicated in systemic inflammation and met...
BACKGROUND: Osteoarthritis (OA) affects over half a billion people globally, representing a major public health burden. Serum neurofilament light chain (sNFL) has recently been implicated in systemic inflammation and metabolic disorders. RESEARCH DESIGN AND METHODS: This dual-cohort study analyzed data from the National Health and Nutrition Examination Survey (NHANES) and the UK Biobank. In NHANES, sNFL was measured via a high-sensitivity immunoassay, while in UKB, NfL was quantified using the Olink Explore 3072 proteomics platform. OA was defined by self-report in NHANES, and a combination of self-report and ICD-10 hospital records in UKB. The associations were evaluated using multivariate logistic regression and RCS. RESULTS: Higher sNFL levels were significantly associated with increased OA odds in both cohorts. In fully adjusted models, each 1-unit increase in log-transformed sNFL corresponded to 85% higher odds in NHANES [OR = 1.85, 95% CI: (1.51, 2.23)] and 28% higher odds in UKB [OR = 1.28, 95% CI: (1.21, 1.36)]. Comparing the highest to lowest quartiles, ORs were 4.41 (95% CI: 2.71, 7.13) and 1.46 (95% CI: 1.34, 1.59), respectively (both for trend <0.01). CONCLUSIONS: Elevated sNFL levels are independently and consistently associated with a higher prevalence of OA across two distinct national cohorts.
Diagnostics and novel laboratory approaches to combat antimicrobial resistance.
Soge OO, Fifer H, Alexander S … +1 more , Buss SN
Expert Rev Mol Diagn · 2026 Jul · PMID 42295988 · Publisher ↗
INTRODUCTION: (gonococcus, GC) has developed resistance to all antimicrobials recommended for gonorrhea treatment, owing to its genetic plasticity and capacity to acquire antimicrobial resistance (AMR). This review exam...
INTRODUCTION: (gonococcus, GC) has developed resistance to all antimicrobials recommended for gonorrhea treatment, owing to its genetic plasticity and capacity to acquire antimicrobial resistance (AMR). This review examines the crucial role of diagnostics and novel laboratory approaches in mitigating the spread of GC-AMR and in preserving the long-term effectiveness of current and future antimicrobials for gonorrhea. AREAS COVERED: Recent advances in diagnostics and novel laboratory approaches for detection of GC-AMR, enhancing GC-AMR surveillance and clinical management of gonorrhea. EXPERT OPINION: The rapid emergence and global dissemination of multidrug-resistant GC including ceftriaxone-resistant strains poses a grave challenge to current gonorrhea control and prevention strategies. The implementation of rapid diagnostics and novel laboratory approaches can, when used appropriately, support the rapid detection of GC-AMR, ensure timely treatment, reduce transmission, and preserve last-line antibiotics by enabling resistance-guided therapy. These diagnostics and novel laboratory approaches are also crucial for the early detection of emerging resistance to antimicrobials recently approved by the FDA, and other antimicrobials currently under development and anticipated for future clinical use. Integrating culture-based GC-AMR surveillance with rapid molecular assays targeting genetic determinants of AMR offers a comprehensive approach for robust monitoring and timely response to the ever-evolving GC-AMR.
Fluid biomarkers in cerebral amyloid angiopathy: current limitations and future directions.
Del Chicca M, Mignani G, Iannaccone F … +8 more , Piccarducci R, Giannini N, Tognoni G, Masi S, Ceravolo R, Siciliano G, Mancuso M, Baldacci F
Expert Rev Mol Diagn · 2026 Jul · PMID 42287242 · Publisher ↗
INTRODUCTION: Cerebral amyloid angiopathy (CAA) is a major cause of lobar intracerebral hemorrhage and cognitive decline in older adults. Current diagnosis relies mainly on neuroimaging, which lacks pathophysiological sp...
INTRODUCTION: Cerebral amyloid angiopathy (CAA) is a major cause of lobar intracerebral hemorrhage and cognitive decline in older adults. Current diagnosis relies mainly on neuroimaging, which lacks pathophysiological specificity. AREAS COVERED: This narrative review summarizes evidence on cerebrospinal fluid (CSF) and plasma biomarkers in sporadic CAA. In CSF, CAA is typically associated with reduced Aβ42 and Aβ42/Aβ40 ratio, although similar alterations are observed in Alzheimer's disease (AD), limiting diagnostic specificity. Lower Aβ40 levels may reflect vascular amyloid deposition and appear more characteristic of CAA, but alone provide insufficient discrimination. Plasma biomarker studies have yielded inconsistent findings due to methodological and population heterogeneity. Nevertheless, amyloid isoforms, phosphorylated tau species, and neurofilament light chain (NfL) show potential, with NfL correlating with imaging markers and disease burden. The increasing need to distinguish CAA from AD and other cerebral small vessel diseases has driven growing interest in fluid biomarkers. EXPERT OPINION: Despite promising findings, no fluid biomarker currently demonstrates sufficient specificity or validation for routine clinical use in CAA. Significant overlap with AD pathology remains a major limitation. Large longitudinal real-world studies are needed to determine the diagnostic, prognostic, and incremental clinical value of fluid biomarkers in CAA.
Diagnostic performance of circulating cell-free DNA as a minimally invasive biomarker for breast cancer: a systematic review and meta-analysis of methylation, quantitative, and integrity markers.
Wael N, Owid AZ, Fadlalla H
Expert Rev Mol Diagn · 2026 Jul · PMID 42266071 · Publisher ↗
INTRODUCTION: We evaluated the diagnostic accuracy of circulating cell-free DNA (cfDNA) and circulating tumor DNA (ctDNA) compared to tissue biopsy in breast cancer across three assay modalities. METHODS: We searched Pub...
INTRODUCTION: We evaluated the diagnostic accuracy of circulating cell-free DNA (cfDNA) and circulating tumor DNA (ctDNA) compared to tissue biopsy in breast cancer across three assay modalities. METHODS: We searched PubMed, Scopus, and Cochrane for studies published from January 2014 to March 2026. Bivariate random effects models pool sensitivity, specificity, and area under the curve (AUC). Registered under (CRD420261333264). RESULTS: Eighteen studies with 4,743 participants were included. Quantitative assays achieved the highest sensitivity of 0.930 (95% CI: 0.603-0.991), specificity of 0.899 (95% CI: 0.802-0.951), and AUC of 0.928. Methylation assays showed a sensitivity of 0.752 (95% CI: 0.595-0.862), specificity of 0.841 (95% CI: 0.737-0.908), and AUC of 0.862. Integrity assays yielded a sensitivity of 0.863 (95% CI: 0.682-0.948), specificity of 0.874 (95% CI: 0.781-0.931), and AUC of 0.927. Substantial statistical heterogeneity (I) occurred across all subgroups. Overall certainty was low, due to case-control designs and inconsistency. CONCLUSION: While cfDNA cannot replace tissue biopsies, current pooled estimates demonstrate high specificity, suggesting promising potential as an adjunctive diagnostic tool. Quantitative assays show the greatest potential for optimizing patient triage. However, the overall low certainty of evidence highlights an urgent need for standardized prospective studies.
KIM-1 and beyond: emerging biomarkers for adjuvant immunotherapy in clear cell renal cell carcinoma.
Rosellini M, Danielli L, Bibbò A … +6 more , Musio M, Ricci C, Piazza P, Santoni M, Mollica V, Massari F
Expert Rev Mol Diagn · 2026 Jul · PMID 42261901 · Publisher ↗
INTRODUCTION: Adjuvant immunotherapy has transformed the management of high-risk resected ccRCC, with pembrolizumab demonstrating improvements in DFS and OS. However, divergent outcomes across recent phase III trials hig...
INTRODUCTION: Adjuvant immunotherapy has transformed the management of high-risk resected ccRCC, with pembrolizumab demonstrating improvements in DFS and OS. However, divergent outcomes across recent phase III trials highlight the limitations of clinicopathologic staging alone for guiding postoperative treatment decisions. A substantial proportion of patients may receive adjuvant therapy without deriving meaningful benefit, underscoring the urgent need for biologically informed risk stratification. AREAS COVERED: KIM-1, a circulating biomarker derived from proximal tubular epithelium, has emerged as a promising candidate in this setting. Elevated postoperative KIM-1 levels are consistently associated with inferior oncologic outcomes and may reflect minimal residual disease. Exploratory analyses from IMmotion010 suggest a potential predictive enrichment effect for adjuvant immunotherapy benefit in patients with high baseline KIM-1. Additional biomarkers including sarcomatoid differentiation, specific genomic drivers (PBRM1, BAP1, VHL), circulating tumor DNA, epigenetic signatures, and systemic inflammatory markers, provide complementary insights into tumor biology and host-tumor interaction. EXPERT OPINION: Although none of these biomarkers are currently validated for routine clinical decision-making, integrative models combining clinicopathologic and molecular features may enable more precise selection of patients for adjuvant immunotherapy and help reduce overtreatment in localized ccRCC.
Assessing biomarkers for patients with breast cancer who are suited for adjuvant therapy.
Rakha EA
Expert Rev Mol Diagn · 2026 Jun · PMID 42210689 · Publisher ↗
INTRODUCTION: Biomarker-guided stratification is essential for optimizing adjuvant systemic therapy in early-stage breast cancer, requiring a balance between therapeutic benefit and avoidance of overtreatment. AREAS COVE...
INTRODUCTION: Biomarker-guided stratification is essential for optimizing adjuvant systemic therapy in early-stage breast cancer, requiring a balance between therapeutic benefit and avoidance of overtreatment. AREAS COVERED: This review summarizes established and emerging prognostic and predictive biomarkers guiding adjuvant therapy selection. Evidence was synthesized from structured searches of PubMed, EMBASE, clinical trial databases and author expertise, focusing on morphological and molecular biomarkers, including multigene assays, protein and immune-based markers, mutation profiling, liquid biopsy and artificial intelligence (AI). EXPERT OPINION: Although clinicopathological factors such as tumor size, grade, and nodal status remain fundamental, clinical decision-making is increasingly driven by biologically informed precision. ER and HER2 status continue to underpin prognostic and predictive assessment. In hormone receptor-positive disease, multigene assays refine recurrence risk and chemotherapy benefit, while tools such as HER2DX improve stratification in HER2-positive tumors. Immune and DNA-repair biomarkers inform targeted therapy in HER2-positive and triple-negative subtypes. Mutation profiling of , and increasingly informs targeted treatment, particularly in advanced disease. Emerging approaches, including liquid biopsy, AI, and multi-omics integration, offer dynamic insights but require prospective validation. Future progress depends on assay standardization, equitable access, and validation within adaptive clinical trial frameworks, supporting integrated molecular-clinical and AI-enhanced models for personalized therapy.
The estradiol-to-oocyte ratio as a predictor of ART outcomes: evidence and implications in PCOS.
Perovic M, Salovic B, Zafirović S … +4 more , Nikolic A, Gerginić V, Sudar-Milovanović E, Isenovic ER
Expert Rev Mol Diagn · 2026 Jul · PMID 42210663 · Publisher ↗
INTRODUCTION: Polycystic ovary syndrome (PCOS) is an endocrine disease involving reproductive dysfunction, with anovulation and diminished oocyte quality, and is related to endometrial dysfunction. Estradiol-to-oocyte ra...
INTRODUCTION: Polycystic ovary syndrome (PCOS) is an endocrine disease involving reproductive dysfunction, with anovulation and diminished oocyte quality, and is related to endometrial dysfunction. Estradiol-to-oocyte ratio (EOR) surfaced as a measure of success in reproductive effects in PCOS during assisted reproductive technical expertise. AREAS COVERED: This review provides a comprehensive summary of current evidence on EOR, its physiological significance, relationship with oocyte maturation, and impact on embryo viability in IVF. We will explore molecular mechanisms of EOR's action in follicular development, integrating data from imaging technologies and biomarker studies. It also discusses its clinical utility in optimizing individualized fertility treatment and improving reproductive prognoses for PCOS patients during IVF. EXPERT OPINION: EOR may empower IVF specialists by enabling more refined assessments, helping them make more personalized and confident treatment decisions for patients (embryo transfer and subsequent cycle protocol). It provides guidance for treatment adjustments in subsequent cycles, especially when prior responses were high in quantity but suboptimal in quality. Incorporating EOR into clinical practice complements clinical expertise and supports the balance between efficacy and safety in managing PCOS-related infertility.
Correction.
Expert Rev Mol Diagn · 2026 Jul · PMID 42210628 · Publisher ↗
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Diagnostic accuracy of fine-needle aspiration cytology in salivary gland neoplasms: a systematic review and meta-analysis.
Ali H, Abbas R, Urs AB … +2 more , Kumar P, Augustine J
Expert Rev Mol Diagn · 2026 Jun · PMID 42179292 · Publisher ↗
INTRODUCTION: Fine-needle aspiration cytology is a widely used minimally invasive tool for salivary gland lesions, though diagnostic challenges arise due to overlapping features between benign and malignant tumors. This...
INTRODUCTION: Fine-needle aspiration cytology is a widely used minimally invasive tool for salivary gland lesions, though diagnostic challenges arise due to overlapping features between benign and malignant tumors. This systematic review and meta-analysis evaluate its diagnostic performance in salivary gland neoplasms. METHODS: A comprehensive literature search was conducted in PubMed/MEDLINE, Embase, Scopus, and Web of Science. Studies reporting sensitivity, specificity, or sufficient data to construct 2 × 2 tables were included. Data extraction was performed independently by two reviewers, and study quality was assessed using the QUADAS-2 tool. Diagnostic accuracy was pooled using a bivariate random-effects model, and summary receiver operating characteristic curves were generated. Publication bias was evaluated using Deeks' funnel plot. RESULTS: A total of 56 studies were included, of which 32 were eligible for meta-analysis. The pooled sensitivity of FNAC was 0.79 (95% CI: 0.75-0.83), and specificity was 0.94 (95% CI: 0.93-0.96). The summary analysis demonstrated good discriminative ability with an area under the curve of 0.89. No significant publication bias was detected. CONCLUSIONS: FNAC demonstrates high diagnostic accuracy, with high specificity and moderate sensitivity, supporting its role as a reliable first-line diagnostic tool in salivary gland neoplasms.
Comparative review of diagnostic techniques for DNA methylation analysis.
Loureiro de Araújo L, Azevedo Cintra H, Guimarães Fonseca LLC … +7 more , de Faria LL, Rocha DN, da Costa Cipitelli M, Xavier Cenciani C, Correa Gonçalves JA, Ferreira Gomes LH, da Cunha Guida L
Expert Rev Mol Diagn · 2026 May · PMID 42171599 · Publisher ↗
INTRODUCTION: DNA methylation is a crucial epigenetic modification regulating gene expression, essential for embryonic development, cellular differentiation, and disease susceptibility. Aberrant methylation is associated...
INTRODUCTION: DNA methylation is a crucial epigenetic modification regulating gene expression, essential for embryonic development, cellular differentiation, and disease susceptibility. Aberrant methylation is associated with cancer, neurodegenerative and cardiovascular diseases, and imprinting disorders, highlighting the need for reliable biomarkers. AREAS COVERED: This review summarizes six widely used DNA methylation analysis techniques: Methylation-Specific PCR (MSP), quantitative (qMSP), Methylation-Specific MLPA (MS- MLPA), Methylation-Sensitive High-Resolution Melting (MS-HRM), pyrosequencing, MassARRAY, and digital droplet PCR (ddPCR). Their principles, clinical applications, strengths, and limitations are discussed, focusing on sensitivity, specificity, cost, and laboratory requirements. MS-HRM is cost-effective and highly sensitive for clinical screening; MS- MLPA enables multiplexed detection of methylation and copy number changes; pyrosequencing and MassARRAY offer quantitative CpG-level resolution; and ddPCR allows absolute quantification in low-DNA or mosaic samples. EXPERT OPINION: These techniques offer important advances for epigenetic diagnostics, yet further validation, protocol standardization, and simplification are needed for routine clinical use. Choosing the optimal method depends on study goals, sample type, and clinical needs. Integrating these approaches into standardized workflows can enhance early disease detection, therapeutic monitoring, and personalized epigenetic interventions, supporting precision medicine.
Human papillomavirus viral load as promising surrogate biomarker of cervical cancer risk and clinical outcome.
Mboumba Bouassa RS, Muwonga Tukisadila J, Loemba H … +1 more , Bélec L
Expert Rev Mol Diagn · 2026 Jun · PMID 42133446 · Publisher ↗
INTRODUCTION: Persistent high-risk human papillomavirus (HR-HPV) causes cervical precancerous lesions and cancer. While molecular HPV DNA testing offers superior sensitivity over cytology as a primary screening method, i...
INTRODUCTION: Persistent high-risk human papillomavirus (HR-HPV) causes cervical precancerous lesions and cancer. While molecular HPV DNA testing offers superior sensitivity over cytology as a primary screening method, its limited specificity leads to unnecessary follow-up procedures. Therefore, identifying surrogate biomarkers to distinguish transient infections from clinically relevant, persistent ones is essential for improving risk stratification. A comprehensive literature search across PubMed/MEDLINE, Embase, Scopus, and Web of Science databases up to December 2025 identified studies evaluating HR-HPV viral load in cervical lesion progression. AREAS COVERED: Oncogenic HPV viral load, the quantity of HPV genomes in a sample, is a promising biomarker. Levels correlated positively with HR-HPV persistence, increasing the risk of high-grade lesions and invasive cervical cancer. Furthermore, quantification provides prognostic information regarding disease severity, therapeutic response, and post-treatment recurrence. EXPERT OPINION: Recent standardization and validation of multiplex real-time PCR techniques supports integrating HPV viral load into clinical pratice. Incorporating viral load assessment into screening and management algorithms could significantly enhance diagnostic precision, enable personalized follow-up, and guide therapeutic decisions for women with HR-HPV-associated cervical disease. Refining these protocols will ultimately minimize over-treatment while ensuring rigorous monitoring for high-risk patients.
α-synuclein PET imaging: early human evidence and the path toward clinical proof-of-concept.
Filippi L, Urbano N
Expert Rev Mol Diagn · 2026 Jun · PMID 42132158 · Publisher ↗
INTRODUCTION: Aggregation of misfolded α-synuclein is the defining pathological hallmark of synucleinopathies, including Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy (MSA). Despite major ad...
INTRODUCTION: Aggregation of misfolded α-synuclein is the defining pathological hallmark of synucleinopathies, including Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy (MSA). Despite major advances in the field of molecular neuroimaging, the detection of α-synuclein remains one of the most challenging goals in positron emission tomography (PET), largely due to the low abundance of aggregates, structural heterogeneity of fibrillar strains, and the need for high selectivity over other amyloid proteins. AREAS COVERED: This Special Report summarizes advances in the development of small-molecule PET tracers targeting α-synuclein aggregates, with particular emphasis on the transition from preclinical radiotracer discovery to early clinical imaging studies. The article discusses key methodological challenges in tracer development, emerging chemical scaffolds, and the first translational efforts enabling initial human PET investigations. EXPERT OPINION: Although no tracer is yet clinically validated, emerging evidence is consistent but still preliminary, particularly in MSA, where several compounds show regionally specific signals. However, important challenges remain, including limited sensitivity in early or prodromal disease and the need to further establish tracer specificity and biological interpretability . Further multicenter studies will be essential to establish α-synuclein PET as a reliable biomarker for diagnosis, patient stratification, and therapeutic monitoring.
Role of liquid biopsy in genitourinary (GU) cancers.
Kayaalp M, Yekedüz E, Ürün Y
Expert Rev Mol Diagn · 2026 Jun · PMID 42130297 · Publisher ↗
INTRODUCTION: Liquid biopsy is a noninvasive diagnostic and monitoring method that provides molecular information about disease by analyzing tumor-derived biomaterials obtained from body fluids-primarily blood, as well a...
INTRODUCTION: Liquid biopsy is a noninvasive diagnostic and monitoring method that provides molecular information about disease by analyzing tumor-derived biomaterials obtained from body fluids-primarily blood, as well as plasma, urine, saliva, and others-including circulating tumor DNA (ctDNA), RNA, circulating tumor cells, and exosomes. Consequently, liquid biopsy has become one of the most intensely investigated and rapidly evolving fields in contemporary oncology. AREAS COVERED: This narrative review covers the molecular components and isolation techniques underlying liquid biopsy platforms, and examines their clinical applications across prostate cancer, bladder cancer, renal cell carcinoma, and testicular germ cell tumors, encompassing pre-biopsy risk stratification, treatment-response monitoring, detection of resistance mechanisms, and minimal residual disease surveillance. EXPERT OPINION: Clinical utility is now the main barrier to routine adoption of liquid biopsy in genitourinary cancers. Prospective studies must demonstrate that liquid biopsy-guided strategies, including biopsy avoidance, perioperative MRD driven escalation or de-escalation, and adaptation of therapy in the metastatic setting, improve clinically meaningful outcomes and are cost-effective. Standardized pre-analytical procedures, harmonized reporting thresholds, and clear management algorithms for discordant results will be essential for reliable real world implementation.
Predicting 28-day all-cause mortality in critically ill ischemic stroke patients using white blood cell-to-hemoglobin ratio and dual-feature selection machine learning models.
Yu H, Hu A, Huang X … +8 more , Tao L, Hang J, Chen X, Zhou L, Chen Y, Wang T, Li Y, Shao J
Expert Rev Mol Diagn · 2026 Jun · PMID 42112586 · Publisher ↗
BACKGROUND: The white blood cell-to-hemoglobin ratio (WHR) is a composite biomarker of inflammation and nutrition, but its prognostic role in critically ill ischemic stroke (IS) patients is unclear. METHODS: A cohort of...
BACKGROUND: The white blood cell-to-hemoglobin ratio (WHR) is a composite biomarker of inflammation and nutrition, but its prognostic role in critically ill ischemic stroke (IS) patients is unclear. METHODS: A cohort of 3,112 patients from MIMIC-IV was analyzed. WHR was calculated from first 24-hour ICU lab values. Its association with 28-day all-cause mortality(ACM) was assessed via survival analysis, Cox regression, restricted cubic splines (RCS), and subgroup analysis. Machine learning (ML) models were developed and evaluated using Receiver Operating Characteristic curve(AUC), calibration, and decision curve analysis. RESULTS: Mortality differed significantly across WHR quartiles (Log-rank < 0.0001). A higher WHR was independently associated with increased 28-day ACM (adjusted HR per SD = 1.42; 95% CI: 1.22-1.65, < 0.001), showing a near-linear dose-response. WHR (AUC = 0.644) outperformed its components (white blood cells, hemoglobin). The association was stronger in non-ventilated patients (interaction = 0.003). Among ML models, the Gradient Boosting Machine (GBM) performed best (test-set AUC = 0.814) and WHR was a key predictive feature. CONCLUSION: WHR is an independent predictor of short-term mortality in critically ill IS patients. Integrating WHR into ML models like GBM improves risk stratification, offering a valuable tool for clinical prognosis.
Evaluating emerging molecular diagnostics for severe infections in neutropenic patients with hematological malignancies.
Liborio MP, Peri AM, Harris PNA
Expert Rev Mol Diagn · 2026 Apr · PMID 42112573 · Publisher ↗
INTRODUCTION: Neutropenia significantly increases infection risk in hematologic malignancies. Clinical signs are often subtle and fever may be the only indicator. Molecular diagnostic methods promise faster, more sensiti...
INTRODUCTION: Neutropenia significantly increases infection risk in hematologic malignancies. Clinical signs are often subtle and fever may be the only indicator. Molecular diagnostic methods promise faster, more sensitive pathogen detection compared to conventional methods, aiming to improve timely and appropriate therapy. AREAS COVERED: This review summarizes emerging molecular diagnostics for severe infections in neutropenic hematological malignancies, focusing on microbiological performance and, where available, clinical impact. We conducted a search in PubMed and Embase using subject headings: 'molecular diagnosis,' 'neutropenic,' 'infections,' 'hematological malignancies,' supplemented by information from manufacturers of commercial assays. The technologies reviewed include multiplex polymerase chain reaction, microarray-based assays, metagenomic and targeted next-generation sequencing, host transcriptomics, and methods for diagnosing invasive fungal infections. For each, we describe key characteristics, diagnostic performance, and clinical utility when reported. EXPERT OPINION: Emerging molecular diagnostics shorten time to pathogen and resistance identification and broaden detection of organisms in febrile neutropenic patients with hematological malignancies. These methods are best integrated as complements to culture-based methods within centers with antimicrobial stewardship programs, where they inform earlier targeted therapy and rational de-escalation. Priority actions include prospective trials powered for measuring clinical outcomes and economic endpoints, with standardized workflows, reporting, and quality assurance to enable clinical implementation.
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