Journal of Molecular Diagnostics最新文献

{"title":"In Vitro Functional Analysis Can Aid Precision Diagnostics of HNF1B-MODY","authors":"Aishwarya Pavithram ,&nbsp;Haichen Zhang ,&nbsp;Kristin A. Maloney ,&nbsp;Monika Ringdal ,&nbsp;Alba Kaci ,&nbsp;Jørn V. Sagen ,&nbsp;Jeffrey Kleinberger ,&nbsp;Linda J.B. Jeng ,&nbsp;Pål R. Njølstad ,&nbsp;Toni I. Pollin ,&nbsp;Janne Molnes ,&nbsp;Bente B. Johansson","doi":"10.1016/j.jmoldx.2024.03.006","DOIUrl":"10.1016/j.jmoldx.2024.03.006","url":null,"abstract":"<div><p>Precision medicine relies on accurate and consistent classification of sequence variants. A correct diagnosis of hepatocyte nuclear factor (HNF) 1B maturity-onset diabetes of the young, caused by pathogenic variants in the <em>HNF1B</em> gene, is important for optimal disease management and prognosis, and it has implications for genetic counseling and follow-up of at-risk family members. We hypothesized that the functional characterization could provide valuable information to assist the interpretation of pathogenicity of <em>HNF1B</em> variants. Using different <em>in vitro</em> functional assays, variants identified among 313 individuals, suspected to have monogenic diabetes with or without kidney disease, were characterized. The data from the functional assays were subsequently conjugated with obtained clinical, biochemical, and <em>in silico</em> data. Two variants (p.A167P, p.H336Pfs∗22) showed severe loss of function due to impaired transactivation, reduced DNA binding (p.A167P), and mRNA instability (p.A167P). Although both these variant carriers were diagnosed with diabetes, the p.H336Pfs∗22 carrier also had congenital absence of a kidney, which is a characteristic trait for HNF1B maturity-onset diabetes of the young. Functional analysis of the p.A167P variant revealed damaging effects on HNF-1B protein function, which may warrant imaging of the kidneys and/or pancreas. In addition, the current study has generated important data, including evidence supporting the benign functional impact of five variants (p.D82N, p.T88A, p.N394D, p.V458G, and p.T544A), and piloting new approaches that will prove critical for the growth of HNF1B-diabetes diagnosis.</p></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"26 6","pages":"Pages 530-541"},"PeriodicalIF":4.1,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1525157824000758/pdfft?md5=5e2fc7bd58ea3d469c63b2288fc470f1&pid=1-s2.0-S1525157824000758-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140570380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Application of Knowledge Engineering via the Use of a Biomimetic Digital Twin Ecosystem, Phenotype-Driven Variant Analysis, and Exome Sequencing to Understand the Molecular Mechanisms of Disease","authors":"William G. Kearns ,&nbsp;Georgios Stamoulis ,&nbsp;Joseph Glick ,&nbsp;Lawrence Baisch ,&nbsp;Andrew Benner ,&nbsp;Dalton Brough ,&nbsp;Luke Du ,&nbsp;Bradford Wilson ,&nbsp;Laura Kearns ,&nbsp;Nicholas Ng ,&nbsp;Maya Seshan ,&nbsp;Raymond Anchan","doi":"10.1016/j.jmoldx.2024.03.004","DOIUrl":"10.1016/j.jmoldx.2024.03.004","url":null,"abstract":"<div><p>Applied artificial intelligence, particularly large language models, in biomedical research is accelerating, but effective discovery and validation requires a toolset without limitations or bias. On January 30, 2023, the National Academies of Sciences, Engineering, and Medicine (NAS) appointed an ad hoc committee to identify the needs and opportunities to advance the mathematical, statistical, and computational foundations of digital twins in applications across science, medicine, engineering, and society. On December 15, 2023, the NAS released a 164-page report, “Foundational Research Gaps and Future Directions for Digital Twins.” This report described the importance of using digital twins in biomedical research. The current study was designed to develop an innovative method that incorporated phenotype-ranking algorithms with knowledge engineering via a biomimetic digital twin ecosystem. This ecosystem applied real-world reasoning principles to nonnormalized, raw data to identify hidden or \"dark\" data. Clinical exome sequencing study on patients with endometriosis indicated four variants of unknown clinical significance potentially associated with endometriosis-related disorders in nearly all patients analyzed. One variant of unknown clinical significance was identified in all patient samples and could be a biomarker for diagnostics. To the best of our knowledge, this is the first study to incorporate the recommendations of the NAS to biomedical research. This method can be used to understand the mechanisms of any disease, for virtual clinical trials, and to identify effective new therapies.</p></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"26 7","pages":"Pages 543-551"},"PeriodicalIF":4.1,"publicationDate":"2024-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S152515782400062X/pdfft?md5=2eced04f2604074e0e758338fecfe11e&pid=1-s2.0-S152515782400062X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140332277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leveraging Off-Target Reads in Panel Sequencing for Homologous Recombination Repair Deficiency Screening in Tumor","authors":"Markus Ball ,&nbsp;Iordanis Ourailidis ,&nbsp;Klaus Kluck ,&nbsp;Michael Menzel ,&nbsp;Martina Kirchner ,&nbsp;Michael Allgäuer ,&nbsp;Timothy Kwang Yong Tay ,&nbsp;Fabian Schnecko ,&nbsp;Anna-Lena Volckmar ,&nbsp;Hannah Goldschmid ,&nbsp;Olaf Neuman ,&nbsp;Stefan Fröhling ,&nbsp;Peter Schirmacher ,&nbsp;Jan Budczies ,&nbsp;Albrecht Stenzinger ,&nbsp;Daniel Kazdal","doi":"10.1016/j.jmoldx.2024.02.008","DOIUrl":"10.1016/j.jmoldx.2024.02.008","url":null,"abstract":"<div><p>Targeted tumor only sequencing has become a standard practice in cancer diagnostics. This study aims to develop an approach for robust copy number variant calling in tumor samples using only off-target region (OTR) reads. We also established a clinical use case for homologous recombination deficiency (HRD) score estimation (HRDest) using the sum of telomeric-allelic imbalance and large-scale state transition scores without the need for loss of heterozygosity information. A strong correlation was found between HRD score and the sum of telomeric-allelic imbalance + large-scale state transition in The Cancer Genome Atlas cohort (ρ = 0.99, <em>P</em> &lt; 2.2 × 10⁻¹⁶) and in a clinical in-house cohort of 34 tumors (ρ = 0.9, <em>P</em> = 5.1 × 10⁻¹³) comparing whole-exome sequencing and targeted sequencing data. HRDest scores from 1086 clinical cases were compared with The Cancer Genome Atlas data set. There were no significant differences in HRD score distribution within the analyzed tumor types. As a control, commercially available HRD standards were also sequenced, and the HRDest scores obtained from the OTR reads were well within the HRD reference range provided by the manufacturer. In conclusion, OTR reads of tumor-only panel sequencing can be used to determine genome-wide copy number variant profiles and to approximate HRD scores.</p></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"26 6","pages":"Pages 479-486"},"PeriodicalIF":4.1,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1525157824000606/pdfft?md5=7a06fe716ddff0a70ffe3ef747d45c52&pid=1-s2.0-S1525157824000606-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140208100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Implementation of a Noninvasive, Multi-Analyte Droplet Digital PCR Test to Screen for Androgen Receptor Alterations","authors":"Regina Stitz ,&nbsp;Franz Stoiber ,&nbsp;Renè Silye ,&nbsp;Georgios Vlachos ,&nbsp;Silvia Andaloro ,&nbsp;Elisabeth Rebhan ,&nbsp;Michael Dunzinger ,&nbsp;Franz Pühringer ,&nbsp;Caroline Gallo ,&nbsp;Amin El-Heliebi ,&nbsp;Ellen Heitzer ,&nbsp;Cornelia Hauser-Kronberger","doi":"10.1016/j.jmoldx.2024.02.009","DOIUrl":"10.1016/j.jmoldx.2024.02.009","url":null,"abstract":"<div><p>Alterations of the androgen receptor (<em>AR</em>) are associated with resistance to AR-directed therapy in prostate cancer. Thus, it is crucial to develop robust detection methods for <em>AR</em> alterations as predictive biomarkers to enable applicability in clinical practice. We designed and validated five multiplex droplet digital PCR assays for reliable detection of 12 <em>AR</em> targets including <em>AR</em> amplification, AR splice variant 7, and 10 <em>AR</em> hotspot mutations, as well as <em>AR</em> and <em>KLK3</em> gene expression from plasma-derived cell-free DNA and cell-free RNA. The assays demonstrated excellent analytical sensitivity and specificity ranging from 95% to 100% (95% CI, 75% to 100%). Intrarun and interrun variation analyses revealed a high level of repeatability and reproducibility. The developed assays were applied further in peripheral blood samples from 77 patients with advanced prostate cancer to assess their feasibility in a real-world scenario. Optimizing the reverse transcription of RNA increased the yield of plasma-derived cell-free RNA by 30-fold. Among 23 patients with castration-resistant prostate cancer, 6 patients (26.1%) had one or a combination of several <em>AR</em> alterations, whereas only 2 of 54 patients (3.7%) in the hormone-sensitive stage showed <em>AR</em> alterations. These findings were consistent with other studies and suggest that implementation of comprehensive <em>AR</em> status detection in clinical practice is feasible and can support the treatment decision-making process.</p></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"26 6","pages":"Pages 467-478"},"PeriodicalIF":4.1,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1525157824000618/pdfft?md5=2382d1c57a13af37b800f9072c1c5f14&pid=1-s2.0-S1525157824000618-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140208098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine Learning Analysis Using RNA Sequencing to Distinguish Neuromyelitis Optica from Multiple Sclerosis and Identify Therapeutic Candidates","authors":"Lukasz S. Wylezinski ,&nbsp;Cheryl L. Sesler ,&nbsp;Guzel I. Shaginurova ,&nbsp;Elena V. Grigorenko ,&nbsp;Jay G. Wohlgemuth ,&nbsp;Franklin R. Cockerill III ,&nbsp;Michael K. Racke ,&nbsp;Charles F. Spurlock III","doi":"10.1016/j.jmoldx.2024.03.003","DOIUrl":"10.1016/j.jmoldx.2024.03.003","url":null,"abstract":"<div><p>This study aims to identify RNA biomarkers distinguishing neuromyelitis optica (NMO) from relapsing-remitting multiple sclerosis (RRMS) and explore potential therapeutic applications leveraging machine learning (ML). An ensemble approach was developed using differential gene expression analysis and competitive ML methods, interrogating total RNA-sequencing data sets from peripheral whole blood of treatment-naïve patients with RRMS and NMO and healthy individuals. Pathway analysis of candidate biomarkers informed the biological context of disease, transcription factor activity, and small-molecule therapeutic potential. ML models differentiated between patients with NMO and RRMS, with the performance of certain models exceeding 90% accuracy. RNA biomarkers driving model performance were associated with ribosomal dysfunction and viral infection. Regulatory networks of kinases and transcription factors identified biological associations and identified potential therapeutic targets. Small-molecule candidates capable of reversing perturbed gene expression were uncovered. Mitoxantrone and vorinostat—two identified small molecules with previously reported use in patients with NMO and experimental autoimmune encephalomyelitis—reinforced discovered expression signatures and highlighted the potential to identify new therapeutic candidates. Putative RNA biomarkers were identified that accurately distinguish NMO from RRMS and healthy individuals. The application of multivariate approaches in analysis of RNA-sequencing data further enhances the discovery of unique RNA biomarkers, accelerating the development of new methods for disease detection, monitoring, and therapeutics. Integrating biological understanding further enhances detection of disease-specific signatures and possible therapeutic targets.</p></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"26 6","pages":"Pages 520-529"},"PeriodicalIF":4.1,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140208101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FMR1 Protein Expression Correlates with Intelligence Quotient in Both Peripheral Blood Mononuclear Cells and Fibroblasts from Individuals with an FMR1 Mutation","authors":"Poonnada Jiraanont ,&nbsp;Marwa Zafarullah ,&nbsp;Noor Sulaiman ,&nbsp;Glenda M. Espinal ,&nbsp;Jamie L. Randol ,&nbsp;Blythe Durbin-Johnson ,&nbsp;Andrea Schneider ,&nbsp;Randi J. Hagerman ,&nbsp;Paul J. Hagerman ,&nbsp;Flora Tassone","doi":"10.1016/j.jmoldx.2024.02.007","DOIUrl":"10.1016/j.jmoldx.2024.02.007","url":null,"abstract":"<div><p>Fragile X syndrome (FXS) is the most common heritable form of intellectual disability and is caused by CGG repeat expansions exceeding 200 (full mutation). Such expansions lead to hypermethylation and transcriptional silencing of the fragile X messenger ribonucleoprotein 1 (<em>FMR1</em>) gene. As a consequence, little or no <em>FMR1</em> protein (FMRP) is produced; absence of the protein, which normally is responsible for neuronal development and maintenance, causes the syndrome. Previous studies have demonstrated the causal relationship between FMRP levels and cognitive abilities in peripheral blood mononuclear cells (PBMCs) and dermal fibroblast cell lines of patients with FXS. However, it is arguable whether PBMCs or fibroblasts would be the preferred surrogate for measuring molecular markers, particularly FMRP, to represent the cognitive impairment, a core symptom of FXS. To address this concern, CGG repeats, methylation status, <em>FMR1</em> mRNA, and FMRP levels were measured in both PBMCs and fibroblasts derived from 66 individuals. The findings indicated a strong association between <em>FMR1</em> mRNA expression levels and CGG repeat numbers in PBMCs of premutation males after correcting for methylation status. Moreover, FMRP expression levels from both PBMCs and fibroblasts of male participants with a hypermethylated full mutation and with mosaicism demonstrated significant association between the intelligence quotient levels and FMRP levels, suggesting that PBMCs may be preferable for FXS clinical studies, because of their greater accessibility.</p></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"26 6","pages":"Pages 498-509"},"PeriodicalIF":4.1,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140208099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Panel Comparative Analysis Tool","authors":"André Oszwald ,&nbsp;Lucia Zisser ,&nbsp;Eva Compérat ,&nbsp;Leonhard Müllauer","doi":"10.1016/j.jmoldx.2024.01.015","DOIUrl":"10.1016/j.jmoldx.2024.01.015","url":null,"abstract":"<div><p>Multigene next-generation sequencing (NGS) panels have become a routine diagnostic method in the contemporary practice of personalized medicine. To avoid inadequate test choice or interpretation, a detailed understanding of the precise panel target regions is required. However, the necessary bioinformatic expertise is not always available, and publicly accessible and easily interpretable analyses of target regions are scarce. To address this critical knowledge gap, we present the Panel Comparative Analysis Tool (PanelCAT), an open-source application to analyze, visualize, and compare NGS panel DNA target regions. PanelCAT uses Reference Sequence, ClinVar, and Catalogue of Somatic Mutations in Cancer mutation census databases to quantify the exon and mutation coverage of target regions and provides interactive graphical representations and search functions to inspect the results. We demonstrate the utility of PanelCAT by analyzing two large NGS panels (TruSight Oncology 500 and Human Pan Cancer Panel) to validate the advertised target genes, quantify targeted exons and mutations, and identify differences between panels. PanelCAT will enable institutions and researchers to catalog and visualize NGS panel target regions independent of the manufacturer, promote transparency of panel limitations, and share this information with employees and requisitioners.</p></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"26 5","pages":"Pages 423-429"},"PeriodicalIF":4.1,"publicationDate":"2024-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1525157824000564/pdfft?md5=3cbb26f6bddb209a195561c3ddb67d17&pid=1-s2.0-S1525157824000564-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140177474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deconvoluting the Complexity of Congenital Sideroblastic Anemias through Genetic and Functional Profiling","authors":"FNU Alnoor ,&nbsp;Robert S. Ohgami","doi":"10.1016/j.jmoldx.2024.03.002","DOIUrl":"10.1016/j.jmoldx.2024.03.002","url":null,"abstract":"","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"26 5","pages":"Pages 321-322"},"PeriodicalIF":4.1,"publicationDate":"2024-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1525157824000576/pdfft?md5=5035c823b78157604d948c036367e8ea&pid=1-s2.0-S1525157824000576-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140141051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA Reference Reagents for Genotyping RH Variants","authors":"Emilia Sippert ,&nbsp;Evgeniya Volkova ,&nbsp;Meagan Rippee-Brooks ,&nbsp;Gregory A. Denomme ,&nbsp;Willy A. Flegel ,&nbsp;Christine Lee ,&nbsp;Richardae Araojo ,&nbsp;Orieji Illoh ,&nbsp;Zhugong Liu ,&nbsp;Maria Rios","doi":"10.1016/j.jmoldx.2024.02.005","DOIUrl":"10.1016/j.jmoldx.2024.02.005","url":null,"abstract":"<div><p>Patients who carry Rhesus (RH) blood group variants may develop Rh alloantibodies requiring matched red blood cell transfusions. Serologic reagents for Rh variants often fail to specifically identify variant Rh antigens and are in limited supply. Therefore, red blood cell genotyping assays are essential for managing transfusions in patients with clinically relevant Rh variants. Well-characterized DNA reference reagents are needed to ensure quality and accuracy of the molecular tests. Eight lyophilized DNA reference reagents, representing 21 polymorphisms in <em>RHD</em> and <em>RHCE,</em> were produced from an existing repository of immortalized B-lymphoblastoid cell lines at the Center for Biologics Evaluation and Research/US Food and Drug Administration. The material was validated through an international collaborative study involving 17 laboratories that evaluated each DNA candidate using molecular assays to characterize <em>RHD</em> and <em>RHCE</em> alleles, including commercial platforms and laboratory-developed testing, such as Sanger sequencing, next-generation sequencing, and third-generation sequencing. The genotyping results showed 99.4% agreement with the expected results for the target <em>RH</em> polymorphisms and 87.9% for <em>RH</em> allele agreement. Most of the discordant <em>RH</em> alleles results were explained by a limited polymorphism coverage in some genotyping methods. Results of stability and accelerated degradation studies support the suitability of these reagents for use as reference standards. The collaborative study results demonstrate the qualification of these eight DNA reagents for use as reference standards for <em>RH</em> blood group genotyping assay development and analytical validation.</p></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"26 6","pages":"Pages 456-466"},"PeriodicalIF":4.1,"publicationDate":"2024-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140144491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of Pre-Analytical Variables for Human Papillomavirus Primary Screening from Self-Collected Vaginal Swabs","authors":"Michelle Qi ,&nbsp;Anissa R. Naranjo ,&nbsp;Abigail J. Duque ,&nbsp;Thomas S. Lorey ,&nbsp;Jeffrey M. Schapiro ,&nbsp;Betty J. Suh-Burgmann ,&nbsp;Michael Rummel ,&nbsp;Stephen J. Salipante ,&nbsp;Nicolas Wentzensen ,&nbsp;Dina N. Greene","doi":"10.1016/j.jmoldx.2024.02.006","DOIUrl":"10.1016/j.jmoldx.2024.02.006","url":null,"abstract":"<div><p>Human papillomavirus (HPV) primary screening is an effective approach to assessing cervical cancer risk. Self-collected vaginal swabs can expand testing access, but the data defining analytical performance criteria necessary for adoption of self-collected specimens are limited, especially for those occurring outside the clinic, where the swab remains dry during transport. Here, we evaluated the performance of self-collected vaginal swabs for HPV detection using the Cobas 6800. There was insignificant variability between swabs self-collected by the same individual (<em>n</em> = 15 participants collecting 5 swabs per participant), measured by amplification of HPV and human β-globin control DNA. Comparison of self-collected vaginal swab and provider-collected cervical samples (<em>n</em> = 144 pairs) proved highly concordant for HPV detection (total agreement = 90.3%; positive percentage agreement = 84.2%). There was no relationship between the number of dry storage days and amplification of HPV (<em>n</em> = 68; range, 4 to 41 days). Exposure of self-collected dry swabs to extreme summer and winter temperatures did not affect testing outcomes. A second internal control (RNase P) demonstrated that lack of amplification for β-globin from self-collected specimens was consistent with poor, but not absent, cellularity. These data suggest that self-collected vaginal samples enable accurate clinical HPV testing, and that extended ambient dry storage or exposure to extreme temperatures does not influence HPV detection. Furthermore, lack of β-globin amplification in HPV-negative samples accurately identified participants who required recollection.</p></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"26 6","pages":"Pages 487-497"},"PeriodicalIF":4.1,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1525157824000552/pdfft?md5=2bd70eec725bee4de6ccd1056a8bc7f2&pid=1-s2.0-S1525157824000552-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140144492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}