Analytical Validation of NavDx, a cfDNA-Based Fragmentomic Profiling Assay for HPV-Driven Cancers

Diagnostics, Journal Year: 2023, Volume and Issue: 13(4), P. 725 - 725

Published: Feb. 14, 2023

The NavDx® blood test analyzes tumor tissue modified viral (TTMV)-HPV DNA to provide a reliable means of detecting and monitoring HPV-driven cancers. has been clinically validated in large number independent studies integrated into clinical practice by over 1000 healthcare providers at 400 medical sites the US. This Clinical Laboratory Improvement Amendments (CLIA), high complexity laboratory developed test, also accredited College American Pathologists (CAP) New York State Department Health. Here, we report detailed analytical validation NavDx assay, including sample stability, specificity as measured limits blank (LOBs), sensitivity illustrated via detection quantitation (LODs LOQs). LOBs were 0-0.32 copies/μL, LODs 0-1.10 LOQs <1.20-4.11 demonstrating data provided NavDx. In-depth evaluations accuracy intra- inter-assay precision shown be well within acceptable ranges. Regression analysis revealed degree correlation between expected effective concentrations, excellent linearity (R2 = 1) across broad range analyte concentrations. These results demonstrate that accurately reproducibly detects circulating TTMV-HPV DNA, which aid diagnosis surveillance

Language: Английский

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Current and Emerging Diagnostic, Prognostic, and Predictive Biomarkers in Head and Neck Cancer

Biomedicines, Journal Year: 2024, Volume and Issue: 12(2), P. 415 - 415

Published: Feb. 10, 2024

Head and neck cancers (HNC) are a biologically diverse set of that responsible for over 660,000 new diagnoses each year. Current therapies HNC require comprehensive, multimodal approach encompassing resection, radiation therapy, systemic therapy. With an increased understanding the mechanisms behind HNC, there has been growing interest in more accurate prognostic indicators disease, effective post-treatment surveillance, individualized treatments. This chapter will highlight commonly used studied biomarkers head squamous cell carcinoma.

Language: Английский

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HPV and head and neck cancers: Towards early diagnosis and prevention

Tumour Virus Research, Journal Year: 2022, Volume and Issue: 14, P. 200245 - 200245

Published: Aug. 14, 2022

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide with an increasing trend of its incidence. Alcohol consumption, smoking, viral infections, such as mucosal high-risk (HR) human papillomaviruses (HPVs) are major risk factors for HNSCC development. In particular, HR HPVs mainly associated a subset oropharyngeal (OPSCC), while other head sites marginally affected by HPV infection. HPV16 frequently type HNSCC. contrast to cervix, no screening programs or identifiable pre-malignant lesions have been characterized HPV-related Therefore, identification general diagnostic algorithms biomarkers that could facilitate early diagnosis, disease evolution recurrence HPV-driven HNSCCs urgently needed. We herein review role in focus on epidemiology, biology, applied available body fluids tools HNSCCs.

Language: Английский

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Absolute Risk of Oropharyngeal Cancer After an HPV16-E6 Serology Test and Potential Implications for Screening: Results From the Human Papillomavirus Cancer Cohort Consortium

Journal of Clinical Oncology, Journal Year: 2022, Volume and Issue: 40(31), P. 3613 - 3622

Published: June 14, 2022

PURPOSE Seropositivity for the HPV16-E6 oncoprotein is a promising marker early detection of oropharyngeal cancer (OPC), but absolute risk OPC after positive or negative test unknown. METHODS We constructed an prediction model that integrates (1) relative odds serostatus and cigarette smoking from human papillomavirus (HPV) Cancer Cohort Consortium (HPVC3), (2) US population factor data National Health Interview Survey, (3) sex-specific rates mortality. RESULTS The nine HPVC3 cohorts included 365 participants with up to 10 years between blood draw diagnosis 5,794 controls. estimated 10-year seropositive males at age 50 was 17.4% (95% CI, 12.4 28.6) 60 27.1% 19.2 45.4). Corresponding 5-year estimates were 7.3% 14.4%, respectively. For females, 3.6% 2.5 5.9) 5.5% 3.8 9.2) 1.5% 2.7%, Over 30 years, result 49.9% 13.3% females would develop OPC. By contrast, risks among seronegative people very low, ranging 0.01% 0.25% depending on age, sex, status. CONCLUSION estimate substantial proportion individuals will OPC, 17%-27% 4%-6% 50-60 in United States. This high level may warrant periodic, minimally invasive surveillance serology test, particularly high-incidence regions. However, appropriate clinical protocol remains be established.

Language: Английский

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Circulating tumour DNA alterations: emerging biomarker in head and neck squamous cell carcinoma

Journal of Biomedical Science, Journal Year: 2023, Volume and Issue: 30(1)

Published: Aug. 9, 2023

Head and Neck cancers (HNC) are a heterogeneous group of upper aero-digestive tract cancer account for 931,922 new cases 467,125 deaths worldwide. About 90% these squamous cell origin (HNSCC). HNSCC is associated with excessive tobacco alcohol consumption infection oncogenic viruses. Genotyping tumour tissue to guide clinical decision-making becoming common practice in modern oncology, but the management patients HNSCC, cytopathology or histopathology remains mainstream diagnosis treatment planning. Due heterogeneity lack access due its anatomical location, alternative methods evaluate activities urgently needed. Liquid biopsy approaches can overcome issues such as heterogeneity, which analysis small biopsy. In addition, liquid offers repeat sampling, even tumours limitations. refers biomarkers found body fluids, traditionally blood, that be sampled provide clinically valuable information on both patient their underlying malignancy. To date, majority research has focused blood-based biomarkers, circulating DNA (ctDNA), cells (CTCs), microRNA. this review, we will focus ctDNA biomarker because robustness, presence many adaptability existing laboratory-based technology platforms, ease collection transportation. We discuss mechanisms release into circulation, technological advances ctDNA, management, some challenges translating future perspectives. provides minimally invasive method prognosis disease surveillance pave way personalized medicine, thereby significantly improving outcomes reducing healthcare costs.

Language: Английский

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The Promise of Circulating Tumor DNA in Head and Neck Cancer

Cancers, Journal Year: 2022, Volume and Issue: 14(12), P. 2968 - 2968

Published: June 16, 2022

As the seventh most common cancer globally, head and neck cancers (HNC) exert considerable disease burden, with an estimated 277,597 deaths worldwide in 2020 alone. Traditional risk factors for HNC include tobacco, alcohol, betel nut; more recently, human papillomavirus has emerged as a distinct driver of disease. Currently, limitations screening surveillance methods often lead to identifying advanced stages, associated poor outcomes. Liquid biopsies, particular circulating tumor DNA (ctDNA), offer potential enhancing screening, early diagnosis, patients, improvements patient In this review, we examine current methodologies detecting ctDNA highlight research illustrating viral non-viral biomarker utilities treatment response, prognosis. We also summarize challenges future directions testing patients.

Language: Английский

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Unraveling Emerging Anal Cancer Clinical Biomarkers from Current Immuno-Oncogenomics Advances

Molecular Diagnosis & Therapy, Journal Year: 2024, Volume and Issue: 28(2), P. 201 - 214

Published: Jan. 24, 2024

Anal squamous cell carcinoma (ASCC) is a rare gastrointestinal malignancy associated with high-risk human papillomavirus (HPV) and currently one of the fastest-growing causes cancer incidence mortality in developed countries. Although next-generation sequencing technologies (NGS) have revolutionized immuno-genomic research various tumor types, limited amount clinical has been to investigate expression functional characterization genomic data ASCC. Herein, we comprehensively assess recent advancements "omics" research, including systematic analysis genome-based studies, aiming identify most relevant ASCC driver gene expressions their signaling pathways. We also highlight significant biomarkers anal progression, potential diagnostic biomarkers, therapeutic drug targets, emerging treatment opportunities. This review stresses urgent need for developing target-specific therapies By illuminating molecular characteristics drug-target ASCC, this study aims provide insights development precision medicine cancer.

Language: Английский

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Preoperative Circulating Tumor HPV DNA and Oropharyngeal Squamous Cell Disease

JAMA Otolaryngology–Head & Neck Surgery, Journal Year: 2024, Volume and Issue: 150(5), P. 444 - 444

Published: April 4, 2024

Importance The utility of preoperative circulating tumor tissue-modified viral human papillomavirus DNA (TTMV-HPV DNA) levels in predicting (HPV)–associated oropharyngeal squamous cell carcinoma (HPV+ OPSCC) disease burden is unknown. Objective To determine if HPV (ctHPVDNA) associated with patients HPV+ OPSCC who have undergone transoral robotic surgery (TORS). Design, Setting, and Participants This cross-sectional study comprised underwent primary TORS between September 2021 April 2023 at one tertiary academic institution. Patients treatment-naive (p16-positive) ctHPVDNA were included, those neck mass excision before collection excluded. Main Outcomes Measures main outcome was the association increasing size lymph node involvement surgical pathology. secondary adverse pathology, which included lymphovascular invasion, perineural or extranodal extension. Results A total 70 (65 men [93%]; mean [SD] age, 61 [8] years). Baseline ranged from 0 fragments/milliliter plasma (frag/mL) to 49 452 frag/mL (median [IQR], 272 [30-811] frag/mL). Overall, 58 (83%) had positive results for ctHPVDNA, 1 (1.4%) indeterminate results, 11 (15.6%) negative results. sensitivity detectable identifying pathology-confirmed 84%. Twenty-seven (39%) pathologic (pT) staging pT0 pT1, 34 (49%) pT2 staging, 9 (13%) pT3 pT4 staging. No clinically meaningful difference undetectable cohorts found Although median appeared be higher through stages pN1 pN2 stages, effect sizes small (pT stage: η2, 0.002 [95% CI, −1.188 0.827]; pN 0.043 −0.188 2.600]). Median log(TTMV-HPV active smokers (8.79 3.55-5.76]), compared never (5.92 −0.97 1.81]) former (4.99 0.92-6.23]). Regression analysis did not show an dimension metastatic deposit DNA). After univariate analysis, no Conclusions Relevance In this study, TORS.

Language: Английский

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Circulating HPV DNA in HPV-associated cancers

Clinica Chimica Acta, Journal Year: 2023, Volume and Issue: 542, P. 117269 - 117269

Published: Feb. 24, 2023

Language: Английский

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ctDNA as an Adjunct to Posttreatment PET for Head and Neck Cancer Recurrence Risk Assessment

Otolaryngology, Journal Year: 2024, Volume and Issue: 171(2), P. 439 - 444

Published: April 9, 2024

Abstract Objective Circulating tumor DNA (ctDNA) detection is an emerging technique that identifies minimal residual disease in patients with solid tumors. ctDNA can act as adjunct method to help overcome the limitations of positron emission tomography (PET) and select who are at high risk for recurrence. Study Design Retrospective Single Institutional Study. Setting University Hospital Setting. Methods Twenty‐nine underwent definitive treatment squamous cell carcinoma head neck (HNSCC) from 8/2021 01/2023 had levels analyzed 1 3, 6, 9, 12 months after treatment. A personalized, tumor‐informed, multiplex polymerase chain reaction (PCR) next‐generation sequencing (NGS) assay was used detect levels. The primary outcome recurrence‐free probability (RFP), secondary outcomes were overall survival (OS), sensitivity, specificity, test's negative (NPV) positive predictive values (PPV). Results median age 65 years (interquartile range: 56‐69), majority being males (n = 22, 76%). sites larynx 12), oropharynx 10), oral cavity 6). Posttreatment detected 7 patients, all whom associated a higher recurrence (hazard ratio: 9.94, 95% confidence interval: 1.56‐63.3, P .015). identified 100% specificity 78% sensitivity. NPV PPV 91% 100%. PET sensitivity but only 68% 86% NPV, 54% PPV. Conclusion Based on our data, be excellent test posttreatment guide physicians cases where results inconclusive difficult interpret.

Language: Английский

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