Detection of Occult Recurrence Using Circulating Tumor Tissue Modified Viral HPV DNA among Patients Treated for HPV-Driven Oropharyngeal Carcinoma

Clinical Cancer Research, Год журнала: 2022, Номер 28(19), С. 4292 - 4301

Опубликована: Май 16, 2022

Despite generally favorable outcomes, 15% to 25% of patients with human papillomavirus (HPV)-driven oropharyngeal squamous cell carcinoma (OPSCC) will have recurrence. Current posttreatment surveillance practices rely on physical examinations and imaging are inconsistently applied. We assessed circulating tumor tissue modified viral (TTMV)-HPV DNA obtained during routine among a large population real-world patients.This retrospective clinical case series included 1,076 consecutive across 108 U.S. sites who were ≥ 3 months for HPV-driven OPSCC had one or more TTMV-HPV tests (NavDx, Naveris Laboratories) between February 6, 2020, June 29, 2021. Test results compared subsequent evaluations.Circulating was positive in 80 (7.4%) patients, follow-up available all. At first testing, 21 (26%) known recurrence while 59 (74%) not recurrent disease. Among these 55 (93%) subsequently confirmed recurrence, 2 clinically suspicious lesions, "no evidence disease" (NED) at last follow-up. To date, the overall predictive value testing disease is 95% (N = 76/80). In addition, point-in-time negative 1,198/1,256).These findings highlight potential practice. As tool, positivity indication majority cases, pre-dating identification by exams. These data may inform future guideline-endorsed strategies malignancy surveillance. See related commentary Colevas, p. 4171.

Язык: Английский

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Association of Pretreatment Circulating Tumor Tissue–Modified Viral HPV DNA With Clinicopathologic Factors in HPV-Positive Oropharyngeal Cancer

JAMA Otolaryngology–Head & Neck Surgery, Год журнала: 2022, Номер 148(12), С. 1120 - 1120

Опубликована: Окт. 27, 2022

Circulating tumor tissue-modified viral (TTMV) human papillomavirus (HPV) DNA is a dynamic, clinically relevant biomarker for HPV-positive oropharyngeal squamous cell carcinoma. Reasons its wide pretreatment interpatient variability are not well understood.To characterize clinicopathologic factors associated with TTMV HPV DNA.This cross-sectional study included patients evaluated carcinoma at Dana-Farber Cancer Institute in Boston, Massachusetts, between December 2019 and January 2022 who were undergoing curative-intent treatment.Clinicopathologic characteristics including demographic variables, nodal staging, genotype, imaging findings.Pretreatment circulating from 5 genotypes (16, 18, 31, 33, 35) assessed using commercially available digital droplet polymerase chain reaction-based assay, considered as either detectable/undetectable or continuous score (fragments/mL).Among 110 patients, 96 men (87%) 104 White (95%), mean (SD) age of 62.2 (9.4) years. was detected 98 (89%), median (IQR) 315 (47-2686) fragments/mL (range, 0-60 061 fragments/mL). Most detectable genotype 16 (n = 86 [88%]), while 12 (12%) harbored other genotypes. detection most strongly clinical N stage. Although few had stage N0 disease, only 4 these 11 (36%) compared 94 99 (95%) N1 to N3 disease (proportion difference, 59%; 95% CI, 30%-87%). Among undetectable DNA, more than half (7 [58%]) disease. The prevalence increased progressively higher stage, diameter largest lymph node, maximum standardized uptake value on positron emission tomography/computed tomography. In multivariable analysis, each score. 27 surgically treated without lymphovascular invasion (12 [100%] vs 9 15 [60%]).In this study, statistically significantly OPSCC diagnosis. levels predominantly suggesting assay sensitivity diagnostic purposes may be lower among cervical lymphadenopathy. Mechanisms underlying association, the use surveillance baseline values, warrant further investigation.

Язык: Английский

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

Diagnostics, Год журнала: 2023, Номер 13(4), С. 725 - 725

Опубликована: Фев. 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

Язык: Английский

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Negative Predictive Value of Circulating Tumor Tissue Modified Viral (TTMV)-HPV DNA for HPV-driven Oropharyngeal Cancer Surveillance

Clinical Cancer Research, Год журнала: 2023, Номер 29(20), С. 4306 - 4313

Опубликована: Авг. 11, 2023

Abstract Purpose: Human papillomavirus (HPV) is causally linked to oropharyngeal squamous cell carcinoma (OPSCC). Consensus guidelines recommend clinical exams and imaging in decreasing frequency as part of posttreatment surveillance for recurrence. Plasma tumor tissue modified viral (TTMV)-HPV DNA testing has emerged a biomarker which can inform disease status during surveillance. Experimental Design: This retrospective observational cohort study involved 543 patients who completed curative-intent therapy HPV-associated OPSCC between February 2020 January 2022 at eight U.S. cancer care institutions. We determined the negative predictive value (NPV) TTMV-HPV recurrence when matched physician-reported outcome data (median follow-up time: 27.9 months; range: 4.5–154). Results: The included mostly men with median age 61 had locoregionally advanced disease. HPV was by p16 positivity 87% patients, positive PCR/ISH among 55%; while pretreatment unknown most (79%) patients. Patients mean 2.6 tests almost half three or more results per-test per-patient sensitivity assay 92.5% [95% confidence interval (CI): 87.5–97.5] 87.3% (95% CI: 79.1–95.5), respectively. NPV 99.4% 98.9–99.8) 98.4% 97.3–99.5), Conclusions: yields few false missed recurrences. These could decisions on pursue reimaging following first restaging future practice. Additional how impacts needed.

Язык: Английский

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

Biomedicines, Год журнала: 2024, Номер 12(2), С. 415 - 415

Опубликована: Фев. 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.

Язык: Английский

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Circulating tumor DNA determines induction chemotherapy response in HPV associated oropharyngeal squamous cell carcinoma: A pilot study

Oral Oncology, Год журнала: 2025, Номер 161, С. 107179 - 107179

Опубликована: Янв. 18, 2025

Язык: Английский

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Circulating Tumor HPV DNA for Surveillance of HPV-Positive Oropharyngeal Squamous Cell Carcinoma

JAMA Oncology, Год журнала: 2023, Номер 9(12), С. 1716 - 1716

Опубликована: Окт. 12, 2023

Human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma has an overall favorable prognosis, yet a subset of patients will experience devastating disease recurrence. Current surveillance standards for detection recurrent are imperfect. There is growing interest in improving through the use plasma-based assays able to detect circulating tumor HPV DNA.Although most DNA remain research domain, tissue-modified viral assay became commercially available United States early 2020 and been increasingly used clinical setting. With rapidly increasing incidence HPV-positive concomitant expansion biomarker capabilities this disease, it critical reexamine current posttreatment practices determine whether emerging technologies may be improve outcomes survivor population. However, caution advised; not known biomarker-based truly beneficial, as true with any intervention, capacity cause harm.Using Margaret Pepe's classic 5 phases development cancer framework, article reviews state knowledge, highlights existing knowledge gaps, suggests that should prioritized understand association between patient outcomes. Specific attention paid assay, given its use. This review serve road map future guide clinicians considering adoption practice. Enrollment into trials incorporating prioritized.

Язык: Английский

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The Promise of Circulating Tumor DNA in Head and Neck Cancer

Cancers, Год журнала: 2022, Номер 14(12), С. 2968 - 2968

Опубликована: Июнь 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.

Язык: Английский

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Predictive impact of human papillomavirus circulating tumorDNAin treatment response monitoring ofHPV‐associated cancers; a meta‐analysis on recurrent event endpoints

Cancer Medicine, Год журнала: 2023, Номер 12(17), С. 17592 - 17602

Опубликована: Июль 26, 2023

Abstract Background HPV infection can cause cancer, and standard treatments often result in recurrence. The extent to which liquid biopsy using circulating tumor DNA (HPV ctDNA) be used as a promising marker for predicting recurrence HPV‐related cancers remains validated. Here we conducted systematic review meta‐analysis assess its effectiveness treatment response. Methods We literature search of online databases, including PubMed, Embase, Scopus, the Cochrane Library, up December 2022. goal was identify survival studies that evaluated potential plasma ctDNA at baseline end‐of‐treatment (EoT) related cancers. Hazard ratios were estimated directly from models or extracted Kaplan–Meier plots. Results pooled effect presence on disease HR = 7.97 (95% CI: [3.74, 17.01]). Subgroup analysis showed risk 2.17 [1.07, 4.41]) baseline‐positive cases 13.21 [6.62, 26.36]) EoT‐positive cases. Significant associations also observed between oropharyngeal squamous cell carcinoma (HR 12.25 [2.62, 57.36])) cervical cancer 4.60 [2.08, 10.17])) ctDNA‐positive patients. Conclusions study found detection predict rate relapse after treatment, with post‐treatment measurement being more effective than assessment. could surrogate incorporated other methods detecting residual disease.

Язык: Английский

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Commercial ctDNA Assays for Minimal Residual Disease Detection of Solid Tumors

Molecular Diagnosis & Therapy, Год журнала: 2021, Номер 25(6), С. 757 - 774

Опубликована: Ноя. 1, 2021

Язык: Английский

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