Seminars in Radiation Oncology, Год журнала: 2025, Номер 35(2), С. 285 - 300
Опубликована: Март 14, 2025
Язык: Английский
JAMA Otolaryngology–Head & Neck Surgery, Год журнала: 2023, Номер 149(11), С. 971 - 971
Опубликована: Июль 9, 2023
Importance There is growing interest in the use of circulating plasma tumor human papillomavirus (HPV) DNA for diagnosis and surveillance patients with HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). Recent advances assays, combining identification HPV fragment analysis (tumor tissue–modified viral [TTMV]-HPV DNA), have been shown to be highly accurate. However, these newer techniques has limited small cohort studies clinical trials. Objective To establish efficacy TTMV-HPV testing OPSCC a contemporary setting. Design, Setting, Participants This retrospective observational study included who underwent between April 2020 September 2022 during course routine care. For cohort, at least 1 measurement prior initiation primary therapy were included. Patients if they had test performed after completion definitive or salvage therapy. Main Outcomes Measures Per-test performance metrics, including sensitivity, specificity, positive predictive value, negative testing. Results Of 399 analysis, 163 diagnostic (median [IQR] age, 63 [56-68.5] years; 142 [87.1%] male), 290 [57-70] 237 [81.7%] male). 152 (93.3%) while 11 (6.7%) HPV-negative OPSCC. The sensitivity pretreatment was 91.5% (95% CI, 85.8%-95.4% [139 tests]), specificity 100% 71.5%-100% [11 tests]). In 591 tests conducted evaluated. A total 23 molecularly confirmed pathologic recurrences. demonstrated 88.4% 74.9%-96.1% [38 43 tests]) 99.3%-100% [548 548 detecting Positive value 90.7%-100% 38 99.1% 97.9%-99.7% 553 median (range) lead time from confirmation 47 (0-507) days. Conclusions Relevance that when evaluated setting, assay both surveillance. signifying nearly 10 among false negative. Additional research required validate assay’s and, validated, then further into implementation this standard practice guidelines will required.
Язык: Английский
Процитировано
42
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
Процитировано
39
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
Процитировано
27
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
Процитировано
24
Diagnostics, Год журнала: 2024, Номер 14(13), С. 1448 - 1448
Опубликована: Июль 7, 2024
Head and neck cancer (HNC) represents a significant global health challenge, with squamous cell carcinomas (SCCs) accounting for approximately 90% of all HNC cases. These malignancies, collectively referred to as head carcinoma (HNSCC), originate from the mucosal epithelium lining larynx, pharynx, oral cavity. The primary risk factors associated HNSCC in economically disadvantaged nations have been chronic alcohol consumption tobacco use. However, more affluent countries, landscape has shifted identification human papillomavirus (HPV) infection, particularly HPV-16, major factor, especially among nonsmokers. Understanding evolving distinct biological behaviors HPV-positive HPV-negative is critical developing targeted treatment strategies improving patient outcomes this complex diverse group cancers. Accurate diagnosis essential comprehensive model that integrates molecular characteristics, immune microenvironment, clinical outcomes. aim review was summarize current knowledge advances DNA, RNA, protein biomarkers bodily fluids tissues introduced new possibilities minimally or non-invasive diagnosis, monitoring, assessment therapeutic responses.
Язык: Английский
Процитировано
12
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
Процитировано
10
Clinical Cancer Research, Год журнала: 2024, Номер 30(15), С. 3329 - 3336
Опубликована: Июнь 2, 2024
Many patients with locoregionally advanced human papillomavirus-negative head and neck squamous cell carcinoma (HNSCC) relapse. ctDNA has the potential to identify minimal residual disease, but its clinical utility for virus-negative HNSCC is not well understood.
Язык: Английский
Процитировано
10
American Society of Clinical Oncology Educational Book, Год журнала: 2023, Номер 43
Опубликована: Янв. 1, 2023
Head and neck squamous cell carcinoma (HNSCC) encompasses a spectrum of heterogeneous diseases originating in the oral cavity, pharynx, larynx. Within United States, head cancer (HNC) accounts for 66,470 new cases, or 3% all malignancies, annually. 1 The incidence HNC is rising, largely driven by increases oropharyngeal cancer. 2 - 4 Recent molecular clinical advancements, particularly with regard to tumor biology, reflect heterogeneity subsites contained within neck. Despite this, existing guidelines post-treatment surveillance remain broad without much consideration given different anatomic etiologic factors (such as human papillomavirus [HPV] status tobacco exposure). 5 Surveillance incorporating physical examination, imaging, emerging biomarkers an essential part care patients treated allows detection locoregional recurrence, distant metastases, second primary malignancies aiming better functional survival outcomes. Additionally, it evaluation management complications.
Язык: Английский
Процитировано
20
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
Процитировано
17
Journal of Experimental & Clinical Cancer Research, Год журнала: 2024, Номер 43(1)
Опубликована: Авг. 3, 2024
Abstract Background Human papilloma virus (HPV) related cancers of the oropharynx are rapidly increasing in incidence and may soon represent majority all head neck cancers. Improved monitoring surveillance methods thus an urgent need public health. Main text The goal is to highlight current potential limitations liquid biopsy through a meta analytic study on ctHPVDNA TTMV-HPVDNA. It was performed Literature search articles published until December 2023 using three different databases: MEDLINE, Embase, Cochrane Library. Studies that evaluated post-treatment TTMV-HPVDNA patients with HPV + OPSCC, studies reporting complete data diagnostic accuracy recurrence, or which number true positives, false negatives, negatives extractable, detection viral DNA clearly defined. meta-analysis conducted following Meta-analysis Of Observational Epidemiology (MOOSE) guidelines. aim this evaluate sensitivity, specificity, TTMV by ddPCR define its efficacy clinical setting for follow up HPV-OPSCC. Conclusion 12 included provided total 1311 analysis (398 valuated 913 TTMV-HPVDNA). Pooled sensitivity specificity were 86% (95% CI: 78%-91%) 96% 91%-99%), respectively; negative positive likelihood ratios 0.072 0.057–0.093) 24.7 6.5–93.2), pooled DOR 371.66 179.1–918). area under curve (AUC) 0.81 CI, 0.67–0.91). Liquid identification cell free might identify earlier recurrence OPSCC patients. At present time, protocol needs be standardized cannot yet used setting. In future, multidimensional integrated approach links multiple clinical, radiological, laboratory will contribute obtain best follow-up strategies
Язык: Английский
Процитировано
7