Performance of Liquid Biopsy for Diagnosis and Surveillance of Human Papillomavirus–Associated Oropharyngeal Cancer

JAMA Otolaryngology–Head & Neck Surgery, Journal Year: 2023, Volume and Issue: 149(11), P. 971 - 971

Published: July 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.

Language: 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, Journal Year: 2023, Volume and Issue: 29(20), P. 4306 - 4313

Published: Aug. 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.

Language: Английский

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

JAMA Oncology, Journal Year: 2023, Volume and Issue: 9(12), P. 1716 - 1716

Published: Oct. 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.

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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Biomarkers of pembrolizumab efficacy in advanced anal squamous cell carcinoma: analysis of a phase II clinical trial and a cohort of long-term responders

Journal for ImmunoTherapy of Cancer, Journal Year: 2024, Volume and Issue: 12(1), P. e008436 - e008436

Published: Jan. 1, 2024

Recent trials suggest that programmed cell death 1 (PD-1)-directed immunotherapy may be beneficial for some patients with anal squamous carcinoma and biomarkers predictive of response are greatly needed. This multicenter phase II clinical trial (NCT02919969) enrolled metastatic or locally advanced incurable (n=32). Patients received pembrolizumab 200 mg every 3 weeks. The primary endpoint the was objective rate (ORR). Exploratory objectives included analysis potential including assessment tumor-associated immune populations multichannel immunofluorescence circulating tumor tissue modified viral-human papillomavirus DNA (TTMV-HPV DNA) using serially collected blood samples. To characterize features long-term responders, we combined data from our prospective a retrospective cohort cancer treated anti-PD-1 (n=18). In study, ORR to monotherapy 9.4% median progression-free survival 2.2 months. Despite high level HPV positivity observed TTMV-HPV testing, majority had low levels CD8+PD-1+ T cells on pretreatment biopsy. who benefited decreasing scores complete responder's became undetectable. Long-term responses were in one patient (5.3 years) three (2.5, 6, 8 cohort. responders HPV-positive tumors, lacked liver metastases, achieved radiological response. Pembrolizumab has durable efficacy rare subset cancers. However, despite persistence infection, indicated by DNA, most cancers have numbers resistant pembrolizumab.

Language: Английский

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Utility of TTMV-HPV DNA in resolving indeterminate findings during oropharyngeal cancer surveillance

Oral Oncology, Journal Year: 2024, Volume and Issue: 155, P. 106874 - 106874

Published: June 14, 2024

Language: Английский

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Highly-Multiplex Detection of Plasma Cell-Free Human Papillomavirus-16 DNA in Oropharyngeal Carcinoma

Journal of Clinical Virology, Journal Year: 2025, Volume and Issue: 176, P. 105760 - 105760

Published: Jan. 2, 2025

Language: Английский

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Evaluating Tumor Tissue Modified Viral (TTMV)-HPV DNA for the Early Detection of Anal Squamous Cell Carcinoma Recurrence

Cancers, Journal Year: 2025, Volume and Issue: 17(2), P. 174 - 174

Published: Jan. 8, 2025

The incidence and mortality of anal squamous cell carcinoma (ASCC) are rising, with greater than 80% cases linked to human papillomavirus (HPV), primarily HPV16. Post-treatment surveillance can be challenging due the limitations anoscopy, digital rectal exam (DARE), imaging. Plasma tumor tissue modified viral (TTMV)-HPV DNA has shown strong sensitivity, specificity, predictive value in detecting recurrence HPV-driven oropharyngeal cancer. Here, we investigate ability TTMV-HPV for early detection ASCC. This retrospective clinical case series included 117 patients ASCC across 7 U.S. centers, monitored during routine care between March 2020 June 2024. Physician-reported data biomarker testing were combined create a comprehensive, longitudinal dataset evaluating test performance metrics. Patients had median age 63 years post-diagnosis follow-up 19 months. HPV status was confirmed by (52%) or p16 immunohistochemistry (39%). Of those tested pretreatment, 85% positive result. clearance within three months post-treatment associated significantly better recurrence-free survival. per-patient (PPV), negative (NPV) 82.8%, 98.4%, 96.0%, 92.5%. 24 documented test, first evidence 14 (58.3%), lead time 59 days (range: 10-536). accurately resolved 94.3% indeterminate findings. provides sensitive specific approach recurrent resolving

Language: Английский

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Evolution of testing for the diagnosis of human papillomavirus (HPV) status in head and neck squamous cell carcinoma: Where from and where to?

Oral Oncology, Journal Year: 2025, Volume and Issue: 162, P. 107208 - 107208

Published: Feb. 2, 2025

Language: Английский

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Pretreatment Liquid Biopsy and Clinicopathologic Features in HPV−Associated Oropharyngeal Squamous Cell Carcinoma

JAMA Otolaryngology–Head & Neck Surgery, Journal Year: 2025, Volume and Issue: unknown

Published: March 13, 2025

Importance Despite the favorable prognosis for HPV−positive oropharyngeal squamous cell carcinoma (HPV + OPSCC), efforts to de-escalate treatment intensity, while maintaining low recurrence and mortality rates, have proven challenging. Identifying appropriate prognostic factors remains elusive; however, association of pretreatment circulating tumor tissue viral−modified HPV (TTMV-HPV) DNA level with known characteristics disease burden—clinical staging, imaging, aggressive histopathologic features surgical specimen—may offer insights that could shift paradigms OPSCC. Objective To investigate TTMV-HPV levels clinical, radiologic, histopathologic, outcome metrics in patients Design, Setting, Participants This cohort study OPSCC positive test results fragment used data from a single tertiary center April 2020 September 2023. fragments were categorized into 3 cohorts: (≤99 fragments/mL), moderate (100-999/mL), high (≥1000/mL). Main Outcomes Measures Association clinical (cT) nodal (cN) staging level. Secondary outcomes included between emission tomography−computed tomography (PET-CT) as well specimen. The receiving adjuvant therapy was also analyzed. Recurrence-free survival disease-specific assessed. Results population 203 (mean [SD] age, 62 [10] years; 24 [12%] females 179 males [88%]), 58 (29%) whom low, 73 (36%) moderate, 72 (35%) fragment-level cohort. Compared cT0/1 stage, those cT2 stage cT3/4 had increased odds higher levels, adjusted ratios (aORs) 2.33 (95% CI, 1.24-4.46) 2.51 1.17-5.46), respectively. cN0 cN1 cN2/3 aORs 4.26 1.82-10.34) 3.64 1.46-9.36), In analysis PET-CT characteristics, total primary plus volume associated an aOR 1.04 1.02-1.07). Among 94 patients, no significant found lymphovascular invasion, perineural pathologic T number nodes, or extranodal extension on pathological No differences recurrence-free found. Conclusion Relevance more advanced aggregate cervical results. Future studies are needed explore how may influence decisions.

Language: Английский

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