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循环肿瘤组织修饰的病毒人乳头瘤病毒DNA及其与口咽癌疾病负担的相关性

Circulating Tumor Tissue-Modified-Viral HPV DNA and Correlations With Disease Burden in Oropharyngeal Cancer.

作者信息

Lee Jaclyn, McAdoo Ashtyn, Fassler Carly, Sun Tianyi, Liu Dandan, Lockney Natalie, Whitaker Ryan, Topf Michael C, Mannion Kyle

机构信息

Department of Otolaryngology-Head and Neck Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

Brody School of Medicine, East Carolina University, Greenville, South Carolina, USA.

出版信息

Otolaryngol Head Neck Surg. 2025 Oct;173(4):911-918. doi: 10.1002/ohn.1345. Epub 2025 Jul 7.

DOI:10.1002/ohn.1345
PMID:40624873
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12461791/
Abstract

INTRODUCTION

Tumor-tissue modified viral (TTMV)-human papillomavirus (HPV) DNA is an increasingly utilized biomarker for patients with HPV-mediated oropharyngeal squamous cell carcinoma (OPSCC). However, much remains to be studied regarding the quantitative importance of a positive pre-treatment result and correlations with disease burden.

STUDY DESIGN

Retrospective cohort study.

SETTING

Single tertiary care center; January 2022 to July 2024.

METHODS

Patients with HPV-associated OPSCC and baseline pre-treatment TTMV-HPV DNA levels were evaluated for primary tumor and lymph node disease extent on clinical imaging, exam, and surgical pathology results when applicable. Associations with log(pre-treatment TTMV-HPV DNA levels) were evaluated via multivariable linear regression. A commercially available TTMV-HPV DNA test was used.

RESULTS

In total, 94 patients were included, who were 93% male, with median age of 63 years (interquartile range [IQR] 55-70). Most patients were clinical tumor class cT1 (40%) or cT2 (38%) and clinical nodal class cN1 (77%). Surgical resection was performed in 37% of patients. Median pretreatment TTMV-HPV level was 225 (IQR 46-1132) fragments/mL. Independent associations were found between pretreatment TTMV-HPV levels and clinical nodal staging (P < .001), largest lymph node dimension on pretreatment CT (r = 0.63 [95% confidence interval [CI]: 0.46-1.2]; P < .001) and surgical pathology (r = 0.63 [0.18-1.08; P = .01), number of metastatic nodes on CT (r = 0.52 [0.2-0.84]; P < .001), clinical signs of extranodal extension (r = 1.66 [0.12-3.2]; P = 0.04), and SUV-max of lymph nodes (r = 0.16 [0.05-0.27]; P < 0.001).

CONCLUSIONS

Pre-treatment TTMV-HPV DNA was significantly associated with lymph node disease burden in HPV-associated OPSCC, on pre-treatment CT, PET, and surgical pathology.

摘要

引言

肿瘤组织修饰病毒(TTMV)-人乳头瘤病毒(HPV)DNA越来越多地被用作人乳头瘤病毒介导的口咽鳞状细胞癌(OPSCC)患者的生物标志物。然而,关于治疗前阳性结果的定量重要性以及与疾病负担的相关性,仍有许多需要研究的地方。

研究设计

回顾性队列研究。

研究地点

单一三级医疗中心;2022年1月至2024年7月。

方法

对人乳头瘤病毒相关的口咽鳞状细胞癌患者和治疗前基线TTMV-HPV DNA水平进行评估,根据适用情况,依据临床影像学、检查和手术病理结果判断原发性肿瘤和淋巴结疾病范围。通过多变量线性回归评估与log(治疗前TTMV-HPV DNA水平)的相关性。使用市售的TTMV-HPV DNA检测方法。

结果

总共纳入94例患者,其中93%为男性,中位年龄63岁(四分位间距[IQR]55 - 70)。大多数患者为临床肿瘤分级cT1(40%)或cT2(38%),临床淋巴结分级cN1(77%)。37%的患者接受了手术切除。治疗前TTMV-HPV的中位水平为225(IQR 46 - 1132)片段/毫升。在治疗前TTMV-HPV水平与临床淋巴结分期(P < 0.001)、治疗前CT上最大淋巴结尺寸(r = 0.63[95%置信区间[CI]:0.46 - 1.2];P < 0.001)和手术病理(r = 0.63[0.18 - 1.08;P = 0.01])、CT上转移淋巴结数量(r = 0.52[0.2 - 0.84];P < 0.001)、结外扩展的临床体征(r = 1.66[0.12 - 3.2];P = 0.04)以及淋巴结的SUV最大值(r = 0.16[0.05 - 0.27];P < 0.001)之间发现了独立相关性。

结论

在治疗前的CT、PET和手术病理检查中,治疗前TTMV-HPV DNA与人乳头瘤病毒相关的口咽鳞状细胞癌中的淋巴结疾病负担显著相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa51/12461791/c29b5b3242a5/OHN-173-911-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa51/12461791/c29b5b3242a5/OHN-173-911-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa51/12461791/c29b5b3242a5/OHN-173-911-g001.jpg

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本文引用的文献

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Association of circulating tumor HPV16DNA levels and quantitative PET parameters in patients with HPV-positive head and neck squamous cell carcinoma.循环肿瘤 HPV16DNA 水平与 HPV 阳性头颈部鳞状细胞癌患者定量 PET 参数的相关性。
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Negative Predictive Value of Circulating Tumor Tissue Modified Viral (TTMV)-HPV DNA for HPV-driven Oropharyngeal Cancer Surveillance.
循环肿瘤组织改良病毒(TTMV)-HPV DNA 对 HPV 驱动型口咽癌监测的阴性预测值。
Clin Cancer Res. 2023 Oct 13;29(20):4306-4313. doi: 10.1158/1078-0432.CCR-23-1478.
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Performance of Liquid Biopsy for Diagnosis and Surveillance of Human Papillomavirus-Associated Oropharyngeal Cancer.液体活检在人乳头瘤病毒相关口咽癌诊断和监测中的应用。
JAMA Otolaryngol Head Neck Surg. 2023 Nov 1;149(11):971-977. doi: 10.1001/jamaoto.2023.1937.
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Human Papilloma Virus (HPV) and the Current State of Oropharyngeal Cancer Prevention and Treatment.人乳头瘤病毒(HPV)与口咽癌防治现状
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