循环肿瘤DNA作为人乳头瘤病毒相关头颈部鳞状细胞癌治疗评估的补充工具：一项观察性队列研究
Circulating Tumour DNA as a Complementary Tool for Treatment Evaluation in HPV-Associated Head and Neck Squamous Cell Carcinoma: An Observational Cohort Study.
作者信息
Almerén Anna Oldaeus, Waenerlund Max, Landström Fredrik, von Beckerath Mathias, Qvick Alvida, Carlsson Jessica, Helenius Gisela
机构信息
Department of Otolaryngology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
出版信息
Clin Otolaryngol. 2025 Apr 22. doi: 10.1111/coa.14317.
OBJECTIVES
HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) and head and neck carcinoma of unknown primary (HNCUP) are increasing. Despite good prognosis, recurrence rates range from 10% to 25%. Surveillance with clinical controls and imaging is not always reliable. Circulating tumour human papillomavirus DNA (ctHPV-DNA) has emerged as a potential biomarker for treatment evaluation and detection of recurrence. We aimed to investigate the correlation between ctHPV-DNA in HPV+ OPSCC/HNCUP and radiologic tumour burden. Additionally, we sought to assess whether ctHPV-DNA could serve as a tool in treatment evaluation.
DESIGN
A prospective observational cohort study.
SETTING
This multicenter study involved three otolaryngology units located in central Sweden. We utilised HPV genotype-specific assays for droplet digital PCR (ddPCR) to detect ctHPV-DNA in plasma at diagnosis and follow-up. ctHPV-DNA levels were correlated to radiological tumour burden and radiological response using the Kendall Rank correlation coefficient and the Kruskal-Wallis test.
PARTICIPANTS
Patients with HPV+ OPSCC/HNCUP undergoing definitive (chemo)radiotherapy and enrolled in the CIRCOS study.
RESULTS
Out of 54 patients, 51 were eligible for analyses. At baseline, ctHPV-DNA was detectable in 88%. A majority of patients with a favourable radiological evaluation according to RECIST had a corresponding undetectable ctHPV-DNA at follow-up. The levels of ctHPV-DNA at baseline correlated with total tumour volume and nodal volume (rτ = 0.39, p < 0.01, respectively rτ = 0.26, p < 0.01).
CONCLUSION
ctHPV-DNA shows correlation with tumour burden. This study strengthens the role of ctHPV-DNA as a promising biomarker for treatment evaluation in HPV-related OPC/HNCUP. With further research on serial plasma sampling, ctHPV-DNA could complement radiological treatment evaluation in HPV+ OPSCC/HNCUP.
TRIAL REGISTRATION
NCT05904327 [ClinicalTrials.gov].
目的
人乳头瘤病毒（HPV）阳性的口咽鳞状细胞癌（OPSCC）和原发灶不明的头颈癌（HNCUP）的发病率正在上升。尽管预后良好，但复发率在10%至25%之间。临床检查和影像学监测并不总是可靠的。循环肿瘤人乳头瘤病毒DNA（ctHPV-DNA）已成为一种用于治疗评估和复发检测的潜在生物标志物。我们旨在研究HPV+ OPSCC/HNCUP患者的ctHPV-DNA与放射学肿瘤负荷之间的相关性。此外，我们试图评估ctHPV-DNA是否可作为治疗评估的工具。
设计
一项前瞻性观察队列研究。
背景
这项多中心研究涉及瑞典中部的三个耳鼻喉科单位。我们利用针对液滴数字PCR（ddPCR）的HPV基因型特异性检测方法，在诊断和随访时检测血浆中的ctHPV-DNA。使用肯德尔等级相关系数和克鲁斯卡尔-沃利斯检验，将ctHPV-DNA水平与放射学肿瘤负荷和放射学反应相关联。
参与者
参加CIRCOS研究并接受确定性（化疗）放疗的HPV+ OPSCC/HNCUP患者。
结果
54例患者中，51例符合分析条件。基线时，88%的患者可检测到ctHPV-DNA。根据实体瘤疗效评价标准（RECIST），大多数放射学评估良好的患者在随访时相应的ctHPV-DNA检测不到。基线时ctHPV-DNA水平与肿瘤总体积和淋巴结体积相关（τ分别为0.39，p < 0.01；τ为0.26，p < 0.01）。
结论
ctHPV-DNA与肿瘤负荷相关。本研究强化了ctHPV-DNA作为HPV相关口咽癌/头颈癌治疗评估中有前景的生物标志物的作用。随着对连续血浆采样的进一步研究，ctHPV-DNA可补充HPV+ OPSCC/HNCUP的放射学治疗评估。
试验注册
NCT05904327 [ClinicalTrials.gov]
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