评估p16表达作为单一标志物用于选择HPV驱动的口咽癌患者进行降阶梯治疗。

Evaluation of p16 expression as a single marker to select patients with HPV-driven oropharyngeal cancers for treatment de-escalation.

作者信息

Wagner Steffen, Prigge Elena-Sophie, Wuerdemann Nora, Reder Henrike, Bushnak Ayman, Sharma Shachi Jenny, Obermueller Theresa, von Knebel Doeberitz Magnus, Dreyer Thomas, Gattenlöhner Stefan, Wolf Gregor, Pons-Kühnemann Jörn, Wittekindt Claus, Klussmann Jens Peter

机构信息

Department of Otorhinolaryngology, Head and Neck Surgery, University of Giessen, Giessen, Germany.

Department of Applied Tumor Biology, Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.

出版信息

Br J Cancer. 2020 Sep;123(7):1114-1122. doi: 10.1038/s41416-020-0964-x. Epub 2020 Jul 6.

DOI:10.1038/s41416-020-0964-x

PMID:32624580

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7525437/

Abstract

BACKGROUND

A remarkably better prognosis is associated with oropharyngeal squamous cell carcinomas (OPSCC) driven by human papillomaviruses (HPV) compared with HPV-negative OPSCC. Consequently, de-escalation of standard treatment has been suggested. Due to modest specificity rates, debates are ongoing, whether p16, a surrogate marker for HPV-driven OPSCC, is sufficient to correctly identify those tumours and avoid substantial HPV misattribution and thus undertreatment of patients by de-escalation. Robust data estimating the proportion of potentially undertreated patients are missing.

METHODS

We assessed a large-scale cohort of consecutively included OPSCC diagnosed between 2000 and 2017 for HPV-DNA, HPV genotypes, p16 expression and multiple tumour- and patient-related risk factors, and investigated their impact on patients' survival in comprehensive uni- and multivariate analyses.

RESULTS

Aetiological relevance of HPV (p16- and high-risk HPV-DNA-positivity) was detected in 27.1% (n = 192) of OPSCC, with HPV being the most abundant HPV type (94.6%). In 5.5% patients (n = 39), p16 overexpression but no HPV-DNA was detected. Principal component and survival analyses revealed that 60.6% of these p16-positive OPSCC lacking HPV-DNA did not resemble HPV-driven but HPV-negative OPSCC regarding risk-factor profile and overall survival. Notably, this group represented 10.6% of all p16-overexpressing OPSCC.

CONCLUSIONS

p16 as a single marker appears insufficient to indicate OPSCC patients suitable for treatment de-escalation.

摘要

背景

与人类乳头瘤病毒（HPV）阴性的口咽鳞状细胞癌（OPSCC）相比，由HPV驱动的OPSCC具有明显更好的预后。因此，有人提出降低标准治疗强度。由于特异性率不高，关于p16（HPV驱动的OPSCC的替代标志物）是否足以正确识别这些肿瘤并避免大量HPV误判，从而避免因降低治疗强度而导致患者治疗不足的争论仍在继续。目前尚缺乏估计潜在治疗不足患者比例的可靠数据。

方法

我们评估了一个连续纳入的大型OPSCC队列，这些患者在2000年至2017年间被诊断，检测其HPV-DNA、HPV基因型、p16表达以及多种肿瘤和患者相关危险因素，并在综合单因素和多因素分析中研究它们对患者生存的影响。

结果

在27.1%（n = 192）的OPSCC中检测到HPV的病因学相关性（p16和高危HPV-DNA阳性），其中HPV是最常见的HPV类型（94.6%）。在5.5%的患者（n = 39）中，检测到p16过表达但未检测到HPV-DNA。主成分分析和生存分析显示，这些缺乏HPV-DNA的p16阳性OPSCC中，60.6%在危险因素谱和总生存方面与HPV驱动的OPSCC不同，而更类似于HPV阴性的OPSCC。值得注意的是，该组占所有p16过表达OPSCC的10.6%。