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p16免疫组化与HPV-PCR基因分型在口咽鳞状细胞癌病毒诊断中的一致性研究

Study of the concordance between p16 immunohistochemistry and HPV-PCR genotyping for the viral diagnosis of oropharyngeal squamous cell carcinoma.

作者信息

Fonmarty D, Cherrière S, Fleury H, Eimer S, Majoufre-Lefebvre C, Castetbon V, de Monès E

机构信息

Service d'oto-rhino-laryngologie, CHU de Bordeaux, Hôpital Pellegrin, place Amélie-Raba-Léon, 33056 Bordeaux cedex, France.

Laboratoire de virologie, CHU de Bordeaux, Hôpital Pellegrin, place Amélie-Raba-Léon, 33056 Bordeaux cedex, France.

出版信息

Eur Ann Otorhinolaryngol Head Neck Dis. 2015 Jun;132(3):135-9. doi: 10.1016/j.anorl.2015.01.003. Epub 2015 Feb 14.

DOI:10.1016/j.anorl.2015.01.003
PMID:25687724
Abstract

OBJECTIVE

The diagnosis of HPV-related oropharyngeal cancer in clinical practice is based on p16 immunohistochemistry and PCR detection of viral DNA (HPV-PCR). The primary objective of this study was to evaluate the concordance between these 2 diagnostic tests. The secondary objective was to study the clinical characteristics of these patients.

MATERIALS AND METHODS

This single-centre prospective study was conducted between February 2010 and July 2012. Immunohistochemical analysis of p16 and HPV-PCR were performed on tumour biopsies. Concordance was evaluated according to Cohen's kappa coefficient and was interpreted according to the Landis and Koch scale. The patients' clinical data were analysed as a function of the diagnostic test results.

RESULTS

Seventy-one patients were included in this study. The prevalence of HPV was 43.7% according to p16 and 31% according to HPV-PCR. The concordance study revealed a kappa coefficient of 0.615. A tumour of the tonsil or base of the tongue was detected in 100% of p16+/HPV-PCR+ cases. Smoking and alcohol abuse were significantly less frequent among HPV+ patients regardless of the method of detection. These patients were older and presented tumours with a lower grade of histological differentiation.

CONCLUSION

p16 immunohistochemistry or HPV-PCR used alone appear to be insufficient. These results confirm the high prevalence of HPV-related oropharyngeal squamous cell carcinoma (OSCC) and the previously reported specific clinical and histological features, apart from age. It appears essential for future clinical trials to be stratified according to smoking and tumour HPV status, defined by means of reliable virological tests targeting E6/E7 mRNA and no longer a simple positive response to the p16 marker, as is frequently the case at the present time. New tests suitable for use in routine practice therefore need to be developed.

摘要

目的

临床实践中HPV相关口咽癌的诊断基于p16免疫组织化学和病毒DNA的PCR检测(HPV-PCR)。本研究的主要目的是评估这两种诊断测试之间的一致性。次要目的是研究这些患者的临床特征。

材料与方法

本单中心前瞻性研究于2010年2月至2012年7月进行。对肿瘤活检组织进行p16免疫组织化学分析和HPV-PCR检测。根据Cohen卡帕系数评估一致性,并根据Landis和Koch量表进行解释。根据诊断测试结果分析患者的临床数据。

结果

本研究纳入71例患者。根据p16检测,HPV患病率为43.7%,根据HPV-PCR检测为31%。一致性研究显示卡帕系数为0.615。在所有p16阳性/HPV-PCR阳性病例中均检测到扁桃体或舌根肿瘤。无论检测方法如何,HPV阳性患者中吸烟和酗酒的频率明显较低。这些患者年龄较大,肿瘤组织学分化程度较低。

结论

单独使用p16免疫组织化学或HPV-PCR似乎并不充分。这些结果证实了HPV相关口咽鳞状细胞癌(OSCC)的高患病率以及先前报道的特定临床和组织学特征,但年龄除外。对于未来的临床试验,根据吸烟和肿瘤HPV状态进行分层似乎至关重要,HPV状态应通过针对E6/E7 mRNA的可靠病毒学检测来定义,而不再像目前常见的那样仅仅是对p16标志物的简单阳性反应。因此,需要开发适用于常规实践的新检测方法。

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