Department of Otolaryngology - Head and Neck Surgery, Institut Gustave Roussy, 114 rue Edouard Vaillant, Villejuif, France.
Am J Otolaryngol. 2014 Jan-Feb;35(1):25-32. doi: 10.1016/j.amjoto.2013.08.007. Epub 2013 Oct 7.
HPV-related oropharyngeal squamous cell carcinomas clearly represent a growing entity in the head and neck with distinct carcinogenesis, clinico-pathological presentation and survival profile. We aimed to compare the HPV prevalence rates and clinico-pathological correlations obtained with three distinct commonly used HPV detection methods.
p16-immunohistochemistry (IHC), HPV DNA viral load by real-time PCR (qPCR), and HPV genotyping by a reverse hybridization-based line probe assay (INNO-LiPA) were performed on pretreatment formalin-fixed paraffin-embedded tumor samples from 46 patients treated for single primary oropharyngeal carcinomas.
Twenty-eight patients (61%) had a p16 overexpression in IHC. Twenty-nine patients (63%) harbored HPV DNA on qPCR. Thirty-four patients (74%) harbored HPV DNA on INNO-LiPA. The concordance analysis revealed a good agreement between both HPV DNA detection methods (κ=0.65); when both tests were positive, the depicted HPV subtypes were always concordant (HPV16 in 27 cases, HPV18 in 1 case). Agreement was moderate between IHC and qPCR (κ=0.59) and fair between IHC and INNO-LiPA (κ=0.22).
Certain highly sensitive methods are able to detect the mere presence of HPV without any carcinogenetic involvement while other more specific tests provide proof of viral transcriptional activity and thus evidence of clinically relevant infections. The use of a stepwise approach allows reducing false positives; p16-immunostaining seems to be an excellent screening test and in situ hybridization may overcome some of the PCR limitations.
HPV 相关的口咽鳞状细胞癌在头颈部明显是一个不断增长的实体,具有独特的发病机制、临床病理表现和生存特征。我们旨在比较三种常用 HPV 检测方法所获得的 HPV 流行率和临床病理相关性。
对 46 例经单一原发性口咽癌治疗的患者的预处理福尔马林固定石蜡包埋肿瘤样本进行 p16 免疫组化(IHC)、实时聚合酶链反应(qPCR)检测 HPV 病毒载量和基于反向杂交的线探针分析(INNO-LiPA)HPV 基因分型。
28 例患者(61%)的 IHC 出现 p16 过表达。29 例患者(63%)的 qPCR 检测到 HPV DNA。34 例患者(74%)的 INNO-LiPA 检测到 HPV DNA。一致性分析显示两种 HPV DNA 检测方法之间具有良好的一致性(κ=0.65);当两种检测均为阳性时,所描述的 HPV 亚型始终一致(27 例 HPV16,1 例 HPV18)。IHC 与 qPCR 之间的一致性为中度(κ=0.59),IHC 与 INNO-LiPA 之间的一致性为适度(κ=0.22)。
某些高度敏感的方法能够检测 HPV 的存在而无需任何致癌作用,而其他更特异的检测方法则提供病毒转录活性的证据,从而证明存在具有临床意义的感染。采用逐步方法可以减少假阳性;p16 免疫组化似乎是一种极好的筛查试验,原位杂交可能克服 PCR 的一些局限性。