The high-risk human papillomavirus (HPV) infection represents one of the main etiologic pathways of penile carcinogenesis in approximately 30–50 % of cases. Several techniques for the detection of HPV are currently available including Polymerase chain reaction-based techniques, DNA and RNA in situ hybridization (ISH), p16 immunohistochemistry (IHC). The multiplex HPV RNA ISH/p16 IHC is a novel technique for the simultaneous detection of HPV E6/E7 transcripts and p16INK4a overexpression on the same slide in a single assay. The main aim of this study was to evaluate the discrepancy of p16 IHC expression relatively to HPV RNA ISH in penile cancer tissue. We collected a series of 60 PCs. HPV has been analysed through the RNA ISH, p16 IHC and the multiplex HPV RNA ISH/p16 IHC. The multiplex HPV RNA ISH /p16 IHC results in the series were in complete agreement with the previous results obtained through the classic p16 IHC and HPV RNA scope carried out on two different slides. The multiplex HPV RNA ISH /p16 IHC showed that HPV positivity in our series is more frequently in usual squamous cell carcinoma than in special histotypes (19 out of 60 − 15 %- versus 6 out of 60 − 10 %-), in high-grade than in moderate/low grade carcinomas (6 out of 60 − 10 %- versus 4 out of 60 − 6.7 %-). In addition, our data revealed that in 5 out of 20 cases with p16 high intensity expression is not associated with HPV RNA ISH positivity. Our findings emphasize that the use of p16 as a surrogate of HPV positivity was unsuccessful in approximatively 8 % of cases analysed in our series. Indeed, p16 IHC showed a sensitivity of 100 % and a specificity of 71 %, with a positive predictive value (PPV) of 54 % and a negative predictive value of 100 %; when considering high intensity, p16 IHC showed a sensitivity of 100 %, a specificity of 89 %, with a PPV of 75 % and NPV of 100 %. Since HPV positivity could represent a relevant prognostic and predictive value, the correct characterization offered by this approach appears to be of paramount importance.

中文翻译：

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阴茎癌中p16免疫组织化学表达与HPV RNA的差异。多重原位杂交/免疫组织化学方法研究

高危型人乳头瘤病毒（HPV）感染是约30–50％的病例中阴茎致癌作用的主要病因途径之一。目前有几种检测HPV的技术，包括基于聚合酶链反应的技术，DNA和RNA原位杂交（ISH），p16免疫组织化学（IHC）。多重HPV RNA ISH / p16 IHC是一项新颖的技术，可在一次测定中同时检测同一载玻片上的HPV E6 / E7转录本和p16INK4a过表达。这项研究的主要目的是评估阴茎癌组织中p16 IHC表达相对于HPV RNA ISH的差异。我们收集了一系列60台PC。已通过RNA ISH，p16 IHC和多重HPV RNA ISH / p16 IHC对HPV进行了分析。该系列中的多重HPV RNA ISH / p16 IHC结果与通过在两个不同的载玻片上进行的经典p16 IHC和HPV RNA范围获得的先前结果完全一致。多重HPV RNA ISH / p16 IHC显示，在普通鳞状细胞癌中，我们系列中的HPV阳性率比特殊组织型更常见（60 − 15％-中的19相对于60 − 10％-中的6），在高与中度/低度癌相比（60％至10％-6个中60％-6.7％-中的4个）。此外，我们的数据显示，在20例p16病例中，有5例高强度表达与HPV RNA ISH阳性无关。我们的发现强调，在我们的系列分析中，约有8％的病例无法成功使用p16替代HPV阳性。确实，p16 IHC的敏感性为100％，特异性为71％，阳性预测值（PPV）为54％，阴性预测值为100％；当考虑高强度时，p16 IHC的敏感性为100％，特异性为89％，PPV为75％，NPV为100％。由于HPV阳性可以代表相关的预后和预测价值，因此这种方法提供的正确表征似乎至关重要。