Department of Pathology, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain.
Department of Gynecology, Obstetrics and Neonatology, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain.
Mod Pathol. 2014 Mar;27(3):343-51. doi: 10.1038/modpathol.2013.155. Epub 2013 Sep 13.
It has been reported that high-risk human papillomavirus (HPV) is a causative agent of a subgroup of oropharyngeal carcinomas. In these tumors, the presence of the transcriptionally active HPV has been proved through the identification of HPV E6 or E7 messenger RNA (mRNA) transcripts. The aim of the study was to assess the HPV-active transcription in a series of sinonasal carcinomas, in correlation with the HPV DNA identification and the p16 immunohistochemistry. Seventy patients with squamous cell carcinomas of the sinonasal tract were included in the survey. The main clinicopathological characteristics were recorded. All tumors were investigated for HPV through the HPV DNA detection by PCR, using the SPF10 primers and by in situ hybridization, using the high-risk GenPoint probe (Dako, Glostrup, Denmark). HPV16 E7 mRNA transcripts detection was performed by RT-PCR in 27 cases. The immunostaining for p16 was performed in all cases. Fourteen carcinomas (20%) were positive for high-risk HPV by PCR: 13 HPV16 and one HPV35. In situ hybridization showed a dotted nuclear positivity in all these cases. HPV16 E7 mRNA was detected in seven tumors harboring HPV16; in the remaining HPV-positive cases, RNA did not reach the quality for analysis. Strong, diffuse positivity for p16 was observed only in the HPV-positive cases. The 14 HPV-positive squamous cell carcinomas were non-keratinizing or scarcely keratinizing tumors. No significant differences were found in terms of gender, age, or staging at diagnosis between HPV-positive and HPV-negative tumors. However, differences in disease-free survival and overall survival between both groups of patients were significant (P=0.004 and P=0.028, respectively). In conclusion, we have shown that HPV is the etiological agent of a subset of sinonasal carcinomas demonstrating the transcriptionally active HPV in these tumors. Immunostaining for p16 can be used as a surrogate marker to identify these tumors.
据报道，高危型人乳头瘤病毒（HPV）是口咽癌亚群的致病因子。在这些肿瘤中，通过鉴定 HPV E6 或 E7 信使 RNA（mRNA）转录本，已经证明了转录活性 HPV 的存在。本研究旨在评估一系列鼻腔鼻窦癌中 HPV 的活跃转录，与 HPV DNA 鉴定和 p16 免疫组化相关。调查纳入了 70 例鼻腔鼻窦鳞状细胞癌患者。记录了主要的临床病理特征。所有肿瘤均通过聚合酶链反应（PCR）使用 SPF10 引物和原位杂交（使用高危 GenPoint 探针（丹麦哥本哈根 Dako））检测 HPV DNA。在 27 例病例中通过 RT-PCR 检测 HPV16 E7 mRNA 转录物。所有病例均进行 p16 免疫染色。14 例（20%）癌组织经 PCR 检测呈高危型 HPV 阳性：13 例 HPV16 和 1 例 HPV35。在所有这些病例中，均显示点状核阳性。在含有 HPV16 的 7 个肿瘤中检测到 HPV16 E7 mRNA；在其余 HPV 阳性病例中，RNA 未达到分析质量。只有在 HPV 阳性病例中才观察到 p16 的强弥漫阳性。14 例 HPV 阳性的鳞状细胞癌是非角化或角化不足的肿瘤。HPV 阳性和 HPV 阴性肿瘤在性别、年龄或诊断时的分期方面无显著差异。然而，两组患者的无病生存率和总生存率差异有统计学意义（P=0.004 和 P=0.028）。总之，我们已经证明 HPV 是一组鼻腔鼻窦癌的病因，这些肿瘤中存在转录活性 HPV。p16 的免疫染色可作为识别这些肿瘤的替代标志物。
