Sikl's Department of Pathology, The Faculty of Medicine and Faculty Hospital in Pilsen, Charles University, Pilsen, Czech Republic.
Biopticka laborator, s.r.o., Pilsen, Czech Republic.
Neoplasma. 2020 Nov;67(6):1456-1463. doi: 10.4149/neo_2020_200330N332. Epub 2020 Aug 27.
Sinonasal cancers represent a highly heterogeneous group of head and neck cancers, for which etiological and prognostic significance of high-risk human papillomavirus (HPV) infections has not yet been conclusively established. We investigated the presence of transcriptionally-active high-risk HPV in a series of 34 sinonasal squamous cell cancer (SNSCC) cases and evaluated the effect of transcriptionally-active HPV on the overall survival. In addition, we performed a meta-analysis of previously published studies, including this study, to summarize the prevalence of HPV positivity across histological subtypes of SNSCC. The presence of transcriptionally-active HPV was detected by HPV mRNA using the polymerase chain reaction (PCR) or in situ hybridization (ISH). p16 expression was evaluated as a surrogate marker for transcriptionally-active HPV infection by immunohistochemistry (IHC), the presence of high-risk HPV DNA was tested by PCR and the HPV genotypes were determined by sequencing of PCR amplicons. Transcriptionally-active HPV infections were found in 25% of the SNSCC cases. The role of HPV infection in keratinizing SNSCC may be higher than previously reported (32% in our study vs. ~0-6.3% in all other studies). Patients with transcriptionally-active HPV-positive SNSCCs were more likely to be diagnosed at earlier stages (p<0.05) and displayed better mean overall survival, although the difference between HPV-positive and HPV-negative groups was not statistically significant. In contrast to other non-oropharyngeal squamous cell carcinomas (non-OPSCCs) of the head and neck, in SNSCCs, p16/IHC and p16/IHC+HPV DNA displayed high specificity as surrogate markers of transcriptionally-active HPV infections. However, p16/IHC may have significantly lower sensitivity as a surrogate marker of transcriptionally-active HPV in SNSCCs compared to OPSCCs. Furthermore, in our group of SNSCCs, all cases positive for high-risk HPV DNA by PCR were also transcriptionally-active (causative) infections with positive HPV mRNA by ISH. Our results imply a possible different role of HPV-mediated carcinogenesis of squamous cell epithelium in oropharyngeal and sinonasal sites with the latter displaying a lower proportion of causative HPV infections; nevertheless, most cases positive for high-risk HPV DNA, p16/IHC or combination thereof were also found positive for transcriptionally-active HPV. The prognostic significance of HPV status in SNSCCs remains inconclusive and future studies should investigate the presence of transcriptionally-active HPV by direct HPV testing.
鼻窦鳞状细胞癌（SNSCC）是一组高度异质性的头颈部癌症，高危型人乳头瘤病毒（HPV）感染的病因学和预后意义尚未得到明确证实。我们研究了 34 例鼻窦鳞状细胞癌（SNSCC）病例中转录活跃的高危 HPV 的存在，并评估了转录活跃的 HPV 对总生存率的影响。此外，我们对之前发表的研究进行了荟萃分析，包括这项研究，以总结 SNSCC 组织学亚型中 HPV 阳性的流行率。通过聚合酶链反应（PCR）或原位杂交（ISH）使用 HPV mRNA 检测转录活跃的 HPV 的存在。通过免疫组织化学（IHC）评估 p16 表达作为转录活跃 HPV 感染的替代标志物，通过 PCR 检测高危 HPV DNA 的存在，并通过 PCR 扩增子的测序确定 HPV 基因型。在大约 25%的 SNSCC 病例中发现了转录活跃的 HPV 感染。HPV 感染在角化型 SNSCC 中的作用可能高于之前的报道（我们的研究中约为 32%，而所有其他研究中约为 0-6.3%）。转录活跃的 HPV 阳性 SNSCC 患者更有可能在早期阶段被诊断（p<0.05），并且总体生存率较好，尽管 HPV 阳性组和 HPV 阴性组之间的差异无统计学意义。与头颈部其他非口咽鳞状细胞癌（非 OPSCC）不同，在 SNSCC 中，p16/IHC 和 p16/IHC+HPV DNA 作为转录活跃 HPV 感染的替代标志物具有很高的特异性。然而，与 OPSCC 相比，p16/IHC 作为 SNSCC 中转录活跃 HPV 的替代标志物可能具有显著较低的敏感性。此外，在我们的 SNSCC 组中，所有通过 PCR 检测到高危 HPV DNA 阳性的病例也通过 ISH 检测到 HPV mRNA 转录活跃（病因）感染。我们的结果表明，HPV 介导的鳞状上皮癌变在口咽和鼻窦部位可能具有不同的作用，后者的病因性 HPV 感染比例较低；然而，大多数高危 HPV DNA、p16/IHC 或两者阳性的病例也被发现 HPV 转录活跃。HPV 状态在 SNSCC 中的预后意义仍不确定，未来的研究应通过直接 HPV 检测来研究转录活跃的 HPV 的存在。
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