Department of Anatomic Pathology, Kyushu University, Graduate School of Medical Sciences, Fukuoka, Japan.
Department of Otorhinolaryngology, Kyushu University, Graduate School of Medical Sciences, Fukuoka, Japan.
Histopathology. 2021 Sep;79(3):358-369. doi: 10.1111/his.14337. Epub 2021 May 6.
p16 is a sensitive surrogate marker for transcriptionally active high-risk human papillomavirus (HR-HPV) infection in oropharyngeal squamous cell carcinoma (OPSCC), but it is not sufficient in all clinical settings.
We examined the p16 and Rb expression status in 177 OPSCC cases by immunohistochemistry and the presence of transcriptionally active HR-HPV infection by mRNA in-situ hybridisation. The 177 cases were divided into p16 /HPV (n = 105, 59.3%), p16 /HPV (n = 8, 4.5%) and p16 /HPV (n = 64, 36.2%) groups. The p16 /HPV and p16 /HPV groups had a trend towards worse overall survival (OS) or significantly worse OS than the p16 /HPV group (n = 105) (P = 0.0610, P = 0.0004, respectively). We divided the Rb status into preserved expression (> 90%, n = 68), partial loss (PL) (10-90%, n = 97) and complete loss (CL) (< 10%, n = 12). Among the HPV-positive cases (n = 105), the Rb pattern was typically PL (n = 97, 92.4%) and rarely CL (n = 8, 7.6%), but never preserved expression (0%). In contrast, among the HPV-negative cases (n = 72), the Rb pattern was typically preserved expression (n = 68, 94.4%) and rarely CL (n = 4, 5.6%), but never PL (0%). Compared to p16 alone, the combination of p16 overexpression and Rb-PL/CL showed equally excellent sensitivity (each 100%) and improved specificity (97.2 versus 88.9%) and positive predictive values (98.1 versus 92.9%).
These results suggest that the combined use of p16 and Rb immunohistochemistry could be a reliable, cost-effective method to predict HR-HPV infection in OPSCCs; however, HPV specific testing is necessary on inconclusive cases. We propose a diagnostic algorithm for practical use of these markers.
p16 是口咽鳞状细胞癌（OPSCC）中转录活跃的高危型人乳头瘤病毒（HR-HPV）感染的敏感替代标志物，但在所有临床环境中都不充分。
我们通过免疫组织化学检查了 177 例 OPSCC 病例的 p16 和 Rb 表达状态，并通过 mRNA 原位杂交检查了转录活跃的 HR-HPV 感染情况。177 例病例分为 p16 /HPV（n=105，59.3%）、p16 /HPV（n=8，4.5%）和 p16 /HPV（n=64，36.2%）组。p16 /HPV 和 p16 /HPV 组的总生存（OS）或 OS 明显差于 p16 /HPV 组（n=105）（P=0.0610，P=0.0004）。我们将 Rb 状态分为保留表达（>90%，n=68）、部分缺失（PL）（10-90%，n=97）和完全缺失（CL）（<10%，n=12）。在 HPV 阳性病例（n=105）中，Rb 模式通常为 PL（n=97，92.4%），很少为 CL（n=8，7.6%），但从未有保留表达（0%）。相比之下，在 HPV 阴性病例（n=72）中，Rb 模式通常为保留表达（n=68，94.4%），很少为 CL（n=4，5.6%），但从未有 PL（0%）。与 p16 单独相比，p16 过表达和 Rb-PL/CL 的联合使用具有同样优异的敏感性（均为 100%）和更高的特异性（97.2%对 88.9%）和阳性预测值（98.1%对 92.9%）。
这些结果表明，联合使用 p16 和 Rb 免疫组织化学检查可能是预测 OPSCC 中 HR-HPV 感染的一种可靠、具有成本效益的方法；然而，对不确定的病例需要进行 HPV 特异性检查。我们提出了一种用于这些标志物实际应用的诊断算法。
