Background Oropharyngeal squamous cell carcinomas (OPSCCs) are traditionally caused by smoking and excessive alcohol consumption. However, in the last decades high-risk human papillomavirus (HPV) infections play an increasingly important role in tumorigenesis. HPV-driven OPSCCs are known to have a more favorable prognosis, which has led to important and marked changes in the recently released TNM-8. In this 8th edition, OPSCCs are divided based on p16 immunostaining, with p16 overexpression as surrogate marker for the presence of HPV. The aims of this study are to evaluate TNM-8 on a Dutch consecutive cohort of patients with p16-positive OPSCC and to determine the relevance of additional HPV DNA testing. Patients and methods All OPSCC patients without distant metastases at diagnosis and treated with curative intent at VU University Medical Center (2000-2015) and Erasmus Medical Center (2000-2006) were included (N = 1204). HPV status was determined by p16 immunostaining followed by HPV DNA PCR on the p16-immunopositive cases. We compared TNM-7 and TNM-8 using the Harrell's C index. Results In total, 388 of 1204 (32.2%) patients were p16-immunopositive. In these patients, TNM-8 had a markedly better predictive prognostic power than TNM-7 (Harrell's C index 0.63 versus 0.53). Of the 388 p16-positive OPSCCs, 48 tumors (12.4%) were HPV DNA-negative. This subgroup had distinct demographic, clinical and morphologic characteristics and showed a significantly worse five-year overall survival compared with the HPV DNA-positive tumors (P < 0.001). Conclusions TNM-8 has a better predictive prognostic power than TNM-7 in patients with p16-positive OPSCC. However, within p16-positive OPSCCs, there is an HPV DNA-negative subgroup with distinct features and a worse overall survival, indicating the importance to perform additional HPV DNA testing when predicting prognosis and particularly for selecting patients for de-intensified treatment regimens.

中文翻译：

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在荷兰对p16阳性口咽鳞状细胞癌进行的第八次TNM分类评估以及其他HPV DNA检测的重要性。

背景口咽鳞状细胞癌（OPSCC）传统上是由吸烟和过量饮酒引起的。然而，在过去的几十年中，高危的人乳头瘤病毒（HPV）感染在肿瘤发生中起着越来越重要的作用。HPV驱动的OPSCC的预后更佳，这导致最近发布的TNM-8发生了重要且显着的变化。在此第8版中，OPSCC根据p16免疫染色进行划分，其中p16过表达是HPV存在的替代标志。这项研究的目的是评估荷兰p16阳性OPSCC患​​者的连续队列中的TNM-8，并确定其他HPV DNA检测的相关性。患者和方法包括所有在VU大学医学中心（2000-2015）和伊拉斯姆斯医学中心（2000-2006）诊断且无远处转移且经治愈性治疗的OPSCC患​​者（N = 1204）。通过对p16免疫阳性的病例进行p16免疫染色，然后进行HPV DNA PCR来确定HPV的状态。我们使用Harrell的C指数比较了TNM-7和TNM-8。结果总共有1204名患者中的388名（32.2％）为p16免疫阳性。在这些患者中，TNM-8的预测预后能力明显优于TNM-7（Harrell's C指数为0.63对0.53）。在388个p16阳性OPSCC中，有48个肿瘤（12.4％）是HPV DNA阴性的。与HPV DNA阳性肿瘤相比，该亚组具有独特的人口统计学，临床和形态学特征，并显示五年总生存期明显差（P <0。001）。结论TNM-8对p16阳性OPSCC的患者具有比TNM-7更好的预测预后能力。但是，在p16阳性OPSCC中，有一个HPV DNA阴性亚组，具有不同的特征，并且总生存期较差，这表明在预测预后尤其是选择患者进行低强度治疗时，进行额外的HPV DNA检测非常重要。