Department of Otolaryngology/Head and Neck Surgery, VU University Medical Center, Cancer Center Amsterdam, The Netherlands.
Department of Oral and Maxillofacial Surgery/Oral Pathology, VU University Medical Center Amsterdam, The Netherlands; Academic Center for Dentistry Amsterdam (ACTA), The Netherlands; Departments of Pathology.
Ann Oncol. 2018 May 1;29(5):1273-1279. doi: 10.1093/annonc/mdy060.
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.
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.
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).
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.
口咽鳞状细胞癌（OPSCC）传统上由吸烟和过量饮酒引起。然而，在过去几十年中，高危型人乳头瘤病毒（HPV）感染在肿瘤发生中发挥着越来越重要的作用。已知 HPV 驱动的 OPSCC 具有更好的预后，这导致最近发布的第 8 版 TNM 发生了重要而显著的变化。在第 8 版中，OPSCC 根据 p16 免疫染色进行分类，p16 过表达作为 HPV 存在的替代标志物。本研究的目的是评估第 8 版 TNM 在荷兰连续队列的 p16 阳性 OPSCC 患者中的应用，并确定额外的 HPV DNA 检测的相关性。
所有诊断时无远处转移且在 VU 大学医学中心（2000-2015 年）和伊拉斯谟医学中心（2000-2006 年）接受根治性治疗的 OPSCC 患者均被纳入研究（N=1204）。HPV 状态通过 p16 免疫染色确定，然后对 p16 免疫阳性病例进行 HPV DNA PCR。我们使用 Harrell 的 C 指数比较了 TNM-7 和 TNM-8。
总共，1204 例患者中有 388 例（32.2%）为 p16 免疫阳性。在这些患者中，TNM-8 比 TNM-7 具有明显更好的预测预后能力（Harrell 的 C 指数为 0.63 对 0.53）。在 388 例 p16 阳性的 OPSCC 中，48 例肿瘤（12.4%）HPV DNA 阴性。该亚组具有明显不同的人口统计学、临床和形态学特征，与 HPV DNA 阳性肿瘤相比，五年总生存率明显较差（P<0.001）。
在 p16 阳性的 OPSCC 患者中，TNM-8 比 TNM-7 具有更好的预测预后能力。然而，在 p16 阳性的 OPSCC 中，存在一个 HPV DNA 阴性的亚组，其特征和总生存率均较差，这表明在预测预后，特别是在选择接受减毒治疗方案的患者时，进行额外的 HPV DNA 检测非常重要。
