Chen William S, Bindra Ranjit S, Mo Allen, Hayman Thomas, Husain Zain, Contessa Joseph N, Gaffney Stephen G, Townsend Jeffrey P, Yu James B
Yale School of Medicine, New Haven, CT, United States.
Department of Therapeutic Radiology, Yale School of Medicine, New Haven, CT, United States.
Front Oncol. 2018 Apr 4;8:95. doi: 10.3389/fonc.2018.00095. eCollection 2018.
HPV infection is associated with high p16 expression and good prognosis in head and neck squamous cell carcinomas (HNSCCs). Analysis of CDKN2A, the gene encoding p16, may further elucidate the association between p16 expression and prognosis. We sought to determine whether CDKN2A copy number loss was associated with poor survival in HPV-negative HNSCCs.
The Cancer Genome Atlas HNSCC clinical and genomic data were obtained and integrated. Patients <80 years old with a primary tumor in the oral cavity, oropharynx, hypopharynx, or larynx were included. Stratifying by copy number loss status, CDKN2A mRNA and p16 protein expression levels were examined and overall survival (OS) and disease-free survival (DFS) were evaluated.
401 patients with HPV-negative HNSCC were identified. 146 patients demonstrated CDKN2A copy number loss. The CDKN2A copy number loss group expressed significantly lower levels of CDKN2A mRNA and p16 protein than did the non-copy number loss group. Median OS for patients with and without CDKN2A copy number loss was 16.5 and 46.6 months, respectively ( = 0.007). Median DFS for both groups was 11.6 and 19.2 months, respectively ( = 0.03). In both univariate and multivariable analyses, stage IV designation, receipt of chemotherapy and CDKN2A copy number loss were predictive of OS.
CDKN2A copy number loss predicted poor survival independently of other patient and treatment factors and may be a clinically useful prognostic factor.
人乳头瘤病毒（HPV）感染与头颈部鳞状细胞癌（HNSCC）中p16高表达及良好预后相关。对编码p16的基因CDKN2A进行分析，可能会进一步阐明p16表达与预后之间的关联。我们试图确定CDKN2A拷贝数缺失是否与HPV阴性的HNSCC患者生存率低相关。
获取并整合癌症基因组图谱HNSCC的临床和基因组数据。纳入年龄小于80岁、原发肿瘤位于口腔、口咽、下咽或喉的患者。根据拷贝数缺失状态进行分层，检测CDKN2A mRNA和p16蛋白表达水平，并评估总生存期（OS）和无病生存期（DFS）。
共确定了401例HPV阴性的HNSCC患者。146例患者存在CDKN2A拷贝数缺失。与无拷贝数缺失组相比，CDKN2A拷贝数缺失组的CDKN2A mRNA和p16蛋白表达水平显著降低。有和无CDKN2A拷贝数缺失患者的中位OS分别为16.5个月和46.6个月（P = 0.007）。两组的中位DFS分别为11.6个月和19.2个月（P = 0.03）。在单因素和多因素分析中，IV期、接受化疗和CDKN2A拷贝数缺失均为OS的预测因素。
CDKN2A拷贝数缺失可独立于其他患者和治疗因素预测不良生存，可能是一个具有临床应用价值的预后因素。
