Trembley Janeen H, Li Bin, Kren Betsy T, Peltola Justin, Manivel Juan, Meyyappan Devi, Gravely Amy, Klein Mark, Ahmed Khalil, Caicedo-Granados Emiro
Research Service, Minneapolis VA Health Care System, Minneapolis, MN, United States of America.
Department of Laboratory Medicine and Pathology, University of Minnesota - Twin Cities Campus, Minneapolis, MN, United States of America.
PeerJ. 2021 Dec 13;9:e12519. doi: 10.7717/peerj.12519. eCollection 2021.
Oropharyngeal squamous cell carcinoma (OPSCC) incidence is rising worldwide, especially human papillomavirus (HPV)-associated disease. Historically, high levels of protein kinase CK2 were linked with poor outcomes in head and neck squamous cell carcinoma (HNSCC), without consideration of HPV status. This retrospective study examined tumor CK2α protein expression levels and related clinical outcomes in a cohort of Veteran OPSCC patient tumors which were determined to be predominantly HPV(+).
Patients at the Minneapolis VA Health Care System with newly diagnosed primary OPSCC from January 2005 to December 2015 were identified. A total of 119 OPSCC patient tumors were stained for CK2α, p16 and Ki-67 proteins and E6/E7 RNA. CK2α protein levels in tumors and correlations with HPV status and Ki-67 index were assessed. Overall survival (OS) analysis was performed stratified by CK2α protein score and separately by HPV status, followed by Cox regression controlling for smoking status. To strengthen the limited HPV(-) data, survival analysis for HPV(-) HNSCC patients in the publicly available The Cancer Genome Atlas (TCGA) PanCancer RNA-seq dataset was determined for .
The patients in the study population were all male and had a predominant history of tobacco and alcohol use. This cohort comprised 84 HPV(+) and 35 HPV(-) tumors. CK2α levels were higher in HPV(+) tumors compared to HPV(-) tumors. Higher CK2α scores positively correlated with higher Ki-67 index. OS improved with increasing CK2α score and separately OS was significantly better for those with HPV(+) as opposed to HPV(-) OPSCC. Both remained significant after controlling for smoking status. High mRNA levels from TCGA data associated with worse patient survival in HPV(-) HNSCC.
High CK2α protein levels are detected in HPV(+) OPSCC tumors and demonstrate an unexpected association with improved survival in a strongly HPV(+) OPSCC cohort. Worse survival outcomes for high mRNA levels in HPV(-) HNSCC are consistent with historical data. Given these surprising findings and the rising incidence of HPV(+) OPSCC, further study is needed to understand the biological roles of CK2 in HPV(+) and HPV(-) HNSCC and the potential utility for therapeutic targeting of CK2 in these two disease states.
口咽鳞状细胞癌（OPSCC）在全球范围内的发病率正在上升，尤其是与人乳头瘤病毒（HPV）相关的疾病。从历史上看，蛋白激酶CK2的高水平与头颈部鳞状细胞癌（HNSCC）的不良预后相关，而未考虑HPV状态。这项回顾性研究检查了一组主要为HPV（+）的退伍军人OPSCC患者肿瘤中的肿瘤CK2α蛋白表达水平及相关临床结果。
确定了2005年1月至2015年12月在明尼阿波利斯退伍军人事务部医疗保健系统中 newly diagnosed 原发性OPSCC的患者。总共119例OPSCC患者肿瘤进行了CK2α、p16和Ki-67蛋白以及E6/E7 RNA染色。评估肿瘤中的CK2α蛋白水平及其与HPV状态和Ki-67指数的相关性。通过CK2α蛋白评分分层并分别按HPV状态进行总生存（OS）分析，然后进行控制吸烟状态的Cox回归分析。为了加强有限的HPV（-）数据，确定了公开可用的癌症基因组图谱（TCGA）泛癌RNA测序数据集中HPV（-）HNSCC患者的生存分析。
研究人群中的患者均为男性，主要有吸烟和饮酒史。该队列包括84例HPV（+）和35例HPV（-）肿瘤。与HPV（-）肿瘤相比，HPV（+）肿瘤中的CK2α水平更高。较高的CK2α评分与较高的Ki-67指数呈正相关。OS随着CK2α评分的增加而改善，并且对于HPV（+）的患者，其OS明显优于HPV（-）的OPSCC患者。在控制吸烟状态后两者仍具有显著性。来自TCGA数据的高mRNA水平与HPV（-）HNSCC患者较差的生存相关。
在HPV（+）OPSCC肿瘤中检测到高CK2α蛋白水平，并且在一个强HPV（+）OPSCC队列中显示出与生存改善的意外关联。HPV（-）HNSCC中高mRNA水平的较差生存结果与历史数据一致。鉴于这些令人惊讶的发现以及HPV（+）OPSCC发病率的上升，需要进一步研究以了解CK2在HPV（+）和HPV（-）HNSCC中的生物学作用以及在这两种疾病状态下CK2治疗靶向的潜在效用。
