Stephen Josena K, Divine George, Chen Kang Mei, Chitale Dhananajay, Havard Shaleta, Worsham Maria J
Department of Otolaryngology/Head and Neck Research, Henry Ford Hospital, Detroit, USA.
Cancer Clin Oncol. 2013;2(1):51-61. doi: 10.5539/cco.v2n1p51.
Expression of p16 (p16 positive) is highly correlated with human papilloma virus (HPV) infection in head and neck squamous cell carcinoma (HNSCC), however, p16-positivity is not limited to HPV positive tumors and therefore, not a perfect surrogate for HPV. p16 survival outcomes are best documented for the oropharyngeal site (OP); non-OP sites such as the oral cavity (OC), larynx, and hypopharynx (HP) are understudied. The goal of this study was to evaluate p16 in the context of HPV16 and examine p16 survival outcomes in HPV16 positive and HPV16 negative site-specific HNSCC. p16 and HPV16 status were determined by immunohistochemistry and qPCR respectively, on 80 primary HNSCC from four sites: OC, OP, larynx and HP. p16 expression was different across sites (p<0.001), was more frequent in OP than non-OP sites (p<0.0001), and was different between Caucasian Americans (CA) and African Americans (AA) (p=0.031), similar to HPV (p=0.013). p16 was associated with marital status (p=0.008) and smoking (p=0.014). p16 positive patients had improved survival (similar to HPV16 positive cases). Patients with p16 negative/HPV16 negative status had the worst survival for all sites combined as well as for OP. p16 status is an important prognostic indicator in both OPSCC and non-OPSCC and the p16 positive/HPV16 negative group is likely a distinct subgroup lacking any HPV genotype. Cohorts with larger representations of non-OP sites examining multiple molecular markers will be key to deciphering and dissecting out p16's role as a useful prognostic indicator when assessed in combination with HPV status.
p16（p16阳性）的表达与头颈部鳞状细胞癌（HNSCC）中的人乳头瘤病毒（HPV）感染高度相关，然而，p16阳性并不局限于HPV阳性肿瘤，因此，它不是HPV的完美替代指标。p16生存结果在口咽部位（OP）记录得最为完善；口腔（OC）、喉和下咽（HP）等非OP部位的研究较少。本研究的目的是在HPV16的背景下评估p16，并检查HPV16阳性和HPV16阴性的特定部位HNSCC中p16的生存结果。通过免疫组织化学和qPCR分别测定了来自四个部位（OC、OP、喉和HP）的80例原发性HNSCC的p16和HPV16状态。p16表达在不同部位之间存在差异（p<0.001），在OP中比非OP部位更常见（p<0.0001），在白种美国人（CA）和非裔美国人（AA）之间也存在差异（p=0.031），与HPV情况类似（p=0.013）。p16与婚姻状况（p=0.008）和吸烟（p=0.014）有关。p16阳性患者的生存率有所提高（类似于HPV16阳性病例）。p16阴性/HPV16阴性状态的患者在所有部位以及OP部位的生存率最差。p16状态在口咽鳞状细胞癌（OPSCC）和非OPSCC中都是重要的预后指标，p16阳性/HPV16阴性组可能是一个缺乏任何HPV基因型的独特亚组。在检查多个分子标志物时，包含更多非OP部位样本的队列对于解读和剖析p16与HPV状态联合评估时作为有用预后指标的作用至关重要。
