Human papillomavirus and p16 protein expression as prognostic biomarkers in mobile tongue cancer

Objectives: The objectives were to determine the prevalence of human papillomavirus (HPV) in mobile tongue cancer (MTC) and evaluate associations and survival.
Materials and methods: Patients who underwent surgical resection as primary treatment for MTC (n = 127) were retrospectively evaluated. Formalin-fixed paraffin-embedded (FFPE) specimens were assessed for p16 and p53 by immunohistochemistry; for HPV DNA by nested multiplex polymerase chain reaction (PCR) using two pairs of consensus primers (MY09–MY11 and GP5+–GP6+); and for E6 and E7 oncogenes from 13 high-risk HPV types (16, 18, 31, 33, 35, 39, 45, 52, 56, 58, 59, 66, and 68) by real-time reverse transcription PCR (RT-PCR).
Results: There were 18 (14.2%) p16-positive, 45 (35.4%) p53-positive, 9 (7.1%) HPV DNA-positive, and 7 (5.5%) E6 and/or E7 mRNA-positive tumors, but the correlation of all pairs was poor. There was no demographic or histopathologic association with HPV status. Cause-specific survival was significantly better with p16-positive than with p16-negative tumors (p = .037).
Conclusions: The prevalence of HPV and p16 positivity was relatively low and p16 status was a poor surrogate marker for HPV status. The results showed the importance of p16 expression in prognosticating mobile tongue cancer.

研究目的：本研究旨在明确舌活动部癌（mobile tongue cancer, MTC）中人乳头瘤病毒（human papillomavirus, HPV）的检出率，并分析其与临床病理特征及患者生存的相关性。
材料与方法：对127例以手术切除作为舌活动部癌初始治疗方案的患者进行回顾性分析。采用免疫组化法检测福尔马林固定石蜡包埋（FFPE）标本中的p16与p53蛋白表达；采用巢式多重聚合酶链反应（PCR），以两对通用引物（MY09–MY11与GP5+–GP6+）扩增检测HPV DNA；采用实时逆转录聚合酶链反应（RT-PCR）检测13种高危型HPV亚型（16、18、31、33、35、39、45、52、56、58、59、66、68）的E6、E7癌基因表达。
结果：本研究中共检出p16阳性肿瘤18例（占比14.2%）、p53阳性肿瘤45例（占比35.4%）、HPV DNA阳性肿瘤9例（占比7.1%）、E6和/或E7 mRNA阳性肿瘤7例（占比5.5%），但各指标间相关性均较弱。HPV感染状态与患者人口学特征及组织病理学特征均无显著关联。p16阳性患者的病因特异性生存率显著优于p16阴性患者（p=0.037）。
结论：本研究中HPV感染率及p16阳性率均相对较低，且p16表达状态并非HPV感染状态的可靠替代标志物。本研究结果证实了p16表达在舌活动部癌预后评估中的重要价值。