Translational Radiobiology Group, Institute of Cancer Sciences, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK.
Clin Oncol (R Coll Radiol). 2013 Nov;25(11):630-8. doi: 10.1016/j.clon.2013.07.003. Epub 2013 Jul 31.
There is an increasing incidence of human papillomavirus (HPV)-positive oropharyngeal squamous cell cancers (OPSCC) mostly associated with favourable outcomes. p16 immunohistochemistry is a surrogate marker for HPV positivity in OPSCC. The prognostic strength of p16 over traditional prognostic factors is not fully characterised. In this study, we evaluated the clinical and demographic differences between p16-positive and -negative OPSCC and characterised its prognostic strength versus traditional prognostic factors.
Formalin-fixed, paraffin-embedded blocks and clinical information from 217 OPSCC patients, treated with radiotherapy (alone or in combination with other therapies) between 2000 and 2010 were collected retrospectively. Immunohistochemistry for p16 protein was carried out; cancer-specific survival (CSS), recurrence-free survival (RFS) and locoregional control (LRC) were calculated for both univariate and multivariate analyses.
Ninety-two per cent of the OPSCC originated from tonsil and tongue base sites, 61% were p16 positive. Patients with p16-positive OPSCC were younger (P < 0.0001), with lower alcohol (P = 0.0002) and tobacco (P = 0.0001) exposure. The tumours were less differentiated (P = 0.0069), had a lower T stage (P = 0.0027), higher nodal status (P = 0.014) and higher American Joint Committee on Cancer (AJCC) prognostic group (P = 0.0036). AJCC prognostic group was significant for RFS (P = 0.0096) and CSS (P = 0.018) in patients with p16-negative OPSCC, but not those with p16-positive tumours (P = 0.30 and 0.54). Other significant factors for CSS and RFS in univariate analysis were: pretreatment haemoglobin (P < 0.0001 and <0.0001), chemoradiotherapy (P = 0.005 and 0.03) and P16 status (P < 0.0001 and 0.0001). In multivariate analysis, p16 positivity was the strongest independent prognostic variable for both CSS, RFS and LRC (P < 0.0001, hazard ratio 4.15; 95% confidence interval 2.43-7.08), (P < 0.0001, hazard ratio 6.15; 95% confidence interval 3.57-10.61) and (P = 0.001, hazard ratio 3.74; confidence interval 1.76-7.95).
This study shows that p16 is the single most important prognostic variable in OPSCC, surpassing traditional prognostic factors for both CSS and RFS. Furthermore, disease stage has no prognostic significance in p16-positive patients, highlighting the need for routine p16 assessment in OPSCC.
人乳头瘤病毒（HPV）阳性口咽鳞状细胞癌（OPSCC）的发病率不断上升，其预后通常较好。p16 免疫组化是 OPSCC 中 HPV 阳性的替代标志物。p16 比传统预后因素在预后方面的优势尚未完全明确。本研究评估了 p16 阳性和阴性 OPSCC 之间的临床和人口统计学差异，并对其与传统预后因素相比的预后优势进行了特征描述。
回顾性收集了 217 例接受单纯放疗或联合其他治疗的 OPSCC 患者的福尔马林固定、石蜡包埋组织块和临床资料，这些患者于 2000 年至 2010 年接受治疗。对 p16 蛋白进行免疫组织化学检测，对单因素和多因素分析中的癌症特异性生存率（CSS）、无复发生存率（RFS）和局部区域控制率（LRC）进行了计算。
92%的 OPSCC 起源于扁桃体和舌根部位，61%为 p16 阳性。p16 阳性 OPSCC 患者更年轻（P<0.0001），酒精（P=0.0002）和烟草暴露（P=0.0001）程度更低。肿瘤分化程度更低（P=0.0069），T 分期更低（P=0.0027），淋巴结状态更高（P=0.014），美国癌症联合委员会（AJCC）预后组更高（P=0.0036）。在 p16 阴性 OPSCC 患者中，AJCC 预后组对 RFS（P=0.0096）和 CSS（P=0.018）具有显著意义，但在 p16 阳性肿瘤患者中则无显著意义（P=0.30 和 0.54）。CSS 和 RFS 的单因素分析中其他显著因素为：治疗前血红蛋白（P<0.0001 和 <0.0001）、放化疗（P=0.005 和 0.03）和 P16 状态（P<0.0001 和 0.0001）。多因素分析中，p16 阳性是 CSS、RFS 和 LRC 的最强独立预后因素（P<0.0001，风险比 4.15；95%置信区间 2.43-7.08）、（P<0.0001，风险比 6.15；95%置信区间 3.57-10.61）和（P=0.001，风险比 3.74；置信区间 1.76-7.95）。
本研究表明，p16 是 OPSCC 中最重要的单一预后因素，超越了 CSS 和 RFS 的传统预后因素。此外，p16 阳性患者的疾病分期无预后意义，突出了在 OPSCC 中常规进行 p16 评估的必要性。
