Department of Experimental Clinical Oncology, Aarhus University Hospital, Noerrebrogade 44, DK-8000 Aarhus C, Denmark.
Radiother Oncol. 2010 Jan;94(1):30-5. doi: 10.1016/j.radonc.2009.10.008. Epub 2009 Nov 10.
HPV/p16-positive head and neck cancers (HNSCC) show superior response to radiotherapy, compared with virus-negative tumours. Tumour hypoxia induces radioresistance and the randomised DAHANCA 5 trial found that the hypoxic cell radiosensitiser nimorazole significantly improved the outcome in HNSCC. Using p16-status as a retrospective stratification parameter, we aimed to assess the influence of p16-expression on the response to nimorazole in HNSCC.
Pre-treatment tumour blocks were available from 331 of the 414 patients in the DAHANCA 5 trial and evaluated by immunohistochemistry for p16-expression. The influence of p16-expression on outcome was analysed as a function of treatment group (nimorazole/placebo) 5 years after radiotherapy.
Overall, patients treated with nimorazole had significantly better loco-regional control than did those given placebo: hazard ratio (HR) 0.70 [95% CI 0.52-0.93]. Positive expression of p16 also significantly improved outcome after radiotherapy (0.41 [0.28-0.61]). In the subgroup of patients with p16-negative tumours, loco-regional failure was more frequent in the placebo group than in the nimorazole group (0.69 [0.50-0.95]). However, in the p16-positive group, patients treated with nimorazole had a loco-regional control rate similar to patients given placebo (0.93 [0.45-1.91]).
HPV/p16-expression significantly improved outcome after radiotherapy in HNSCC. Hypoxic modification improved outcome in HPV/p16-negative tumours but was of no significant benefit in HPV/p16-positive tumours, suggesting that hypoxic radioresistance may not be clinically relevant in these tumours.
HPV/p16 阳性头颈部癌症（HNSCC）对放疗的反应优于病毒阴性肿瘤。肿瘤缺氧会诱导放射抵抗，随机 DAHANCA 5 试验发现，缺氧细胞放射增敏剂尼莫唑胺显著改善了 HNSCC 的治疗效果。本研究采用 p16 状态作为回顾性分层参数，旨在评估 p16 表达对头颈部癌症对尼莫唑胺反应的影响。
来自 DAHANCA 5 试验的 414 例患者中的 331 例有治疗前肿瘤标本，采用免疫组织化学方法检测 p16 表达情况。分析 p16 表达对放疗后 5 年治疗组（尼莫唑胺/安慰剂）疗效的影响。
总体而言，接受尼莫唑胺治疗的患者局部区域控制明显优于接受安慰剂治疗的患者：风险比（HR）为 0.70（95%CI 0.52-0.93）。p16 阳性表达也显著改善了放疗后的预后（0.41[0.28-0.61]）。在 p16 阴性肿瘤患者亚组中，安慰剂组的局部区域失败率高于尼莫唑胺组（0.69[0.50-0.95]）。然而，在 p16 阳性组中，接受尼莫唑胺治疗的患者局部区域控制率与接受安慰剂治疗的患者相似（0.93[0.45-1.91]）。
HPV/p16 表达对头颈部癌症放疗后疗效有显著改善。缺氧修饰改善了 HPV/p16 阴性肿瘤的疗效，但对 HPV/p16 阳性肿瘤没有显著获益，提示这些肿瘤中缺氧放射抵抗可能在临床上并不重要。
