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首页> 外文期刊>Radiotherapy and oncology: Journal of the European Society for Therapeutic Radiology and Oncology >HPV-associated p16-expression and response to hypoxic modification of radiotherapy in head and neck cancer.
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HPV-associated p16-expression and response to hypoxic modification of radiotherapy in head and neck cancer.

机译：HPV相关的p16表达和对头颈癌放疗低氧修饰的反应。

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摘要

BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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]). CONCLUSIONS: 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.
机译：背景：与病毒阴性肿瘤相比，HPV / p16阳性头颈癌（HNSCC）对放疗的反应更好。肿瘤缺氧可诱导放射抵抗，DAHANCA 5随机试验发现低氧细胞放射增敏剂尼莫拉唑可显着改善HNSCC的预后。使用p16状态作为回顾性分层参数，我们旨在评估p16表达对HNSCC对尼莫拉唑反应的影响。材料与方法：DAHANCA 5试验的414例患者中有331例可获得治疗前肿瘤块，并通过免疫组织化学评估了p16的表达。根据放疗后5年治疗组（尼莫拉唑/安慰剂）的功能分析p16表达对结局的影响。结果：总体而言，与给予安慰剂的患者相比，接受尼莫拉唑治疗的患者的局部区域控制明显更好：危险比（HR）为0.70 [95％CI 0.52-0.93]。 p16的阳性表达也显着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衰竭发生率高于尼莫唑组（0.69 [0.50-0.95]）。然而，在p16阳性组中，接受尼莫拉唑治疗的患者的局部区域控制率与接受安慰剂的患者相似（0.93 [0.45-1.91]）。结论：HNSCC放疗后HPV / p16表达明显改善了预后。缺氧修饰可改善HPV / p16阴性肿瘤的预后，但对HPV / p16阳性肿瘤无明显益处，提示低氧放射抵抗可能与这些肿瘤在临床上无关。

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