Lassen Pernille, Primdahl Hanne, Johansen Jørgen, Kristensen Claus A, Andersen Elo, Andersen Lisbeth J, Evensen Jan F, Eriksen Jesper G, Overgaard Jens
Department of Experimental Clinical Oncology, Aarhus University Hospital, Denmark.
Department of Oncology, Aarhus University Hospital, Denmark.
Radiother Oncol. 2014 Dec;113(3):310-6. doi: 10.1016/j.radonc.2014.11.032. Epub 2014 Nov 26.
HPV is found in head and neck cancer from all sites with a higher prevalence in oropharynx cancer (OPC) compared to non-OPC. HPV/p16-status has a significant impact on radiotherapy (RT) outcome in advanced OPC, but less is known about the influence in non-OPC. We analyzed HPV-associated p16-expression in a cohort of patients with stage III-IV pharynx and larynx cancer treated with primary, curatively intended (chemo-)RT, aiming to test the hypothesis that the impact of HPV/p16 also extends to tumors of non-oropharyngeal origin.
1294 patients enrolled in previously conducted DAHANCA-trials between 1992 and 2012 were identified. Tumors were evaluated by p16-immunohistochemistry and classified as positive in case of staining in >70% of tumors cells.
Thirty-eight percent (490/1294) of the tumors were p16-positive with a significantly higher frequency in OPC (425/815) than in non-OPC (65/479), p<.0001. In OPC p16-positivity significantly improved loco-regional control (LRC) (adjusted HR [95% CI]: 0.43 [0.32-0.57]), event-free survival (EFS) (HR 0.44 [0.35-0.56]), and overall survival (OS) (HR: 0.38 [0.29-0.49]), respectively, compared with p16-negativity. In non-OPC no prognostic impact of p16-status was found for either endpoint: LRC (HR: 1.13 [0.75-1.70]), EFS (HR: 1.06 [0.76-1.47]), and OS (HR: 0.82 [0.59-1.16]).
The independent influence of HPV-associated p16-expression in advanced OPC treated with primary RT was confirmed. However, RT-outcome in the group of non-OPC did not differ by tumor p16-status, indicating that the prognostic impact may be restricted to OPC only.
人乳头瘤病毒（HPV）存在于所有部位的头颈癌中，与非口咽癌（OPC）相比，口咽癌（OPC）中的患病率更高。HPV/p16状态对晚期OPC的放疗（RT）结果有显著影响，但对非OPC的影响了解较少。我们分析了一组接受根治性原发性（化疗）放疗的III-IV期咽癌和喉癌患者中HPV相关的p16表达，旨在检验HPV/p16的影响也扩展至非口咽起源肿瘤这一假设。
确定了1992年至2012年间参加先前进行的DAHANCA试验的1294例患者。通过p16免疫组织化学评估肿瘤，并在>70%的肿瘤细胞染色时分类为阳性。
38%（490/1294）的肿瘤为p16阳性，OPC（425/815）中的频率显著高于非OPC（65/479），p<0.0001。在OPC中，与p16阴性相比，p16阳性分别显著改善了局部区域控制（LRC）（调整后HR[95%CI]：0.43[0.32 - 0.57]）、无事件生存期（EFS）（HR 0.44[0.35 - 0.56]）和总生存期（OS）（HR：0.38[0.29 - 0.49]）。在非OPC中，未发现p16状态对任何终点有预后影响：LRC（HR：1.13[0.75 - 1.70]）、EFS（HR：1.06[0.76 - 1.47]）和OS（HR：0.82[0.59 - 1.16]）。
证实了HPV相关的p16表达在接受原发性放疗的晚期OPC中的独立影响。然而，非OPC组的放疗结果在肿瘤p16状态方面没有差异，表明预后影响可能仅局限于OPC。
