Tehrany Narges, Kitz Julia, Rave-Fränk Margret, Lorenzen Stephan, Li Li, Küffer Stefan, Hess Clemens F, Burfeind Peter, Reichardt Holger M, Canis Martin, Beissbarth Tim, Wolff Hendrik A
Department of Radiotherapy and Radiation Oncology, University Medical Center Göttingen, Robert-Koch-Str. 40, 37075, Göttingen, Germany.
Strahlenther Onkol. 2015 Jul;191(7):566-72. doi: 10.1007/s00066-014-0801-3. Epub 2015 Jan 10.
Superior treatment response and survival for patients with human papilloma virus (HPV)-positive head and neck cancer (HNSCC) are documented in clinical studies. However, the relevance of high-grade acute organ toxicity (HGAOT), which has also been correlated with improved prognosis, has attracted scant attention in HPV-positive HNSCC patients. Hence we tested the hypothesis that both parameters, HPV and HGAOT, are positive prognostic factors in patients with HNSCC treated with definite radiotherapy (RT) or radiochemotherapy (RCT).
Pretreatment tumor tissue and clinical records were available from 233 patients receiving definite RT (62 patients) or RCT (171 patients). HPV infection was analysed by means of HPV DNA detection or p16(INK4A) expression; HGAOT was defined as the occurrence of acute organ toxicity >grade 2 according to the Common Toxicity Criteria. Both variables were correlated with overall survival (OS) using Cox proportional hazards regression.
Positivity for HPV DNA (44 samples, 18.9 %) and p16(INK4A) expression (102 samples, 43.8 %) were significantly correlated (p < 0.01), and HGAOT occurred in 77 (33 %) patients. Overall, the 5-year OS was 23 %; stratified for p16(INK4A) expression and HGAOT, OS rates were 47 %, 42 %, 20 % and 10 % for patients with p16(INK4A) expression and HGAOT, patients with HGAOT only, patients with p16(INK4A) expression only, and patients without p16(INK4A) expression or HGAOT, respectively. After multivariate testing p16(INK4A) expression (p = 0.003) and HGAOT (p < 0.001) were significantly associated with OS.
P16(INK4A) expression and HGAOT are independent prognostic factors for OS of patients with HNSCC, whereas p16(INK4A) expression is particularly important for patients without HGAOT.
临床研究已证实，人乳头瘤病毒（HPV）阳性的头颈部癌（HNSCC）患者具有更好的治疗反应和生存率。然而，高级别急性器官毒性（HGAOT）与预后改善也相关，在HPV阳性的HNSCC患者中却很少受到关注。因此，我们检验了以下假设：HPV和HGAOT这两个参数都是接受确定性放疗（RT）或放化疗（RCT）的HNSCC患者的阳性预后因素。
有233例接受确定性RT（62例）或RCT（171例）患者的治疗前肿瘤组织和临床记录。通过HPV DNA检测或p16（INK4A）表达分析HPV感染情况；HGAOT根据常见毒性标准定义为急性器官毒性>2级的发生情况。使用Cox比例风险回归分析这两个变量与总生存期（OS）的相关性。
HPV DNA阳性（44份样本，18.9%）与p16（INK4A）表达阳性（102份样本，43.8%）显著相关（p<0.01），77例（33%）患者发生HGAOT。总体而言，5年总生存率为23%；按p16（INK4A）表达和HGAOT分层，p16（INK4A）表达和HGAOT均有的患者、仅有HGAOT的患者、仅有p16（INK4A）表达的患者以及无p16（INK4A）表达或HGAOT的患者的总生存率分别为47%、42%、20%和10%。多因素检验后，p16（INK4A）表达（p=0.003）和HGAOT（p<0.001）与总生存期显著相关。
p16（INK4A）表达和HGAOT是HNSCC患者总生存期的独立预后因素，而p16（INK4A）表达对无HGAOT的患者尤为重要。
