High-risk human papillomavirus affects prognosis in patients with surgically treated oropharyngeal squamous cell carcinoma
High-risk human papillomavirus affects prognosis in patients with surgically treated oropharyngeal squamous cell carcinoma
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DOI：
10.1200/jco.2005.04.6136
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发表时间：
2006-12-20
影响因子：
45.3
通讯作者：
Pilotti, Silvana
中科院分区：
文献类型：
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作者：
Licitra, Lisa;Perrone, Federica;Pilotti, Silvana
目的人乳头瘤病毒（HPV） DNA肿瘤积极整合E6和E7癌基因，具有独特的生物学行为，预后较好。病毒自身整合和/或相关野生型（wt） TP53状态和/或功能性p16在多大程度上影响预后尚不清楚。为了阐明高危(HR)-HPV、TP53和p16（INK4a）状态的存在如何与临床结果相互作用，我们考虑了90例主要接受手术治疗的连续口咽癌患者的回顾性研究。结果17例（19%）患者显示完整的HPV 16 DNA （HPV阳性），除2例患者外，其余患者均有TP53, 15例可评估患者p16（INK4a）正常，17例患者均有p16表达。35例（39%）患者携带TP53突变，其中2例为HPV阳性。p16（INK4a）缺失和p16无免疫表型分别发生在28例和58例患者中，并且在突变TP53患者（分别为48%和82%）和wt TP53患者（分别为46%和77%）中分布相似。统计分析显示，hpv阳性状态对总生存率（P = 0.0018）、肿瘤复发率（P = 0.071）、二次肿瘤发生率（P = 0.0152）均有显著影响，而TP53、p16（INK4a）状态及p16表达对预后无影响。结论：我们的分子和临床结果与先前的发现一致，但与hpv阴性肿瘤相比，提供了HR-HPV口咽癌参与的生物学机制的额外信息。根据HR-HPV阳性的口咽癌复发和二次肿瘤的风险降低，治疗策略和随访程序应进行审查。
Purpose Human papillomavirus (HPV) DNA tumors actively integrating the E6 and E7 oncogenes have a distinct biologic behavior resulting in a more favorable prognosis. To which extent the viral integration by itself, and/or the associated wild-type (wt) TP53 status, and/or a functional p16 contribute to prognosis is unclear.Patients and Methods To clarify how the presence of high-risk (HR)-HPV, TP53, and p16(INK4a) status interact with clinical outcome, we considered a retrospective series of 90 consecutive oropharyngeal cancer patients treated primarily with surgery.Results Seventeen (19%) patients showed integrated HPV 16 DNA (HPV positive), wt TP53 in all but two patients, normal p16(INK4a) in 15 assessable patients, and p16 expression in all 17 patients. Thirty-five patients (39%), two of whom were HPV positive, harbored TP53 mutations. p16(INK4a) deletion and p16 null immunophenotype occurred in 28 and 58 patients, respectively, and was similarly distributed in both patients with mutated TP53 (48% and 82%, respectively) and in patients with wt TP53 (46% and 77%, respectively). Statistical analysis showed that HPV-positive status significantly affects all investigated end points: overall survival (P = .0018), incidence of tumor relapse (P = .0371), and second tumor (P = .0152), whereas TP53 and p16(INK4a) status and p16 expression were not prognostic by themselves.Conclusion Our molecular and clinical results are in agreement with previous findings but provide additional information into the biologic mechanisms involved in HR-HPV oropharyngeal cancer in comparison to HPV-negative tumors. According to the reduced risk of relapse and second tumors associated with HR-HPV positivity of oropharyngeal cancer, the therapeutic strategy and follow-up procedures should be reviewed.