The relationship between human papillomavirus status and other molecular prognostic markers in head and neck squamous cell carcinomas.

The relationship between human papillomavirus status and other molecular prognostic markers in head and neck squamous cell carcinomas.
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DOI:
10.1016/j.ijrobp.2009.02.015
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发表时间:
2009-06-01
影响因子:
7
通讯作者:
Le, Quynh-Thu
Le, Quynh-Thu
中科院分区:
医学1区
文献类型:
--
作者:
Kong, Christina S.;Narasimhan, Balasubramanian;Cao, Hongbin;Kwok, Shirley;Erickson, Julianna P.;Koong, Albert;Pourmand, Nader;Le, Quynh-Thu

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探讨人乳头瘤病毒(HPV)感染状态与肿瘤缺氧、表皮生长因子受体(EGFR)表达及肿瘤内T细胞水平等已知的头颈部肿瘤预后指标之间的关系,并探讨HPV感染状态对预后的影响。应用焦磷酸测序法对82例可评价的头颈部鳞状细胞癌患者进行了HPV检测,并与p16INK4a染色和治疗结果进行了相关分析。它与肿瘤缺氧(肿瘤PO2和碳酸氢酶[CAIX]染色)、EGFR状态和瘤内淋巴细胞表达(CD3染色)相关。通过焦磷酸测序,44%的可评估肿瘤具有较强的HPV信号。HPV强信号与p16INK4a染色及口咽部位置密切相关。在所有患者和口咽部亚组患者的进展时间(TTP,p=0.008)和总存活率(OS,p=0.004)方面,强HPV信号组的表现都明显好于其他组。P16INK4a阳性与TTP(p=0.014)和OS(p=0.00002)密切相关。HPV状态与肿瘤PO2、CAIX染色无关。然而,HPV状态与表皮生长因子受体反应性呈负相关(p=0.0006),与CD3(+)T淋巴细胞水平呈正相关(p=0.03)。无论HPV状态如何,CAIX和EGFR的过度表达都是负面预后因素,而CD3(+)T细胞水平仅在HPV(−)肿瘤中可预测预后。HPV状态是病情进展和生存的预后因素。与EGFR表达呈负相关,与T细胞浸润呈正相关。CAIX和EGFR的表达对预后的影响不受HPV状态的影响,而瘤内T细胞水平仅对HPV(−)肿瘤显著。
To evaluate the relationship between human papillomavirus (HPV) status and known prognostic makers for head and neck cancers including tumor hypoxia, epidermal growth factor receptor (EGFR) expression and intratumoral T-cell levels and to determine the prognostic impact of these markers by HPV status. HPV status in 82 evaluable head and neck squamous cell carcinomas patients was determined by pyrosequencing and related to p16INK4a staining and treatment outcomes. It was correlated with tumor hypoxia (tumor pO2 and carbonic anhydrase [CAIX] staining), EGFR status, and intratumoral lymphocyte expression (CD3 staining). Forty-four percent of evaluable tumors had strong HPV signal by pyrosequencing. There was a significant relationship between strong HPV signal and p16INK4a staining as well as oropharynx location. The strong HPV signal group fared significantly better than others, both in time to progression (TTP, p = 0.008) and overall survival (OS, p = 0.004) for all patients and for the oropharyngeal subset. Positive p16INK4a staining was associated with better TTP (p = 0.014) and OS (p = 0.00002). There was no relationship between HPV status and tumor pO2 or CAIX staining. However, HPV status correlated inversely with EGFR reactivity (p = 0.0006) and directly with CD3(+) T-lymphocyte level (p = 0.03). Whereas CAIX and EGFR overexpression were negative prognostic factors regardless of HPV status, CD3(+) T-cell levels was prognostic only in HPV(−) tumors. HPV status was a prognostic factor for progression and survival. It correlated inversely with EGFR expression and directly with T-cell infiltration. The prognostic effect of CAIX and EGFR expression was not influenced by HPV status, whereas intratumoral T-cell levels was significant only for HPV(−) tumors.
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