Marked differences in survival rate between smokers and nonsmokers with HPV 16-associated tonsillar carcinomas
Marked differences in survival rate between smokers and nonsmokers with HPV 16-associated tonsillar carcinomas
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DOI：
10.1002/ijc.23458
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发表时间：
2008-06-15
影响因子：
6.4
通讯作者：
Speel, Ernst-Jan M.
中科院分区：
文献类型：
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作者：
Hafkamp, Harriet C.;Manni, J. J.;Speel, Ernst-Jan M.
致瘤性人乳头瘤病毒（HPV）是头颈部癌，特别是扁桃体鳞状细胞癌（TSCC）亚群的一种病原体。由于HPV- dna的物理状态和使用p16（INK4A）过表达作为替代HPV标志物存在争议的数据，以及HPV和烟草消费对TSCC临床病程的影响，因此开展了本研究。采用HPV 16特异性荧光原位杂交（FISH）和p（16INK4A）特异性免疫组织化学对81例TSCC组织切片进行分析。结果与临床和人口学资料相关。在81例TSCC中，有33例（41%）通过FISH检测到HPV 16整合为点状信号，其中32例显示p16（INK4A）积累。48例hpv阴性肿瘤中仅有5例显示p16（INK4A）免疫染色（p < 0.0001）。此外，HPV的存在与低烟草摄入量（p = 0.002）和低酒精摄入量（p = 0.0117）、低分化等级（p = 0.019）、小肿瘤大小（p = 0.024）、存在局部转移（p = 0.001）和降低（loco）区域复发率（p = 0.039）显著相关。统计分析显示，吸烟显著增加TSCC的癌症死亡风险，而不吸烟的含hpv的TSCC患者的疾病特异性生存率显著提高。HPV 16整合在41%的TSCC中，并与p16（INK4A）过表达密切相关，这意味着后者是可靠的HPV生物标志物。与hpv阴性肿瘤患者相比，hpv阳性肿瘤患者预后良好，但吸烟是最强的预后指标。这些发现表明，非吸烟者扁桃体的致癌过程与吸烟者不同，前者与HPV 16感染有关。(C) 2008 Wiley-Liss, Inc。
Oncogenic human papillomavirus (HPV) is a causative agent in a subgroup of head and neck carcinomas, particularly tonsillar squamous cell carcinomas (TSCC). This study was undertaken because controversial data exist on the physical status of HPV-DNA and the use of p16(INK4A) overexpression as surrogate HPV marker, and to examine the impact of HPV and tobacco consumption on the clinical course of TSCC. Tissue sections of 81 TSCC were analyzed by HPV 16-specific fluorescence in situ hybridization (FISH) and p(16INK4A)-specific immunohistochemistry. Results were correlated with clinical and demographic data. HPV 16 integration was detected by FISH as punctate signals in 33 out of 81 (41%) TSCC, 32 of which showed p16(INK4A) accumulation. Only 5 out of 48 HPV-negative tumors showed p16(INK4A) immunostaining (p < 0.0001). The presence of HPV furthermore correlates signiticantly with low tobacco (p = 0.002) and alcohol intake (p = 0.0117), poor differentiation grade (p = 0.019), small tumor size (p = 0.024), presence of a local metastasis (p = 0.001) and a decreased (loco)regional recurrence rate (p = 0.039). Statistical analysis revealed that smoking significantly increases the risk of cancer death from TSCC and that non-smoking patients with HPV-containing TSCC show a remarkably better disease-specific survival rate. HPV 16 is integrated in 41% of TSCC and strongly correlates with p16(INK4A) overexpression, implicating the latter to be a reliable HPV biomarker. Patients with HPV-positive tumors show a favorable prognosis as compared to those with HPV-negative tumors, but tobacco use is the strongest prognostic indicator. These findings indicate that oncogenic processes in the tonsils of non-smokers differ from those occurring in smokers, the former being related to HPV 16 infection. (C) 2008 Wiley-Liss, Inc.