Biological and clinical relevance of transcriptionally active human papillomavirus (HPV) infection in oropharynx squamous cell carcinoma
Biological and clinical relevance of transcriptionally active human papillomavirus (HPV) infection in oropharynx squamous cell carcinoma
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DOI：
10.1002/ijc.24911
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发表时间：
2010-04-15
影响因子：
6.4
通讯作者：
Wasylyk, Bohdan
中科院分区：
文献类型：
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作者：
Jung, Alain C.;Briolat, Jenny;Wasylyk, Bohdan
人乳头瘤病毒 (HPV) 与头颈鳞状细胞癌 (HNSCC) 的一部分相关，特别是 HPV16。本研究分析了 231 例连续 HNSCC 中高危 HPV 的存在和基因型、病毒 DNA 载量以及 E6/E7 mRNA 的转录。 30 个 HPV16 DNA 阳性肿瘤中有 12 个显示出高 E6/E7 mRNA 水平，并且位于口咽区域。虽然无 HPV 和非转录活性 HPV 相关患者的 5 年生存率相似，但 E6/E7 表达与更好的预后相关。这强调了考虑 HPV 阳性肿瘤的转录状态对于患者分层的重要性。对这些不同类型的肿瘤进行了基因表达谱分析。最显着的差异表达基因是 CDKN2A，它是 HPV 相关癌症的已知生物标志物。需要评估 HNSCC 中 E6/E7 mRNA 和 CDKN2A 的表达水平来检测活动性 HPV 感染。通过对具有转录活性 HPV 的肿瘤和 HPV 阴性肿瘤进行比较基因组杂交 (CGH) 分析来研究染色体改变。发现染色体区域 16q 的丢失是 HPV 阳性病变中的一个主要遗传事件。位于 16q21-24 的一组基因表现出表达水平下降，特别是参与 p53 转录活性调节的 APP-BP1。总之，这项研究强调了预测临床活跃 HPV 感染所需的重要标准，确定了与 HPV 肿瘤发生有关的新生物学途径，并增加了对 HPV-HNSCC 病理生理学的了解，这是开发新治疗靶点所需的。
Human papillomaviruses (HPV) are associated with a subset of head and neck squamous cell carcinoma (HNSCC), particularly HPV16. This study analyzed the presence and genotype of high risk HPVs, viral DNA load and transcription of the E6/E7 mRNAs, in 231 consecutive HNSCC. Twelve out of 30 HPV16 DNA-positive tumors displayed high E6/E7 mRNAs levels and were localized in the oropharyngeal region. While HPV-free and non-transcriptionally active HPV-related patients showed similar 5-years survival rates, E6/E7 expression was associated with a better prognosis. This emphasizes the importance of considering the transcriptional status of HPV-positive tumors for patient stratification. A gene expression profiling analysis of these different types of tumors was carried out. The most significant differentially expressed gene was CDKN2A, a known biomarker for HPV-related cancer. Assessing both the expression level of the E6/E7 mRNAs and of CDKN2A in HNSCC is required to detect active HPV infection. Chromosomic alterations were investigated by Comparative Genomic Hybridation (CGH) analysis of tumors with transcriptionally active HPV and HPV-negative tumors. The loss of the chromosomal region 16q was found to be a major genetic event in HPV-positive lesions. A cluster of genes located in 16q21-24 displayed decreased expression levels, notably APP-BP1 that is involved in the modulation of the transcriptional activity of p53. In conclusion, this study highlights important criteria required to predict clinically active HPV infection, identifies new biological pathways implicated in HPV tumorigenesis and increases the understanding of HPV-HNSCC physiopathology that is required to develop new targets for therapy.