Stephen A L, Thompson C H, Tattersall M H, Cossart Y E, Rose B R
Department of Infectious Diseases, Faculty of Medicine, University of Sydney, Sydney, Australia.
Int J Cancer. 2000 Jun 1;86(5):695-701. doi: 10.1002/(sici)1097-0215(20000601)86:5<695::aid-ijc15>3.0.co;2-c.
High rates of cervical cancer have been reported from parts of China and this may reflect a predominance of cervical infection with particularly aggressive human papillomavirus (HPV) variants. This PCR-based investigation of cervical tumours from Sichuan province in central China demonstrated an HPV positivity rate of 88%. HPV 16 was most common (21/34, 61%), followed by HPV 18 (3/34, 9%), while types 33, 45, 58 and 59 were each identified in one specimen. Sequencing of up to 1349 bases of the 21 HPV 16-positive isolates, encompassing the enhancer/promoter of the upstream regulatory region (URR) and the E6 and E7 genes, revealed distinct patterns of genomic stability and variability. An overall mutation rate of 5% was seen in the URR. One isolate had a large deletion of 436 bases in the enhancer; while varying combinations of 21 point mutations were identified in the remainder, impacting several YY1, NF1, TEF-1 and Oct-1 sites. More sequence variations were found in E6 compared to E7 (81% vs. 52% of isolates showing at least one mutation), some of which resulted in changes to the translated amino acids. Since the E6/E7 genes encode the oncogenic proteins essential for malignant transformation, and as their expression is controlled by the URR, it is possible that some of the identified mutations altered the oncogenicity of the virus: either directly by changing amino acid sequences of the E6 or E7 oncoproteins, or indirectly through alterations to transcription factor binding sites in the URR.
中国部分地区报告了较高的宫颈癌发病率，这可能反映出宫颈感染了具有特别侵袭性的人乳头瘤病毒（HPV）变异株。这项基于聚合酶链反应（PCR）对中国中部四川省宫颈肿瘤的调查显示，HPV阳性率为88%。HPV 16最为常见（21/34，61%），其次是HPV 18（3/34，9%），而33、45、58和59型各在一个标本中被鉴定出来。对21株HPV 16阳性分离株长达1349个碱基进行测序，包括上游调控区（URR）的增强子/启动子以及E6和E7基因，揭示了基因组稳定性和变异性的不同模式。URR的总体突变率为5%。一个分离株在增强子中有436个碱基的大片段缺失；而在其余分离株中鉴定出21种点突变的不同组合，影响了几个YY1、NF1、TEF-1和Oct-1位点。与E7相比，E6中发现了更多的序列变异（81%的分离株与52%的分离株显示至少一个突变），其中一些导致了翻译后的氨基酸变化。由于E6/E7基因编码恶性转化所必需的致癌蛋白，并且它们的表达受URR控制，因此有可能一些已鉴定的突变改变了病毒的致癌性：要么直接通过改变E6或E7致癌蛋白的氨基酸序列，要么间接通过改变URR中转录因子结合位点。
