Pande Shailja, Jain Neeraj, Prusty Bhupesh K, Bhambhani Suresh, Gupta Sanjay, Sharma Rajyashri, Batra Swaraj, Das Bhudev C
Division of Molecular Oncology, Institute of Cytology and Preventive Oncology, I-7, Sector 39, Noida 201301, India.
J Clin Microbiol. 2008 Mar;46(3):1060-6. doi: 10.1128/JCM.02202-07. Epub 2008 Jan 16.
High-risk human papillomaviruses (HPVs), particularly HPV types 16 and 18 (HPV-16 and HPV-18, respectively), play a cardinal role in the etiology of cervical cancer. The most prevalent type, HPV-16, shows intratypic sequence variants that are known to differ in oncogenic potential and geographic distribution. This study was designed to analyze sequence variations in E6, E7, and L1 genes and the LCR (for long control region) of HPV-16 in cervical cancer patients to identify the most prevalent and novel HPV-16 variants and to correlate them with the severity of the disease. Cervical biopsies from 60 HPV-16-positive cancer cases were analyzed by PCR and DNA sequencing. The most frequently observed variations were T350G (100%) in E6, T789C (87.5%) in E7, A6695C (54.5%) in L1, and G7521A (91.1%) in the LCR. In addition, only one novel variant (T527A) in E6 and four new variants each in L1 (A6667C, A6691G, C6906T, and A6924C) and in the LCR (C13T, A7636C, C7678T, and G7799A) were identified. While E7 was found to be highly conserved, the variant 350G of E6 was the most prevalent in all of the histopathological grades. The majority of LCR variants were found at the YY1 transcription factor binding sites. Interestingly, a complete absence of the Asian lineage and a high prevalence of European lineages in E6, E7, L1, and the LCR (85, 86.7, 67.7, and 63.3%, respectively) indicate a possible epidemiological linkage between Europe and India with regard to the dissemination of HPV-16 infections in India.
高危型人乳头瘤病毒（HPV），尤其是16型和18型HPV（分别为HPV-16和HPV-18），在宫颈癌病因学中起主要作用。最常见的类型HPV-16，显示出已知在致癌潜力和地理分布上存在差异的型内序列变异。本研究旨在分析宫颈癌患者中HPV-16的E6、E7和L1基因以及长控制区（LCR）的序列变异，以确定最常见和新的HPV-16变异体，并将它们与疾病严重程度相关联。通过PCR和DNA测序分析了60例HPV-16阳性癌症病例的宫颈活检样本。最常观察到的变异为E6中的T350G（100%）、E7中的T789C（87.5%）、L1中的A6695C（54.5%）以及LCR中的G7521A（91.1%）。此外，仅在E6中鉴定出一个新变异体（T527A），在L1（A6667C、A6691G、C6906T和A6924C）和LCR（C13T、A7636C、C7678T和G7799A）中各鉴定出四个新变异体。虽然发现E7高度保守，但E6的350G变异体在所有组织病理学分级中最为常见。大多数LCR变异体位于YY1转录因子结合位点。有趣的是，在E6、E7、L1和LCR中完全没有亚洲谱系，而欧洲谱系的高流行率（分别为85%、86.7%、67.7%和63.3%）表明在印度HPV-16感染传播方面欧洲和印度之间可能存在流行病学联系。
