Brady Claire S, Duggan-Keen Margaret F, Davidson Judith A, Varley Jenny M, Stern Peter L
Departments of Immunology1 and Cancer Genetics2, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Wilmslow Road, Manchester M20 4BX, UK.
Transplantation Laboratory, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, UK3.
J Gen Virol. 1999 Dec;80 ( Pt 12):3233-3240. doi: 10.1099/0022-1317-80-12-3233.
Infection with human papillomavirus type 16 (HPV-16) confers a high risk for the development of cervical neoplasia. Variants of this virus may interact differentially with host genetic factors, possibly altering the disease course. Thus, HPV-16 E6 variants may differ in their ability to degrade p53 whereas the polymorphic p53 alleles may provide more or less susceptible substrates for the viral oncogene product. Also, E6 variants may differ in immunogenicity by generating different peptides for presentation by polymorphic HLA molecules to specific T cells. This study examines HPV-16 E6 sequence variation in cervical carcinomas from the UK and its relationship to polymorphism of HLA and p53 and to clinical parameters. Sequence analysis of the HPV-16 E6 ORF from 77 tumour biopsies detected the viral prototype sequence in 38% of cases. The most common variation detected was a T to G transition at base pair 350, resulting in an amino acid change from a leucine to a valine. Overall, the frequencies of 350T and 350G sequences were similar (49. 4% and 50.6% respectively). Other mutations of lower frequencies were detected together with and independently of 350G. HPV-16 E6 sequence variation at base pair 350 did not correlate with HLA genotype or clinical outcome. There was no difference in the distribution of p53 proline and arginine alleles between HPV-16-positive cervical carcinoma patients and local controls, and no influence on clinical outcome; however, there was a trend for an increased frequency of p53 arginine homozygotes among the 350T carcinoma patients.
人乳头瘤病毒16型（HPV - 16）感染会使宫颈癌变风险升高。该病毒的变体可能与宿主遗传因素存在不同的相互作用，从而可能改变疾病进程。因此，HPV - 16 E6变体在降解p53的能力上可能存在差异，而多态性p53等位基因可能为病毒癌基因产物提供或多或少易感的底物。此外，E6变体可能因产生不同的肽段，经多态性HLA分子呈递给特定T细胞，从而在免疫原性上有所不同。本研究检测了英国宫颈癌中HPV - 16 E6序列变异及其与HLA和p53多态性以及临床参数的关系。对77例肿瘤活检组织的HPV - 16 E6开放阅读框进行序列分析，在38%的病例中检测到病毒原型序列。检测到的最常见变异是第350个碱基对处的T到G转换，导致氨基酸从亮氨酸变为缬氨酸。总体而言，350T和350G序列的频率相似（分别为49.4%和50.6%）。还检测到其他低频突变，这些突变与350G同时出现或独立出现。第350个碱基对处的HPV - 16 E6序列变异与HLA基因型或临床结果无关。HPV - 16阳性宫颈癌患者与当地对照组之间p53脯氨酸和精氨酸等位基因的分布没有差异，且对临床结果没有影响；然而，在350T癌患者中，p53精氨酸纯合子的频率有增加的趋势。
