Junes-Gill Katiana, Sichero Laura, Maciag Paulo Cesar, Mello Wyller, Noronha Vânia, Villa Luisa Lina
Department of Virology, Ludwig Institute for Cancer Research, São Paulo, Brazil.
J Med Virol. 2008 Sep;80(9):1639-45. doi: 10.1002/jmv.21238.
Several studies indicate that molecular variants of HPV-16 have different geographic distribution and risk associated with persistent infection and development of high-grade cervical lesions. In the present study, the frequency of HPV-16 variants was determined in 81 biopsies from women with cervical intraepithelial neoplasia grade III or invasive cervical cancer from the city of Belem, Northern Brazil. Host DNAs were also genotyped in order to analyze the ethnicity-related distribution of these variants. Nine different HPV-16 LCR variants belonging to four phylogenetic branches were identified. Among these, two new isolates were characterized. The most prevalent HPV-16 variant detected was the Asian-American B-2, followed by the European B-12 and the European prototype. Infections by multiple variants were observed in both invasive cervical cancer and cervical intraepithelial neoplasia grade III cases. The analysis of a specific polymorphism within the E6 viral gene was performed in a subset of 76 isolates. The E6-350G polymorphism was significantly more frequent in Asian-American variants. The HPV-16 variability detected followed the same pattern of the genetic ancestry observed in Northern Brazil, with European, Amerindian and African roots. Although African ancestry was higher among women infected by the prototype, no correlation between ethnical origin and HPV-16 variants was found. These results corroborate previous data showing a high frequency of Asian-American variants in cervical neoplasia among women with multiethnic origin.
多项研究表明,人乳头瘤病毒16型(HPV-16)的分子变体具有不同的地理分布,且与持续感染及高级别宫颈病变的发生风险相关。在本研究中,对来自巴西北部贝伦市的81例宫颈上皮内瘤变III级或浸润性宫颈癌女性患者的活检样本进行了HPV-16变体频率测定。还对宿主DNA进行了基因分型,以分析这些变体与种族相关的分布情况。共鉴定出属于四个系统发育分支的九种不同的HPV-16长控制区(LCR)变体。其中,对两个新分离株进行了特征描述。检测到的最常见的HPV-16变体是亚美B-2型,其次是欧洲B-12型和欧洲原型株。在浸润性宫颈癌和宫颈上皮内瘤变III级病例中均观察到多种变体感染。对76个分离株的一个子集进行了E6病毒基因内特定多态性的分析。E6-350G多态性在亚美变体中明显更为常见。检测到的HPV-16变异性与在巴西北部观察到的遗传谱系模式相同,具有欧洲、美洲印第安人和非洲根源。尽管在感染原型株的女性中非洲血统比例较高,但未发现种族起源与HPV-16变体之间存在相关性。这些结果证实了先前的数据,即多民族女性宫颈癌中亚美变体的频率较高。