The high-risk human papillomaviruses (HR-HPVs) are involved in the development of cervical cancer. Nevertheless, there are differences in the oncogenic potential among them. HPV-16 and HPV-18 are associated with approximately 70% of cancer worldwide, and both types are the most extensively studied HR-HPV. Great variations in the prevalence of HR-HPV have been described in different countries. The impact of these variations on the epidemiology of lesions and cervical cancer is currently unknown. A high prevalence of HPV-66 has been detected in Chile. Here, we have analyzed the genetic variability of the L1 gene from HPV-66-infected Chilean women. Higher order interactions between identified mutations were analyzed by co-variation and cluster analyses. Antigenic-index alterations following L1 mutations and B-cell epitopes were predicted by BcePred algorithm. HPV-66 L1 sequences clustered phylogenetically into two main clades. The genetic variability in the HPV-66 L1 gene involved thirty nucleotide changes. Four of these were for the first time identified in this study. Some of these variants are embedded in the B-cell epitope regions. Amino acid homology in the immunodominant epitopes of HPV-66 L1 protein (DE, FG and H1 loops) was 42.9–59.1% and 28.6–68.9% compared with HPV-16 and HPV-18, respectively. The results of this research suggest that the neutralizing epitopes of HPV-66 are antigenically different compared to HPV-16 and HPV-18. Our findings show the need to perform new structural and immunological studies on HPV-66 L1 protein to evaluate the cross-protection conferred by current HPV vaccines.

中文翻译：

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在智利进行宫颈癌筛查的妇女中，人类乳头瘤病毒66型L1基因的遗传变异性。

高危型人乳头瘤病毒（HR-HPV）参与宫颈癌的发展。然而，它们之间的致癌潜力存在差异。HPV-16和HPV-18与全世界约70％的癌症相关，这两种类型都是研究最广泛的HR-HPV。HR-HPV流行率的巨大差异已在不同国家/地区描述。这些变化对病变和宫颈癌的流行病学的影响目前未知。在智利已发现HPV-66的高流行。在这里，我们分析了被HPV-66感染的智利妇女的L1基因的遗传变异。通过协变和聚类分析来分析鉴定出的突变之间的高级相互作用。BcePred算法可预测L1突变和B细胞表位后的抗原指数变化。HPV-66 L1序列在系统发育上聚集成两个主要进化枝。HPV-66 L1基因的遗传变异涉及三十个核苷酸变化。其中有四个是本研究中首次发现的。这些变体中的一些被嵌入B细胞表位区域中。与HPV-16和HPV-18相比，HPV-66 L1蛋白（DE，FG和H1环）免疫显性表位的氨基酸同源性分别为42.9-59.1％和28.6-68.9％。这项研究的结果表明，与HPV-16和HPV-18相比，HPV-66的中和表位在抗原上有所不同。