Department of Obstetrics and Gynecology, Showa University School of Medicine, Shinagawa-ku, Tokyo 142-8666, Japan.
Pathogen Genomics Center, National Institute of Infectious Diseases, Musashi-murayama, Tokyo 208-0011, Japan.
Viruses. 2019 Apr 16;11(4):350. doi: 10.3390/v11040350.
Recent large-scale genomics studies of human papillomaviruses (HPVs) have shown a high level of genomic variability of HPV16, the most prevalent genotype in HPV-associated malignancies, and provided new insights into the biological and clinical relevance of its genetic variations in cervical cancer development. Here, we performed deep sequencing analyses of the viral genome to explore genetic variations of HPV16 that are prevalent in Japan. A total of 100 complete genome sequences of HPV16 were determined from cervical specimens collected from Japanese women with cervical intraepithelial neoplasia and invasive cervical cancer, or without cervical malignancies. Phylogenetic analyses revealed the variant distribution in the Japanese HPV16 isolates; overall, lineage A was the most prevalent (94.0%), in which sublineage A4 was dominant (52.0%), followed by sublineage A1 (21.0%). The relative risk of sublineage A4 for cervical cancer development was significantly higher compared to sublineages A1/A2/A3 (odds ratio = 6.72, 95% confidence interval = 1.78-28.9). Interestingly, a novel cluster of variants that branched from A1/A2/A3 was observed for the Japanese HPV16 isolates, indicating that unique HPV16 variants are prevalent among Japanese women.
最近对人类乳头瘤病毒 (HPV) 的大规模基因组研究表明，HPV16 的基因组变异程度很高，HPV16 是 HPV 相关恶性肿瘤中最常见的基因型，并为其在宫颈癌发展中的遗传变异的生物学和临床相关性提供了新的见解。在这里，我们对 HPV16 的病毒基因组进行了深度测序分析，以探索在日本流行的 HPV16 遗传变异。从日本患有宫颈上皮内瘤变和浸润性宫颈癌或无宫颈癌的女性的宫颈标本中确定了总共 100 个 HPV16 的完整基因组序列。系统发育分析显示了日本 HPV16 分离株中的变异分布；总体而言，A 谱系是最常见的（94.0%），其中亚谱系 A4 占优势（52.0%），其次是亚谱系 A1（21.0%）。与 A1/A2/A3 亚谱系相比，亚谱系 A4 发生宫颈癌的相对风险明显更高（比值比=6.72，95%置信区间=1.78-28.9）。有趣的是，观察到日本 HPV16 分离株中存在一个从 A1/A2/A3 分支出来的新变体簇，表明日本女性中存在独特的 HPV16 变体。
