Yang-Chun Feng, Yuan Zhang, Cheng-Ming Liu, Yan-Chun Huang, Xiu-Min Ma
Clinical Laboratory Center, The First Affiliated Hospital of Xinjiang Medical University Clinical Laboratory Center Institute of Cancer Research, Tumor Hospital Affiliated to Xinjiang Medical University, Urumqi, People's Republic of China.
Medicine (Baltimore). 2017 Mar;96(12):e6409. doi: 10.1097/MD.0000000000006409.
Human papillomavirus (HPV) L1 gene methylation deeply involved in the progression and heterogeneity of cervical cell epithelial lesions. The DNA ploidy also represented the early lesions of cervical cell, and it was associated with different HPV infection status in different ethnic women. So, the research was to explore whether it was possible that HPV L1 gene methylation and HPV infection status as the risk factors to lead to the differences of cervical epithelial cells' lesions in different ethnics women.The flow-through hybridization and gene chip for HPV genotypes test, general characteristics, and cervical exfoliated cell samples were collected from 94 Uygur and 79 Han women with HPV-16 infection. The cases were divided into the single HPV-16 (sHPV-16) infection group and multiple HPV-16 (mHPV-16) infection group in each ethnic women. The DNA ploidy was analyzed by flow cytometry, and the methylation-sensitive high resolution melting (MS-HRM) was used to test the HPV-16 L1 gene methylation, the results of methylation was segmented into mild methylation, moderate methylation, and severe methylation groups. Multifactor logistic analysis explored the relation between DNA heteroploid and HPV-16 infection status, HPV-16 L1 gene methylation in different ethnic women.The higher proportion of mHPV-16 infection in Uygur than Han women (61.7% vs 38.0%). L1 gene methylation had statistic difference between single and mHPV-16 infection under the same ethnic women. The proportion of DNA heteroploid had statistic difference between different HPV-16 infection status or different L1 gene methylation grades in Han or Uygur women. Both L1 gene methylation and HPV infection status were the risk factors of DNA heteroploid. Compared to the sHPV-16 infection, the odds ratio (OR) of mHPV-16 infection were 4.409 (CI: 1.398-13.910) and 3.279 (CI: 1.069-10.060) in Han and Uygur women. Compared the mild L1 gene methylation, the OR of moderate L1 gene methylation were 3.313 (CI: 1.002-10.952) and 5.075 (CI: 1.385-18.603) in Han and Uygur women, the OR of severe L1 gene methylation were 20.592 (CI: 3.691-114.880) and 63.634 (CI: 10.400-389.368) in Han and Uygur women.The study first reported that HPV L1 gene methylation and HPV infection status were the risk factors to the DNA heteroploid of cervical cell in different ethnics women, HPV L1 gene methylation and infection status should be recommended to the existing system of cervical lesion screening in order to provide better serves for the HPV infected women, especially for the ethnic women with high proportion of severe L1 gene methylation and multiple infection status.
人乳头瘤病毒（HPV）L1基因甲基化深度参与宫颈细胞上皮病变的进展和异质性。DNA倍体也代表宫颈细胞的早期病变，并且在不同种族女性中它与不同的HPV感染状态相关。因此，本研究旨在探讨HPV L1基因甲基化和HPV感染状态作为危险因素是否可能导致不同种族女性宫颈上皮细胞病变存在差异。采用流氏杂交和基因芯片进行HPV基因型检测，收集94名维吾尔族和79名汉族HPV-16感染女性的一般特征及宫颈脱落细胞样本。每个种族的女性病例分为单一HPV-16（sHPV-16）感染组和多重HPV-16（mHPV-16）感染组。通过流式细胞术分析DNA倍体，采用甲基化敏感性高分辨率熔解（MS-HRM）检测HPV-16 L1基因甲基化，将甲基化结果分为轻度甲基化、中度甲基化和重度甲基化组。多因素逻辑分析探讨不同种族女性中DNA异倍体与HPV-16感染状态、HPV-16 L1基因甲基化之间的关系。维吾尔族女性中mHPV-16感染的比例高于汉族女性（61.7%对38.0%）。在同一种族女性中，L1基因甲基化在单一感染和mHPV-16感染之间存在统计学差异。汉族或维吾尔族女性中，不同HPV-16感染状态或不同L1基因甲基化等级之间的DNA异倍体比例存在统计学差异。L1基因甲基化和HPV感染状态均为DNA异倍体的危险因素。与sHPV-16感染相比，汉族和维吾尔族女性中mHPV-16感染的比值比（OR）分别为4.409（95%置信区间：1.398 - 13.910）和3.279（95%置信区间：1.069 - 10.060）。与轻度L1基因甲基化相比，汉族和维吾尔族女性中中度L1基因甲基化的OR分别为3.313（95%置信区间：1.002 - 10.952）和5.075（95%置信区间：1.385 - 18.603），重度L1基因甲基化的OR分别为20.592（95%置信区间：3.691 - 114.880）和63.634（95%置信区间：10.400 - 389.368）。该研究首次报道，HPV L1基因甲基化和HPV感染状态是不同种族女性宫颈细胞DNA异倍体的危险因素，应将HPV L1基因甲基化和感染状态纳入现有的宫颈病变筛查体系，以便为HPV感染女性，尤其是L1基因重度甲基化和多重感染状态比例较高的种族女性提供更好的服务。
