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    ZNF772甲基化及HR-HPV检测在意义不明的非典型鳞状细胞病人分流中的意义

    Significance of ZNF772 methylation and HR-HPV detection in shunt of patients with atypical squamous cell of unknown significance

      摘要
    • 摘要:
      目的 探讨锌指蛋白(ZNF)772甲基化及高危型人乳头瘤病毒(HR-HPV)检测在意义不明的非典型鳞状细胞(ASCUS)病人分流中的意义。
      方法 选取初筛ASCUS病人195例，均接受HC2-HPV-DNA检测及ZNF772基因DNA甲基化检测；比较宫颈上皮内瘤样变(CIN)Ⅱ及以上与CINⅡ以下、CINⅢ及以上及CINⅢ以下病人ZNF772基因位点甲基化水平的差异，并评估ZNF772甲基化水平及HR-HPV对ASCUS病人CINⅡ及以上、CINⅢ及以上的分流价值。
      结果 病理学检查显示，195例ASCUS病人中炎症80例(41.03%)、CINⅠ64例(32.82%)、CINⅡ29例(14.87%)、CINⅢ/CIS/AIS 18例(9.23%)、SCC/AC 4例(2.05%)。HR-HPV(HC2)阳性141例(72.31%)、HR-HPV(HC2)阴性54例(27.69%)；CINⅡ及以上病人HR-HPV(HC2)阳性检出率高于CINⅡ以下(P < 0.05)；CINⅢ及以上病人HR-HPV(HC2)阳性检出率高于CINⅢ以下(P < 0.05)。CINⅡ及以上、CINⅢ及以上病人ZNF772基因-420、-422位点甲基化水平分别高于CINⅡ以下、CINⅢ以下病人(P < 0.05)。ZNF772基因-420、-422位点甲基化水平及HR-HPV诊断CINⅡ及以上的AUC(95%CI)分别为0.867(0.811~0.911)、0.806(0.743~0.859)、0.777(0.712~0.834)，诊断CINⅢ及以上的AUC(95%CI)分别为0.891(0.838~0.931)、0.868(0.813~0.912)、0.780(0.716~0.836)。ZNF772基因-420位点甲基化水平诊断CINⅡ及以上、CINⅢ及以上的AUC面积最大。
      结论 相较于HC2-HPV-DNA检测，ZNF772甲基化检测更能准确地识别ASCUS中CINⅡ及以上、CINⅢ及以上病变病人，有望成为分流ASCUS的有效替代手段。

       

      Abstract:
      Objective To explore the significance of zinc finger protein (ZNF) 772 methylation and high-risk human papillomavirus (HR-HPV) detection in the shunt of patients with atypical squamous cell of unknown significance (ASCUS).
      Methods A total of 195 initially screened ASCUS patients were selected, all of whom underwent HC2-HPV-DNA testing and ZNF772 gene DNA methylation testing.The differences in ZNF772 gene site methylation levels between patients with cervical intraepithelial neoplasia (CIN) Ⅱ and above and those with CIN Ⅱ and below, CIN Ⅲ and above and CIN Ⅲ and below were compared, and the ZNF772 methylation level and HR-HPV shunt value for ASCUS patients with CIN Ⅱ and above and CIN Ⅲ and above were evaluated.
      Results Pathological examination showed that among 195 ASCUS patients, there were 80 cases of inflammation (41.03%), 64 cases of CIN Ⅰ (32.82%), 29 cases of CIN Ⅱ (14.87%), 18 cases of CIN Ⅲ/CIS/AIS (9.23%), and 4 cases of SCC/AC (2.05%).One hundred and forty-one cases (72.31%) were positive for HR-HPV (HC2), and 54 cases (27.69%) were negative for HR-HPV (HC2);The positive detection rate of HR-HPV (HC2) in patients with CIN Ⅱ and above was higher than that in patients with CIN Ⅱ and below (P < 0.05).The positive detection rate of HR-HPV (HC2) in patients with CIN Ⅲ and above is higher than that in patients with CIN Ⅲ and below (P < 0.05).The methylation levels at the -420 and -422 loci of the ZNF772 gene in patients with CIN Ⅱ and above and CIN Ⅲ and above were higher than those in patients with CIN Ⅱ and below (P < 0.05).The methylation levels at the -420 and -422 loci of the ZNF772 gene and the AUC (95%CI) for HR-HPV diagnosis of CIN Ⅱ and above were 0.867 (0.811-0.911), 0.806 (0.743-0.859), and 0.777 (0.712-0.834), respectively. The AUC (95%CI) for diagnosis of CIN Ⅲ and above were 0.891 (0.838-0.931), 0.868 (0.813-0.912), and 0.780 (0.716-0.836), respectively.The highest AUC area was detected for CIN Ⅱ and above, as well as CIN Ⅲ and above, based on the methylation level at the -420 locus of the ZNF772 gene.
      Conclusions Compared with HC2-HPV-DNA detection, ZNF772 methylation detection can more accurately identify patients with CIN Ⅱ and above and CIN Ⅲ and above lesions in ASCUS, and is expected to become an effective alternative to shunt ASCUS.

       

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