PAX1基因甲基化与宫颈高级别上皮内病变及高危型HPV分型的关联性

目的 分析397例患者中PAX1基因甲基化与宫颈高级别上皮内病变及高危型人乳头瘤病毒(HR-HPV)分型的关联性。 方法 2019年8月至2020年10月于山东大学第二医院行宫颈薄层液基细胞学检查(TCT)和HR-HPV DNA检查的女性中,选取TCT结果异常:≥意义不明的非典型鳞状细胞(ASCUS)和/或HR-HPV阳性的患者397例;根据2020年阴道镜应用的中国专家共识,转诊阴道镜,阴道镜检查结果异常者行定点活检病理检查;RT-qPCR检测患者的PAX1甲基化程度。 结果 病理分级为宫颈上皮内瘤变3级和宫颈癌(CIN3+)(55例)与正常/宫颈炎(72例)、CIN1(36例)、CIN2(72例)患者比较,PAX1甲基化水平分别为18.64(4.01, 20.83)和20.22(19.24, 20.84)、20.33(19.65, 21.00)、20.43(15.31, 21.08),CIN3+患者PAX1甲基化程度高于正常/CIN1/CIN2的患者,差异有统计学意义(Z值分别为3.03、2.65、3.06;P值分别为0.002、0.008、0.002);HPV16阳性患者(89例)与12型高危型HPV(12HR-HPV)阳性的患者(174例)比较,PAX1甲基化水平分别为19.72(10.00, 20.91)和21.00(18.97, 21.02),前者PAX1甲基化程度高于后者,差异有统计学意义(Z=2.736,P=0.006);TCT诊断为ASCUS的患者, 病理分级CIN2+(23例)与正常/CIN1(19例)比较,PAX1甲基化水平分别为20.47(19.33, 21.18)和18.03(11.2, 20.82),前者PAX1甲基化程度高于后者,差异有统计学意义(Z=2.45, P=0.014)。 结论 PAX1甲基化程度与宫颈高级别上皮内病变及感染的HPV型别有关联,PAX1甲基化检测有助于早期识别CIN3+及ASCUS中的宫颈高级别病变,帮助ASCUS的分流、减少阴道镜的转诊率。

Correlation among PAX1 methylation,high-grade cervical intraepithelial lesions and HR-HPV classification

Objective To analyze the correlation among PAX1 methylation, cervical high-grade intraepithelial neoplasia and the type of high-risk HPV. Methods From Aug. 2019 to Oct. 2020, women who underwent thinprep cytologic test(TCT)and high-risk human papillomavirus(HR-HPV)DNA examinations in The Second Hospital of Shandong University were screened, and 397 patients with abnormal TCT results: ≥atypical squamous cells of undetermined significance(ASCUS), and/or HR-HPV positive were selected. According to the consensus of Chinese experts on the application of colposcopy in 2020, those with abnormal colposcopy results should also undergo biopsy and RT-qPCR to detect PAX1 methylation. Results Pathological grade of 397 patients were CIN3+(55 cases), normal/cervicitis(72 cases), CIN1(36 cases), and CIN2(72 cases); their PAX1 methylation levels were 18.64(4.01, 20.83), 20.22(19.24, 20.84), 20.33(19.65, 21.00), and 20.43(15.31, 21.08). The PAX1 methylation level of CIN3+ patients was higher than that of normal/CIN1/CIN2 patients(Z=3.03, 2.65, 3.06; P=0.002, 0.008, 0.002). The PAX1 methylation levels of HPV16-positive patients(89 cases)and type 12 high-risk HPV(12HR-HPV)-positive patients(174 cases)were 19.72(10.00, 20.91)and 21.00(18.97, 21.02)(Z=2.736, P=0.006). Among ASCUS patients, the methylation levels of CIN2+(23 cases)and normal/CIN1(19 cases)were 20.47(19.33, 21.18)and 18.03(11.2, 20.82)(Z=2.45, P=0.014). Conclusion The degree of PAX1 methylation is related to high-grade cervical intraepithelial lesions and HPV types. PAX1 methylation detection would benefit the early identification of CIN3+ and high-grade cervical lesions in ASCUS, help the diversion of ASCUS, and reduce the referral rate of colposcopy.