SOX1和PAX1甲基化检测对高危型人乳头瘤病毒阳性者的分流作用

The triage effect of SOX1 and PAX1 methylation detection on patients with high-risk HPV infection

目的探讨宫颈脱落细胞中性别决定区Y框蛋白1(sex determining region Y box protein 1,SOX1)和配对盒家族基因1(paired box gene 1,PAX1)甲基化对高危型人乳头瘤病毒(high-risk human papilloma virus,HRHPV)阳性者的分流作用。方法选取2022年12月至2023年6月本院宫颈癌筛查中临床资料完整的HR-HPV阳性者243例,同时进行宫颈液基细胞学(TCT)和SOX1和PAX1甲基化检测,并转诊阴道镜和宫颈活体组织检查。比较PAX1和SOX1甲基化检测在宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)及宫颈癌中的诊断效能。结果在243例患者中,病理检查结果阴性(包括宫颈正常和宫颈炎患者)126例、CIN167例、CIN228例、CIN315例及鳞状细胞癌7例。Spearman相关性分析显示,SOX1和PAX1甲基化检出率与宫颈病变等级呈正相关(r=0.577,P<0.001)。在HR-HPV阳性患者中,SOX1和PAX1甲基化检测的敏感度、特异度、阳性预测值(PPV)、阴性预测值(NPV)及ROC曲线下面积(AUC)为82.0%、89.6%、67.2%、95.1%及0.858,均高于TCT(68.0%、69.9%、37.0%、89.4%及0.690,P<0.001),且SOX1和PAX1甲基化检测与病理结果的一致性(Kappa=0.662)优于TCT与病理结果的一致性(Kappa=0.289)。在非HPV 16/18型高危型HPV患者中,SOX1和PAX1甲基化检测的效能也高于TCT,SOX1和PAX1甲基化与病理结果的一致性(Kappa=0.586)也优于TCT与病理结果的一致性(Kappa=0.242)。结论在HR-HPV阳性者中,SOX1和PAX1甲基化率与CIN级别呈正相关,较TCT而言,HR-HPV检测联合甲基化检测可提高对CIN及宫颈癌的诊断率,降低阴道镜的转诊率。

Objective To explore the triage effect of cervical cytological SOX1 and PAX1 methylation on patients with high-risk human papillomavirus(HR-HPV)infection.Methods A total of 243 HR-HPV positive patients who had complete clinical data in our hospital from December 2022 to June 2023 were selected.All study subjects were tested for TCT and SOX1 and PAX1 methylation detection,as well as colposcopy and cervical biopsy.Compared the diagnostic efficacy of these two screening methods in detecting cervical intraepithelial neoplasia(CIN)and cervical cancer.Results Among 243 patients,126 negative cases(including normal cells or inflammatory lesions),67 cases of CINⅠ,28 cases of CINⅡ,15 cases of CINⅢand 7 cases of squamous cell carcinoma.The SOX1 and PAX1 methylation rate was positively correlated with the severity of cervical lesions by Spearman Correlation(r=0.577,P<0.001).In HR-HPV positive patients,the sensitivity,specificity,positive predictive value,negative predictive value(NPV)and AUC(82.0%,89.6%,67.2%,95.1%and 0.858)of the methylation were higher than those of TCT(68.0%,69.9%,37.0%,89.4%and 0.690,P<0.001).The consistency of the methylation and the pathological diagnosis(Kappa=0.662)was better than that of the TCT(Kappa=0.289).In the HR-HPV(except HPV16/18)positive subgroup analysis,the sensitivity,specificity,positive predictive value,negative predictive value and AUC of the methylation were higher than those of TCT(P<0.001).The consistency of the methylation and the pathological diagnosis(Kappa=0.586)was better than that of the TCT(Kappa=0.242).Conclusions The SOX1 and PAX1 methylation rate was positively correlated with the severity of cervical intraepithelial neoplasia in patients with high-risk HPV infection.Compared with TCT,HR-HPV detection combined with SOX1 and PAX1 methylation detection improves the diagnostic rate of cervical intraepithelial neoplasia and cervical cancer and reduce the referral rate for colposcopy.