探讨高危型人乳头瘤病毒(HR-HPV)检测联合p16基因异常甲基化检测对宫颈癌患者的早期诊断价值。

选择2019年6月至2021年6月在南通市妇幼保健院进行宫颈活组织病理学检查(诊断宫颈病变的金标准)并自愿接受HR-HPV检测与p16基因异常甲基化检测的182例女性受检者为研究对象。对这182例受检者，选取HPV-16、-18、-31、-33等14种HR-HPV进行检测与分析。对不同宫颈病变者的HR-HPV感染阳性率及p16基因异常甲基化阳性率比较，采用线性趋势χ²检验。对不同种类HR-HPV感染呈阳性患者的p16基因异常甲基化阳性率比较，采用χ²检验。采用受试者工作特征(ROC)曲线评价HR-HPV检测、p16基因异常甲基化检测单独及二者联合对宫颈癌患者的诊断价值。本研究遵循的程序符合南通市妇幼保健院医学伦理委员会标准，并经过该伦理委员会批准(审批文号：Y2020090)。

①对182例受检者的宫颈活组织病理学检查结果显示，宫颈组织正常或宫颈炎症、宫颈上皮内瘤变(CIN)1~3、宫颈鳞状细胞癌(SCC)分别为19、30、55、61、17例；HR-HPV检测结果显示，HR-HPV感染阳性率为87.4%(159/182)；p16基因异常甲基化检测结果显示，该基因甲基化阳性率为25.3%(46/182)。②随着宫颈病变程度加重，受检者HPV-16/-18感染阳性率及p16基因异常甲基化阳性率均呈升高趋势(χ²＝7.07、19.51，P＝0.008、<0.001)。HPV-16/-18感染呈阳性者的p16基因异常甲基化阳性率，显著高于其他12种HR-HPV感染呈阳性者(χ²＝10.55，P＝0.001)。③ROC曲线分析结果显示，HR-HPV检测联合p16基因异常甲基化检测，对诊断宫颈癌的曲线下面积(AUC)为0.746(95%CI：0.637~0.855)，敏感度为58.8%，特异度为84.8%；DeLong检验结果显示，上述联合检测的AUC，显著高于单独HR-HPV检测及单独p16基因异常甲基化检测的AUC，并且差异均有统计学意义(Z＝－3.24、P＝0.001，Z＝－3.74，P<0.001)。

HR-HPV检测联合p16基因异常甲基化检测，可提高宫颈癌患者的总体诊断效能及特异度，但是其敏感度仍有限。

To explore the value of combined high-risk human papillomavirus (HR-HPV) testing and abnormal p16 gene methylation detection for the early diagnosis of patients with cervical cancer.

From June 2019 to June 2021, a total of 182 participants undergoing cervical biopsy at the Nantong Maternal and Child Health Care Hospital were selected for this study.All participants were tested for HR-HPV typing and abnormal p16 gene methylation.This study analyzed 14 HR-HPV types, including HPV-16, -18, -31, and -33, from the participants.The HR-HPV positivity rates and abnormal p16 gene methylation positivity rates among different cervical lesion grades were compared by chi-square test for linear trend.The positivity rates of abnormal p16 gene methylation across different HR-HPV types were compared by chi-square test.The diagnostic value of HR-HPV typing, abnormal p16 gene methylation testing, and their combination was assessed using the receiver operating characteristic (ROC) curve.The procedures followed in this study met the standards of the Medical Ethics Committee of Nantong Maternal and Child Health Care Hospital and were approved by the committee (Approval No.Y2020090).

①Among the 182 participants, the cervical biopsy results showed 19 cases with a normal cervix or cervical inflammation, 30 cases with cervical intraepithelial neoplasia (CIN)1, 55 cases with CIN2, 61 cases with CIN3, and 17 cases with cervical squamous cell carcinoma (SCC); the HR-HPV positivity rate was 87.4% (159/182), and the abnormal p16 gene methylation positivity rate was 25.3% (46/182).②With increasing severity of cervical lesions, the positive rates of HPV-16/-18 and abnormal p16 gene methylation showed increasing trends (χ²=7.07, P=0.008; χ²=19.51, P<0.001).The positive rate of abnormal p16 gene methylation was higher in HPV-16/-18-positive participants than in those positive for the other 12 HR-HPV types (χ²=10.55, P=0.001).③ROC curve analysis showed that the area under the curve (AUC) of HR-HPV testing combined with abnormal p16 gene methylation detection for the diagnosis of cervical cancer was 0.746 (95%CI: 0.637-0.855), with a sensitivity of 58.8% and a specificity of 84.8%.The DeLong test showed significant differences in AUC between the combined testing and HPV testing alone, as well as between the combined testing and abnormal p16 gene methylation testing alone (Z=-3.24, P=0.001; Z=-3.74, P<0.001).

Combined HR-HPV testing and abnormal p16 gene methylation detection can improve the overall diagnostic performance and specificity for cervical cancer, although its sensitivity remains limited.