Value of combined high-risk human papillomavirus testing and abnormal p16 gene methylation detection in the early diagnosis of patients with cervical cancer

doi:10.3877/cma.j.issn.1673-5250.2026.05.003

Objective

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.

Methods

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).

Results

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).

Conclusion

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.

Key words: Human papillomavirus viruses, Genes, p16, Methylation, Uterine cervical neoplasms, Early diagnosis, Female

表1 不同宫颈病变受检者HR-HPV感染阳性率和p16基因异常甲基化阳性率比较[例数(%)]

组织学诊断	例数	HR-HPV感染检测^b		p16基因异常甲基化阳性
组织学诊断	例数	HPV-16/-18感染呈阳性	其他12种HR-HPV感染呈阳性	p16基因异常甲基化阳性
宫颈正常或宫颈炎症	19	4(21.1)	3(15.8)	0(0)
CIN1	30	14(46.7)	12(40.0)	5(16.7)
CIN2	55	30(54.5)	21(38.2)	10(18.2)
CIN3	61	34(55.7)	25(41.0)	21(34.4)
SCC	17	11(64.7)	6(35.3)	10(58.8)
χ²值^a		7.07	1.53	19.51
P值		0.008	0.216	<0.001

表1 不同宫颈病变受检者HR-HPV感染阳性率和p16基因异常甲基化阳性率比较[例数(%)]

组织学诊断	例数	HR-HPV感染检测^b		p16基因异常甲基化阳性
组织学诊断	例数	HPV-16/-18感染呈阳性	其他12种HR-HPV感染呈阳性	p16基因异常甲基化阳性
宫颈正常或宫颈炎症	19	4(21.1)	3(15.8)	0(0)
CIN1	30	14(46.7)	12(40.0)	5(16.7)
CIN2	55	30(54.5)	21(38.2)	10(18.2)
CIN3	61	34(55.7)	25(41.0)	21(34.4)
SCC	17	11(64.7)	6(35.3)	10(58.8)
χ²值^a		7.07	1.53	19.51
P值		0.008	0.216	<0.001

表2 HR-HPV感染呈阳性与阴性受检者p16基因异常甲基化阳性率比较[例数(%)]

HR-HPV感染	例数	阳性	阴性
呈阳性	159	43(27.0)	116(73.0)
呈阴性	23	3(13.0)	20(87.0)
χ²值		2.08
P值		0.149

表2 HR-HPV感染呈阳性与阴性受检者p16基因异常甲基化阳性率比较[例数(%)]

HR-HPV感染	例数	阳性	阴性
呈阳性	159	43(27.0)	116(73.0)
呈阴性	23	3(13.0)	20(87.0)
χ²值		2.08
P值		0.149

表3 不同种类HR-HPV感染呈阳性患者p16基因异常甲基化阳性率比较[例数(%)]

不同种类HR-HPV感染呈阳性^a	例数	阳性	阴性
HPV-16/-18	92	34(37.0)	58(63.0)
其他12种HR-HPV	66	9(13.6)	57(86.4)
χ²值		10.55
P值		0.001

表3 不同种类HR-HPV感染呈阳性患者p16基因异常甲基化阳性率比较[例数(%)]

不同种类HR-HPV感染呈阳性^a	例数	阳性	阴性
HPV-16/-18	92	34(37.0)	58(63.0)
其他12种HR-HPV	66	9(13.6)	57(86.4)
χ²值		10.55
P值		0.001

图1 HR-HPV感染呈阳性与p16基因异常甲基化阳性单独及联合对宫颈癌诊断的ROC曲线注：HR-HPV为高危型人乳头瘤病毒，ROC曲线为受试者工作特征曲线

表4 HR-HPV感染呈阳性与p16基因异常甲基化阳性单独及联合对宫颈癌的诊断价值分析

指标	ROC曲线			敏感度(%)	特异度(%)
指标	AUC	AUC 95%CI	P值	敏感度(%)	特异度(%)
HR-HPV感染呈阳性	0.567	0.541~0.593	<0.001	100.0	13.3
p16基因异常甲基化阳性	0.685	0.560~0.810	0.004	58.8	78.2
二者联合	0.746	0.637~0.855	<0.001	58.8	84.8

表4 HR-HPV感染呈阳性与p16基因异常甲基化阳性单独及联合对宫颈癌的诊断价值分析

指标	ROC曲线			敏感度(%)	特异度(%)
指标	AUC	AUC 95%CI	P值	敏感度(%)	特异度(%)
HR-HPV感染呈阳性	0.567	0.541~0.593	<0.001	100.0	13.3
p16基因异常甲基化阳性	0.685	0.560~0.810	0.004	58.8	78.2
二者联合	0.746	0.637~0.855	<0.001	58.8	84.8

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