Application of GYPC gene methylation detection in cervical cancer screening for HR-HPV-positive women

doi:10.16150/j.1671-2870.2025.01.010

Abstract

Abstract:

Objective To investigate the diagnostic efficacy of GYPC (Glypican) gene methylation (GYPC^m) in cervical exfoliated cells for detecting cervical cancer and precancerous lesions among women infected with high-risk human pa-pillomavirus (HR-HPV). Methods This study enrolled a total of 187 HR-HPV-positive women who underwent histopathological examination of colposcopy-guided biopsy at the hospital from October 2022 to July 2023, with a median age of 40.0 years (range: 17-75 years). Cervical exfoliated cells were collected before colposcopy for cytological testing, and the remai-ning specimens were tested for GYPC^m status. Using the results of histopathological examination of colposcopy-guided biopsy as the gold standard, this study analyzed the diagnostic efficacy of GYPC^m for detecting cervical cancer and precancerous lesions and compared it with cytological test results. Results The ΔCp value of GYPC^m decreased significantly with increa-sing severity of cervical lesions. At a cutoff value of 15.975, the areas under the receiver operating characteristic(ROC) curves for detecting cervical intraepithelial neoplasia grade 2 or higher (CIN2+) and grade 3 or higher (CIN3+) were 0.800 (95% CI: 0.733-0.867) and 0.856 (95% CI: 0.784-0.928), respectively. To ensure that the sensitivity of GYPC^m detection for CIN3+ was not inferior to cytological testing, the optimal cutoff value was determined to be ΔCp = 15.975. The positive rate of GYPC^m detection in patients with cervical squamous cell carcinoma (SCC) was 100%. For CIN3+, the diagnostic sensitivity of GYPC^m detection was comparable to that of cytological testing (86.7% vs. 84.4%, P=0.782), with no statistically significant difference. However, GYPC^m detection demonstrated significantly higher specificity (65.5% vs. 29.6%, P<0.001) and positive predictive value (44.3% vs. 27.5%, P<0.001) compared with cytological testing. For CIN2+, the specificity and positive predictive value of GYPC^m were significantly higher than those of cytological testing (both P<0.001). Conclusions GYPC^m detection can serve as an effective triage tool for HR-HPV-positive women in cervical cancer scree-ning, offering better diagnostic efficacy compared with cytological testing.

Key words: GYPC methylation, Cervical intraepithelial neoplasia, Cervical cancer, High-risk human papillomavirus

CLC Number:

R737.33

LUO Haijun, LIAN Yixiang, WANG Zhigan, JIANG Shali. Application of GYPC gene methylation detection in cervical cancer screening for HR-HPV-positive women[J]. Journal of Diagnostics Concepts & Practice, 2025, 24(01): 65-71.

Figures/Tables 5

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Cut-off (n）	Total	Cervicitis	CIN1	CIN2	CIN3	SCC
Cut-off (n）	187	45	62	35	32	13
GYPC^m (%)						0.0(0)
>15.975	53.0(99)	82.2(37)	67.7(42)	40.0(14)	18.8(6)
ΔCp≤15.975	47.0(88)	17.8(8)	32.3(20)	60.0(21)	81.2(26)	100.0(13)
Cytology (%)						23.1(3)
<ASC-US	26.2(49)	42.2(19)	22.6(14)	25.7(9)	12.5(4)
ASC-US+	73.8(138)	57.8(26)	77.4(48)	74.3(26)	87.5(28)	76.9(10)
Cytology (%)						30.8(4)
<LSIL	63.1(118)	84.4(38)	75.8(47)	48.6(17)	37.5(12)
LSIL+	26.9(69)	15.6(7)	24.2(15)	51.4(18)	62.5(20)	69.2(9)

Tests	Cut-off	Sensitivity % (95%CI)	Specificity % (95%CI)	PPV % (95%CI)	NPV % (95%CI)
GYPC^m	ΔCp≤15.975	86.7(76.7-96.6)	65.5(57.7-73.3)	44.3(33.9-54.7)	93.9(89.2-98.6)
Cytology	ASC-US+	84.4(73.9-95.0)	29.6(22.1-37.1)	27.5(20.1-35.0)	85.7(75.9-95.5)
Statistics		0.08	30.6	-4.6	-1.46
P		0.782	<0.001^***	<0.001^***	0.144
Cytology	LSIL+	64.4(50.5-78.4)	71.8(64.4-79.2)	42.0(30.4-53.7)	86.4(80.3-92.6)
Statistics		5.55	1.47	-0.44	-2.14
P		0.018^*	0.225	0.658	0.033^*
HPV16/18/GYPC^m		93.3（86.0-100.0）	50.0（41.8-58.2）	37.2（28.3-46.1）	96.0（91.5-100.0）
HPV16/18/Cytology_{（ASC-US+）}		100.0（100.0-100.0）	13.4（20.1-33.5）	26.8（20.1-33.5）	100.0（100.0-100.0）
Statistics		3.0	0.52	-5.70	1.73
P		0.083	<0.001^***	<0.001^***	0.083

Tests	Cut-off	Sensitivity % (95%CI)	Specificity % (95%CI)	PPV % (95%CI)	NPV % (95%CI)
GYPC^m	ΔCp≤15.975	75.0(65.5-84.5)	73.8(65.5-82.1)	68.2(58.5-77.9)	79.8(1.9-87.7)
Cytology	ASC-US+	80.0(71.2-88.7)	30.8(22.1-39.6)	46.4(38.0-54.7)	67.3(54.2-80.5)
Statistics		0.50	3.21	-4.73	-1.66
P		0.479	<0.001^***	<0.001^***	0.097
Cytology	LSIL+	58.6(48.0-69.5)	79.4(71.8-87.1)	68.1(57.1-79.1)	72.0(64.0-80.1)
Statistics		4.83	0.95	-0.01	-1.80
P		0.028^*	0.330	0.991	0.072
HPV16/18/GYPC^m		87.5（80.3-94.7）	59.8（50.5-69.1）	61.9（53.0-70.9）	86.5（78.7-94.3）
HPV16/18/Cytology_{（ASC-US+）}		100.0（-100.0）	17.8（10.5-25.0）	47.6（40.1-55.2）	100.0（-100.0）
Statistics		10.0	0.45	-5.3	3.2
P		0.002^**	<0.001^***	<0.001^***	0.002^**