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Table 2 Meta-analysis of the performance of DNA methylation assays for the detection of CIN2+ and CIN3+ 

From: DNA methylation as a triage marker for colposcopy referral in HPV-based cervical cancer screening: a systematic review and meta-analysis

 

N datasets

N samples

Pooled prevalence

Pooled Sensitivity, (95% CI)

Pooled Specificity, (95% CI)

Q

(p-value)

I2

(95% CI)

Pooled AUC,

(95% CI)

CIN2 + detection

All studies with all markers a,b[12,13,14,15,16,17,18,19,20,21,22, 24, 25, 27,28,29, 31,32,33,34]

55

16,022

0.35

0.67 (0.63–0.70)

0.80 (0.75–0.83)

422.771 (p < 0.001)

100 (99–100)

0.77 (0.73–0.81)

All studies with best markers a,c[12,13,14,15,16,17,18,19,20,21,22, 24, 25, 27,28,29, 31,32,33,34]

25

9011

0.28

0.68 (0.63–0.72)

0.75 (0.71–0.80)

160.418 (p < 0.001)

99 (98–99)

0.77 (0.73–0.81)

Studies with CADM1, FAM19A4, MAL and miR124-2a[12,13,14, 17,18,19,20,21,22, 28, 33]

15

6693

0.25

0.64 (0.59–0.68)

0.74 (0.69–0.78)

77.518 (p < 0.001)

97 (96–99)

0.74 (0.70–0.77)

Set threshold to achieve 70% specificity[12, 14, 17,18,19,20, 22, 33]

9

3686

0.29

0.59 (0.53–0.65)

0.74 (0.70–0.77)

17.604(p < 0.001)

89 (77–100)

0.73 (0.69–0.77)

All studies with best markers excluding high-bias studies a,d[12,13,14,15, 17,18,19,20,21,22, 24, 25, 27, 29]

20

7736

0.25

0.66 (0.61–0.70)

0.74 (0.69–0.78)

110.195 (p < 0.001)

98 (97–99)

0.75 (0.71- 0.79)

CIN3 + detection

All studies with all markers a,b[12,13,14,15,16,17,18,19,20,21,22,23,24, 26, 27, 29,30,31,32, 34]

55

16,669

0.24

0.78 (0.75–0.81)

0.77 (0.73–0.80)

353.267(p < 0.001)

99 (99–100)

0.85 (0.81–0.87)

All studies with best markers a,e[12,13,14,15,16,17,18,19,20,21,22,23,24, 26, 27, 29,30,31,32, 34]

25

9682

0.18

0.78 (0.74–0.82)

0.74 (0.69–0.78)

87.682 (p < 0.001)

98 (96–99)

0.83 (0.79 -0.86)

Studies with CADM1, FAM19A4, MAL and miR124-2a [12,13,14, 17,18,19,20,21,22,23]

14

7202

0.14

0.72 (0.68–0.76)

0.72 (0.67–0.76)

24.008 (p < 0.001)

92 (84–99)

0.77 (0.74–0.81)

Set threshold to achieve 70% specificity [12, 14, 17,18,19,20, 22, 33]

9

3655

0.17

0.69 (0.63–0.74)

0.74 (0.70–0.77)

2.778 (p = 0.125)

28 (0–100)

0.77 (0.73–0.80)

All studies with best markers excluding high-bias studies a,f[12,13,14,15, 17,18,19,20,21,22,23,24, 27, 29, 30]

20

8681

0.17

0.77 (0.72–0.81)

0.73 (0.68–0.76)

58.123 (p < 0.001)

97 (94–99)

0.81 (0.77- 0.84)

  1. aThe sensitivity and specificity were estimated as reported by authors. When multiple thresholds reported, 70% specificity was selected. bPooled together all the genes and gene combination reported in each study. For studies [16, 23, 25, 26, 29, 32], more than one entrance was considered. cOnly one entrance per study was considered. The best combination reported by the authors was selected. For [16] and [32] was considered JAM3; for [29] and [27] was considered C13orf18/EPB41L3/JAM3; for [25] was considered S5 classifier (EPB41L3/HPV16L1/HPV16L2/HPV18L2/HPV31L1/HPV33L2). dOnly one entrance per study was considered. The best combination reported by the authors was selected. For [29] and [27] was considered C13orf18/EPB41L3/JAM3; for [25] was considered S5 classifier (EPB41L3/HPV16L1/HPV16L2/HPV18L2/HPV31L1/HPV33L2). eOnly one entrance for study was considered. The best combination reported by the authors was selected. For [30] was considered PAX1/ZNF582; for [16] was considered JAM3; for [29] was considered C13orf18/EPB41L3/JAM3; for [25] was considered S5 classifier; for [27] was considered SOX1/ZSCAN1; for [32] was considered SOX1. f Only one entrance for study was considered. The best combination reported by the authors was selected. For [30] was considered PAX1/ZNF582; for [29] was considered C13orf18/EPB41L3/JAM3; for [25] was considered S5 classifier; for [27] was considered SOX1/ZSCAN1; for [32] was considered SOX1
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Clinical Epigenetics

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