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

Table 4 Meta-analysis of the performance of DNA methylation assays for the detection of CIN2+ and CIN3+ according the sample collection method

	N Datasets	N samples	Pooled prevalence	Pooled Sensitivity, (95% CI)	Pooled Specificity, (95% CI)	Q	I2	Pooled AUC,
	N Datasets	N samples	Pooled prevalence	Pooled Sensitivity, (95% CI)	Pooled Specificity, (95% CI)	(p-value)	(95% CI)	(95% CI)
CIN2 + detection ^a,b
Health professional-collected [12, 13, 16,17,18, 20, 24, 25, 27,28,29, 31,32,33,34]	18	6005	0.27	0.70 (0.65–0.74)	0.76 (0.71–0.81)	74.715 (p < 0.001)	97 (96–99)	0.79 (0.75–0.82)
Self-collected ^{(14, 19, 21, 22, 28)}	7	3006	0.30	0.63 (0.54–0.72)	0.73 (0.63–0.81)	84.968 (p < 0.001)	98 (96–99)	0.73 (0.69–0.77)
CIN3 + detection ^a,c
Health professional-collected [12, 13, 16,17,18, 20, 23, 24, 26, 27, 29,30,31,32, 34]	18	6676	0.18	0.81 (0.76–0.85)	0.75 (0.70–0.79)	52.628 (p < 0.001)	96 (93–99)	0.85 (0.82–0.88)
Self-collected [14, 15, 19, 21, 22]	7	3006	0.19	0.72 (0.63–0.80)	0.70 (0.60–0.78)	32.355 (p < 0.001)	94 (88–99)	0.77 (0.74–0.81)

^aThe sensitivity and specificity were estimated as reported by authors. When multiple thresholds reported, 70% specificity was selected. ^bOnly 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). ^cOnly 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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