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Table 1 Performance characteristics of the included studies 2012–2020

From: Novel biomarkers with promising benefits for diagnosis of cervical neoplasia: a systematic review

Authors

No. Part

Biomarkers

Current Status

Test platform

Sample type

Sensitivity

Specificity

PPV

NPV

AUC

Mean TAT

Farzanehpour et al, 2019 [2]

72

miRNA (miR-9)

Not validated

RT-qPCR

Tissue

64.7%

76.4%

0.71

≤ 5 h.

Farzanehpour et al. 2019 [2]

72

miRNA (miR-9)

Not validated

RT-qPCR

Serum

52.9%

94.4%

0.85

≤ 5 h.

Park et al., 2017 [11]

102

miRNA (miR-9)

Not validated

RT-qPCR

Tissue

67.3%

80%

77.7%

70.2%

0.76

≤ 5 h.

Wentzensen et al, 2012 [12]

673

p16INK4a / ki-67

Not validated

ICC

CINtec PLUS

LBC

85.5%

59.4%

48.4%%

90.2%%

≤24 h

Zhu et al, 2019 [13]

300

p16INK4a / ki-67

Not validated

ICC

CINtec PLUS

LBC

98.2%

82.5%

55.2%

99.5%%

0.90

≤24 h

Areán-Cun., et al, 2018 [14]

1945

p16INK4a / ki-67

Not validated

ICC

CINtec PLUS

LBC

98%

39%

44.8%

97.5%

≤24 h

Wentzensen et al, 2015 [15]

1509

p16INK4a / ki-67

Not validated

ICC

CINtec PLUS

LBC

83.4%

58.9%

21%

96.4%

≤24 h

Yu et al, 2016 [16]

231

p16INK4a / ki-67

Not validated

ICC

CINtec PLUS

LBC

90.9%

79.5%

49.2%

97.6%

0.85

≤24 h

Tay et al., 2017 [17]

97

p16INK4a / ki-67

Not validated

ICC

CINtec PLUS

LBC

92.9%

76.7%

88.1%

86.7%

0.85

≤24 h

Ebisch et al., 2017 [18]

462

p16INK4a / ki-67

Not validated

ICC

CINtec PLUS

LBC

92%

61%

52%

95%

≤24 h

Hu et al., 2020 [19]

846

p16INK4a / ki-67

Not validated

ICC

CINtec PLUS

LBC

86.5%

62.5%

28.8%

96.4%

≤24 h

Ordi et al., 2014 [20]

1169

p16INK4a / ki-67

Not validated

ICC

CINtec PLUS

LBC

90.9%

72.1%

63.9%

93.6%

0.82

≤24 h

Uijterwaal et al., 2015 [21]

762

p16INK4a / ki-67

Not validated

ICC

CINtec PLUS

LBC

68.8%

72.8%

25.2%

94.6%

≤24 h

White et al., 2016 [22]

1346

p16INK4a / ki-67

Not validated

ICC

CINtec PLUS

LBC

75.4%

88.3%

26.6%

97%

≤24 h

Schmitz et al., 2018 [23]

280

p16INK4a / ki-67

Not validated

ICC

CINtec PLUS

LBC

100%

90.2%

92.3%

100%

≤24 h

Han et al., 2020 [24]

468

p16INK4a / ki-67

Not validated

ICC

CINtec PLUS

LBC

91.5%

77%

73.9%

92.8%

0.76

≤24 h

Li et al., 2020 [25]

4070

p16INK4a / ki-67

Not validated

ICC

CINtec PLUS

LBC

90.9%

67%.

16.5%

99.1%

0.79

≤24 h

Wang et al., 2020 [26]

4070

p16INK4a / ki-67

Not validated

ICC

CINtec PLUS

LBC

91.7%

63.5%

29.3%

97.9%

≤24 h

El-Zein et al., 2020 [27]

1649

p16INK4a / ki-67

Not validated

ICC

CINtec PLUS

LBC

80.7%

69.4%

64%

71.8%

≤24 h

Wentzensen et al, 2019 [28]

3225

p16INK4a / ki-67

Not validated

ICC

CINtec PLUS

LBC

82.8%

55.7%

24.3%

95%

≤24 h

Ren et al., 2019 [29]

300

p16INK4a / ki-67

Not validated

ICC

CINtec PLUS

LBC

50%

75.3%

11.1%

96.1%

0.78

≤24 h

Bergeron, et al., 2015 [30]

27,349

p16INK4a / ki-67

Not validated

ICC

CINtec PLUS

LBC

94.4%

78.7%

16.3%

99.7%

≤24 h

Polman et al., 2016 [31]

364

p16INK4a / ki-67

Not validated

ICC

CINtec PLUS

LBC

69.2%

90.4%

51.9%

95.1%

≤24 h

Ren et al., 2019 [29]

300

HPV E6/E7 mRNA

Not validated

QuantiVirus

®HPV

LBC

100%

44.3%

10%

100%%

0.59

≤ 5 h.

Ren et al, 2018 [32]

160

HPV E6/E7 mRNA

Not validated

QuantiVirus®HPV

LBC

90.3%

49.6%

30.1%

95.5%

0.75

≤ 5 h

Han et al., 2018 [33]

6800

HPV E6/E7 mRNA

Not validated

QuantiVirus

®HPV

LBC

85.2%

66.7%

72.9%

81%

0.75

≤ 5 h

Yao et al., 2017 [34]

404

HPV E6/E7 mRNA

Not validated

QuantiVirus® HPV

LBC

89.5%

49%

39%

92.7%

0.72

≤ 5 h

Zhu et al, 2019 [13]

300

HPV E6/E7 mRNA

Not validated

QuantiVirus® HPV

LBC

87%

42.7%

25%

93.8%

0.70

≤ 5 h

Bountris et al, 2014 [35]

740

HPV E6/E7 mRNA

Not validated

NASBA assay

LBC

77%

90.2%

68.5%

93.4%

≤ 5 h

Li et al, 2016 [36]

186

HPV E6/E7 mRNA

Not validated

QuantiVirus® HPV

LBC

65%

86.7%

85.9%

66.7%

0.76

≤ 5 h

Camus et al, 2018 [37]

502

HPV E6/E7 mRNA

Not validated

qRT-PCR

LBC

90%

50%

64%

83%

0.80

≤ 5 h

Kong et al, 2020 [38]

600

DNA methylation

Not validated

qPCR

LBC

67.7%

94.9%

95.4%

65.5%

0.86

≤ 5 h

Dong et al, 2020 [39]

1997

DNA methylation

Not validated

qPCR

LBC

92.9%

73%

56.5%

96.4%

0.83

≤ 5 h

Schmitz et al, 2018 [23]

280

DNA methylation

Not validated

RT-PCR

LBC

59.7%

98%

91.5%

87.3%

≤ 5 h

van Leeuwen et al.,2019 [40]

262

DNA methylation

Not validated

qPCR

LBC

68%

67%

15%

96%

≤ 5 h

De Strooper et al, 2016 [41]

375

DNA methylation

Not validated

qPCR

LBC

70.5%

67.8%

35.5%

90.2%

≤ 5 h

Chujan et al, 2014 [42]

94

DNA methylation

Not validated

qPCR

LBC

83.3%

96.8%

92.6%

92.5%

≤ 5 h

Kottaridi et al, 2017 [43]

151

DNA methylation

Not validated

qPCR

LBC

75.7%

77.5%

74.7%

78.5%

0.81

≤ 5 h

Leeman et al, 2019 [44]

262

DNA methylation

Not validated

qPCR

LCB

77.8%

69.3%

36.4%

98.3%

≤ 5 h

Chen et al, 2020 [45]

103

SCC-Ag

Validated

Elisa

Serum

80%

100%

100%

82.6%

0.89

≤ 5ihrs

Zajkowska et al, 2018 [46]

100

SCC-Ag

Validated

Elisa

Serum

78.8%

74%

66.7%

84.1%

0.79

≤ 5 h

Sidorkiewicz et al., 2019 [5]

85

SCC-Ag

Validated

Elisa

Serum

81.2%

74%

0.79

≤ 5 h

Lubowicka et al,2020 [47]

89

SCC-Ag

Validated

Elisa

Serum

78.6%

74%

0.79

≤ 5 h

Zajkowska et al, 2018 [46]

85

M-CSF

Not

validated

Elisa

Serum

72.7%

86%

77.4%

82.7%

0.79

≤ 5 h

Lubowicka et al, 2020 [47]

89

M-CSF

Not validated

Elisa

Serum

75%

86%

0.81

≤ 5 h

Sidorkiewicz et al., 2019 [5]

85

M-CSF

Not validated

Elisa

serum

69.4%

86%

0.81

≤ 5 h

Ruan et al, 2020 [48]

68

M-CSF

Not validated

Elisa

Serum

87.7%

64.7%

0.75

≤ 5 h

Będkowska et al., 2015 [49]

110

M-CSF

Not validated

Elisa

Serum

68%

94%

92%

75%

0.86

≤ 5 h

Lawicki et al, 2016 [50]

100

VEGF

Not validated

Elisa

Serum

56%

96%

86%

82%

0.85

≤ 5 h

Sidorkiewicz et al.,2019 [5]

85

VEGF

Not validated

Elisa

Serum

81.2%

76%

0.86

≤ 5 h

Cheng et al., 2013 [51]

109

VEGF

Not validated

Elisa

Serum

83.3%

74.6%

0.83

≤ 5 h

Urquidi et al, 2012 [52]

127

VEGF

Not validated

Elisa

Urine

83%

87%

0.88

≤ 5 h

  1. DNA Deoxyribonucleic Acid, HPV E6/7 Human Papilloma Virus Early protein 6/7, mRNA Messenger ribonucleic acid, NPV Negative Predictive Value, RT PCR Reverse Transcriptase Polymerase Chain Reaction, PPV Positive Predictive Value, AUC Area Under Receiver Operating Characteristic Curve, SCC-Ag Squamous Cell Carcinoma Antigen, M-CSF Macrophage Colony Stimulating Factor, VEGF Vascular Endothelial Growth Factor, LBC Liquid Based Cytology, TAT Turnaround Time, miRNA-9 micro ribonucleic acid-9, Elisa Enzyme Linked Immunosorbent Assay. No Part: Number of Participants; ICC Immunocytochemistry; NASBA Nucleic acid sequence based amplification for the identification of E6/E7 mRNA of the HPV types; (−) means not done; Validated: means approved for use; Not validated means investigation in progress