Table 3 Characteristics of the 12 studies included in our review

Liu; Xin; Ma [11]

2015

qPCR

RNU6B

2^−ΔΔCt

MiR-196a expression levels are not correlated to HPV infection

miR-196a

Yes

N/A

N/A

N/A

CC Patients showed a significantly higher level of serum miR-196a than CIN patients p < 0.05) and controls (p < 0.01). CIN patients expressed higher MiR-196a levels than C volunteers (p < 0.05). 67% of CIN III patients showed significantly higher expression of miR-196 than CIN II(32%) and CIN I (21%) patients. CC Patients with higher miR-196a serum levels had a poorer overall survival rate.

Zhang et al. [8]

2015

qPCR

cel-miR-67

2^−ΔΔCt

N/I

miR-497

miR-16-2

miR-195

miR-2861

No

4 miRs:

CC vs. C: 0.849

CC vs. NIC: 0.829

NIC vs. C: 0,734

4 miRs:

CC vs. C: 73,1%

CC vs. NIC: 71,4%

NIC vs. C: 62,6%

4 miRs:

CC vs. C: 88,4%

CC vs. NIC: 67,2%

NIC vs. C: 88,9%

MIR-195 expression level was significantly decreased, while miR-16-2* and miR-497 were significantly increased in CC patients, compared to CIN and control groups. miR-2861 expression levels are significantly decreased in CIN and CC patients compared to the control group.

Nagamitsu et al. [12]

2016

qPCR

miR-16

2^−ΔΔCt

N/I

miR-1290

No

CC vs. C: 0.7957

CC vs. C: 90.3%

CC vs. C: 62.2%

MiR-1290 expression level was significantly elevated in CC patients compared to CIN and control patients. MiR-1290 increased expression was also related to the CC stage.

Sun et al. [13]

2016

qPCR

Geometric mean of miR-16 miR-223 and miR-31

2^−ΔΔCt

N/I

miR-425-5p

Yes

N/A

N/A

N/A

MiR-425-5p expression levels were significantly the higher in CC group compared to CIN (p< 0.0001) or control groups (p< 0.0001). Elevated levels of miR-425-5p were significantly correlated with TNM stage (p = 0.0003) and lymph node metastasis (p = 0.0037). High levels of serum miR-425have expression that has been correlated with poor overall survival.

Kong et al. [14]

2017

qPCR

Cel-39-3p

2^−ΔΔCt

MiR-92a expression levels are not correlated to HPV infection

hsa-mir-92a

No

0,83

69.6%

80.4%

Serum miR-92a levels were significantly higher in CIN and CC patients than in healthy subjects (p< 0.01). MiR-92a expression was also significantly higher in patients with advanced-stage CC than in those with early-stage CC.

Wei;

Wen-Ming; Jun-Bo [15]

2017

qPCR

RNU6B

2^−ΔΔCt

Lower plasmatic miR-145 expression levels significantly associated to HPV infection (p 0,016)

miR-145

No

CC vs. C: 0,848

CC vs. CIN: 0,828

CC vs. C: 81,7%

CC vs. CIN: 91,7%

CC vs. C: 63,3%

CC vs. CIN: 54,2%

MiR-145 plasma levels were significantly lower in CC patients than in CIN patients and healthy controls (p < 0.01). CC patients who achiea ved complete response to radiotherapy had higher plasma miR-145 levels than incomplete responders (p 0.005).

Wang et al. [16]

2018

qPCR

U6

2^−ΔΔCt

N/I

miR-1266

Yes

N/A

N/A

N/A

Serum miR-126upregulatedulated in CC patients also correlates with metastatic progression. Serum MiR-1266 expression was significantly higher in patients with LSIL, HSIL and CC compared to healthy controls (p< 0.05). CC patients with high miR-1266 expression had lower overall survival rates than patients with low miR-1266 expression.

Farzanehpour et al. [17]

2019

qPCR

U6

2^−ΔΔCt

N/I

miR-9

miR-192

miR-205

No

CC vs. C

miR-9: 0,99

miR-192:

miR-205: 0,96

CIN vs. C

miR-9: 0,90

miR-192: 0,98

miR-205: 0,75

CC vs. CIN

miR-9: 0,85

miR-192: 0,82

miR-205: 0,75

CC vs. C

miR-9: 100%

miR-192: 100%

miR-205: 88,2%

CIN vs. C

miR-9: 77,8%

miR-192: 83,3%

miR-205: 66,7%

CC vs. CIN

miR-9: 52,9%

miR-192: 58,8%

miR-205: 35,3%

CC vs. C

miR-9: 94,4%

miR-192: 94,4%

miR-205: 88,9%

CIN vs. C

miR-9: 94,4%

miR-192: 94,4%

miR-205: 88,9%

CC vs. CIN

miR-9: 94,4%

miR-192: 83,3%

miR-205: 94,4%

Increased expression levels of miR-9, miR-192 and miR-205 were observed in the CC group compared to normal samples (p< 0.0001). MiR-9, miR-192, and miR-205 expression levels were significantly increased in the CIN group compared to the control group. MiR-205 expression showed to be increased in the CC group compared to the CIN group (p< 0.0001).

Wang et al. [18]

2019

qPCR

U6

2^−ΔΔCt

N/I

miR-21

miR-214

miR-34a

miR-200a

No

CIN I- vs. CIN II+

miR-21: 0,613

miR-34a: 0,508

miR-200a: 0,615

miR-214: 0,505

N/I

N/I

MiRNA-21 plasma expression was increased in patients with cervical lesions (including CIN I, CIN II, CI, II,I and CC patients).

MiRNA-21,−34a, and -200a expression levels were decreased in patients with severe cervical lesions (CIN I, CIN II, CIN, III and CC). Differences between these miRNAs expression levels were significant when comparing controls and CIN II e III patients(p< 0.05).

Yang; Zhang [19]

2019

qPCR

U6

2^−ΔΔCt

N/I

miR-152

No

CIN vs. C: 0.831

CC vs. C: 0.935

N/I

N/I

MiR-152 expression levels were increased in CIN patients compared to control and higher in CC patients. Furthermore, miR-152 expression level in peripheral blood was higher in patients with high-grade CIN compared to those with low-grade CIN. MiR-152 expression levels also increased with the CC stage and were associated with serum SCC-Ag levels. A miR-152 expression reduction was observed after treatment.

Zheng et al. [20]

2019

Digital PCR

miR-128-3p

miR-129-5p

miR-320

let-7i-5p

R_score

N/I

let-7d-3p

miR-30d-5p

No

let-7d-3p: 0.822

miR-30d-5p: 0.79

Combined: 0.828

N/I

N/I

Let-7d-3p and miR-30d-5p expression levels were significantly decreased in CIN II + group when compared to CIN I – group.

Zheng et al. [21]

2020

qPCR

cel-miR-39

2^−ΔΔCt

N/I

miR-638

miR-203a-3p

miR-1914-5p

miR-521

No

CC vs. CIN

miR-638: 0,681

miR-203a-3p: 0,651

miR-1914-5p: 0,717

miR-521: 0,716

CC vs. C

miR-638: 0,734

miR-203a-3p: 0,660

miR-1914-5p: 0,626

miR-521: 0,742

CC vs. CIN

miR-638: 85%

miR-203a-3p: 42,5%

miR-1914-5p: 82,5%

miR-521: 62,5%

CC vs. C

miR-638: 80%

miR-203a-3p: 75%

miR-1914-5p: 85%

miR-521: 80%

CC vs. CIN

miR-638: 46,15%

miR-203a-3p: 82,05%

miR-1914-5p: 61,54%

miR-521: 76,92%

CC vs. C

miR-638: 60,98%

miR-203a-3p: 53,66%

miR-1914-5p: 43,90%

miR-521: 65,85%

Lower expression levels of miR-638, miR-203a-3p, miR-1914-5p and and MiR-521 were observed in the group compared to CIN. Furthermore, miR-638, miR-203a-3,p and miR-521 expression levels were lower in CC patients compared to healthy controls.

Qiu et al [22]

2020

qPCR

cel-miR-39

2^−ΔΔCt

N/I

miR-21

miR-125b

miR-370

No

CC vs. C

miR-21: 0,783

miR-125b: 0,642

miR-370: 0,822

CC vs. CIN

miR-21: 0,689

miR-125b: 0,735

miR-370: 0,821

Combined

CC vs. C: 0,912

CC vs. CIN: 0,897

N/I

N/I

Higher miR-21 serum expression was observed in CC than in CIN and healthy women. The expression of miR-125b and miR-370 was lower in CC women compared to healthy and CIN patients. Combined expression of the three miRNAs performed well to identify early-stage CC compared to CIN or healthy controls. High levels of miR-21 and low levels of miR-125b and miR-370 were associated with metastasis and recurrences.

Aftab et al [23]

2021

qPCR

snRNA U6

2^−ΔΔCt

Lower miRNA-145-5p expression

in samples

LSIL/HSIL

HPV 16 + and CC HPV 16+ samples.

miR-21-5p

miR-199a-5p

miR-155-5p

miR-34a-5p

miR-145-5p

miR-218-5p

No

miR-21-5p: 0,97

miR-199a-5p: 0,831

miR-155-5p: 0,719

miR-34a-5p: 0,888

miR-145-5p: 0,575

miR-218-5p: 0,609

Combined: 0,942

miR-21-5p

miR-199a-5p

miR-155-5p

Combined: 0,969

miR-34a-5p

miR-145-5p

miR-218-5p

Combined: 1

miR-21-5p

miR-199a-5p

miR-155-5p

miR-34a-5p

miR-145-5p

miR-218-5p

miR-21-5p: 88

miR-199a-5p: 86.7

miR-155-5p: 93.8

miR-34a-5p: 89.1

miR-145-5p: 67.7

miR-218-5p: 83.3

Combined: 100

miR-21-5p

miR-199a-5p

miR-155-5p

Combined: 100

miR-34a-5p

miR-145-5p

miR-218-5p

Combined: 100

miR-21-5p

miR-199a-5p

miR-155-5p

miR-34a-5p

miR-145-5p

miR-218-5p

miR-21-5p: 98

miR-199a-5p: 91.7

miR-155-5p: 88.3

miR-34a-5p: 91.7

miR-145-5p: 60

miR-218-5p: 72.7

Combined: 78.9

miR-21-5p

miR-199a-5p

miR-155-5p

Combined: 92.8

miR-34a-5p

miR-145-5p

miR-218-5p

Combined: 100

miR-21-5p

miR-199a-5p

miR-155-5p

miR-34a-5p

miR-145-5p

miR-218-5p

Significant up-regulation of miR-21-5p, miR-199a-5p and miR-155-5p and down-regulation of miR-145-5p, miR-34a-5p and miR-218-5p was observed in women with LSIL/HSIL and CC when compared to healthy controls.

Hoelzle et al [24]

2021

qPCR

miR-23a-3p

2^−ΔΔCt

Higher plasmatic miR-let-7a expression levels awithociated with HPV infection

miR-21

miR-let-7a

miR-214

Yes

N/I

N/I

N/I

No significant differences were found between groups.

Ocadiz-Delgado et al [25]

2021

qPCR

Beta2mHu

2^−ΔΔCt

N/I

miR-15b

miR-34a

miR-218

No

LSIL

miR-34a: 0,9952

miR-15b: 0,6765

miR-218: 0,9872

CC

miR-34a: 0,9505

miR-15b: 0,8173

miR-218: 0,8421

N/I

N/I

MiR-15b expression was higher in LSIL group and even higher in CC patients compared to healthy controls. MiR-34a and miR-218 expression increased in LSIL and decreased in CC, compared to control group.

Yamanaka et al [26]

2021

qPCR

miR-16

2^−ΔΔCt

N/I

miR-100

No

0,879

91,2%

80,4%

MiR-100 serum expression was high in healthy women, intermediate in women with CIN and low in CC women.