Table 1 Details and main outcomes on studies investigating miRNA expression in relation to CC progression

Pereira PM et al., 2010 [48]

Samples (n = 25): 4 SCC, 5 HSIL, 9 LSIL and 19 normal cervical tissues snap-frozen in liquid nitrogen and stored -80C

HPV genotyping not available (only HPV + or -)

281 miRNAs (in house microarray)

miR-10a

miR-132

miR-148a

miR-196a

miR-302b

miR-16

miR-27a

miR-197

miR-106a

miR-142-5p

miR-205

miR-522*(miR-522-5p)

miR-512-3p

miR-26a

miR-29a

miR-99a

miR-143

miR-145

miR-199a

miR-203

miR-513

Li B et al., 2010 [30]

Samples (n = 140): 108 tissue biopsy of patients with abnormal cytological results and/or HR-HPV infection, 32 normal with HPV, 32 normal without HPV, 32 CIN with HPV, 12 CIN without HPV infection and 32 CC

HPV genotyping not available (only HPV + or -)

1 miRNA

(semi-quantitative RT-PCR)

pri-mir-34a

Li Y et al., 2010 [31]

Samples (n = 78): tissue biopsy of patients with 22 CIN1, 27 CIN2 and 29 CIN3 (washed in sterile saline and placed in RNA later and then stored in liquid nitrogen)

HPV genotyping available

1 miRNA

(qPCR)

miR-218

Li Y et al., 2011 [49]

Samples (n = 18): tissue biopsy of patients 6 HPV16-positive SCCs, 6 HPV 16-positive CIN2/3, and 6 normal cervical tissues for discovery

Samples (n = 91): tissue biopsy of patients 24 HPV positive SCCs, 24 HPV positive CIN2/3 and 43 normal cervical tissues for validation

Snap-frozen in liquid nitrogen and stored -80C

HPV genotyping available

Discovery: 875 miRNAs (microarray)

Validation: 6 miRNAs

(qPCR)

miR-15b

miR-16

miR-17

miR-20a

miR-20b

miR-25

miR-31

miR-92a (also by validation)

miR-92b

miR-93

miR-106a

miR-182

miR-185

miR-155 (also by validation)

miR-221

miR-222

miR-224

let-7b

miR-10b

miR-29a (also by validation)

miR-29c

miR-99a (also by validation)

miR-100

miR-125b

miR-126

miR-145

miR-195 (also by validation)

miR-199a-3p

miR-218

miR-375 (also by validation)

miR-424

Li BH et al., 2011 [32]

Samples (n = 125): 20 negative HR-HPV normal cervical epithelium, 20 HR-HPV infected normal cervical epithelium, 14 CIN1, 13 CIN2, 16 CIN3 and 42 CC

Snap frozen in liquid nitrogen and stored -70C

HPV genotyping not available

1 miRNA

(qPCR)

miR-100

Deftereos G et, 2011 [33]

Samples (n = 142): 23 normal histology and negative HR- HPV, 21 HR-HPV, 15 CIN1, 51 CIN2/3 (CIS), 23 ICC

Samples were FFPE

HPV genotyping available (only HPV + or -)

2 miRNAs (qPCR)

miR-21

Cheung TH et al., 2012 [51]

Samples (n = 33): biopsy specimens of patients with 12 CIN2, 12 CIN3, 9 CC and 9 normal epithelial cells for discovery.

Samples (n = 24): 6 CIN2 and 18 CIN3 new and, 9 normal from discovery for validation

All tissue specimens were embedded into Optimal cutting temperature compound and stored at − 80 °C

202 miRNAs (qPCR)

miR-9

miR-20b

miR-10a

miR-34b

miR-34c

miR-338

miR-345

miR-424

miR-512-5p

miR-518a

miR-193b

miR-203

Wilting SM et al., 2013 [16]

Samples (n = 47): 10 SCC, 9 AdCAs, 18 CIN2/3 and 10 normal cervical squamous epithelial tissue

No information on sample collection/storage

HPV genotyping available

472 miRNAs (Agilent microarray)

let-7i

miR-19b

miR-21

miR-25

miR-28-5p

miR-30e

miR-34a

miR-34b*(miR-34b-5p)

miR-92a

miR-92b

miR-106b

miR-146a

miR-181d

miR-200a*(miR-200a-5p)

miR-206

miR-338-5p

miR-592

miR-595

miR-7d

miR-9

miR-15a

miR-15b

miR-16

miR-17

miR-17*(miR-17-3p)

miR-18a

miR-19a

miR-20b

miR-24

miR-27

miR-30d

miR-93

miR-106a

miR-107

miR-130b

miR-141

miR-151-3p

miR-155

miR-185

miR-200c

miR-331-3p

miR-339-5p

miR-363

miR-425

miR-652

let-7 g

miR-10a

miR-26a

miR-29a

miR-29b

miR-29c

miR-30a

miR-34c-5p

miR-101

miR-125a-5p

miR-135b

miR-143

miR-145

miR-146b-5p

miR-150

miR-181b

miR-191

miR-192

miR-193a-3p

miR-205

miR-212

miR-221

miR-27a

miR-27b

miR-484

miR-636

miR-770-5p

miR-100

miR-125b

miR-148a

miR-188-5p

miR-195

miR-199a-5p

miR-199b-3p

miR-218

mir-26b

miR-375

mir-376a

miR-378

miR-486-5p

miR-494

miR-497

miR-513b

miR-660

miR-671-5p

miR-99a

miR-134

miR-149

miR-193b

miR-203

miR-210

miR-23b

miR-296-5p

miR-365

miR-370

miR-493

miR-572

miR-575

miR-617

miR-622

miR-638

Bierkens M et al., 2013 [52]

Samples (n = 28): frozen samples of 6 HPV-positive normal cervical squamous epithelial specimens, 13 CDKN2A-positive hg-CIN and 9 SCC

HPV genotyping not available

1 miRNA

(RT-PCR)

miR-375

Wang X et al., 2014 [34]

Samples (n = 158): 38 normal cervical tissues without HPV infection, 13 CIN1/2, 39 CIN3 and 68 CC tissues with HR-HPV infection

HPV genotyping available

8 miRNAs (qPCR)

miR-7a

miR-25

miR-92a

miR-378

(miR-25, miR-92a, and miR-378 more elevated in HPVpositive group than in negative)

miR-16

miR-29a

Leung C et al., 2014 [35]

Samples (n = 37): micro-dissected cervical specimens from 10 SCC, 16 CIN2/3 and 11 CIN 1

HPV genotyping not available

1 miRNA

(qPCR)

miR-135a

Villegas-Ruiz V et al., 2014 [47]

Samples (n = 8): 4 healthy, 4 CC (and 12 cell lines) for discovery (but not on cancer progression)

Samples (n = 45): 25 CC, 10 HSIL, 10 LSIL and healthy cervical tissue obtained from patients subjected to hysterectomy by uterine myomatosis for validation on cancer progression

HPV typing and sequencing

The biopsies were stored in RNA later

Discovery: 7788 miRNAs of different organisms (Affimetrix microarray): 942 different in tumor vs. healthy (518 up and 424 down) but only 123 humans

Validation: 1 miRNA in relation to progression (qPCR)

miR-196a

Zeng K et al., 2015 [50]

Samples (n = 12): 3 SCC, 3 HSIL (CIN2 or CIN3), 3 LSIL (CIN1) and 3 normal cervices for discovery

Samples (n = 103): 40 SCC, 35 HSIL, 15 LSIL and 13 normal cervices for validation

HPV genotyping available

Discovery: 866 human and 89 viral miRNAs (Agilent microarray) in tumor vs. healthy tissue

Validation: 9 miRNAs in relation to progression

(qPCR)

miR-9

miR-21

miR-31

miR-195

miR-199b-5p

miR-218

miR-376a

miR-497

Gocze K et al., 2015 [36]

Samples (n = 98): FFPE tissue samples of 38 SCC, 20 HPV-positive CIN3, 10 HPV-positive CIN2 and 30 HPV-positive CIN1

HPV genotyping not available

6 miRNAs

(qPCR)

miR-21 (but not statistically significant)

miR-27a

miR-155

miR-196

miR-34a

miR-203

Shishodia G et al., 2015 [37]

Samples (n = 102): fresh cervical tissue collected in PBS from 56 cancer lesions, 23 premalignant (and 23 non-malignant control tissues (comprising 3 normal and 20 tissues with cervicitis)

HPV genotyping available

2 miRNAs

(qPCR)

miR-21

let- 7a

Zheng W et al., 2015 [38]

Samples (n = 140): FFPE tissue samples of

80 SCC, 30 HSIL, 15 LSIL, 15 benign gynecological disease hysterectomy as controls

HPV genotyping available only + or - for SCC

1 miRNA

(qPCR)

miR-31 (but only SCC resulted significantly increased)

Ma L et al., 2015 [39]

Samples (n = 163): FFPE tissues samples of 29 SCC, 99 CIN, 35 cervicitis

HPV genotyping not available

1 miRNA

(qPCR)

miR-146a

Bumrungthai S et al., 2015 [40]

Samples for miRNA profiling (n = 111):

Fresh tissue from 43 SCC, 22 CIN II-III, CIN I, 12 cervicitis and 20 normal

HPV genotyping available, only + or -

1 miRNA

(qPCR)

miR-21 (no significant increase between CIN II-III and CIN I)

Jimenez-Vences H et al., 2016 [41]

Samples for miRNA profiling (n = 49): 16SCC, 16 LSIL, 7 NON-SIL HPV16 positive, 10 NON-SIL-HPV-negative

HPV genotyping available (only HPV16 or negative in the study)

3 miRNAs

(qPCR)

miR-193b

miR-218

miR-124

(No clear trend since these miRNAs were also higher than in NON-SIL samples)

Wen F et al., 2017 [42]

Samples (n = 607): fresh tissue from 185 SCC, 148 CIN II-III, 124 CIN I, 150 normal

HPV genotyping available only + or – for SCC

1 miRNA

(qPCR)

miR-15b

Sun P et al., 2017 [43]

Samples (n = 165): fresh tissue from 56 SCC, 60 CIN (not further classified), 49 benign uterine disease as controls

HPV genotyping available only + or - for SCC

1 miRNA

(qPCR)

miR-466

Studies on exfoliated cells

Tian Q et al., 2014 [44]

Samples (n = 1021): cervical exfoliated cells from 833 HPV - positive women underwent cervical biopsy under colposcopy, among whom 392 presented with abnormal pap test (ASCUS +) and 441 presented with normal Pap test but positive colposcopies, 188 with normal Pap tests and negative colposcopies did not undergo biopsies

HPV genotyping available

6 miRNAs, selected from Li Y et al., 2011

(qPCR)

miR-34a

miR-218

miR-375

miR-424

Ribeiro J et al., 2015 [45]

Samples (n = 114): cervical exfoliated cells (normal epithelium with HPV infection (20) and without (29), 28 LSIL, 29 HSIL and 8 ICC)

HPV genotyping available

2 miRNAs (qPCR)

miR-34a

miR-125b

Malta M et al., 2015 [46]

Samples (n = 73): cervical exfoliated cells (normal epithelium with (17) and without (21) HPV infection, 14 LSIL, 21HSIL)

HPV genotyping not available

1 miRNA (qPCR)

let-7c