Cervical cancer and the need for a bedside assay
Current diagnosis of cervical cancer: the need for triage
CVF as a candidate body fluid for cervical cancer screening by self-testing
Self-sampling
Self-testing
CVF biomarkers for cervical cancer
HPV DNA assay
Host and viral DNA methylation
DNA methylation of miRNA
Exosomes
First discovered protein markers
Immunological proteins
Alpha-actinin-4
Discovery
Cohort | Sample | Group | Condition | Genotype | Viral load (copies/cell) | Colposcopy | Cytology | Collection medium | ACTN4 (/mg prot) |
---|---|---|---|---|---|---|---|---|---|
H07 | Healthy | HPV neg | Normal | Normal | 5% AA | 42.8 | |||
H12 | Healthy | HPV neg | Normal | Normal | 5% AA | 0.6 | |||
H52 | Healthy | HPV neg | Normal | Normal | 5% AA | 6.1 | |||
H54 | Healthy | HPV neg | Normal | Normal | 5% AA | 1.9 | |||
H62 | Healthy | HPV neg | Normal | Normal | 5% AA | 7.2 | |||
H20 | Healthy | HPV neg | Normal | Normal | 5% AA | 0.5 | |||
H05 | Healthy | HPV neg | Normal | Normal | 5% AA | 3.1 | |||
H64 | Healthy | HPV neg | Normal | Normal | 5% AA | 3.6 | |||
H28 | Healthy | HPV neg | Normal | Normal | 5% AA | 0.0 | |||
H69 | Healthy | HPV neg | Normal | Normal | 5% AA | 5.3 | |||
H70 | Healthy | HPV neg | Normal | Normal | 5% AA | 0.1 | |||
H08 | Healthy | HPV neg | Normal | Normal | 5% AA | 8.7 | |||
H14 | Healthy | HPV neg | Normal | Normal | 5% AA | 7.5 | |||
H73 | Healthy | HPV neg | Normal | Normal | 5% AA | 3.5 | |||
H87 | Healthy | HPV neg | Normal | Normal | 5% AA | 0.0 | |||
H90 | Healthy | HPV neg | Normal | Normal | 5% AA | 8.2 | |||
H09 | Low risk | 6 | 96,249 | ASCUS | Normal | 5% AA | 12.7 | ||
H35 | Low risk | 11 | 51,740 | ASCUS | CIN1 | 5% AA | 10.7 | ||
H182 | Low risk | 6 | 1.00 | Normal | Normal | 5% AA | 20.7 | ||
H213 | Low risk | 6 | 0.05 | Normal | Normal | 5% AA | 29.9 | ||
P24 | High risk | 16/39 | 7729/1661 | ASCUS | CIN3 | 5% AA | 17.1 | ||
P27 | High risk | 52 | 129 | LSIL | CIN1 | 5% AA | 113.9 | ||
P60 | High risk | 16/31/52/66 | 0.02/11/12/31 | LSIL | CIN1 | 5% AA | 32.6 | ||
P61 | High risk | 16/31/39/52/66 | 288/0.20/4/7416/179 | LSIL | CIN1 | 5% AA | 22.2 | ||
P41 | High risk | 16/58 | 11571/253 | HSIL | CIN2 | 5% AA | 45.0 | ||
P36 | High risk | 16/53/58/59 | 9126/79/2733/1510 | LSIL | CIN1 | 5% AA | 70.4 | ||
P70 | High risk | 35 | 5159 | LSIL | CIN2 | 5% AA | 15.3 | ||
P40 | High risk | 31 | 1696 | HSIL | CIN1 | 5% AA | 15.5 | ||
Additional samples (cohort Van Raemdonck et al. [63]) | 205 | Healthy | HPV neg | Normal | 5% AA | 0.0 | |||
207 | Healthy | HPV neg | Normal | 5% AA | 0.0 | ||||
211 | Healthy | HPV neg | Normal | 5% AA | 0.0 | ||||
212 | Healthy | HPV neg | Normal | 5% AA | 0.0 | ||||
229 | Healthy | HPV neg | Normal | 5% AA | 36.1 | ||||
206 | High risk | HPV neg | ASCUS | 5% AA | 154.5 | ||||
204 | High risk | 45 | LSIL/HSIL | 5% AA | 0.0 | ||||
210 | High risk | 16 | LSIL | 5% AA | 52.1 | ||||
224 | High risk | 18/39/56 | LSIL | 5% AA | 0.0 | ||||
225 | High risk | 56 | LSIL | 5% AA | 0.0 | ||||
42 | Patient L1 | High risk new infection | 52/53/59/66 | 178/0.07/50/6 | LSIL | 5% AA | 0.5 | ||
119 | 52 | 26.00 | Normal | 5% AA | 5.0 | ||||
308 | 16/52 | 171/283 | ASCUS | 5% AA | 22.7 | ||||
85 | Patient L2 | High risk clearing | 33/52/58/66 | 0.01/9147/268/526 | LSIL | 5% AA | 32.1 | ||
146 | HPV neg | 0.00 | LSIL | 5% AA | 11.2 | ||||
281 | HPV neg | 0.00 | Normal | 5% AA | 0.5 | ||||
36 | Patient L4 | High risk persisting | 16/53/58/59 | 9126/79/2733/1510 | LSIL | 5% AA | 17.7 | ||
105 | 16/53/58 | 99,999/11/4123 | LSIL | 5% AA | 37.1 | ||||
172 | 16/58 | 3/99,999 | LSIL | 5% AA | 39.7 | ||||
290 | 58 | 4997.00 | LSIL | 5% AA | 46.0 | ||||
154 | Patient L5 | Healthy | HPV neg | 0.00 | Normal | 5% AA | 4.2 | ||
242 | 31 | 0.62 | Normal | 5% AA | 0.5 | ||||
302 | HPV neg | 0.00 | Normal | 5% AA | 2.0 | ||||
15 | Patient L6 | High risk clearing | 16/39/53 | 2627/12,052/0.51 | LSIL | 5% AA | 10.1 | ||
135 | 16 | 4.00 | Normal | 5% AA | 0.5 | ||||
271 | 16 | 33.00 | Normal | 5% AA | 1.8 | ||||
S266 | Patient L7 | High risk clearing | 16/31/51/56 | 111/0.2452/33/271 | LSIL | 5% AA | 15.0 | ||
23 | HPV neg | 0.00 | Normal | 5% AA | 0.5 | ||||
127 | HPV neg | 0.00 | Normal | 5% AA | 3.1 | ||||
359 | HPV neg | 0.00 | Normal | 5% AA | 1.3 | ||||
43 | Patient L8 | High risk new infection | HPV neg | 0.00 | Normal | 5% AA | 0.5 | ||
147 | 51/59 | 99,999/46 | LSIL | 5% AA | 17.4 | ||||
348 | 51/59 | 0.13/165 | ASCUS | 5% AA | 7.2 | ||||
70 | Patient L9 | High risk clearing | 35 | 5159.00 | HSIL | 5% AA | 6.3 | ||
177 | HPV neg | 0.00 | Normal | 5% AA | 0.6 | ||||
342 | HPV neg | 0.00 | Normal | 5% AA | 0.5 | ||||
103 | Patient L10 | High risk persisting | 31 | 351.00 | Normal | 5% AA | 18.1 | ||
218 | 31 | 1556.00 | Normal | 5% AA | 25.0 | ||||
343 | 31 | 3479.00 | ASCUS | 5% AA | 60.8 | ||||
Berlin cohort | DS77 | High risk | 16/31/52 | CIN3 | PBS | 0.0 | |||
DS78 | High risk | 16 | CIN3 | PBS | 896.2 | ||||
DS72 | Cancerous | 16 | CxCa | PBS | 782.9 | ||||
DS73 | Cancerous | HPV neg | CxCa after conisation | PBS | 719.0 | ||||
DS80 | Cancerous | 18/56 | Cx AdenoCa | PBS | 355.2 | ||||
DS86 | Cancerous | 16 | CxCa | PBS | 463.8 | ||||
DS90 | Cancerous | HPV neg | CxCa FIGO IIIb N1 (1/10) | PBS | 559.0 | ||||
DS74 | Cancerous | 16 | CxCa 1a1 VAIN III | PBS | 2316.7 | ||||
DS79 | Cancerous | 16 | ZxCa susp. Peritoneal | PBS | 3075.2 | ||||
DS84 | Cancerous | HPV neg | CxCa | PBS | 500.0 | ||||
DS87 | Cancerous | HPV neg | CxCa pT1a2 G2 L1 V0 R1 | PBS | 178.1 | ||||
DS88 | Cancerous | 16 | CxCa FIGO IIa | PBS | 949.2 | ||||
DS89 | Cancerous | 16 | CxCa FIGO IIb | PBS | 1354.8 | ||||
DS91 | Cancerous | 18/43 | CxCa FIGO lib | PBS | 636.4 | ||||
Van Raemdonck et al. [64] | 5714 | No HIV | ESN population | HPV neg | – | – | PBS | 2.5 | |
3896 | No HIV | ESN population | HPV neg | – | – | PBS | 4.2 | ||
6624 | HIV | ESN population | HPV neg | – | – | PBS | 0.0 | ||
6589 | HIV | ESN population | HPV neg | – | – | PBS | 0.0 | ||
6488 | HIV | ESN population | HPV neg | – | – | PBS | 0.0 |
Alpha-actinin-4 and cancer
Efficiency of alpha-actinin-4 as a CVF biomarker for cervical cancer
Network biomarkers
Name | Acc. No | ID |
---|---|---|
Increased levels in CVF from women with adenocarcinoma: | ||
Carcino embryonic antigen (CEA) | Q13984 | Q13984_HUMAN |
carbohydrate antigen disialyl Lewis a, CA19-9 | Q969X2 | SIA7F_HUMAN |
Increased levels in CVF from women with precancerous lesions with stringent selection (p < 0.05) | ||
Van Raemdonck et al. [63] | ||
14-3-3 protein epsilon | P62258 | 1433E_HUMAN |
Actin-related protein 3 | P61158 | ARP3_HUMAN |
Alpha-actinin-4 | O43707 | ACTN4_HUMAN |
Annexin A2 | P07355 | ANXA2_HUMAN |
ATP synthase subunit beta, mitochondrial | P06576 | ATPB_HUMAN |
Cellular retinoic acid-binding protein 2 | P29373 | RABP2_HUMAN |
Nicotinamide phosphoribosyltransferase | P43490 | NAMPT_HUMAN |
Phosphoglycerate kinase 1 | P00558 | PGK1_HUMAN |
Putative elongation factor 1-alpha-like 3 | Q5VTE0 | EF1A3_HUMAN |
Pyruvate kinase isozymes M1/M2 | P14618 | KPYM_HUMAN |
Serpin B13 | Q9UIV8 | SPB13_HUMAN |
Squamous cell carcinoma antigen 1 (SCCA-1); Serpin B3 | P29508 | SPB3_HUMAN |
Exclusive occurrence in CVF from women with precancerous lesions and described to be involved in cervical cancer | ||
14-3-3 protein theta | P27348 | 1433T_HUMAN |
Angiotensinogen | P01019 | ANGT_HUMAN |
Annexin A4 | P09525 | ANXA4_HUMAN |
Cathepsin B | P07858 | CATB_HUMAN |
CD59 glycoprotein | P13987 | CD59_HUMAN |
Ceruloplasmin | P00450 | CERU_HUMAN |
Gelsolin | P06396 | GELS_HUMAN |
High mobility group protein B2 | P26583 | HMGB2_HUMAN |
Interleukin-18 | Q14116 | IL18_HUMAN |
Macrophage migration inhibitory factor | P14174 | MIF_HUMAN |
Macrophage-capping protein | P40121 | CAPG_HUMAN |
Mucin-5B | Q9HC84 | MUC5B_HUMAN |
Myosin light polypeptide 6 | P60660 | MYL6_HUMAN |
Phosphoglycerate mutase 1 | P18669 | PGAM1_HUMAN |
Protein disulfide isomerase A3 | P30101 | PDIA3_HUMAN |
Protein S100-P | P25815 | S100P_HUMAN |
Serpin B13 | Q9UIV8 | SPB13_HUMAN |
Superoxide dismutase [Mn] | P04179 | SODM_HUMAN |