Table 1 Characteristics of 43 included studies
Author, year | Study ID | Country | Study design | First screen test | Sample | Median age (IQR/range) | n CIN2+ (%)a | n ICC (%) | Genes studied | Markers evaluated singly/in combination | Threshold for methylation positivity pre-defined |
|---|---|---|---|---|---|---|---|---|---|---|---|
Van Zummern 201734 | C2 | South Africa-Pretoria | Cohort | None | 321 | 40 [IQR; 35–46] | 94 (29.3%) | 2 (0.6%) | CADM1/MAL/miR124-2 | Combination only | Yes |
Kim 201645 | C3 | South Korea-Seoul | Convenience | HPV+ | 122 | NR | 48 (39.3%) | 0 (0.0%)b | ADM1, MAL, PAX1 | Single only | Yes |
Van Baars 201646 | C4 | Spain-Barcelona | Convenience | Abnormal cytology | 60 | 33 [19–92] | 25 (41.7%) | 0 (0.0%) | CADM1/MAL | Combination + single | Yes |
De Vuyst 201535 | C5 | Kenya-Nairobi | Cohort | HR-HPV (Genotyping) | 248 | 37 [33–42] | 93 (37.5%) | 0 (0.0%) | CADM1/MAL/miR124-2 | Combination + single | Obtained from ROC |
Verhoef 201526 | C6 | The Netherlands | Population-based screening—referral population | HR-HPV | 364 | 42 [38–48] | 90 (24.7%) | 6 (1.6%) | CADM1/MAL | Combination only | Yes |
De Strooper 201447 | C7 | The Netherlands | Convenience | None (HR-HPV >80%) | 168 | 37–48 | 48 (28.6%) | 0 (0.0%)b | CADM1/MAL/MIR124-2 | Combination only | Yes |
De Strooper 201448 | C8 | The Netherlands | Convenience | HR-HPV | 234 | 34–40 | 58 (24.8%) | 4 (1.7%) | CADM1/MAL | Combination only | Obtained from ROC |
Verhoef 201427 | C9 | The Netherlands | Population-based screeningreferral population | HR-HPV | 1019 | 43 [33–63] | 225 (22.1%) | 13 (1.3%) | MAL/MIR-124-2 | Combination only | Yes |
Hesselink 201432 | C10 | The Netherlands | Population-based screening– referral population | HR-HPV | 355 | 41 [31–62] | 94 (26.5%) | 5 (1.4) | CADM1/MAL/MIR124-2 | Combination + single | Obtained from ROC |
Hesselink 201149 | C11 | The Netherlands | Convenience | HR-HPV | 236 | 40 [19–62] | 58 (24.6%) | 4 (1.7) | CADM1/MAL | Combination + single | Yes |
Overmeer 201150 | C12 | The Netherlands | Convenience | HR-HPV | 70 | 34 [21–52] | 30 (42.9%) | 2 (2.9) | CADM1/MAL | Combination + single | Yes |
De Strooper 201630 | F1 | The Netherlands | Population-based screening – referral population | HR-HPV | 254 | 36 (30–62) | 99 (39.0%) | 4 (1.6) | FAM194A/MIR1242 | Combination only | Yes |
Luttmer 201631 | F2 | The Netherlands | Population-based screening– referral population | HR-HPV | 508 | ~30yrs | 180 (35.4%) | 3 (0.6) | FAM194A | Single only | Yes |
De Strooper 201465 | F3 | The Netherlands | Convenience | HR-HPV | 218 | 39 (19–62) | 52 (23.9) | 3 (1.4) | FAM194A | Single only | Yes |
Bu, 2018c 37 | F4 | China-Guangdong | Cohort | HR-HPV | 154 | NR | 57 (37.0) | 0 (0.0) | FAM194A | Single only | Obtained from ROC |
Kocsis 201724 | P1 | Hungary | Population-based screening– referral population | HR-HPV | 1287 | 36 (25–40) | 91 (7.1%) | 12 (0.9%) | POU4F3 | Single only | Yes |
Kelly 2018 (BF)25 | E1 | Burkina Faso-Ouagadougou | Case-control | None (HR-HPV >80%) | 94 | 39 (35–43) | 28 (29.8) | 1 (1.0%) | EPB41L3 | Single only | Obtained from ROC |
Kelly 2018 (SA)25 | E1 | South Africa- Johannesburg | Case-control | None (HR-HPV >80%) | 268 | 33 (30–38) | 124 (46.3) | 0 (0.0%) | EPB41L3 | Single only | Obtained from ROC |
Lorincz 201642 | E2 | UK-London | Case-control | HR-HPV (Aptima) | 341 | NR | 39 (11.4) | 1 (0.3%) | EPB41L3/HPV-16/-18/-31/-33 (S5 classifier) | Combination only | Pre-defined + ROC |
Louvanto 201557 | E3 | Canada-Montreal | Case-control | HPV16 positive | 151 | NR | 94 (62.3) | 0 (0.0%)b | EPB41L3, HPV16 | Single only | Yes |
Vasiljevic 201428 | E4 | UK-London | Population-based screening– referral population | HR-HPV | 1429 | NR | 531 (37.2) | 0 (0.0%) | EPB41L3 | Single only | Obtained from ROC |
Boers 201451 | E5 | The Netherlands | Convenience | HR-HPV | 128 | NR | 34 (26.6) | 9 (7.0) | EPB41L3 | Single only | Pre-defined + ROC |
Eijinsk 201252 | E6 | The Netherlands-Groningen | Convenience | HR-HPV | 200 | 20–85 | 66 (33.0) | 0 (0.0%)b | EPB41L3 | Single only | Yes |
van Leeuwan 201829 | E7 | Slovenia | Population-based screening– referral population | HR-HPV | 235 | NR | 35 (14.9) | 3 (1.3) | EPB41L3, SOX1 | Single | Yes |
Cook 201810 | E8 | Canada-British Colombia | Case-control | HR-HPV | 257 | NR | 107 (41.6) | 0 (0.0) | EPB41L3/HPV-16/-18/-31/-33 (S5 classifier) | Combination | Obtained from ROC |
Boers 201653 | E9 | The Netherlands-Groningen | Convenience | Cytology ASCUS+ | 171 | 20–85 | 106 (62.0) | 0 (0.0%)b | EPB41L3 | Single | Yes |
Rogeri 201836 | E11 | Brazil-Sao Paulo | Cohort | None (63% HR-HPV-positive) | 402 | NR | 126 (31.3) | 0 (0.0) | EPB41L3, SOX1 | Single only | Yes |
Xu 201543 | PS1 | China-Shanghai | Case-control | None (HR-HPV >76%) | 94 | 36–44 | 34 (36.2) | 0 (0.0%)b | PAX1 | Single only | Obtained from ROC |
Kan 201438 | PS2 | Taiwan-Taipei | Cohort | None | 419 | NR | 43 (10.3) | 4 (1.0) | PAX1, SOX1 | Single only | Yes |
Lai 201444 | PS3 | Taiwan | Case-control | Abnormal cytology | 346 | 46 | 92 (26.6) | 30 (8.7) | PAX1, SOX1 | Single only | Pre-defined + ROC |
Li 201539 | PS4 | China-Weifang | Cohort | Abnormal cytology (ASCUS+) | 463 | 46 (25–68) | 34 (7.3) | 2 (0.4%) | PAX1 | Single only | Pre-defined + ROC |
Lin 201140 | PS5 | Taiwan | Cohort | Abnormal cytology (ASCUS+) | 220 | NR | 42 (19.1) | 11 (5.0) | PAX1 | Single only | Yes-but unclear how |
Huang 201054 | PS6 | Taiwan | Convenience | Abnormal cytology | 59 | 32 (54.2) | 0 (0.0) | PAX1 | Single only | Yes | |
Tian 201741 | PS8 | Taiwan | Cohort | HR-HPV | 173 | NR | 79 (45.7) | 17 (9.8) | PAX1, SOX1 | Combination | Yes |
Bryant 201558 | H16-1 | UK-Cardiff | Case-control (HPV16+) | HPV16 positive | 200 | 21 (mean) | 145 (72.5) | 2 (1.0%) | HPV16-L1/L2 | Single only | Obtained from ROC |
Mirabello 201559 | H16-2 | USA-California | Case-control (HPV16+) | HPV16 positive | 99 | 34 [21–64] | 59 (59.6) | 0 (0.0%) | HPV16-L1 | Single only | Obtained from ROC |
Qiu 201561 | H16-3 | China-Zhengzhou | Convenience (HPV16+) | HPV16 positive | 114 | 37 [25–74] | 72 (63.2) | 11 (9.6) | HPV16-L1 | Single only | Yes |
Simanaviciene 201562 | H16-4 | Lithuania-Vilnius | Convenience (HPV16+) | HPV16 positive | 126 | NR | 87 (69.0) | 0 (0.0%)b | HPV16-L1 | Single only | Yes |
Brandsma 201463 | H16-5 | Senegal-Dakar/USA-New Haven | Convenience (HPV16+) | HPV16 positive | 33 | 34 (23–65) | 12 (36.4) | 0 (0.0%)b | HPV16-L1/L2/E2 | Single only | Yes |
Brentnall 201433 | H16-6 | UK-London | Population-based screening– referral population | Abnormal cytology and HPV16+ | 1493 | NR | 556 (37.2) | 0 (0.0%) | EPB41L3/HPV-16/-18/-31/-33 (S5 classifier) | Combination only | Obtained from ROC |
Lorincz 201355 | H16-7 | UK-Wales | Cohort (HPV16+) | HPV16 positive | 73 | NR | 25 (34.2) | 0 (0.0%) | HPV16-L1/L2 | Single only | Pre-defined + ROC |
Mirabello 201360 | H16-8 | Costa-Rica-Guanacaste | Case-control (HPV16+) | Abnormal VI or cyto and HPV16+ | 273 | NR | 109 (39.9) | 13 (4.8%) | HPV16 L1 | Single only | Obtained from ROC |
Kottaridi 201756 | H16-9 | Greece-Athens & UK-London | Case-control (HPV16+) | HPV16 positive | 150 | 36 (21–62) | 115 (76.6) | 9 (7.8) | HPV16 L1 | Single only | Yes |
