Background
Methods
Data source and study design
Cytology-based screening procedures
HPV-based screening procedures
Outcomes
Statistical analysis
Results
Characteristics of the study participants
Cytology | HPV testing | |||
---|---|---|---|---|
Overall HPV testing | HPV testing with cytology triage | HPV testing with genotyping triage | ||
Participants | 327,512 | 833,469 | 243,174 | 590,295 |
Mean age (years [SD]) | 48.1 (7.6) | 47.2 (7.7) | 46.6 (7.8) | 47.5 (7.6) |
Age group | ||||
35–44 | 115,312 (35.2) | 327,535 (39.3) | 103,752 (42.7) | 223,783 (37.9) |
45–54 | 143,483 (43.8) | 354,744 (42.6) | 98,279 (40.4) | 256,465 (43.5) |
55–64 | 68,717 (21.0) | 151,190 (18.1) | 41,143 (16.9) | 110,047 (18.6) |
Ever screening (yes) a | 116,802 (36.2) | 284,159 (34.1) | 67,754 (27.9) | 216,405 (36.7) |
Per protocol (yes) | 324,522 (99.1) | 775,379 (93.0) | 224,236 (92.2) | 551,143 (93.4) |
Place of residence (lower-middle-income area) | 157,394 (48.1) | 247,780 (29.7) | 43,243 (17.8) | 204,537 (34.7) |
Relative performance of HPV testing and cytology
Cytology | HPV testing | ||||||
---|---|---|---|---|---|---|---|
Overall HPV testing | aOR (95%CI) | HPV testing with cytology triage | aOR (95%CI) | HPV testing with genotyping triage | aOR (95%CI) | ||
Screen positivity, n (%) | 13 224 (4.0) | 84 591 (10.1) | 2.65 (2.59–2.70) | 24 251 (10.0) | 2.57 (2.52–2.63) | 60 340 (10.2) | 2.67 (2.62–2.72) |
Per protocol colposcopy referral, n (%)a | 13 224 (4.0) | 29 032 (3.5) | 0.85 (0.83–0.87) | 5 256 (2.2) | 0.51 (0.49–0.52) | 23 776 (4.0) | 0.98 (0.96–1.00) |
Overall colposcopy referral, n (%) | 12 312 (4.4) | 33 067 (4.5) | 1.03 (1.00–1.05) | 7 395 (3.3) | 0.76 (0.74–0.78) | 25 672 (5.0) | 1.13 (1.10–1.15) |
Per protocol detection rate of CIN or cancer, n (per 1000) | |||||||
CIN2+ | 1222 (4.4) | 3860 (5.5) | 1.18 (1.11–1.25) | 962 (4.4) | 0.92 (0.85–1.00) | 2898 (5.9) | 1.28 (1.20–1.36) |
CIN2 or 3 | 1125 (4.0) | 3523 (5.0) | 1.17 (1.09–1.24) | 859 (4.0) | 0.89 (0.82–0.97) | 2664 (5.4) | 1.28 (1.20–1.36) |
Invasive cervical cancer | 97 (0.3) | 337 (0.5) | 1.33 (1.08–1.64) | 103 (0.5) | 1.31 (1.00–1.70) | 234 (0.5) | 1.34 (1.07–1.66) |
Overall detection rate of CIN or cancer, n (per 1000) b | |||||||
CIN2+ | 1302 (4.6) | 4099 (5.7) | 1.17 (1.10–1.24) | 1076 (4.9) | 0.96 (0.88–1.03) | 3023 (6.1) | 1.26 (1.18–1.33) |
CIN2 or 3 | 1171 (4.2) | 3698 (5.2) | 1.17 (1.09–1.24) | 945 (4.3) | 0.93 (0.85–1.01) | 2753 (5.6) | 1.27 (1.19–1.35) |
Invasive cervical cancer | 131 (0.5) | 401 (0.6) | 1.18 (0.98–1.43) | 131 (0.6) | 1.23 (0.97–1.56) | 270 (0.5) | 1.16 (0.95–1.41) |
Positive predictive value, n (%) c | |||||||
CIN2+ | 1222 (10.9) | 4030 (13.8) | 1.29 (1.21–1.37) | 1045 (16.8) | 1.60 (1.47–1.75) | 2985 (13.0) | 1.22 (1.14–1.30) |
CIN2 or 3 | 1125 (10.0) | 3668 (12.6) | 1.27 (1.19–1.36) | 926 (14.9) | 1.52 (1.39–1.66) | 2742 (12.0) | 1.21 (1.13–1.30) |
Invasive cervical cancer | 97 (0.9) | 362 (1.2) | 1.42 (1.16–1.75) | 119 (1.9) | 2.20 (1.70–2.85) | 243 (1.1) | 1.24 (0.99–1.54) |
Relative performance of HPV testing and cytology by income classifications
Lower-middle-income areas | Upper-middle-income areas | |||||
---|---|---|---|---|---|---|
Cytology | Overall HPV testing | aOR (95%CI) | Cytology | Overall HPV testing | aOR (95%CI) | |
Screen positivity (%, 95%CI) | 4879 (3.1) | 23 764 (9.6) | 3.40 (3.29–3.51) | 8345 (4.9) | 60 827 (10.4) | 2.27 (2.21–2.32) |
Per protocol colposcopy referral (%, 95%CI)a | 4879 (3.1) | 9050 (3.7) | 1.21 (1.17–1.25) | 8345 (4.9) | 19 982 (3.4) | 0.69 (0.67–0.71) |
Overall colposcopy referral (%, 95%CI) | 4206 (2.7) | 9721 (3.9) | 1.55 (1.50–1.61) | 8106 (4.8) | 23 346 (4.0) | 0.83 (0.80–0.85) |
Per protocol detection rate of CIN or cancer (per 1000, 95%CI) | ||||||
CIN2+ | 406 (3.0) | 993 (4.7) | 1.53 (1.37–1.70) | 816 (5.6) | 2867 (5.7) | 1.03 (0.96–1.11) |
CIN2 or 3 | 368 (2.7) | 912 (4.3) | 1.55 (1.38–1.73) | 757 (5.2) | 2611 (5.2) | 1.01 (0.94–1.09) |
Invasive cervical cancer | 38 (0.3) | 81 (0.4) | 1.32 (0.92–1.89) | 59 (0.4) | 256 (0.5) | 1.32 (1.02–1.71) |
Overall detection rate of CIN or cancer b (per 1000, 95%CI) | ||||||
CIN2+ | 417 (3.1) | 1039 (4.9) | 1.56 (1.40–1.73) | 885 (6.0) | 3060 (6.1) | 1.01 (0.95–1.09) |
CIN2 or 3 | 373 (2.8) | 938 (4.4) | 1.57 (1.41–1.76) | 798 (5.5) | 2760 (5.5) | 1.01 (0.94–1.09) |
Invasive cervical cancer | 44 (0.3) | 101 (0.5) | 1.44 (1.03–2.01) | 87 (0.6) | 300 (0.6) | 1.08 (0.86–1.35) |
Positive predictive value c (%, 95%CI) | ||||||
CIN2+ | 406 (9.9) | 1018 (12.4) | 1.23 (1.10–1.38) | 816 (11.4) | 3012 (14.3) | 1.31 (1.21–1.41) |
CIN2 or 3 | 368 (9.0) | 936 (11.4) | 1.25 (1.11–1.40) | 757 (10.6) | 2732 (13.0) | 1.27 (1.17–1.38) |
Invasive cervical cancer | 38 (0.9) | 82 (1.0) | 1.02 (0.71–1.46) | 59 (0.8) | 280 (1.3) | 1.65 (1.27–2.14) |
Detection of CIN or invasive cancer in HPV-16/18-positive women
HPV testing with genotyping triage | HPV testing with cytology triage | ||
---|---|---|---|
HPV-16/18 | Non-16-18 HPV genotypes | ||
Women who attended immediate colposcopy adherence to the protocola | |||
CIN2+, n/N (%) | 1922/13 488 (17.3) | 902/7167 (13.8) | 870/4127 (24.1) |
aOR (95% CI) | 1.32 (1.22–1.43) | Ref (1.00) | 1.96 (1.77–2.16) |
Colposcopies per CIN2+ detection | 5.8 | 7.2 | 4.1 |
CIN2 or 3, n/N (%) | 1736/13 488 (15.6) | 861/7167 (13.1) | 785/4127 (21.8) |
aOR (95% CI) | 1.24 (1.14–1.34) | Ref (1.00) | 1.82 (1.64–2.01) |
ICC, n/N (%) | 186/13 488 (1.7) | 41/7167 (0.6) | 85/4127 (2.4) |
aOR (95% CI) | 2.75 (2.00–3.78) | Ref (1.00) | 3.64 (2.55–5.20) |
Women who needed intensified screening but attended immediate colposcopy b | |||
CIN2+, n/N (%) | NA | 102/3507 (2.9) | 83/1673 (5.0) |
aOR (95% CI) | NA | Ref (1.00) | 1.92 (1.38–2.67) |
Colposcopies per CIN2+ detection | NA | 34.5 | 20.0 |
CIN2 or 3, n/N (%) | NA | 91/3507 (2.6) | 67/1673 (4.0) |
aOR (95% CI) | NA | Ref (1.00) | 1.68 (1.18–2.39) |
ICC, n/N (%) | NA | 11/3507 (0.3) | 16/1673 (1.0) |
aOR (95% CI) | NA | Ref (1.00) | 3.94 (1.61–9.63) |