Background
Objective
Methods
Systematic review
Eligibility criteria, information sources, search strategy
Study selection
Data extraction and assessment of the risk of bias
Data synthesis
The Korea HPV cohort study
Cohort design
Analysis of disease progression to HSIL
Results
Systematic review
Study selection
Type-specific HPV prevalence by cervical cytology
HPV type | Cervical cytology | ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Overalla | Normal | ASCUS+b | LSIL | HSIL | HSIL+c | ||||||||||||||||||||
Study | Sample size | Positive | Prevalence (95% CI) | Study | Sample size | Positive | Prevalence (95% CI) | Study | Sample size | Positive | Prevalence (95% CI) | Study | Sample size | Positive | Prevalence (95% CI) | Study | Sample size | Positive | Prevalence (95% CI) | Study | Sample size | Positive | Prevalence (95% CI) | ||
High-risk | HPV-16 | 23 | 16,700 | 3,247 | 19.4 (18.8–20.0) | 17 | 8,627 | 1,188 | 13.8 (13.0–14.5) | 18 | 4,185 | 635 | 15.2 (14.1–16.3) | 17 | 1,293 | 218 | 16.9 (14.8–18.9) | 14 | 1,061 | 375 | 35.3 (32.5–38.2) | 13 | 1,534 | 831 | 54.2 (51.7–56.7) |
HPV-18 | 22 | 16,188 | 1,126 | 7.0 (6.6–7.3) | 16 | 8,364 | 571 | 6.8 (6.3–7.4) | 17 | 4,026 | 238 | 5.9 (5.2–6.6) | 16 | 1,238 | 83 | 6.7 (5.3–8.1) | 13 | 1,022 | 73 | 7.1 (5.6–8.7) | 13 | 1,534 | 161 | 10.5 (9.0–12.0) | |
HPV-26 | 5 | 9808 | 26 | 0.3 (0.2–0.4) | 4 | 6,193 | 16 | 0.3 (0.1–0.4) | 4 | 2,753 | 7 | 0.3 (0.1–0.4) | 5 | 587 | 3 | 0.5 (0.0–1.1) | 3 | 181 | 0 | 0.0 (0.0–0.0) | 0 | 0 | 0 | NA | |
HPV-31 | 18 | 15,033 | 483 | 3.2 (2.9–3.5) | 12 | 7,912 | 227 | 2.9 (2.5–3.2) | 13 | 3,772 | 142 | 3.8 (3.2–4.4) | 12 | 1,003 | 21 | 2.1 (1.2–3.0) | 9 | 868 | 32 | 3.7 (2.4–4.9) | 11 | 1,478 | 61 | 4.1 (3.1–5.1) | |
HPV-33 | 19 | 15,138 | 555 | 3.7 (3.4–4.0) | 13 | 7,936 | 222 | 2.8 (2.4–3.2) | 14 | 3,795 | 142 | 3.7 (3.1–4.3) | 13 | 1,040 | 38 | 3.7 (2.5–4.8) | 10 | 889 | 67 | 7.5 (5.8–9.3) | 11 | 1,478 | 86 | 5.8 (4.6–7.0) | |
HPV-35 | 20 | 15,687 | 585 | 3.7 (3.4–4.0) | 14 | 8,204 | 308 | 3.8 (3.3–4.2) | 15 | 3,886 | 152 | 3.9 (3.3–4.5) | 14 | 1,106 | 35 | 3.2 (2.1–4.2) | 11 | 968 | 52 | 5.4 (4.0–6.8) | 12 | 1,523 | 38 | 2.5 (1.7–3.3) | |
HPV-39 | 19 | 14,455 | 647 | 4.5 (4.1–4.8) | 13 | 7,523 | 442 | 5.9 (5.3–6.4) | 14 | 3,661 | 134 | 3.7 (3.1–4.3) | 13 | 997 | 46 | 4.6 (3.3–5.9) | 10 | 837 | 11 | 1.3 (0.5–2.1) | 11 | 1,437 | 14 | 1.0 (0.5–1.5) | |
HPV-45 | 15 | 13,906 | 263 | 1.9 (1.7–2.1) | 11 | 7,579 | 152 | 2.0 (1.7–2.3) | 11 | 3,248 | 52 | 1.6 (1.2–2.0) | 11 | 854 | 14 | 1.6 (0.8–2.5) | 8 | 835 | 11 | 1.3 (0.5–2.1) | 10 | 1,390 | 34 | 2.4 (1.6–3.3) | |
HPV-51 | 18 | 15,062 | 788 | 5.2 (4.9–5.6) | 13 | 7,792 | 441 | 5.7 (5.1–6.2) | 14 | 3,856 | 204 | 5.3 (4.6–6.0) | 14 | 1,140 | 104 | 9.1 (7.5–10.8) | 11 | 901 | 34 | 3.8 (2.5–5.0) | 10 | 1,349 | 5 | 0.4 (0.0–0.7) | |
HPV-52 | 23 | 16,700 | 1,593 | 9.5 (9.1–10.0) | 17 | 8,627 | 842 | 9.8 (9.1–10.4) | 18 | 4,185 | 493 | 11.8 (10.8–12.8) | 17 | 1,293 | 113 | 8.7 (7.2–10.3) | 14 | 1,061 | 95 | 9.0 (7.2–10.7) | 13 | 1,534 | 50 | 3.3 (2.4–4.1) | |
HPV-53 | 14 | 13,781 | 1,474 | 10.7 (10.2–11.2) | 10 | 7,312 | 956 | 13.1 (12.3–13.8) | 12 | 3,633 | 362 | 10.0 (9.0–10.9) | 11 | 964 | 115 | 11.9 (9.9–14.0) | 8 | 699 | 26 | 3.7 (2.3–5.1) | 8 | 1,173 | 15 | 1.3 (0.6–1.9) | |
HPV-56 | 21 | 15,323 | 845 | 5.5 (5.2–5.9) | 15 | 7,870 | 465 | 5.9 (5.4–6.4) | 16 | 3,870 | 215 | 5.6 (4.8–6.3) | 15 | 1,154 | 119 | 10.3 (8.6–12.1) | 12 | 947 | 23 | 2.4 (1.4–3.4) | 12 | 1,482 | 23 | 1.6 (0.9–2.2) | |
HPV-58 | 23 | 16,700 | 1,790 | 10.7 (10.2–11.2) | 17 | 8,627 | 875 | 10.1 (9.5–10.8) | 18 | 4,185 | 477 | 11.4 (10.4–12.4) | 17 | 1,293 | 142 | 11.0 (9.3–12.7) | 14 | 1,061 | 180 | 17.0 (14.7–19.2) | 13 | 1,534 | 116 | 7.6 (6.2–8.9) | |
HPV-59 | 16 | 13,602 | 266 | 2.0 (1.7–2.2) | 11 | 6,873 | 159 | 2.3 (2.0–2.7) | 13 | 3,635 | 75 | 2.1 (1.6–2.5) | 12 | 956 | 13 | 1.4 (0.6–2.1) | 9 | 814 | 5 | 0.6 (0.1–1.2) | 8 | 1,324 | 14 | 1.1 (0.5–1.6) | |
HPV-66 | 16 | 13,394 | 575 | 4.3 (3.9–4.6) | 10 | 6,795 | 330 | 4.9 (4.3–5.4) | 13 | 3,635 | 152 | 4.2 (3.5–4.8) | 11 | 881 | 62 | 7.0 (5.3–8.7) | 8 | 750 | 14 | 1.9 (0.9–2.8) | 8 | 1,333 | 17 | 1.3 (0.7–1.9) | |
HPV-68 | 16 | 13,615 | 900 | 6.6 (6.2–7.0) | 11 | 6,873 | 623 | 9.1 (8.4–9.7) | 11 | 3,537 | 209 | 5.9 (5.1–6.7) | 12 | 956 | 46 | 4.8 (3.5–6.2) | 9 | 814 | 11 | 1.4 (0.6–2.1) | 9 | 1,412 | 11 | 0.8 (0.3–1.2) | |
HPV-73 | 3 | 9,340 | 55 | 0.6 (0.4–0.7) | 2 | 5,836 | 37 | 0.6 (0.4–0.8) | 2 | 2,281 | 15 | 0.7 (0.3–1.0) | 2 | 390 | 3 | 0.8 (0.0–1.6) | 1 | 127 | 0 | 0.0 (0.0–0.0) | 1 | 706 | 0 | 0.0 (0.0–0.0) | |
HPV-82 | 4 | 9,887 | 159 | 1.6 (1.4–1.9) | 4 | 6,178 | 104 | 1.7 (1.4–2.0) | 4 | 2,860 | 44 | 1.5 (1.1–2.0) | 4 | 601 | 7 | 1.2 (0.3–2.0) | 3 | 233 | 4 | 1.7 (0.0–3.4) | 1 | 15 | 0 | 0.0 (0.0–0.0) | |
Low-risk | HPV-6 | 8 | 3,319 | 65 | 2.0 (1.5–2.4) | 6 | 926 | 34 | 3.7 (2.5–4.9) | 7 | 948 | 15 | 1.6 (0.8–2.4) | 7 | 392 | 7 | 1.8 (0.5–3.1) | 5 | 529 | 3 | 0.6 (0.0–1.2) | 5 | 524 | 6 | 1.1 (0.2–2.1) |
HPV-11 | 9 | 4,260 | 44 | 1.0 (0.7–1.3) | 6 | 896 | 11 | 1.2 (0.5–1.9) | 6 | 964 | 9 | 0.9 (0.3–1.5) | 7 | 490 | 9 | 1.8 (0.6–3.0) | 6 | 608 | 10 | 1.6 (0.6–2.7) | 6 | 1,302 | 5 | 0.4 (0.0–0.7) | |
HPV-40 | 9 | 3,543 | 34 | 1.0 (0.6–1.3) | 7 | 840 | 14 | 1.7 (0.8–2.5) | 6 | 1,010 | 6 | 0.6 (0.1–1.1) | 7 | 317 | 0 | 0.0 (0.0–0.0) | 6 | 620 | 8 | 1.3 (0.4–2.2) | 6 | 603 | 6 | 1.0 (0.2–1.8) | |
HPV-42 | 6 | 2,796 | 19 | 0.7 (0.4–1.0) | 6 | 886 | 6 | 0.7 (0.1–1.2) | 6 | 757 | 6 | 0.8 (0.2–1.4) | 6 | 402 | 5 | 1.2 (0.2–2.3) | 4 | 295 | 2 | 0.7 (0.0–1.6) | 5 | 456 | 0 | 0.0 (0.0–0.0) | |
HPV-43 | 8 | 3,153 | 27 | 0.9 (0.5–1.2) | 8 | 1,013 | 11 | 1.1 (0.4–1.7) | 7 | 760 | 12 | 1.6 (0.7–2.5) | 8 | 480 | 2 | 0.4 (0.2–1.0) | 6 | 365 | 2 | 0.5 (0.0–1.3) | 6 | 535 | 0 | 0.0 (0.0–0.0) | |
HPV-44 | 8 | 3,152 | 14 | 0.4 (0.2–0.7) | 6 | 631 | 3 | 0.5 (0.1–1.0) | 6 | 626 | 3 | 0.5 (0.0–1.0) | 6 | 328 | 1 | 0.3 (0.0–0.9) | 4 | 326 | 3 | 0.9 (0.0–2.0) | 7 | 1,241 | 4 | 0.3 (0.0–0.6) | |
HPV-54 | 7 | 2,928 | 75 | 2.6 (2.0–3.1) | 4 | 704 | 33 | 4.7 (3.1–6.2) | 6 | 1,079 | 31 | 2.9 (1.9–3.9) | 5 | 349 | 1 | 0.3 (0.0–0.8) | 3 | 407 | 2 | 0.5 (0.0–1.2) | 4 | 389 | 8 | 2.1 (0.6–3.5) | |
HPV-61 | 2 | 1,069 | 29 | 2.7 (1.7–3.7) | 2 | 357 | 13 | 3.6 (1.7–5.6) | 2 | 472 | 12 | 2.5 (1.1–4.0) | 2 | 186 | 4 | 2.2 (0.1–4.2) | 2 | 54 | 0 | 0.0 (0.0–0.0) | 0 | 0 | 0 | NA | |
HPV-70 | 10 | 9,827 | 768 | 7.8 (7.3–8.3) | 7 | 4,200 | 447 | 10.6 (9.7–11.6) | 8 | 3,221 | 258 | 8.0 (7.1–8.9) | 8 | 672 | 43 | 6.4 (4.5–8.2) | 6 | 601 | 15 | 2.5 (1.2–3.7) | 6 | 1,110 | 5 | 0.5 (0.1–0.8) | |
HPV-72 | 3 | 755 | 8 | 1.1 (0.3–1.8) | 3 | 206 | 5 | 2.4 (0.3–4.5) | 3 | 217 | 2 | 0.9 (0.0–2.2) | 3 | 162 | 1 | 0.6 (0.0–1.8) | 3 | 140 | 0 | 0.0 (0.0–0.0) | 1 | 15 | 0 | 0.0 (0.0–0.0) | |
HPV-81 | 4 | 1,719 | 24 | 1.4 (0.8–2.0) | 4 | 598 | 11 | 1.8 (0.8–2.9) | 4 | 647 | 9 | 1.4 (0.5–2.3) | 4 | 285 | 4 | 1.4 (0.0–2.8) | 3 | 152 | 0 | 0.0 (0.0–0.0) | 3 | 37 | 0 | 0.0 (0.0–0.0) | |
Other | 14 | 12,864 | 216 | 1.7 (1.5–1.9) | 10 | 6,790 | 81 | 1.2 (0.9–1.5) | 10 | 3,239 | 74 | 2.3 (1.8–2.8) | 11 | 907 | 34 | 3.7 (2.5–5.0) | 8 | 513 | 3 | 0.6 (0.0–1.2) | 8 | 1,329 | 24 | 1.8 (1.1–2.5) |
The Korea HPV cohort study
Risk of disease progression by HPV type
N | Progression | Probability of progression within 36 months (95% CI)a | Hazard ratio (95% CI) | P valuec | ||
---|---|---|---|---|---|---|
Unadjusted | Adjustedb | |||||
ASCUS to HSIL | 441 | 60 | 17.6 (13.3–21.7) | |||
Age | ||||||
20–29 | 76 | 7 | 13.9 (3.4–23.4) | Ref | Ref | |
30–39 | 142 | 21 | 18.4 (10.8–25.5) | 1.64 (0.70–3.87) | 1.51 (0.64–3.56) | 0.351 |
40–49 | 128 | 20 | 19.7 (11.4–27.3) | 1.65 (0.70–3.91) | 1.67 (0.70–4.00) | 0.245 |
50–59 | 95 | 12 | 15.9 (6.7–24.1) | 1.32 (0.52–3.36) | 1.21 (0.47–3.10) | 0.699 |
HPV type at baseline | ||||||
Low-risk | 155 | 10 | 8.6 (3.1–13.8) | Ref | Ref | |
HPV-16 | 93 | 15 | 19.7 (9.9–28.4) | 2.67 (1.12–5.94) | 2.64 (1.18–5.90) | 0.018 |
HPV-18 | 44 | 3 | 10.6 (0.0–21.5) | 1.15 (0.32–4.17) | 1.08 (0.29–3.97) | 0.913 |
HPV-31 | 24 | 6 | 30.9 (5.8–49.3) | 4.01 (1.46–11.04) | 3.96 (1.43–10.94) | 0.008 |
HPV-33 | 18 | 3 | 20.6 (0.0–39.0) | 2.42 (0.67–8.81) | 2.34 (0.64–8.54) | 0.198 |
HPV-45 | 13 | 2 | 20.5 (0.0–42.3) | 2.24 (0.49–10.21) | 2.16 (0.47–9.90) | 0.320 |
HPV-52 | 87 | 12 | 19.6 (8.2–29.5) | 2.37 (1.02–5.48) | 2.32 (1.00–5.42) | 0.051 |
HPV-58 | 89 | 21 | 28.5 (16.9–38.4) | 3.64 (1.71–7.73) | 3.54 (1.66–7.55) | 0.001 |
Type-specific persistent infection | 200 | 28 | 30.7 (14.6–43.7) | |||
Low-risk | 88 | 4 | 6.6 (0.0–12.9) | Ref | Ref | |
HPV-16 | 27 | 6 | 29.2 (5.2–47.1) | 4.86 (1.37–17.23) | 5.04 (1.40–18.11) | 0.013 |
HPV-18 | 10 | 2 | 28.9 (0.0–56.7) | 4.13 (0.76–22.65) | 4.59 (0.82–25.70) | 0.083 |
HPV-31 | 8 | 2 | 31.4 (0.0–59.7) | 4.12 (0.75–22.56) | 3.86 (0.70–21.39) | 0.122 |
HPV-33 | 6 | 1 | 33.3 (0.0–70.0) | 2.58 (0.29–23.46) | 3.01 (0.33–27.56) | 0.331 |
HPV-45 | 4 | 1 | NA | 3.01 (0.34–27.02) | 2.80 (0.31–25.27) | 0.359 |
HPV-52 | 34 | 4 | 13.8 (0.0–27.6) | 2.43 (0.61–9.74) | 2.57 (0.64–10.39) | 0.185 |
HPV-58 | 33 | 10 | 61.7 (6.1–84.4) | 5.46 (1.71–17.42) | 5.84 (1.83–18.67) | 0.003 |
N | Progression | Probability of progression within 36 months (95% CI)a | Hazard ratio (95% CI) | P valuec | ||
---|---|---|---|---|---|---|
Unadjusted | Adjustedb | |||||
LSIL to HSIL | 245 | 45 | 25.7 (18.3–32.3) | |||
Age | ||||||
20–29 | 59 | 10 | 22.5 (8.4–34.3) | Ref | Ref | |
30–39 | 71 | 17 | 30.6 (16.3–42.5) | 1.30 (0.60–2.84) | 1.30 (0.58–2.90) | 0.520 |
40–49 | 69 | 15 | 32.0 (15.8–45.0) | 1.14 (0.51–2.53) | 1.10 (0.49–2.48) | 0.818 |
50–59 | 46 | 3 | 10.5 (0.0–21.2) | 0.34 (0.09–1.24) | 0.39 (0.11–1.48) | 0.167 |
HPV type at baseline | ||||||
Low-risk | 104 | 8 | 10.9 (2.9–18.4) | Ref | Ref | |
HPV-16 | 49 | 17 | 45.2 (24.8–60.0) | 4.69 (2.03–10.88) | 4.71 (2.02–11.02) | 0.001 |
HPV-18 | 22 | 4 | 20.9 (0.3–37.3) | 2.34 (0.71–7.78) | 2.72 (0.81–9.13) | 0.105 |
HPV-31 | 12 | 2 | 16.7 (0.0–35.3) | 3.08 (0.65–14.53) | 2.87 (0.60–13.68) | 0.186 |
HPV-33 | 14 | 4 | 68.2 (0.0–92.8) | 3.96 (1.19–13.18) | 4.17 (1.25–13.94) | 0.021 |
HPV-45 | 9 | 1 | 11.1 (0.0–29.4) | 1.59 (0.20–12.74) | 2.96 (0.36–24.64) | 0.316 |
HPV-52 | 34 | 7 | 22.2 (6.1–35.5) | 2.64 (0.96–7.29) | 3.42 (1.23–9.52) | 0.019 |
HPV-58 | 51 | 15 | 43.1 (22.0–58.5) | 4.17 (1.77–9.84) | 4.37 (1.84–10.41) | 0.001 |
Type-specific persistent infection | 135 | 29 | 38.8 (22.4–51.7) | |||
Low-risk | 78 | 7 | 12.4 (2.8–21.0) | Ref | Ref | |
HPV-16 | 15 | 8 | 66.6 (20.5–85.9) | 4.01 (1.45–11.10) | 4.24 (1.49–12.10) | 0.007 |
HPV-18 | 5 | 1 | 20.0 (0.0–48.4) | 2.04 (0.25–16.62) | 2.25 (0.27–18.44) | 0.451 |
HPV-31 | 2 | 0 | NA | NA | NA | NA |
HPV-33 | 5 | 3 | 70.0 (0.0–93.7) | 5.95 (1.53–23.09) | 4.56 (1.165–18.04) | 0.030 |
HPV-45 | 1 | 0 | NA | NA | NA | NA |
HPV-52 | 12 | 2 | 9.1 (0.0–24.6) | 1.49 (0.31–7.18) | 1.81 (0.37–8.91) | 0.464 |
HPV-58 | 20 | 9 | 50.3 (17.0–70.3) | 4.23 (1.58–11.37) | 4.18 (1.54–11.33) | 0.005 |