Summary of findings for the main comparison. HPV vaccine effects on cervical lesions in adolescent girls and women negative for hrHPV DNA at baseline.
| HPV vaccine effects on cervical lesions in adolescent girls and women who are hrHPV DNA negative at baseline | ||||||
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Patient or population: adolescent girls and women aged 15 to 26 years who are hrHPV negative before vaccination Setting: Europe, Asia Pacific countries, South & North America Intervention: HPV vaccines (at least one dose of bivalent or quadrivalent vaccines) Comparison: Placebo | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | № of participants (studies) | Certainty of the evidence (GRADE) | Comments | |
| Risk with placebo | Risk with HPV vaccination1 | |||||
| Cervical cancer ‐ not measured | ‐ | ‐ | ‐ | ‐ | ‐ | |
| CIN2+ associated with HPV16/18. Follow‐up: 3 to 5 years |
164 per 10,000 | 2 per 10,000 (0 to 8) | RR 0.01 (0.00 to 0.05) | 23,676 (3 RCTs) | ⊕⊕⊕⊕ HIGH | |
| CIN3+ associated with HPV16/18 Follow‐up: 3 to 5 years |
70 per 10,000 | 0 per 10,000 (0 to 7) | RR 0.01 (0.00 to 0.10) | 20,214 (2 RCTs) | ⊕⊕⊕⊕ HIGH | Continuity correction |
| AIS associated with HPV16/18 Follow‐up: 3 to 5 years |
9 per 10,000 | 0 per 10,000 (0 to 7) | RR 0.10 (0.01 to 0.82) | 20,214 (2 RCTs) | ⊕⊕⊕⊝ MODERATE 2 | Continuity correction |
| Any CIN2+ irrespective of HPV type, bivalent or quadrivalent vaccine Follow‐up: 2 to 6 years |
287 per 10,000 | 106 per 10,000 (72 to 158) | RR 0.37 (0.25 to 0.55) | 25,180 (5 RCTs) | ⊕⊕⊕⊕ HIGH | Substantial subgroup heterogeneity was observed (I2= 84.3%) for bi‐ and quadrivalent vaccines. So results are reported separately for the 2 vaccines (see next 2 rows). |
| Any CIN2+ irrespective of HPV type Follow‐up (bivalent): 3.5 to 6 years Follow‐up (quadrivalent): 3.5 years |
Bivalent vaccine | RR 0.33 (0.25 to 0.43) |
15,884 (4 RCTs) |
⊕⊕⊕⊕ HIGH | ||
| 285 per 10,000 | 94 per 10,000 (71 to 122) |
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| Quadrivalent vaccine | RR 0.57 (0.44 to 0.76) |
9296 (1 RCT) |
⊕⊕⊕⊝ MODERATE3 | |||
| 291 per 10,000 | 166 per 10,000 (128 to 221) |
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| Any CIN3+ irrespective of HPV type, bivalent or quadrivalent vaccine Follow‐up: 3.5 to 4 years |
109 per 10,000 | 23 per 10,000 (4 to 120) | RR 0.21 (0.04 to 1.10) | 20,719 (3 RCTs) | ⊕⊕⊕⊝ MODERATE 3 | Substantial subgroup heterogeneity was observed (I2 = 84.3%) for bi‐ and quadrivalent vaccines. So results are reported separately for the 2 vaccines (see next 2 rows). |
| Any CIN3+ irrespective of HPV type Follow‐up (bivalent): 4 years Follow‐up (quadrivalent): 3.5 years |
Bivalent vaccine | RR 0.08 (0.03 to 0.23) |
11,423 (2 RCTs) |
⊕⊕⊕⊕ HIGH | ||
| 81 per 10,000 | 6 per 10,000 (3 to 19) |
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| Quadrivalent vaccine | RR 0.54 (0.36 to 0.82) |
9296 (1 RCT) |
⊕⊕⊕⊝ MODERATE3 | |||
| 143 per 10,000 | 77 per 10,000 (51 to 117 ) |
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| Any AIS irrespective of HPV type Follow‐up: 3 to 5 years | 10 per 10,000 | 0 per 10,000 (0 to 8) | RR 0.10 (0.01 to 0.76) | 20,214 (2 RCTs) | ⊕⊕⊕⊝ MODERATE 2 | Continuity correction |
| 1The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). When risk in vaccine group is zero, the 95% CI is computed using an exact binomial method. AIS: adenocarcinoma in situ; CI: Confidence interval; CIN: cervical intraepithelial neoplasia; RR: Risk ratio | ||||||
| GRADE Working Group grades of evidence High certainty: We are very confident that the true effect lies close to that of the estimate of the effect Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect | ||||||
1 Assumed risk calculated from the sum of control group event rates.
2 Downgraded due to serious imprecision in effect estimate (width 95% CI around RR > 0.6).
3 Downgraded one level due to serious imprecision. Few events observed in the two studies (9 in placebo arms and 0 in vaccination arms for the outcome of AIS HPV16/18 and 7 in placebo arms and 0 in vaccination arms for outcome of AIS of any type).