A Cochrane review [Abstract] 2 included 26 trials with a total of 73 428 participants. Persistent infection with high-risk human papillomaviruses (hrHPV) types is causally linked with the development of cervical intraepithelial neoplasia grade 2 and above (CIN2+), CIN grade 3 and above (CIN3+), and cervical cancer. HPV types 16 and 18 cause approximately 70% of cervical cancers worldwide. Regardless of HPV DNA statusin younger women (aged 15 to 26), HPV vaccines reduced the risk of CIN2+, CIN3+, and adenocarcinoma-in-situ (AIS) associated with HPV16/18. (table T1). The reduction in any CIN3+ differed by vaccine type (bivalent vaccine: RR 0.55, 95% CI 0.43 to 0.71 and quadrivalent vaccine: RR 0.81, 95% CI 0.69 to 0.96).In women vaccinated at 24 to 45 years of age, the risks of CIN2+ associated with HPV16/18 and any CIN2+ are similar between vaccinated and unvaccinated women, which may be due to previous exposure to HPV. Studies were not of sufficient power or duration to evaluate cervical cancer outcomes.
| Outcome | Relative effect(95% CI)RR | Risk with placebo | Risk with HPV vaccination (95% CI) | №of participants(studies)Certainty of evidence |
|---|---|---|---|---|
| CIN2+ associated with HPV16/18Follow-up (age 15 to 26 years): 3.5 to 8.5 years | RR 0.46(0.37 to 0.57 | 341 per 10 000 | 157 per 10 000(126 to 194) | 34 852(3) High |
| CIN2+ associated with HPV16/18Follow-up (age 24 to 45 years): 3.5 years | 0.74(0.52 to 1.05) | 145 per 10 000 | 107 per 10 000(76 to 152) | 9 200(2) Moderate |
| CIN3+ associated with HPV16/18Follow-up: 3.5 years | 0.55(0.45 to 0.67) | 165 per 10 000 | 91 per 10 000(74 to 127) | 34 562(2) High |
| Adeno carcinoma in situ (AIS) associated with HPV16/18Follow-up: 3.5 years | 0.36(0.17 to 0.78) | 14 per 10 000 | 5 per 10 000(3 to 11) | 34 562(2) High |
| Any CIN2+ irrespective of HPV type(age 15 to 26 years) Follow-up : 3.5 to 8.5 years | 0.70(0.58 to 0.85) | 559 per 10 000 | 391 per 10 000(324 to 475) | 35 779(4) High |
| Any CIN2+ irrespective of HPV type(age 24 to 45 years) Follow-up : 3.5 to 6 years | RR 1.04(0.83 to 1.30) | 343 per 10 000 | 356 per 10 000(284 to 445) | 9287(2) Moderate |
In a randomised trial 1 in Costa Rica 2189 women (aged 18 to 25 years) with pre-existing infection were randomly assigned to receive 3 doses of a bivalent HPV-16/18 L1 protein viruslike particle AS04 candidate vaccine (n=1 088) or a control hepatitis A vaccine (n=1 101) over 6 months. Clearance rates for HPV-16/18 infections at 6 months were 33.4% (82/248) in the HPV vaccine group and 31.6% (95/298) in the control group (vaccine efficacy for viral clearance VEVC, 2.5%; 95% CI -9.8% to 13.5%) and at 12 months 48.8% (86/177) and 49.8% (110/220) respectively (VEVC -2.0%; 95% CI -24.3% to 16.3%). There was no evidence of a therapeutic effect for other oncogenic or nononcogenic HPV categories.
Comment: The quality of evidence is downgraded by study quality (more than 20% loss to follow up).
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