HPV vaccines against human papillomavirus
Sübutlu məlumatların xülasələri
03.07.2018 • Sonuncu dəyişiklik 03.07.2018
Editors
The bivalent and quadrivalent HPV L1 virus-like particle vaccines induce a high degree of protection against HPV-16/18 or HPV 6/11/16/18 infection and associated cervical lesions as compared with placebo, and are safe.
A Cochrane review 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. Studies were not of sufficient duration to evaluate cervical cancer outcomes. In adolescent girls and women (aged 15 to 26) negative for hrHPV DNA at baseline, HPV vaccines reduce CIN2+, CIN3+, adenocarcinoma-in-situ (AIS) associated with HPV16/18 compared with placebo in adolescent girls and women (table ). In those HPV16/18 negative
(aged 15 to 26 years), vaccines reduce CIN2+ associated with HPV16/18 from 113 to 6 /10 000 (RR 0.05, 95% CI 0.03 to 0.10). In women 24 years or older the absolute and relative reduction in the risk of these lesions is smaller (from 45 to 14/10,000; RR 0.30, 95% CI 0.11 to 0.81). HPV vaccines reduce the risk of CIN3+ and AIS associated with HPV16/18 in younger women (RR 0.05, 95% CI 0.02 to 0.14), and (RR 0.09, 95% CI 0.01 to 0.72), respectively. The risk of serious adverse events was similar between control and HPV vaccines in women of all ages (669 versus 656/10 000, RR 0.98, 95% CI 0.92 to 1.05; high certainty).
In an RCT
1 113 women between 15–25 years of age were randomised to receive three doses (at 0, 1, 6 months) of either the AS04 vaccine (HPV-16/18) or placebo in North America and Brazil. Vaccine efficacy was 95.1% (95% CI 63.5 to 99.3) against persistent cervical infection with HPV-16/18 and 92.9% (95% CI 70.0 to 98.3) against cytological abnormalities associated with HPV-16/18 infection. The vaccine was generally safe and well tolerated.
In the follow-up (vaccine n=393, placebo n=383) more than 98% seropositivity was maintained for HPV-16/18 antibodies up to 4.5 years. Vaccine efficacy against incident infection was 96.9% (95% CI 81.3 to 99.9); persistent infection: 6 month definition, 94.3 % (95% CI 63.2 to 99.9); 12 month definition, 100% (95% CI 33.6 to 100). In a combined analysis of the initial efficacy and extended follow-up studies, vaccine efficacy of 100% (95% CI 42.4 to 100) against cervical intraepithelial neoplasia (CIN) lesions associated with
vaccine types. Broad protection against cytohistological outcomes was noted for HPV 16/18 and protection against incident infection with HPV 45 and HPV 31. In the combined analysis of initial study and extended follow-up study (776 women up to 6.4 years), the vaccine efficacy against CIN2+ was 100% (51.3-100) for lesions associated with HPV-16/18 and 71.9% (20.6-91.9) for lesions independent of HPV DNA.
In another trial 18 644 young women were randomly assigned to receive either HPV16/18 vaccine or hepatitis A vaccine at 0, 1, and 6 months. The primary endpoint – vaccine efficacy against cervical intraepithelial neoplasia (CIN) 2+ associated with HPV16 or HPV18 – was assessed in women (n=16 626) who were seronegative and DNA negative for the corresponding vaccine type at baseline. Vaccine efficacy against CIN2+ containing HPV16/18 DNA was 90.4% (97.9% CI 53.4 to 99.3). Mean length of follow-up was 14.8 months.
In a double-blind trial 12 167 women (15–26 years) were randomly assigned to receive either HPV-6/11/16/18 vaccine or placebo, administered at 0, 2, and 6 months. An average follow-up time was 3 years. Vaccine efficacy for the prevention of cervical intraepithelial neoplasia grade 2 or 3, adenocarcinoma in situ, or cervical cancer was 98% (95.89% CI 86 to 100) in the per-protocol susceptible population and 44% (95% CI 26 to 58) in an intention-to-treat population of all women who had undergone randomization (those with or without previous infection).
The estimated vaccine efficacy against all high-grade cervical lesions, regardless of causal HPV type was 17% (95% CI 1 to 31). The results of two other trials with quadrivalent HPV 6/11/16/18 vaccine are of same magnitude.
"?>
HPV vaccine effects in adolescent girls and women negative for hrHPV DNA at baseline
| Outcome | Relative effect
(95% CI)
RR | Risk with placebo
| Risk with HPV vaccination (95% CI) | № of participants
(studies)
Certainty of evidence
|
| CIN2+ associated with HPV16/18.
Follow-up: 3 to 5 years
| 0.01
(0.00 to 0.05)
| 164 per 10 000
| 2 per 10 000
(0 to 8)
| 23 676
(3) High |
| CIN3+ associated with HPV16/18.
Follow-up: 3 to 5 years
|
0.01
(0.00 to 0.10)
| 70 per 10 000 | 0 per 10 000
(0 to 7) | 20 214
(2) High |
| Adenoca in situ associated with HPV16/18.
Follow-up: 3 to 5 years
|
0.10
(0.01 to 0.82)
| 9 per 10 000 | 0 per 10 000
(0 to 7) | 20 214
(2) Moderate |
| Any CIN2+ irrespective of HPV type, bivalent or quadrivalent vaccine
Follow-up: 2 to 6 years
| 0.37
(0.25 to 0.55)
| 287 per 10 000
| 106 per 10 000
(72 to 158)
| 25 180 (5) High |
| Any CIN3+ irrespective of HPV type
Follow-up (bivalent): 4 years | 0.08
(0.03 to 0.23)
| 81 per 10 000
| 6 per 10 000
(3 to 19) | 11 423
(2) High |
|
Any CIN3+ irrespective of HPV type Follow-up (quadrivalent): 3.5 years | R0.54
(0.36 to 0.82)
| 143 per 10 000
| 77 per 10 000
(51 to 117 ) | 9296
(1) Moderate |
Ədəbiyyat
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