Department of Vaccines, National Institute for Health & Welfare, Helsinki, Finland.
Department of Laboratory Medicine, Karolinska Institute, Huddinge, Sweden.
Cancer Med. 2021 Nov;10(21):7759-7771. doi: 10.1002/cam4.4299. Epub 2021 Sep 27.
We conducted a community-randomized trial (NCTBLINDED) in Finland to assess gender-neutral and girls-only vaccination strategies with the AS04-adjuvanted human papillomavirus (HPV)-16/18 (AS04-HPV-16/18)vaccine.
Girls and boys (12-15 years) were invited. We randomized 33 communities (1:1:1 ratio): Arm A: 90% of randomly selected girls and boys received AS04-HPV-16/18 vaccine and 10% received hepatitis B vaccine (HBV); Arm B: 90% of randomly selected girls received AS04-HPV-16/18 vaccine, 10% of girls received HBV, and all boys received HBV; Arm C: all participants received HBV. Effectiveness measurements against prevalence of HPV-16/18 cervical infection were estimated in girls at 18.5 years. The main measures were: (1) overall effectiveness comparing Arms A or B, regardless of vaccination status, vs Arm C; (2) total effectiveness comparing AS04-HPV-16/18 vaccinated girls in pooled Arms A/B vs Arm C; (3) indirect effectiveness (herd effect) comparing girls receiving HBV or unvaccinated in Arm A vs Arm C. Co-primary objectives were overall effectiveness following gender-neutral or girls-only vaccination.
Of 80,272 adolescents invited, 34,412 were enrolled. Overall effectiveness was 23.8% (95% confidence interval: -19.0, 51.1; P = 0.232) with gender-neutral vaccination. Following girls-only vaccination, overall effectiveness was 49.6% (20.1, 68.2; P = 0.004). Total effectiveness was over 90% regardless of vaccination strategy. No herd effect was found. Immunogenicity of the AS04-HPV-16/18 vaccine was high in both sexes.
This study illustrates the difficulty in conducting community randomized trials. It is not plausible that vaccinating boys would reduce overall effectiveness, and the apparent lack of herd effect was unexpected given findings from other studies. This analysis was likely confounded by several factors but confirms the vaccine's high total effectiveness as in clinical trials.
我们在芬兰进行了一项社区随机试验（NCTBLINDED），以评估使用 AS04 佐剂的人乳头瘤病毒（HPV）-16/18（AS04-HPV-16/18）疫苗的性别中性和仅限女孩接种策略。
邀请了女孩和男孩（12-15 岁）。我们将 33 个社区随机分组（1:1:1 比例）：A 组：90%的随机选择的女孩和男孩接种 AS04-HPV-16/18 疫苗，10%接种乙肝疫苗（HBV）；B 组：90%的随机选择的女孩接种 AS04-HPV-16/18 疫苗，10%的女孩接种 HBV，所有男孩接种 HBV；C 组：所有参与者接种 HBV。在 18.5 岁时，对 HPV-16/18 宫颈感染的流行率进行了针对女孩的效果测量。主要措施包括：（1）比较 A 组或 B 组，无论接种状况如何，与 C 组相比的总体效果；（2）比较汇总 A 组/ B 组中接种 AS04-HPV-16/18 的女孩的总效果与 C 组；（3）在 A 组中比较接受 HBV 或未接种疫苗的女孩与 C 组的间接效果（群体效应）。主要目的是评估性别中性或仅限女孩接种的总体效果。
在 80272 名被邀请的青少年中，有 34412 人入组。中性接种的总体效果为 23.8%（95%置信区间：-19.0，51.1；P=0.232）。仅接种女孩的总体效果为 49.6%（20.1，68.2；P=0.004）。无论接种策略如何，总效果均超过 90%。未发现群体效应。AS04-HPV-16/18 疫苗的免疫原性在两性中均很高。
本研究说明了进行社区随机试验的困难。接种男孩不太可能降低总体效果，而且考虑到其他研究的结果，明显缺乏群体效应是出乎意料的。尽管存在多种因素的混杂，但这种分析证实了疫苗在临床试验中的高总效果。
