Background

Human papillomavirus (HPV) immunisation with a bivalent vaccine (Cervarix) was introduced in England, UK, in Sept 1, 2008: routine vaccination was offered to girls aged 12–13 years with a catch-up programme for females aged 14–18 years in 2008–10. We quantified the early effect of this immunisation programme on cervical cancer and cervical carcinoma in situ, namely grade 3 cervical intraepithelial neoplasia (CIN3), registrations.

Methods

In this observational study, we used an extension of the age-period-cohort Poisson model to estimate the relative risk of cervical cancer in three vaccinated cohorts compared with earlier cohorts that were not eligible for HPV vaccination. Data from a population-based cancer registry were extracted on Jan 26, 2021, and were assessed for diagnoses of cervical cancer and CIN3 from Jan 1, 2006 to June 30, 2019 in women aged 20–64 years and who were a resident in England. We used three vaccinated cohorts to account for differences in the school year in which the vaccine was offered and its national coverage. Adjustment for confounding was made using information on changes in cervical screening policy and historical events that affected cervical cancer incidence. Results were compared across models with different adjustments for confounders.

Findings

We used data from a total of 13·7 million-years of follow-up of women aged 20 years to younger than 30 years. The estimated relative reduction in cervical cancer rates by age at vaccine offer were 34% (95% CI 25–41) for age 16–18 years (school year 12–13), 62% (52–71) for age 14–16 years (school year 10–11), and 87% (72–94) for age 12–13 years (school year 8), compared with the reference unvaccinated cohort. The corresponding risk reductions for CIN3 were 39% (95% CI 36–41) for those offered at age 16–18 years, 75% (72–77) for age 14–16 years, and 97% (96–98) for age 12–13 years. These results remained similar across models. We estimated that by June 30, 2019 there had been 448 (339–556) fewer than expected cervical cancers and 17 235 (15 919–18 552) fewer than expected cases of CIN3 in vaccinated cohorts in England.

Interpretation

We observed a substantial reduction in cervical cancer and incidence of CIN3 in young women after the introduction of the HPV immunisation programme in England, especially in individuals who were offered the vaccine at age 12–13 years. The HPV immunisation programme has successfully almost eliminated cervical cancer in women born since Sept 1, 1995.

Funding

Cancer Research UK.

中文翻译：

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英国英格兰国家 HPV 疫苗接种计划对宫颈癌和 3 级宫颈上皮内瘤变发病率的影响：一项基于登记的观察研究

背景

2008 年 9 月 1 日，英国英格兰推出了使用二价疫苗 (Cervarix) 进行人乳头瘤病毒 (HPV) 免疫：为 12-13 岁的女孩提供常规疫苗接种，并为 14-18 岁的女性提供补种计划2008-10 年。我们量化了该免疫计划对宫颈癌和宫颈原位癌的早期影响，即 3 级宫颈上皮内瘤变 (CIN3) 登记。

方法

在这项观察性研究中，我们使用年龄-周期队列泊松模型的扩展来估计三个接种疫苗的队列与不适合接种 HPV 疫苗的早期队列相比，宫颈癌的相对风险。2021 年 1 月 26 日从基于人群的癌症登记处提取数据，并在 2006 年 1 月 1 日至 2019 年 6 月 30 日期间对 20-64 岁且居住在英格兰的女性进行宫颈癌和 CIN3 诊断评估. 我们使用三个接种疫苗的队列来解释提供疫苗的学年及其全国覆盖率的差异。使用有关宫颈筛查政策变化和影响宫颈癌发病率的历史事件的信息对混杂因素进行了调整。对不同模型的结果进行了比较，并对混杂因素进行了不同的调整。

发现

我们使用了对 20 岁至 30 岁以下女性进行的总计 13·700 万年的随访数据。16-18 岁（12-13 学年）的宫颈癌发病率按年龄估计相对降低 34%（95% CI 25-41），14-16 岁为 62%（52-71）年（第 10-11 学年）和 12-13 岁（第 8 学年）的 87% (72-94)，与未接种疫苗的参考队列相比。16-18 岁提供的 CIN3 相应风险降低 39% (95% CI 36-41)，14-16 岁提供 75% (72-77) 和 97% (96-98)年龄 12-13 岁。这些结果在不同模型中保持相似。我们估计，到 2019 年 6 月 30 日，在英格兰接种疫苗的队列中，宫颈癌病例比预期少 448 (339–556) 例，CIN3 病例比预期少 17 235 (15 919–18 552) 例。

解释

我们观察到在英格兰引入 HPV 免疫计划后，年轻女性的宫颈癌和 CIN3 发病率显着降低，尤其是在 12-13 岁接种疫苗的个体中。HPV 免疫计划已经成功地几乎消除了自 1995 年 9 月 1 日以来出生的女性的宫颈癌。

资金

英国癌症研究中心。