International Agency for Research on Cancer (IARC/WHO), Early Detection, Prevention and Infections Branch, Lyon, France.
International Agency for Research on Cancer (IARC/WHO), Early Detection, Prevention and Infections Branch, Lyon, France.
Lancet. 2024 Aug 3;404(10451):435-444. doi: 10.1016/S0140-6736(24)01097-3.
Understanding the proportion of invasive cervical cancer (ICC) caused by different human papillomavirus (HPV) genotypes can inform primary (ie, vaccination) and secondary (ie, screening) prevention efforts that target specific HPV genotypes. However, using the global literature to estimate population attributable fractions (AFs) requires a methodological framework to address HPV genotype-specific causality from aggregated data. We aimed to estimate the proportion of ICC caused by different HPV genotypes at the global, regional, and national level.
This systematic review identified studies reporting HPV genotype-specific prevalence in ICC or people with normal cervical cytology. We searched PubMed, Embase, Scopus, and Web of Science up to Feb 29, 2024, using the search terms "cervix" and "HPV", with no language restrictions. Odds ratios (ORs) were estimated by comparing HPV genotype-specific prevalence between HPV-positive ICC and normal cervical cytology with logistic regression models, adjusting for region, year of paper publication, and HPV primer or test. HPV genotypes with a lower bound to the 95% CI of the OR greater than 1·0 were judged as causal to ICC. Corresponding regional genotype-specific AFs were calculated as regional HPV prevalence in ICC multiplied by (1 - [1 / OR]) and were proportionally adjusted to total 100%. Global AFs were calculated from regional AFs weighted by number of regional ICC cases in 2022 (GLOBOCAN).
The systematic review identified 1174 studies with 111 902 cases of HPV-positive ICC and 2 755 734 of normal cervical cytology. 17 HPV genotypes were considered causal to ICC, with ORs ranging widely from 48·3 (95% CI 45·7-50·9) for HPV16 to 1·4 (1·2-1·7) for HPV51. HPV16 had the highest global AF (61·7%), followed by HPV18 (15·3%), HPV45 (4·8%), HPV33 (3·8%), HPV58 (3·5%), HPV31 (2·8%), and HPV52 (2·8%). Remaining causal genotypes (HPV35, 59, 39, 56, 51, 68, 73, 26, 69, and 82) had a combined global AF of 5·3%. AFs for HPV16 and 18 and HPV16, 18, 31, 33, 45, 52, and 58 combined were lowest in Africa (71·9% and 92·1%, respectively) and highest in central, western, and southern Asia (83·2% and 95·9%, respectively). HPV35 had a higher AF in Africa (3·6%) than other regions (0·6-1·6%).
This study provides a comprehensive global picture of HPV genotype-specific AFs in ICC, before the influence of HPV vaccination. These data can inform HPV genotype-specific vaccination and screening strategies to reduce the burden of ICC.
EU Horizon 2020 Research and Innovation Programme.
了解不同人乳头瘤病毒（HPV）基因型引起的浸润性宫颈癌（ICC）的比例，可以为针对特定 HPV 基因型的初级（即疫苗接种）和二级（即筛查）预防措施提供信息。然而，使用全球文献来估计人群归因分数（AFs）需要一个方法框架来解决从汇总数据中确定 HPV 基因型特异性因果关系的问题。我们旨在估计不同 HPV 基因型在全球、区域和国家层面引起 ICC 的比例。
本系统评价确定了报告 HPV 基因型特异性在 ICC 或正常宫颈细胞学患者中流行率的研究。我们使用了“宫颈”和“HPV”这两个术语，在 2024 年 2 月 29 日之前，在 PubMed、Embase、Scopus 和 Web of Science 上进行了无语言限制的搜索。使用逻辑回归模型比较 HPV 阳性 ICC 与正常宫颈细胞学之间 HPV 基因型特异性流行率，调整了区域、论文发表年份、HPV 引物或检测方法，来估计比值比（ORs）。ORs 的下限大于 1.0 的 HPV 基因型被判断为与 ICC 有因果关系。相应的区域基因型特异性 AFs 按 ICC 中 HPV 流行率乘以（1 - [1 / OR]）计算，并按 2022 年区域 ICC 病例数（GLOBOCAN）进行比例调整。
系统评价确定了 1174 项研究，涉及 111902 例 HPV 阳性 ICC 和 2755734 例正常宫颈细胞学。17 种 HPV 基因型被认为与 ICC 有因果关系，OR 范围很广，从 HPV16 的 48.3（95%CI 45.7-50.9）到 HPV51 的 1.4（1.2-1.7）。HPV16 的全球 AF 最高（61.7%），其次是 HPV18（15.3%）、HPV45（4.8%）、HPV33（3.8%）、HPV58（3.5%）、HPV31（2.8%）和 HPV52（2.8%）。其余有因果关系的基因型（HPV35、59、39、56、51、68、73、26、69 和 82）的全球 AF 为 5.3%。HPV16 和 18 以及 HPV16、18、31、33、45、52 和 58 联合的 AF 在非洲最低（分别为 71.9%和 92.1%），在中、西、南亚最高（分别为 83.2%和 95.9%）。HPV35 在非洲的 AF 高于其他地区（3.6%比 0.6-1.6%）。
本研究提供了 ICC 中 HPV 基因型特异性 AFs 的全球综合概况，此前未受到 HPV 疫苗接种的影响。这些数据可以为 HPV 基因型特异性疫苗接种和筛查策略提供信息，以减轻 ICC 的负担。
欧盟地平线 2020 研究与创新计划。
