About 50 years ago, the causality of cervical cancer was attributed to human papillomavirus (HPV) by the German virologist Harald zur Hausen. Since then, HPV has been shown to cause cancer in several anatomical sites and hundreds of HPV types have been discovered, prompting further research into the carcinogenic potential of HPVs. This virus-induced carcinogenicity has evolved and co-diverged with humans over time. For instance, most carcinogenic HPV genotypes belong to the same evolutionary clade in the α genus — these and related HPV genotypes are considered as potentially carcinogenic. From an epidemiological perspective, understanding the carcinogenicity of HPV genotypes in invasive cervical cancer (ICC) is key to predicting the effectiveness of HPV vaccination and screening programmes. Towards this goal, in a recent study published in The Lancet, Wei and colleagues conducted a comprehensive systematic review to evaluate the proportion of ICC in the population that is attributable to individual HPV genotypes (known as the attributable fraction, or AF) at global and regional levels. We selected this paper because it highlights the wide diversity of HPV types with attributable causality of ICC, and serves as a stepping stone towards harnessing this knowledge for improved prevention strategies.

The authors analysed 1,174 studies that performed HPV genotyping on cervical swabs or biopsies, including more than 110,000 HPV-positive ICC cases and 2,750,000 individuals with normal cervical cytology from 121 countries. Genotype-specific prevalences were compared between ICC cases and people with normal cytology and used to calculate odds ratios (ORs), showing whether one group is more or less likely to be associated with individual HPV types. HPV genotypes with an OR significantly higher than one were deemed causal of ICC. To estimate the regional AFs, attributable risks were derived from the ORs and multiplied by the regional HPV genotype-specific prevalence. Global AFs were estimated by weighting the regional AFs by the number of ICC cases in each region. The authors then used a Bayesian model to generate AF estimates, considering both HPV prevalence in ICC and ORs, and providing the 95% credible intervals (a Bayesian analogue to confidence intervals).

大约 50 年前，德国病毒学家 Harald zur Hasen 将宫颈癌的病因归因于人瘤病毒 （HPV）。从那时起，HPV 已被证明会导致多个解剖部位的癌症，并且已经发现了数百种 HPV 类型，这促使对 HPV 的致癌潜力进行进一步研究。随着时间的推移，这种病毒诱导的致癌性已经进化并与人类共同分化。例如，大多数致癌 HPV 基因型属于 α 属的同一进化分支——这些和相关的 HPV 基因型被认为是潜在的致癌物。从流行病学的角度来看，了解 HPV 基因型在浸润性宫颈癌 （ICC） 中的致癌性是预测 HPV 疫苗接种和筛查计划有效性的关键。为了实现这一目标，在最近发表在《柳叶刀》上的一项研究中，Wei 及其同事进行了一项全面的系统评价，以评估全球和区域层面归因于个体 HPV 基因型（称为归因分数，或 AF）的人群中 ICC 的比例。我们选择这篇论文是因为它强调了 HPV 类型的广泛多样性以及 ICC 的可归因因果关系，并作为利用这些知识改进预防策略的垫脚石。

作者分析了 1,174 项对宫颈拭子或活检进行 HPV 基因分型的研究，包括来自 121 个国家的 110,000 多例 HPV 阳性 ICC 病例和 2,750,000 例宫颈细胞学正常的个体。比较 ICC 病例和细胞学正常人群的基因型特异性患病率，并用于计算比值比 （ORs），显示一组是否或多或少可能与个体 HPV 类型相关。OR 显著高于 1 的 HPV 基因型被认为是 ICC 的因果关系。为了估计区域性 AF，从 OR 得出归因风险，并乘以区域 HPV 基因型特异性患病率。全球 AF 是通过按每个地区的 ICC 病例数量对区域 AF 进行加权来估计的。然后，作者使用贝叶斯模型生成 AF 估计值，同时考虑 ICC 和 OR 中的 HPV 患病率，并提供 95% 可信区间（贝叶斯模拟置信区间）。