随着接种人乳头瘤病毒 (HPV) 疫苗的女性加入该计划，宫颈癌筛查计划（包括分类测试）需要重新设计。甲基化标记物提供了一种潜在的解决方案，通过识别具有进展潜力的临床相关宫颈病变来降低假阳性率。在一项巢式病例对照研究中，纳入了 9242 名在社区随机试验中在 12-15 岁或 18 岁接受三剂 HPV16/18 疫苗的女性。随后，他们被重新随机分组进行频繁或不频繁的宫颈癌筛查试验。在截至 2022 年的 15 年疫苗接种后随访中，在第 25 年的筛查中发现了 17 例高级别鳞状上皮内病变 (HSIL) 和 15 例低级别 (LSIL) 病例，以及 371 例年龄和社区匹配的病例接种 HPV16/18 疫苗的对照。对 25 岁时在组织学确诊为 LSIL 或 HSIL 诊断之前收集的宫颈样本进行了甲基化分析。测量病毒 (HPV16/18/31/33) 和宿主细胞基因 (EPB41L3、FAM19A4 和 miR124-2) 的 DNA 甲基化以及 HPV 基因分型。未观察到 HPV16/18 HSIL 病例。主要的 HPV 基因型为 HPV52（29.4%）、HPV59/HPV51/HPV58（各 23.5%）和 HPV33（17.7%）。甲基化水平普遍较低，LSIL/HSIL 和对照之间病毒或宿主细胞基因的平均甲基化水平没有显着差异。然而，当考虑病毒基因和 EPB41L3 的组合时，HSIL 病例和对照之间的甲基化水平存在显着差异（p 值 = .0001）。接种 HPV 疫苗的患有 HSIL 的女性感染了不常见的 HPV 类型，这些类型很少导致癌症，并且甲基化水平较低。有必要进行进一步调查，以了解接种 HPV 疫苗的女性中 HSIL 可能的退化性质及其对治疗的影响。© 2024 作者。约翰·威利出版的《国际癌症杂志》

Cervical cancer screening programs, including triage tests, need redesigning as human papillomavirus (HPV)-vaccinated women are entering the programs. Methylation markers offer a potential solution to reduce false-positive rates by identifying clinically relevant cervical lesions with progressive potential. In a nested case-control study, 9242 women who received the three-dose HPV16/18-vaccine at ages 12-15 or 18 in a community-randomized trial were included. Subsequently, they were re-randomized for either frequent or infrequent cervical cancer screening trials. Over a 15-year post-vaccination follow-up until 2022, 17 high-grade squamous intraepithelial lesion (HSIL) and 15 low-grade (LSIL) cases were identified at the 25-year screening round, alongside 371 age and community-matched HPV16/18-vaccinated controls. Methylation analyses were performed on cervical samples collected at age 25, preceding histologically confirmed LSIL or HSIL diagnoses. DNA methylation of viral (HPV16/18/31/33) and host-cell genes (EPB41L3, FAM19A4, and miR124-2) was measured, along with HPV-genotyping. No HPV16/18 HSIL cases were observed. The predominant HPV-genotypes were HPV52 (29.4%), HPV59/HPV51/HPV58 (each 23.5%), and HPV33 (17.7%). Methylation levels were generally low, with no significant differences in mean methylation levels of viral or host-cell genes between the LSIL/HSIL and controls. However, a significant difference in methylation levels was found between HSIL cases and controls when considering a combination of viral genes and EPB41L3 (p value = .0001). HPV-vaccinated women with HSIL had HPV infections with uncommon HPV types that very rarely cause cancer and displayed low methylation levels. Further investigation is warranted to understand the likely regressive nature of HSIL among HPV-vaccinated women and its implications for management.© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.