Real-world effectiveness of HPV vaccine in women living with HIV and its impact on cervical cancer screening accuracies

HPV 疫苗对 HIV 感染女性的真实有效性及其对宫颈癌筛查准确性的影响

• 批准号: 10682184
• 负责人: ANNA-BARBARA MOSCICKI
• 金额: $ 109.54万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-01 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10682184
• 关键词: Adherence; Adopted; Affect; Age; Age Years; Algorithms; Antibody titer measurement; Anus; Biological Assay; Biopsy; Cancer Burden; Cell Cycle; Cervical; Cervical Cancer Screening; Cervical Intraepithelial Neoplasia; Child; Childhood; Clinic Visits; Clinical; Cohort Studies; Collection; Colposcopy; Country; Coupled; Cytology; DNA Methylation; Data; Detection; Disease; Dose; Effectiveness; Enrollment; FDA approved; General Population; Genotype; Goals; HIV; HIV Infections; HPV-High Risk; Histologic; Human Papilloma Virus Vaccination; Human Papilloma Virus Vaccine; Human Papillomavirus; Human papillomavirus 16; Infection; Infrastructure; International; Malignant Neoplasms; Malignant neoplasm of cervix uteri; Methods; Methylation; Observational Study; Outcome; Pediatric HIV/AIDS Cohort Study; Performance; Perinatal transmission; Persons; Population; Predictive Value; Prevention strategy; Provider; Publishing; Reflex action; Reporting; Research Design; Risk; Safety; Sampling; Specificity; Specimen; Stains; Testing; Time; Triage; Vaccinated; Vaccination; Vaccine Clinical Trial; Vaccines; Vagina; Visit; Vulnerable Populations; Woman; Work; World Health Organization; antiretroviral therapy; cervical cancer prevention; clinically relevant; cohort; cost effectiveness; data management; effectiveness evaluation; experience; immunocytochemistry; immunogenicity; innovation; men who have sex with men; middle age; novel; novel marker; perinatal HIV; prospective; retention rate; screening; sexual debut; unvaccinated; vaccination outcome; vaccine effectiveness; vaccine evaluation; vaccine immunogenicity; vaccine-induced antibodies; young woman

PROJECT SUMMARY/ABSTRACT The World Health Organization has set goals for cervical cancer (CC) elimination through global HPV vaccination and cervical cancer screening (CCS). Unfortunately, neither real-world HPV vaccine effectiveness nor efficient CCS have been established for women living with HIV (WWH) who are disproportionately affected by CC. Our group reported that HPV-vaccinated young women living with perinatal HIV infection (WWPHIV) had very high rates of abnormal cervical cytologic compared with HIV [-] women suggesting reduced vaccine effectiveness. While primary HPV testing used for screening (PHS) with a triage test is the preferred method for CCS in the general population in the U.S., the CDC has not recommended it for WWH because of the lack of scientific support. A recent study by our group showed that PHS with triage 16/18 genotyping in WWH cut the number of unnecessary colposcopies in half without reducing sensitivity (vs HPV/cytology co-testing); however, the positive predictive value remained low. Furthermore, the recently FDA-approved dual immunocytochemistry staining for p16/ki67 as well as novel biomarkers using extended HPV genotyping and DNA methylation show great promise but are vastly understudied in WWH. We have an exceptional opportunity to examine both HPV vaccine effectiveness and PHS screening triage strategies in WWH by partnering with the Pediatric HIV/AIDS Cohort Study (PHACS) led, in part, by our investigative team. PHACS includes a cohort of over 2400 WWH, including WWPHIV and WWH, horizontally (WWHH) infected, who are enrolled along with their HIV exposed children. We estimated that 90% of the WWPHIV and 50% of the WWHH <41 years of age have received at least one HPV dose. Among WWH, we aim to: 1) examine the effectiveness of the HPV vaccine defined by the 3-year cumulative risk of i) vaccine-HPV types that persist 12 months or longer and, ii) histologic (h) cervical intraepithelial neoplasia (CIN)-2+; 2a) examine and compare the sensitivity (Se), specificity (Sp), positive (PPV) and negative predictive values (NPV) to detect hCIN-2+ immediately or in 3 years in PHS[+] women using 4 reflex strategies: (i) cytology, (ii) HPV extended genotyping, (iii) p16/Ki-67 dual staining cytology, and (iv) HPV/host methylation levels; 2b) examine the Se, Sp, PPV, and NPV in self-collected PHS[+} samples for hCIN2+ detection focusing on methylation and HPV genotyping triage tests since these 2 tests are suitable for self-collected samples. We plan to screen ~810 WWH using a self-sampling kit--now a well-accepted mode for screening-- for PHS testing (Roche Cobas) and those who PHS[+] (~570) will attend a clinical visit to have colposcopy/biopsy and the 4 triage tests. WWH with <CIN 2+ are asked to return annually for colposcopy and HPV genotyping for up to 3 yrs. WWH with CIN 2+ are exited. WWH PHS[-] will be asked to return in Year 2 for rescreening. Those PHS[+] will be followed as above and PHS[-] will be asked to obtain self-collected vaginal samples for HPV genotyping annually for 3 years. Impact. Understanding HPV vaccine effectiveness and optimal CCS strategies in WHH will make a significant contribution to decreasing the worldwide burden of CC.

项目总结/摘要 世界卫生组织已经制定了通过全球HPV疫苗接种消除宫颈癌（CC）的目标 和子宫颈癌筛查。不幸的是，无论是现实世界的HPV疫苗的有效性， 已为感染艾滋病毒的妇女建立了社区服务，她们受社区服务的影响特别大。我们 一组报告说，接种HPV疫苗的年轻妇女与围产期艾滋病毒感染（WWPHIV）有非常高的 与HIV阴性妇女相比，宫颈细胞学异常率降低，表明疫苗有效性降低。 虽然用于筛查的主要HPV检测（PHS）与分流检测是CCS的首选方法， 在美国的普通人群中，疾病预防控制中心没有推荐它为WWH，因为缺乏科学的， 支持.我们小组最近的一项研究表明，在WWH中使用分诊16/18基因分型的PHS减少了 一半不必要的阴道镜检查而不降低敏感性（与HPV/细胞学联合检测相比）;然而， 预测值仍然很低。此外，最近FDA批准的双重免疫细胞化学染色， p16/ki 67以及使用扩展HPV基因分型和DNA甲基化的新生物标志物显示出巨大的前景 但在WWH中却被大大地研究不足。我们有一个特殊的机会来检查HPV疫苗 通过与儿科艾滋病毒/艾滋病队列合作，在WWH实施有效性和PHS筛查分诊策略 研究（PHACS）部分由我们的调查团队领导。PHACS包括超过2400个WWH的队列，包括 WWPHIV和WWH，水平（WWHH）感染，与其HIV暴露的子女一起沿着入组。我们 估计90%的WWPHIV和50%的<41岁的WWHH至少接受过一种HPV 次给药结束在WWH中，我们的目标是：1）检查HPV疫苗的有效性， i）持续12个月或更长时间的疫苗HPV类型的累积风险，ii）组织学（h）宫颈 上皮内瘤变（CIN）-2+; 2a）检测并比较敏感性（Se）、特异性（Sp）、阳性（PPV） 和阴性预测值（NPV）检测hCIN-2+立即或在3年内PHS[+]妇女使用4 反射策略：（i）细胞学，（ii）HPV扩展基因分型，（iii）p16/Ki-67双重染色细胞学，和（iv） HPV/宿主甲基化水平; 2b）检查自收集的PHS[+]样品中的Se、Sp、PPV和NPV， hCIN 2+检测侧重于甲基化和HPV基因分型分类测试，因为这2种测试适合 自己收集的样本。我们计划使用自采样工具包筛选~810 WWH-现在是一种广泛接受的模式， 筛查--用于PHS检测（Roche Cobas），PHS[+]（~570）患者将参加临床访视， 阴道镜检查/活检和4个分诊测试。<CIN 2+的WWH被要求每年返回进行阴道镜检查， HPV基因分型长达3年，退出WWH伴CIN 2+。WWH PHS[-]将被要求在第二年返回， 重新筛选PHS[+]将按照上述方法进行随访，PHS[-]将被要求获得自我采集的阴道 每年进行HPV基因分型，持续3年。冲击了解HPV疫苗的有效性和 WHH的最佳CCS策略将为减少全球CC负担做出重大贡献。