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.

项目概要/摘要 世界卫生组织设定了通过全球 HPV 疫苗接种消除宫颈癌 (CC) 的目标 和宫颈癌筛查（CCS）。不幸的是，现实世界中的 HPV 疫苗既没有有效性也没有效率 CCS 是为感染 HIV 的女性 (WWH) 建立的，她们受 CC 的影响尤为严重。我们的 小组报告称，接种 HPV 疫苗的围产期 HIV 感染 (WWPHIV) 年轻女性的感染率非常高 与 HIV 女性相比，宫颈细胞学异常的发生率表明疫苗有效性降低。 虽然用于筛查 (PHS) 和分类测试的初级 HPV 检测是 CCS 的首选方法。 在美国普通人群中，由于缺乏科学依据，CDC 并未推荐将其用于 WWH 支持。我们小组最近的一项研究表明，WWH 中采用分流 16/18 基因分型的 PHS 减少了 在不降低敏感性的情况下，不必要的阴道镜检查减半（与 HPV/细胞学联合检测相比）；然而，积极的 预测值仍然较低。此外，最近 FDA 批准的双重免疫细胞化学染色 p16/ki67 以及使用扩展 HPV 基因分型和 DNA 甲基化的新型生物标志物显示出巨大的前景 但在 WWH 中却没有得到充分的研究。我们有一个难得的机会来检查 HPV 疫苗 通过与儿科艾滋病毒/艾滋病队列合作，WWH 的有效性和 PHS 筛查分类策略 研究 (PHACS) 部分由我们的调查团队领导。 PHACS 包括超过 2400 名 WWH 的队列，其中包括 WWPHIV 和 WWH，横向 (WWHH) 感染者，与其暴露于 HIV 的儿童一起登记。我们 据估计，90% 的 WWPHIV 和 50% <41 岁的 WWHH 至少感染过一种 HPV 剂量。在 WWH 中，我们的目标是：1）检查 3 年期定义的 HPV 疫苗的有效性 i) 疫苗-HPV 类型持续 12 个月或更长时间，以及 ii) 组织学 (h) 宫颈的累积风险 上皮内瘤变（CIN）-2+； 2a) 检查并比较敏感性(Se)、特异性(Sp)、阳性(PPV) 使用 4 立即或 3 年内在 PHS[+] 女性中检测 hCIN-2+ 和阴性预测值 (NPV) 反射策略：(i) 细胞学，(ii) HPV 扩展基因分型，(iii) p16/Ki-67 双染色细胞学，以及 (iv) HPV/宿主甲基化水平； 2b) 检查自行收集的 PHS[+} 样本中的 Se、Sp、PPV 和 NPV hCIN2+ 检测侧重于甲基化和 HPV 基因分型分类测试，因为这 2 个测试适用于 自行采集的样本。我们计划使用自采样套件筛选 ~810 WWH——现在是一种广为接受的模式 筛查——进行 PHS 测试（罗氏 Cobas），PHS[+] (~570) 的人将参加临床访问，以了解 阴道镜检查/活检和 4 项分类测试。患有 <CIN 2+ 的 WWH 需要每年返回进行阴道镜检查，并且 HPV 基因分型有效期长达 3 年。 CIN 2+ 的 WWH 已退出。 WWH PHS[-] 将被要求在第 2 年返回 重新筛选。那些 PHS[+] 将按照上述方式进行，而 PHS[-] 将被要求获取自行采集的阴道样本 每年抽取样本进行 HPV 基因分型，持续 3 年。影响。了解 HPV 疫苗的有效性和 WHH 中的最佳 CCS 策略将为减轻全球 CC 负担做出重大贡献。