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.

项目摘要/摘要 世界卫生组织通过全球HPV疫苗接种设定了宫颈癌（CC）的目标 和宫颈癌筛查（CCS）。不幸的是，现实世界中的HPV疫苗效率均不 为艾滋病毒（WWH）的妇女建立了CC，这些妇女受到CC的影响不成比例的。我们的 小组报告说，患有围产期HIV感染（WWPHIV）的HPV接种疫苗的年轻妇女的患有很高 与HIV [ - ]妇女相比，异常宫颈细胞学率的速率表明疫苗有效性降低。 虽然用于筛选的主要HPV测试（pHS）带有分流测试是CCS中的首选方法 在美国的一般人群，疾病预防控制中心没有为WWH推荐，因为缺乏科学 支持。我们小组最近的一项研究表明，wwh中的分类pHS 16/18基因分型削减了数量 不必要的阴道镜将一半分为一半，而不会降低灵敏度（与HPV/细胞学共同测试）；但是，积极 预测价值保持较低。此外，最近经过FDA批准的双重免疫细胞化学染色 P16/KI67以及使用扩展的HPV基因分型和DNA甲基化的新生物标志物显示出很大的希望 但是在WWH中被大量研究了。我们有一个很棒的机会检查两种HPV疫苗 通过与儿科艾滋病毒/艾滋病队列合作，有效性和pHS筛选triage策略 研究（PHAC）部分由我们的调查团队领导。 PHACS包括超过2400 wwh的队列，包括 WWPHIV和WWH，水平（WWHH）感染了，他们与艾滋病毒一起裸露。我们 据估计，WWPHIV的90％和WWHH <41岁的50％至少收到了一个HPV 剂量。在WWH中，我们的目标是：1）检查由3年定义的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 上皮内肿瘤（CIN）-2+; 2a）检查和比较灵敏度（SE），特异性（SP），正（PPV） 和负预测值（NPV）立即检测HCIN-2+或使用4 pHS [+]女性在3年内 反射策略：（i）细胞学，（ii）HPV扩展基因分型，（iii）p16/ki-67双染色细胞学和（iv） HPV/宿主甲基化水平； 2b）在自收集的pHS中检查SE，SP，PPV和NPV的样本中的SE，SP，PPV和NPV。 HCIN2+检测重点是甲基化和HPV基因分型分类测试，因为这两种测试适合 自收集的样品。我们计划使用一个自动采样套件筛选〜810 wwh - 现在 筛选 - 用于PHS测试（Roche Cobas）和PHS [+]（〜570）的人将参加临床访问 阴道镜/活检和4个分类测试。 WWH带有<cin 2+的WWH每年返回进行阴道镜检查和 HPV基因分型最多3年。 WWH带有CIN 2+退出。 WWH PHS [ - ]将被要求在第二年返回 纠正。将按照上述遵循这些pHS [+]，并要求pHS [ - ]获得自由收集的阴道 HPV基因分型的样本每年3年。影响。了解HPV疫苗有效性和 WHH中的最佳CCS策略将为减轻CC的全球负担做出重大贡献。