Human papillomavirus (HPV) infection and cervical and anal cancers

人乳头瘤病毒 (HPV) 感染与宫颈癌和肛门癌

• 批准号: 10702908
• 负责人: Nicolas Wentzensen
• 金额: $ 70.53万
• 依托单位: DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10702908
• 关键词: AIDS population; Acquired Immunodeficiency Syndrome; Anus; Biological Markers; Biopsy; California; Case/Control Studies; Cervical; Cervical Cancer Screening; Cervix Neoplasms; Cervix Uteri; Clinical; Clinical Management; Clinical Trials; Collaborations; Colposcopy; Country; Cross-Sectional Studies; Cytology; DNA; Detection; Diagnostic; Diagnostic Procedure; Disease; Early Diagnosis; Endocervix; Etiology; Event; Exercise; Exocervix; Freezing; General Population; Genotype; Goals; HIV; HIV Seropositivity; HIV/AIDS; Human; Human Papilloma Virus Vaccine; Human Papilloma Virus-Related Malignant Neoplasm; Human Papillomavirus; Human papilloma virus infection; Human papillomavirus 16; Immune system; Immunologic Markers; Immunosuppression; India; Individual; Integration Host Factors; Latin American; Malignant Neoplasms; Malignant neoplasm of anus; Malignant neoplasm of cervix uteri; Messenger RNA; Methods; Methylation; Minor; Modality; Modeling; Molecular; Natural History; Neoplasms; Oklahoma; Persons; Population; Prevention Research; Prevention strategy; Process; Progressive Disease; Reproducibility; Research; Research Project Grants; Resolution; Resort; Resources; Risk; Risk Factors; Role; Sampling; Screening Result; Screening for cancer; Secondary Prevention; Seroepidemiologic Studies; Sexually Transmitted Agents; Specimen; Standardization; Testing; Time; Tissues; Triage; Viral; Woman; biomarker identification; cancer risk; carcinogenicity; cervical cancer prevention; follow-up; improved; men who have sex with men; neoplastic; novel marker; population based; screening

The following research projects are etiologic and human population based and all have various molecular components:SUCCEED directed by Dr. Wentzensen is a cross-sectional study among women referred for abnormal cevrical cancer screening results focused on the identification of biomarkers of risk at each progressive disease stage, aimed to identify the molecular events that are necessary and sufficient for progression to cervical cancer. Frozen specimens, often multiple, from 2,500 women with varying grades of cervical neoplasia (including the ectocervix, transformation zone, and endocervix) have already been collected. In a new study, the Biopsy Study conducted at the same center in Oklahoma, Dr. Wentzensen is investigating the earliest discernible transitions from HPV infection to CIN3 and the best methods for colposcopic detection of CIN3 to improve current cervical cancer prevention strategies.The ALTS clinical trial evaluated management options for women with abnormal cervical cancer screening results and has been completed several years ago. The specimens collected in women with minor cytological abnormalities and 2 year follow up still serve as an important resource to evaluate HPV tests and novel biomarkers, such as viral methylation.In the Triage of HPV-positive women Study, novel biomarkers are evaluated to decide who among HPV+/cytology- women needs referral to colposcopy.The cervical tissue immune markers study aims at evaluating various components of the cellular and humoral immune system across cervical disease stages in HIV-infected populations.The case control study of invasive cervical cancer in four Latin-American countries is an important resource to study sero-epidemiologic markers of cervical cancer risk.In the Intramural to India project, cervical cancers and its precursors are studied among HIV-infected women in India. The goal of the project is to understand the interactions between HIV and HPV at different steps in the disease process from HPV infection to precancer and cancer. Another important goal is to evaluate biomarkers for cervical precancers in HIV-infected women. Currently, there is no widely standardized approach for early detection of cervical precancers in HIV-infected populations and it is not clear whether established and novel biomarkers perform equally in HIV-infected and non-HIV-infected populations. In the Intramural to India project, we will evaluate a wide range of tests and biomarkers to evaluate risk of cervical precancer and to improve cervical cancer prevention efforts in HIV/ AIDS populations.Although HPV is implicated in over 90% of anal cancers, it is unknown if the natural history of HPV-induced anal cancer is similar to that of the cervix. There is currently no accepted method for anal cancer screening; in the absence of a standard and effective screening modality, clinicians often resort to high-resolution anoscopy, a diagnostic procedure akin to colposcopy, and directed biopsies. Anal cancer is rare in the general population but is 100 times commoner among human immunodeficiency virus (HIV)-positive men who have sex with men (MSM). The role of HIV in anal HPV natural history is not well understood and it is not clear whether the screening approaches for HIV-positive MSM need to be modified. It is crucial to better understand the natural history of HPV-related anal neoplastic disease among HIV-positive individuals to make informed decisions about secondary prevention of anal cancer. In collaboration with Kaiser Permanente Northern California, we have conducted the Anal Cancer Screening Study (ACSS) to describe the natural history of HPV and evaluate the clinical utility of various screening approaches for anal precancer detection. We have evaluated risk factors for anal HPV infection and anal precancer in this population, studied optimal sampling strategies for anal samples, showed that anal cytology is reproducible and the quality is comparable to cervical cytology, conducted modeling exercises to evaluate attribution of anal precancer to individual HPV genotypes and estimate the HPV vaccine-preventable fraction of anal precancer, and have demonstrated the accuracy and clinical utility of several biomarkers that were previously evaluated in cervical cancer screening, including HPV DNA testing with genotyping, HPV mRNA testing, and p16/Ki-67 cytology.

以下研究项目以病因学和人群为基础，并且均具有不同的分子成分：SUCCEED 由 Wentzensen 博士指导，是一项针对因宫颈癌筛查结果异常而转诊的女性的横断面研究，重点是识别每种进展性疾病的风险生物标志物阶段，旨在确定进展为宫颈癌所必需和充分的分子事件。已经收集了来自 2,500 名患有不同级别宫颈肿瘤（包括子宫颈外层、转化区和子宫颈内膜）的女性的冷冻标本（通常是多个）。在俄克拉荷马州同一中心进行的一项新研究中，Wentzensen 博士正在研究从 HPV 感染到 CIN3 的最早可辨别的转变，以及阴道镜检测 CIN3 的最佳方法，以改善当前的宫颈癌预防策略。 ALTS 临床试验评估了宫颈癌筛查结果异常的女性的治疗方案，该试验已于几年前完成。在具有轻微细胞学异常的女性中收集的样本和 2 年随访仍然是评估 HPV 检测和新型生物标志物（例如病毒甲基化）的重要资源。在 HPV 阳性女性分诊研究中，评估新型生物标志物来决定谁是HPV+/细胞学检查-女性需要转诊阴道镜检查。宫颈组织免疫标志物研究旨在评估 HIV 感染人群在宫颈疾病各个阶段的细胞和体液免疫系统的各个组成部分。侵入性病例对照研究四个拉丁美洲国家的宫颈癌是研究宫颈癌风险的血清流行病学标志物的重要资源。在Intramural to India 项目中，对印度感染艾滋病毒的妇女的宫颈癌及其前兆进行了研究。该项目的目标是了解从 HPV 感染到癌前病变和癌症的疾病过程中不同步骤中 HIV 和 HPV 之间的相互作用。另一个重要目标是评估感染艾滋病毒的女性宫颈癌前期的生物标志物。目前，还没有广泛的标准化方法用于艾滋病毒感染人群中宫颈癌前病变的早期检测，也不清楚现有的和新型的生物标志物在艾滋病毒感染者和非艾滋病毒感染者中是否同样有效。在印度校内项目中，我们将评估广泛的检测和生物标志物，以评估宫颈癌前病变的风险，并改善艾滋病毒/艾滋病人群的宫颈癌预防工作。尽管 90% 以上的肛门癌与 HPV 相关，但它尚不清楚 HPV 诱发的肛门癌的自然史是否与子宫颈癌相似。目前还没有公认的肛门癌筛查方法；在缺乏标准和有效的筛查方式的情况下，临床医生经常求助于高分辨率肛门镜检查（一种类似于阴道镜检查的诊断程序）和定向活检。肛门癌在普通人群中很少见，但在人类免疫缺陷病毒 (HIV) 阳性的男男性行为者 (MSM) 中发病率高出 100 倍。 HIV 在肛门 HPV 自然史中的作用尚不清楚，也不清楚 HIV 阳性 MSM 的筛查方法是否需要修改。更好地了解 HIV 阳性个体中 HPV 相关肛门肿瘤疾病的自然史对于做出有关肛门癌二级预防的明智决策至关重要。我们与北加州 Kaiser Permanente 合作，进行了肛门癌症筛查研究 (ACSS)，以描述 HPV 的自然史并评估各种肛门癌前病变筛查方法的临床效用。我们评估了该人群中肛门 HPV 感染和肛门癌前病变的危险因素，研究了肛门样本的最佳采样策略，表明肛门细胞学检查具有可重复性，质量与宫颈细胞学检查相当，进行了建模练习以评估肛门癌前病变对个体的归因HPV 基因型并估计 HPV 疫苗可预防的肛门癌前病变部分，并证明了先前在宫颈癌筛查（包括 HPV DNA 检测）中评估的几种生物标志物的准确性和临床实用性包括基因分型、HPV mRNA 检测和 p16/Ki-67 细胞学检查。