Cross Sectional Association of the Oral Microbiota and the Inflammasome with Oral HPV among HIV+ Adults

HIV 成人口腔微生物群和炎性体与口腔 HPV 的横断面关联

• 批准号: 10669316
• 负责人: Josue Perez-Santiago
• 金额: $ 5.73万
• 依托单位: COMPREHENSIVE CANCER CENTER/ UNIV/PR
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-07 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10669316
• 关键词: 16S ribosomal RNA sequencing; Accounting; Adult; Affect; Behavioral; Bioinformatics; CASP1 gene; Cause of Death; Characteristics; Chemoresistance; Chronic; Clinic; Clinical; Collection; Communities; Complex; Cross-Sectional Studies; Development; Disease; Dysplasia; Early identification; Ecology; Enzyme-Linked Immunosorbent Assay; Epidemiology; Equipment and supply inventories; Evaluation; Future; Gemella; Genes; Genotype; Goals; HIV; HIV Infections; Hemophilus; High Prevalence; Hispanic; Homeostasis; Human Papilloma Virus-Related Malignant Neoplasm; Human Papillomavirus; Human papilloma virus infection; Human papillomavirus 16; IL8 gene; Immune; Immune response; Immune system; Immunity; Impairment; Incidence; Individual; Inflammasome; Inflammation; Inflammatory; Interferon Type II; Interleukin-1 beta; Interleukin-6; Intervention; Lactobacillus; Lead; Lesion; Link; Malignant Neoplasms; Malignant neoplasm of cervix uteri; Measures; Microbe; Microbiology; Natural History; Neoplasm Metastasis; Oral; Oral Characters; Oral cavity; Oral health; Participant; Pathogenesis; Patient Recruitments; Patients; Peptostreptococcus; Periodontal Diseases; Periodontitis; Persons; Play; Porphyromonas; Predisposition; Prevalence; Prevention strategy; Preventive; Preventive Health Services; Prevotella; Prognosis; Proteins; Public Health; Puerto Rican; Puerto Rico; Questionnaires; Ribosomal DNA; Risk; Risk Factors; Role; STI prevention; Saliva; Sexually Transmitted Diseases; Signal Transduction; Streptococcus; TNF gene; Taxonomy; Testing; Therapeutic; Transcriptional Activation; Vaginal Human Papilloma Virus; Viral; Western Blotting; Woman; Work; antiretroviral therapy; base; biomarker discovery; cancer prevention; cancer risk; carcinogenesis; dysbiosis; early detection biomarkers; genetic variant; health disparity; high risk; high risk population; human microbiota; inflammatory marker; malignant oropharynx neoplasm; men; microbial; microbiome; mouth squamous cell carcinoma; novel; oral HPV; oral HPV infection; oral carcinogenesis; oral microbial community; oral microbiome; personalized medicine; personalized therapeutic; premalignant; protein biomarkers; protein complex; recruit; saliva sample; screening guidelines; social determinants; sociodemographics; socioeconomic disadvantage; surveillance strategy; targeted biomarker; transmission process; treatment response; tumor growth; tumor progression; vaginal infection

PROJECT SUMMARY/ABSTRACT HPV-infection is the most common sexually transmitted disease (STI), and it accounts for 70% of oropharyngeal cancers. People living with HIV (PLWH) are disproportionately affected by HPV and are also at an increased risk of cancer development, even with suppressive antiretroviral therapy (ART), suggesting that ART may not fully recover oral HPV-specific immunity. Therefore, understanding other underlying factors that could facilitate the transmission and persistence of HPV in PLWH is crucial for the development of cancer prevention and surveillance strategies, and reduce the burden of HPV-associated malignancies in PLWH. The oral microbiota and inflammasome protein complex are essential factors for maintaining immune homeostasis factors, which are altered by HIV infection and have been observed in the pathogenesis of oropharyngeal cancer. Thus they represent novel targets for biomarker discovery and therapeutics. Our long-term goal is to investigate how these factors could contribute to immune dysregulation, and may affect the natural history of oral HPV infection in PLWH, in order to establish a set of early detection markers for HPV-related malignancies and personalized treatment interventions. We hypothesize that dysbiosis of the oral microbiome and inflammasome dysregulation can be risk factors for HPV-related complications and can contribute to the dampening the immune system promoting subsequent inflammation in PLWH. This cross-sectional study plans to recruit 200 virologically suppressed PLWH (men and women ≥21 and <49 years old) from a community-based organization, Puerto Rico (PR) CONCRA, that offers preventive and health services specialized in the treatment of the HIV and STI. PLWH who attends PR CONCRA constitute a unique high-risk group where the prevalence of both HIV and oral HPV infection is higher, allowing our team of experts in HIV, HPV, epidemiology, microbiology, oral health and bioinformatics to establish these relationships with high efficiency. The specific aims of this proposal are: (1) to characterize the oral microbiota in saliva and investigate its relationship with HPV status and HPV genotypes, and (2) to determine the association between the levels of inflammasome proteins (NLRP3, AIM2, and caspase- 1, IL-1β and cleaved IL-1β) and inflammation markers (IL-1β, IL-6, IL-8, TNF-α, IFN-γ) with oral HPV infection and HPV genotypes. After collection of saliva samples, participants will undergo oral health evaluations. Sociodemographic, behavioral, clinical characteristics, and risk factors will be collected through a questionnaire. Participants will be on stable, suppressive ART for at least 6 months to minimize inflammatory signals due to HIV active replication. We will characterize the oral microbiota by sequencing the 16S rDNA gene and HPV genotypes by PCR. Inflammasome proteins and inflammatory markers will be measured by Western Blot and multiplex ELISA respectively.

项目摘要/摘要 HPV感染是最常见的性传播疾病（STI），占口咽的70％ 癌症。患有艾滋病毒（PLWH）的人受HPV的影响不成比例，风险也增加 即使接受抑制性抗逆转录病毒疗法（ART），癌症的发展也表明艺术可能无法完全 恢复口服HPV特异性免疫。因此，了解其他可能促进的基本因素 HPV在PLWH中的传播和持久性对于预防癌症的发展至关重要 监视策略，并减少PLWH中与HPV相关的恶性肿瘤的燃烧。口服微生物群 和炎性蛋白复合物是维持免疫稳态因子的重要因素，这是 通过HIV感染改变，在口咽癌的发病机理中观察到。那是他们 代表了生物标志物发现和治疗的新靶标。我们的长期目标是调查如何 因素可能导致免疫失调，并可能影响口服HPV感染的自然病史 PLWH，为了建立与HPV相关的恶性肿瘤和个性化的一组早期检测标记 治疗干预措施。我们假设口腔微生物组和炎症体失调的营养不良 可能是HPV相关并发症的危险因素，并可能导致免疫系统抑制 促进PLWH中随后的炎症。这项横断面研究计划在病毒学上招募200个 来自社区组织的抑制PLWH（男性和女性≥21岁，<49岁），波多黎各 （PR）CONCRA，可提供专门治疗艾滋病毒和STI的预防和卫生服务。 plwh 参加PR CONCRA的人构成了一个独特的高风险群体 感染更高，使我们的艾滋病毒，HPV，流行病学，微生物学，口腔健康和口腔健康和 生物信息学以高效建立这些关系。该提议的具体目的是：（1） 表征唾液中的口腔微生物群，并研究其与HPV状态和HPV基因型的关系， （2）确定炎性体蛋白水平（NLRP3，AIM2和caspase-- 1，IL-1β和裂解IL-1β）和炎症标记（IL-1β，IL-6，IL-8，TNF-α，IFN-γ），口服HPV感染 和HPV基因型。收集唾液样本后，参与者将接受口腔健康评估。 社会人口统计学，行为，临床特征和危险因素将通过问卷收集。 参与者将在至少6个月内进行稳定的抑制作用，以最大程度地减少炎症信号 HIV主动复制。我们将通过对16S rDNA基因和HPV进行测序来表征口服微生物群 PCR的基因型。炎性蛋白和炎症标志物将通过蛋白质印迹和 多重ELISA。