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症小体与口腔 HPV 的横断面关联
基本信息
- 批准号:10305164
- 负责人:
- 金额:$ 17.35万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-07-07 至 2023-06-30
- 项目状态:已结题
- 来源:
- 关键词:16S ribosomal RNA sequencingAccountingAdultAffectBehavioralBioinformaticsCASP1 geneCause of DeathCharacteristicsChemoresistanceChronicCleaved cellClinicClinicalCollectionCommunitiesComplexCross-Sectional StudiesDevelopmentDiseaseDysplasiaEarly identificationEcologyEnzyme-Linked Immunosorbent AssayEpidemiologyEquipment and supply inventoriesEvaluationFutureGemellaGenesGenotypeGoalsHIVHIV InfectionsHemophilusHigh PrevalenceHispanicsHomeostasisHuman Papilloma Virus-Related Malignant NeoplasmHuman PapillomavirusHuman papilloma virus infectionHuman papillomavirus 16IL8 geneImmuneImmune responseImmune systemImmunityImpairmentIncidenceIndividualInflammasomeInflammationInflammatoryInterferon Type IIInterleukin-1 betaInterleukin-6InterventionLactobacillusLeadLesionLinkMalignant NeoplasmsMalignant neoplasm of cervix uteriMeasuresMicrobeMicrobiologyNatural HistoryNeoplasm MetastasisOralOral CharactersOral cavityOral healthParticipantPathogenesisPatient RecruitmentsPatientsPeptostreptococcusPeriodontal DiseasesPeriodontitisPlayPorphyromonasPredispositionPrevalencePrevention strategyPreventivePreventive Health ServicesPrevotellaPrognosisProteinsPublic HealthPuerto RicanPuerto RicoQuestionnairesRecombinant DNARiskRisk FactorsRoleSTI preventionSalivaSexually Transmitted DiseasesSignal TransductionStreptococcusTNF geneTaxonomyTestingTherapeuticTranscriptional ActivationVaginal Human Papilloma VirusViralWestern BlottingWomanWorkantiretroviral therapybasebiomarker discoverycancer preventioncancer riskcarcinogenesisdysbiosisearly detection biomarkersgenetic varianthealth disparityhigh riskhigh risk populationhuman microbiotainflammatory markermalignant oropharynx neoplasmmenmicrobialmicrobiomemouth squamous cell carcinomanoveloral HPVoral HPV infectionoral carcinogenesisoral microbial communityoral microbiomepersonalized medicinepersonalized therapeuticpremalignantprotein biomarkersprotein complexrecruitsaliva samplescreening guidelinessocial determinantssociodemographicssocioeconomic disadvantagesurveillance strategytargeted biomarkertransmission processtreatment responsetumor growthtumor progressionvaginal infectionvirology
项目摘要
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.
项目概要/摘要
HPV 感染是最常见的性传播疾病 (STI),占口咽部感染的 70%
癌症。艾滋病毒感染者 (PLWH) 受 HPV 的影响尤为严重,而且风险也更高
即使采用抑制性抗逆转录病毒疗法 (ART),癌症的发展也可能会受到影响,这表明 ART 可能无法完全
恢复口腔HPV特异性免疫力。因此,了解其他可以促进
HPV 在 PLWH 中的传播和持续存在对于癌症预防和治疗的发展至关重要
监测策略,并减少 PLWH 中 HPV 相关恶性肿瘤的负担。口腔微生物群
和炎性体蛋白复合物是维持免疫稳态的重要因素,它们是
因 HIV 感染而改变,并在口咽癌的发病机制中观察到。因此他们
代表生物标志物发现和治疗的新靶点。我们的长期目标是研究这些
因素可能导致免疫失调,并可能影响口腔 HPV 感染的自然史
PLWH,为了建立一套HPV相关恶性肿瘤的早期检测标志物和个性化
治疗干预。我们假设口腔微生物群失调和炎症小体失调
可能是 HPV 相关并发症的危险因素,并可能导致免疫系统受到抑制
促进感染者随后的炎症反应。这项横断面研究计划招募 200 名病毒学研究人员
来自波多黎各社区组织的抑制艾滋病病毒感染者(男性和女性,≥21 岁和 <49 岁)
(PR) CONCRA,提供专门治疗艾滋病毒和性传播感染的预防和保健服务。艾滋病病毒感染者
参加 PR CONCRA 的人构成了一个独特的高危群体,其中 HIV 和口腔 HPV 的流行率
感染率更高,这使得我们的 HIV、HPV、流行病学、微生物学、口腔健康和
生物信息学可以高效地建立这些关系。本提案的具体目标是:(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(NLRP3、AIM2 和 caspase-)水平之间的关联
1、IL-1β和裂解IL-1β)和炎症标志物(IL-1β、IL-6、IL-8、TNF-α、IFN-γ)与口腔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。
将通过问卷收集社会人口统计学、行为、临床特征和风险因素。
参与者将接受稳定的抑制性 ART 治疗至少 6 个月,以最大程度地减少因以下原因引起的炎症信号:
HIV复制活跃。我们将通过对 16S rDNA 基因和 HPV 进行测序来表征口腔微生物群
通过 PCR 确定基因型。炎症体蛋白和炎症标志物将通过蛋白质印迹法进行测量
分别进行多重ELISA。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Josue Perez-Santiago其他文献
Josue Perez-Santiago的其他文献
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{{ truncateString('Josue Perez-Santiago', 18)}}的其他基金
Multi-Omics Predictors of Oral HPV Outcomes among PLWH
PLWH 口腔 HPV 结果的多组学预测
- 批准号:
10557585 - 财政年份:2023
- 资助金额:
$ 17.35万 - 项目类别:
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症小体与口腔 HPV 的横断面关联
- 批准号:
10447167 - 财政年份:2021
- 资助金额:
$ 17.35万 - 项目类别:
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 - 财政年份:2021
- 资助金额:
$ 17.35万 - 项目类别:
Short Chain Fatty Acids: Route for Facilitation of Oral HPV via Inflammasome Dysregulation in People Living with HIV
短链脂肪酸:通过 HIV 感染者炎症小体失调促进口腔 HPV 的途径
- 批准号:
10532974 - 财政年份:2021
- 资助金额:
$ 17.35万 - 项目类别:
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