HPV persistence: An overlooked consequence of helminth infection?

HPV 持续存在：蠕虫感染的一个被忽视的后果？

• 批准号: 8030117
• 负责人: PATTI E GRAVITT
• 金额: $ 18.35万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-01-11 至 2012-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8030117
• 关键词: AIDS prevention; Adult; Aftercare; Age; Area; Cancer Burden; Cancer Etiology; Cervical; Cervical Cancer Screening; Country; Data; Early Diagnosis; Evaluation; Female; Genital system; HPV-High Risk; Helminths; High Prevalence; Human Papillomavirus; Human papilloma virus infection; Immune; Incidence; Infection; Interruption; Intervention; Intestines; Lesion; Malignant neoplasm of cervix uteri; Mucosal Immunity; Natural History; Peru; Prevalence; Prevention; Prevention strategy; Prophylactic treatment; Regulatory T-Lymphocyte; Reproductive Health; Residual state; Resources; Screening procedure; Soil; Source; Vaccination; Woman; aged; base; carcinogenesis; cell mediated immune response; cervical cancer prevention; cost; cytokine; interest; mortality; neoplastic; prevent; prophylactic; reproductive; vaccine evaluation

DESCRIPTION (provided by applicant): Cervical cancer, caused by persistent infection with high risk human papillomavirus (HR-HPV) infection, remains the second leading cause of cancer in women in the world. Vaccines and screening are effective prevention measures, but are simply unaffordable in the countries with the greatest need. We are therefore interested in identifying modifiable factors associated with increased HPV prevalence and persistence as targets for low cost interventions in areas where HPV screening and vaccination are unlikely to be economically feasible. An ecological correlation is observed between regions with high cervical cancer incidence and high soil-transmitted helminth (STH) burden. We hypothesize that the well-known Th2-shift associated with intestinal helminth infection results in a decreased cell-mediated immune response to HPV infection, leading to higher prevalence and burden of multiple HPV infection in helminth-endemic regions. We therefore aim to determine the association between helminth infection and HPV prevalence and burden of multiple infections in women aged 25-45 years in low and high helminth endemic regions of Peru. We will also compare the distribution of cervical Th1/Th2/Treg cytokines in HPV positive vs. HPV negative women and in helminth negative vs. helminth positive women. As a subaim, women found to be infected with helminthes will be treated and HPV prevalence and cervical immune profiles compared before and after treatment. If our hypothesis is proven correct, periodic deforming, at a cost of US $0.21 - US $0.51 per treatment, would offer a highly affordable alternative to reducing the HR-HPV and cervical cancer burden in many resource-poor regions. Furthermore, a comprehensive evaluation of cervical cytokine profiles in reproductive age women from helminth-endemic and non-endemic regions of Peru will provide critical new data that may have a broader impact in areas including reproductive health and HIV prevention. PUBLIC HEALTH RELEVANCE: Cervical cancer, caused by persistent infection with high risk human papillomavirus (HR-HPV) infection, remains the second leading cause of cancer in women in the world. Vaccines and screening are effective prevention measures, but are simply unaffordable in the countries with the greatest need. We hypothesize that the well-known Th2-shift associated with intestinal helminth infection results in a decreased cell-mediated immune response to HPV infection, leading to higher prevalence and burden of multiple HPV infection in helminth-endemic regions. If our hypothesis is proven correct, periodic deworming, at a cost of US $0.21 - US $0.51 per treatment, would offer a highly affordable alternative to reducing the HR-HPV and cervical cancer burden in many resource-poor regions.

描述（申请人提供）：宫颈癌是由高危人乳头瘤病毒（HR-HPV）持续感染引起的，仍然是世界上女性第二大癌症原因。 疫苗和筛查是有效的预防措施，但在最需要的国家根本负担不起。 因此，我们有兴趣确定与 HPV 患病率和持续性增加相关的可改变因素，作为在 HPV 筛查和疫苗接种在经济上不太可行的地区进行低成本干预的目标。 在宫颈癌发病率高和土源性蠕虫（STH）负担高的地区之间观察到了生态相关性。 我们假设与肠道蠕虫感染相关的众所周知的 Th2 转变会导致细胞介导的针对 HPV 感染的免疫反应降低，从而导致蠕虫流行地区多种 HPV 感染的患病率和负担更高。 因此，我们的目标是确定秘鲁蠕虫低流行区和高蠕虫流行区 25-45 岁女性中蠕虫感染与 HPV 患病率和多重感染负担之间的关系。 我们还将比较 HPV 阳性与 HPV 阴性女性以及蠕虫阴性与蠕虫阳性女性中宫颈 Th1/Th2/Treg 细胞因子的分布。 作为一个子目标，将对发现感染蠕虫的女性进行治疗，并比较治疗前后的 HPV 患病率和宫颈免疫特征。 如果我们的假设被证明是正确的，周期性变形术每次治疗的费用为 0.21 美元 - 0.51 美元，将为许多资源匮乏地区减少 HR-HPV 和宫颈癌负担提供一种非常实惠的替代方案。 此外，对秘鲁蠕虫流行区和非流行区育龄妇女的宫颈细胞因子谱进行全面评估将提供重要的新数据，可能对生殖健康和艾滋病毒预防等领域产生更广泛的影响。 公共卫生相关性：宫颈癌是由高危人乳头瘤病毒 (HR-HPV) 持续感染引起的，仍然是世界上女性癌症的第二大原因。 疫苗和筛查是有效的预防措施，但在最需要的国家根本负担不起。 我们假设与肠道蠕虫感染相关的众所周知的 Th2 转变会导致细胞介导的针对 HPV 感染的免疫反应降低，从而导致蠕虫流行地区多种 HPV 感染的患病率和负担更高。 如果我们的假设被证明是正确的，那么定期驱虫，每次治疗的费用为 0.21 美元 - 0.51 美元，将为许多资源匮乏地区减少 HR-HPV 和宫颈癌负担提供一种非常实惠的替代方案。