权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Understanding the Role of HAART in the Progression of HPV-Associated Oral Cancer

了解 HAART 在 HPV 相关口腔癌进展中的作用

基本信息

批准号：
10659250
负责人：
Craig M Meyers
金额：
$ 53.62万
依托单位：
PENNSYLVANIA STATE UNIV HERSHEY MED CTR
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-07-11 至 2027-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10659250
关键词：
AIDS diagnosis Affect Area Biological Markers Cancer Burden Cessation of life Clinical Coupled Development Disease-Free Survival Epithelial Cells Exhibits General Population Glycolysis HIV HPV-negative head and neck cancer Head and Neck Cancer Head and Neck Squamous Cell Carcinoma Highly Active Antiretroviral Therapy Human Human Papilloma Virus-Related Malignant Neoplasm Human Papillomavirus Human papilloma virus infection Human papillomavirus 16 In Vitro Incidence Individual Infection Life Cycle Stages Life Expectancy Malignant Neoplasms Malignant neoplasm of cervix uteri Metabolic Pathway Mitochondria Modeling Morbidity - disease rate Natural History Oropharyngeal Patients Persons Pharyngeal structure Positioning Attribute Prognosis Radio Recording of previous events Recurrence Respiration Risk Role Sampling Sampling Studies Site Testing Tissue Sample Tobacco Woman cancer risk carcinogenicity chemotherapy co-infection cofactor high risk improved malignant mouth neoplasm malignant oropharynx neoplasm men mortality risk oral HPV infection oral HPV-positive head and neck cancers oral cavity epithelium oral tissue premalignant response scale up therapeutic target trend tumor progression

项目摘要

SUMMARY The overall incidence of HPV+ head and neck squamous cell carcinoma (HNSCC) has exhibited an increasing trend over the last few decades, and has now in the U.S. overtaken cervical cancer as the most common site of HPV related cancer. The majority of patients present with advanced-stage HNSCC are without a clinical history of pre-malignancy. Because there is a paucity of pre-cancer clinical samples the studying the steps of cancer progression that would provide an understanding of the carcinogenic we have developed an in vitro progression model. Interestingly, HPV+ patients compared to HPV negative (HPV-) patients have an improved overall prognosis and greater disease-free survival, attributed partly to a better response to radio- and/or chemotherapy. The mechanisms and natural history of oral HPV infection and carcinogenic progression are poorly understood. Men and women infected with human immunodeficiency virus (HIV) have higher rates of HPV16 infection, longer persistence of HPV16, increased incidence of HNSCC, poorer prognosis, as well as more recurrences after definitive therapy. There have been substantial changes in the burden of cancer affecting HIV-infected individuals in the U.S. during the period spanning the introduction of highly active anti- retroviral therapy (HAART). Scaling-up of HAART therapy has dramatically increased the life expectancy of people living with HIV (PLHIV). As a result of these temporal changes, non-AIDS-defining cancers have come to comprise the majority of cancers in HIV-infected persons during the HAART era. Among these emerging malignancies, HPV-associated cancers of the oral cavity/pharynx increased significantly following an AIDS diagnosis. Most patients with HIV/HPV co-infections on HAART therapy have reduced risk of developing HPV-associated cancers such as cervical cancer but have a higher risk of developing HPV-associated oral cancers the risk is suggested to be due to longer life expectancy as a results of HAART therapy. But it is unclear why HAART therapy may have different effects on HPV+ HNCSCC versus HPV+ cervical cancers. Our overarching hypothesis is that HAART therapy affects the progression of HPV+ HNC. This increases the numbers of PLHIV who have persistent oral HPV infections that progress to HNCSCC, poorer prognosis, and death. We propose to focus on three areas to test this hypothesis. Specific Aim 1. Analyze HAART induced differences of HPV carcinogenic propensity in oral epithelial cells. Specific Aim 2: Investigate the effect of HAART on carcinogenic markers and metabolic pathways associated with HPV+ HNSCC. Specific Aim 3: Study the effect of HAART on glycolysis versus mitochondrial respiration.

总结