The role of chronic cannabis and its two major psychoactive ingredients in papillomavirus-associated oropharyngeal disease

慢性大麻及其两种主要精神活性成分在乳头瘤病毒相关口咽疾病中的作用

• 批准号: 9888363
• 负责人: Jiafen Hu
• 金额: $ 23万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9888363
• 关键词: Address; Affect; Animal Model; Animals; Biological Assay; Biology; Canis familiaris; Cannabidiol; Cannabinoids; Cannabis; Cattle; Cells; Chronic; Circumvallate Papilla; Data; Data Set; Developed Countries; Development; Disease; Disease Progression; District of Columbia; Dysplasia; Endocannabinoids; Equus caballus; Exposure to; Female; Genetic Transcription; Gland; Goals; Head and Neck Cancer; Health; Histologic; Human; Human Papilloma Virus Vaccine; Human Papilloma Virus-Related Malignant Neoplasm; Human Papillomavirus; Human papilloma virus infection; Image; Imaging Device; Immune; Immunocompetent; Immunocompromised Host; Immunologics; Immunomodulators; In Vitro; Individual; Infection; Inhalation; Irrigation; Knowledge; Laboratories; Lead; Link; Malignant Neoplasms; Malignant neoplasm of cervix uteri; Marijuana; Methods; Modeling; Mouse Strains; Mucous Membrane; Mus; Oral mucous membrane structure; Oropharyngeal; Oryctolagus cuniculus; Papillomavirus; Papillomavirus Infections; Patients; Population; Positioning Attribute; Production; Publishing; Reagent; Reporting; Robotics; Role; Sexually Transmitted Diseases; Specificity; Swab; Testing; Tissues; Tongue; Tonsil; Viral; Viral Pathogenesis; Virus Diseases; Woman; Youth; clinically relevant; cytokine; imaging system; immune function; in vivo; male; malignant oropharynx neoplasm; marijuana legalization; marijuana smoke; marijuana use; men; mucosal site; novel; novel therapeutic intervention; oral infection; receptor; reproductive tract; tongue root; transcriptome sequencing; translational impact; virology

Human papillomavirus (HPV) infection is the most common sexually transmitted disease. HPV causes more than 5% of all human cancers and claims more than 270,000 women’s lives from cervical cancer worldwide annually. Intriguingly, despite the development of three protective HPV vaccines to HPV related cancers, HPV-associated oropharyngeal cancers are becoming increasingly prevalent in patients, particularly in white men in developed countries. Marijuana (cannabis) usage has been linked to HPV-associated oropharyngeal cancers in some studies. Currently, about 1 in 16 youths in the U.S. is reported to use cannabis daily, and nine states and the District of Columbia have legalized marijuana for recreational use since April 2018. Whether cannabis use is associated with increasing HPV-associated oropharyngeal cancers remains unclear and is difficult to study in humans due to the complexities associated with controlling variables in these studies. Over the past five years, we and others have accumulated a significant published and unpublished data set to support the relevance of our newly established mouse papillomavirus (MmuPV1) model to study HPV-associated oropharyngeal cancer. Our long term goal is to use this unique model to explore clinically relevant questions regarding the biology of papillomavirus infections, and to elucidate the critical mechanisms of HPV-associated oropharyngeal cancer. We have developed in vitro and in vivo assays to conduct virological, immunological and histological analyses, and have used our Toponome Imaging System (TIS), the first robotic imaging machine in the US, to characterize innate immune cell landscapes in the MmuPV1- infected vs non-infected tissues. These preliminary studies have positioned us well to accomplish the proposed studies. We hypothesize that marijuana, via one or both of its two major psychoactive ingredients Δ9- tetrahydocannabinol (THC) and cannabidiol (CBD), promotes viral persistence in the circumvallate papilla (CVP) and adjacent Von Ebners (VE) glands in the oropharyngeal mucosae. In Specific Aim 1, we will define the role of chronic marijuana smoke (up to 36 weeks post viral infection) in viral persistence at the oropharyngeal mucosae. In Specific Aim 2, we will determine the role of the two major psychoactive ingredients of marijuana (up to 36 weeks post viral infection) in viral persistence at the oropharyngeal mucosae. These studies will allow us to establish whether the oropharyngeal mucosae are more susceptible to papillomavirus infections when chronic marijuana smoke or its two major psychoactive ingredients (THC and/or CBD) are administered. This represents a key knowledge gap in HPV-associated oropharyngeal disease and cancer. Furthermore these studies will allow us to determine whether males are preferentially impacted, as has been noted in humans.

人乳头瘤病毒（HPV）感染是最常见的性传播疾病。 HPV原因 所有人类癌症中有5％以上，占据宫颈癌的270,000多名女性生命 每年在全球。有趣的是，使命是将三种受保护的HPV疫苗开发到与HPV相关的 癌症，与HPV相关的口咽癌在患者中变得越来越普遍，尤其是 在发达国家的白人。大麻（大麻）用法已与HPV相关 口咽癌在某些研究中。目前，据报道，约有16名年轻人使用大麻 每日，九个州和哥伦比亚特区自4月以来已将大麻合法化供娱乐使用 2018年。大麻使用是否与HPV相关的口咽癌的增加有关 不清楚，由于与控制变量相关的复杂性，在人类中很难研究 研究。在过去的五年中，我们和其他人积累了大量发表和未出版 数据集以支持我们新建立的鼠标乳头瘤病毒（MMUPV1）模型的相关性 HPV相关的口咽癌。我们的长期目标是使用这种独特的模型在临床上探索 有关乳头瘤病毒感染的生物学的相关问题，并阐明关键机制 HPV相关的口咽癌。我们已经开发了体外和体内测定 病毒学，免疫学和组织学分析，并使用了我们的toponome成像系统（TIS）， 美国的第一台机器人成像机，以表征MMUPV1-的先天免疫细胞景观 感染的与未感染的组织。这些初步研究已经使我们良好地定位了拟议的 研究。我们假设大麻是通过其两种主要的精神活性成分中的一种或两种大麻δ9- 四氢大麻酚（THC）和大麻二酚（CBD）促进乳头乳头的病毒持久性 （CVP）和相邻的von Ebner（VE）粘膜中的腺体。在特定目标1中，我们将定义 慢性大麻烟雾（病毒感染后长达36周）在病毒持续性中的作用 口咽粘膜。在特定目标2中，我们将确定两个主要的精神活性的作用 口咽持续性大麻（病毒感染后最多36周）的成分（最多36周） 粘膜。这些研究将使我们能够确定口咽粘膜是否更容易受到 当慢性大麻烟或其两种主要的精神活性成分（THC和/或 CBD）。这代表了与HPV相关的口咽病和 癌症。此外，这些研究将使我们能够确定男性是否受到影响， 我们在人类中被指出。

项目成果

Immune Responses in Oral Papillomavirus Clearance in the MmuPV1 Mouse Model.

• DOI: 10.3390/pathogens12121452
• 发表时间: 2023-12-14
• 期刊: Pathogens (Basel, Switzerland)
• 作者: Brendle SA;Li JJ;Walter V;Schell TD;Kozak M;Balogh KK;Lu S;Christensen ND;Zhu Y;El-Bayoumy K;Hu J
• 通讯作者: Hu J