PO.MCB08.03 · 分子与细胞生物学
一种用于定义HPV相关头颈癌中病毒和宿主基因组异质性的多模态测序框架
A multimodal sequencing framework to define viral and host genomic heterogeneity in HPV associated head and neck cancer
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
背景:本研究旨在将病毒和宿主基因组分析与健康社会决定因素(SDOH)相结合,以改善人乳头瘤病毒相关头颈癌(HPV+ HNC)患者的生物学风险分层。
方法:纳入活检证实为p16阳性的HPV+ HNC患者。存档或新鲜肿瘤组织经DNA提取后,进行靶向L1位点的HPV共识引物基因分型(MY09/MY11引物序列)以确定病毒类型。确认HPV感染的样本进入短读长测序以进行病毒基因型鉴定和宿主突变谱分析,以及长读长测序以定义HPV整合结构、HPV-宿主融合事件和较大的结构变异。收集人口统计学、临床和SDOH变量,以探究患者背景与基因组异质性之间的关联。
结果:迄今为止,10例患者已提供知情同意并纳入本研究。此外,还分析了8份存档肿瘤标本。该队列由7名白人男性、2名西班牙裔或拉丁裔男性和1名白人女性患者组成。存档标本来自3名白人、2名亚裔、2名黑人和1名西班牙裔患者。初步HPV基因分型显示高危型HPV的分布,包括HPV16、HPV18、HPV33、HPV35和HPV59。这些早期结果提示,跨祖源和SDOH定义的聚类之间可能存在差异,白人患者主要表现为HPV16基因型,而在其他种族和族裔群体中非16型的患病率较高。
结论:这些早期发现凸显了拓宽HPV基因型鉴定并捕捉患者多样性的价值,以揭示HPV+ HNC中病毒和宿主基因组变异的全貌。持续扩大队列和完成测序分析将是关键的后续步骤,以定义具有临床意义的基因组亚组,并为HPV相关头颈癌的精准风险分层、监测和治疗个体化开发未来框架。
查看英文原文 English abstract
Background: This study aims to integrate viral and host genomic analyses with social determinants of health (SDOH) to improve biologic risk stratification in patients with human papillomavirus-associated head and neck cancer (HPV+ HNC).
Methods: Patients with biopsy-proven, p16-positive HPV+ HNC were enrolled. Archived or fresh tumor tissue underwent DNA extraction followed by HPV consensus-primer genotyping targeted to the L1 locus (MY09/MY11 primer sequences) to determine viral type. Samples with confirmed HPV infection proceed to short-read sequencing for viral genotype characterization and host mutational profiling, and long-read sequencing to define HPV integration architecture, HPV-host fusion events, and larger structural variants. Demographic, clinical, and SDOH variables were collected to explore associations between patient context and genomic heterogeneity.
Results: To date, 10 patients have provided informed consent and have been enrolled in this study. Additionally, eights archived tumor specimens have been analyzed. The cohort consists of seven White male, two Hispanic or Latino male, and one White female patients. Archived specimens were derived from three White, two Asian, two Black, and one Hispanic patient. Preliminary HPV genotyping demonstrates a distribution of high-risk HPV types, including HPV16, HPV18, HPV33, HPV35, and HPV59. These early results suggest a potential variation across ancestry and SDOH-defined clusters, with White patients predominantly demonstrating the HPV16 genotype, while there is a higher prevalence of non-16 types amongst other racial and ethnic groups.
Conclusions: These early findings highlight the value of broadening HPV genotype characterization and capturing patient diversity to uncover the full spectrum of viral and host genomic variation in HPV+ HNC. Ongoing expansion of the cohort and completion of sequencing analyses will be critical next steps toward defining clinically meaningful genomic subgroups and developing future frameworks for precision risk stratification, surveillance, and treatment personalization in HPV-associated head and neck cancer.
利益披露 Disclosure
E. P. Jackert, None..
S. Cheng, None..
S. Vimawala, None..
L. Tang, None..
D. Kwon, None..
N. C. Kokot, None..
U. Sinha, None..
A. Y. Han, None.