PO.MD01.02 · 分子诊断与数据

基于人群的人乳头瘤病毒感染与宫颈癌发病率、驱动突变及总生存的模式

Population-based patterns of human papillomavirus infections and cervical cancer incidence, driver mutations and overall survival

编号 4114 展板 19 时间 4/21 09:00–12:00 区域 Section 1 主讲 Ahmed Hussain, MD

分会场 AACR Project GENIE: Genomic Characterization

查看 PDF 下载 PDF 🔒 查看 / 下载完整 PDF 需登录并开通下载套餐 · 查看套餐 / 开通 AACR 官方页面

作者与单位 Authors & Affiliations

S. Ahmed Hussain¹, Chunqiao Tian², Christopher Tarney¹, Thomas Beltran³, Pouya Javadian¹, Ryan McLaughlin⁴, Paulette Mhawech-Fauceglia⁵, Doris M. Benbrook⁶, Sean Cronin¹, Zachary Kopelman¹, Colin Sitler³, Leslie M. Randall⁷, John Chan⁸, Daniel Kapp⁹, Chad A. Hamilton¹⁰, Charles A. Leath¹¹, Christina Washington¹², Kathleen Moore¹², Kristen Bunch¹, Nicholas Bateman², Thomas P. Conrads¹³, G. Larry Maxwell¹³, Kathleen M. Darcy¹⁴

¹Walter Reed National Military Medical Center, Bethesda, MD,²The Henry M Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD,³Womack Army Medical Center, Fort Liberty, NC,⁴Uniformed Services University of the Health Sciences, Bethesda, MD,⁵Aurora Diagnostics, Las Vegas, NV,⁶OU Health Stephenson Cancer Center, Oklahoma City, OK,⁷Mid-Atlantic Gynecologic Oncology and Pelvic Surgery Associates, Falls Church, VA,⁸California Pacific Medical Center, San Fransisco, CA,⁹Stanford University School of Medicine, Stanford, CA,¹⁰The Ochsner Cancer Institute, New Orleans, LA,¹¹University of Alabama at Birmingham, Birmingham, AL,¹²Oklahoma University Health Sciences Center, Oklahoma City, OK,¹³Women’s Health Integrated Research Center, Falls Church, VA,¹⁴Henry M. Jackson Foundation, Bethesda, MD

摘要 Abstract

中文摘要

背景：人乳头瘤病毒（HPV）感染是宫颈癌的主要病因。HPV 患病率、肿瘤基因组改变和生存结局在不同人群组之间的差异仍未完全表征。理解病毒与宿主肿瘤生物学之间的相互作用对优化宫颈癌的预防和治疗至关重要。方法：使用国家健康与营养检查调查（NHANES，2005-2016）评估了 18-59 岁非西班牙裔白人（NHW）、非西班牙裔黑人（NHB）和西班牙裔（HSP）女性中的高危 HPV 患病率。使用来自 SEER 21 个地区（2004-2020）的数据评估了宫颈癌的年龄调整发病率。使用基因组学证据肿瘤信息交换（GENIE v16.0）分析了宫颈癌患者肿瘤中的体细胞驱动突变。使用 Kaplan-Meier 和 Cox 回归模型在国家癌症数据库（NCDB，2004-2020）中 I-IV 期宫颈癌病例中检查总生存。结果：在 11,033 名 NHANES 参与者中，高危 HPV 患病率在白人和西班牙裔女性中相似，但在黑人女性中更高（任何 HPV 感染的比值高 2.1 倍；HPV16/18 的比值高 1.5 倍）。图 1A 显示与 HSP 或 NHW 患者相比，NHB 患者中高危 HPV 基因型的单独及并发高危感染的分布更高。来自 SEER 的数据显示，与 NHW 患者相比，HSP 和 NHB 患者的宫颈癌年龄调整发病率均更高。2004-2000 年间所有组的发病率均下降（图 1B）。图 1C 显示了 GENIE 中 595 例宫颈癌患者肿瘤中的体细胞突变。BRD4、ERBB3、MTOR 和 GRM3 突变在 NHB 中比 NHW 患者更频繁。与 HSP 患者相比，ERBB3、CIC、PIK3R1 和 PI3K 通路改变在 NHB 中富集，而 SMARCA4、CIC、KDM5C 和 RANBP2 突变在白人中比西班牙裔更常见。在 117,170 例 NCDB 病例中，HSP 患者的 5 年生存率为 76%，NHW 为 69%，NHB 为 60%（图 1D，p<0.0001）。与 HSP 女性相比，NHW 患者的死亡风险高 40%，NHB 患者高 91%（p<0.001）。结论：HPV 感染模式的差异与宫颈癌发病率、体细胞突变和生存相关，反映了不同人群之间的生物学和临床异质性。将病毒基因分型与发病率和肿瘤分子分析相整合，可为精准预防、风险评估和个体化治疗提供参考，从而改善所有患者的结局。转化相关性：本研究将病毒、发病率、基因组和生存数据跨多个国家数据集相关联，揭示了宫颈癌的人群水平变异。这些见解支持加强 HPV 疫苗接种、早期检测以及个体化预防、筛查和治疗决策的努力。

查看英文原文 English abstract

Background : Human papillomavirus (HPV) infection is the primary cause of cervical carcinoma. Variations in HPV prevalence, tumor genomic alterations, and survival outcomes across population groups remain incompletely characterized. Understanding the interplay of viral and host tumor biology is essential to optimize prevention and treatment in cervical cancer. Methods : High-risk HPV prevalence was evaluated in non-Hispanic White (NHW), non-Hispanic Black (NHB), and Hispanic (HSP) females aged 18-59 years using the National Health and Nutrition Examination Survey (NHANES, 2005-2016). Age-adjusted incidence of cervical cancer was evaluated using data from 21 regions in SEER (2004-2020). Somatic driver mutations were analyzed in tumors from patients with cervical cancer using the Genomics Evidence Neoplasia Information Exchange (GENIE v16.0). Overall survival was examined using Kaplan-Meier and Cox regression models among stage I-IV cervical cancer cases in the National Cancer Database (NCDB, 2004-2020). Results : Among 11,033 NHANES participants, high-risk HPV prevalence was similar in White and Hispanic women but higher in Black women (2.1-fold higher odds of any HPV infection; 1.5-fold higher odds of HPV16/18). Fig 1A shows the higher distribution of high-risk HPV genotypes individually and concurrent high-risk infections in NHB patients compared with either HSP or NHW patients. Data from SEER shows that age-adjusted incidence of cervical cancer was higher in both HSP and NHB patients compared with NHW patients. Rates declined in all groups from 2004-2000 (Fig 1B). Fig 1C displays somatic mutations in tumors from 595 cervical cancer patients in GENIE. BRD4, ERBB3, MTOR, and GRM3 mutations were more frequent in NHB than NHW patients. ERBB3, CIC, PIK3R1, and PI3K pathway alterations were enriched in NHB compared with HSP patients, whereas SMARCA4, CIC, KDM5C, and RANBP2 mutations were more common in White than Hispanic patients. In 117,170 NCDB cases, 5-year survival was 76% for HSP, 69% for NHW, and 60% for NHB patients (Fig 1D, p<0.0001). Compared with HSP women, mortality risk was 40% worse for NHW and 91% worse for NHB patients (p<0.001). Conclusions : Differences in HPV infection pattern are linked with cervical cancer incidence, somatic mutations, and survival, reflecting biologic and clinical heterogeneity across populations. Integrating viral genotyping with incidence rates and tumor molecular profiling may inform precision prevention, risk assessment, and personalized treatment to improve outcomes for all patients. Translational Relevance : This study links viral, incidence, genomic and survival data across multiple national datasets to reveal population-level variations in cervical cancer. These insights support efforts to enhance HPV vaccination, early detection, and individualized prevention, screening and therapeutic decision-making.

利益披露 Disclosure

S. Hussain, None.. C. Tian, None.. C. Tarney, None.. T. Beltran, None.. P. Javadian, None.. R. McLaughlin, None.. P. Mhawech-Fauceglia, None.. D. M. Benbrook, None.. S. Cronin, None.. Z. Kopelman, None.. C. Sitler, None.. L. M. Randall, None.. J. Chan, None.. D. Kapp, None.. C. A. Hamilton, None.. C. A. Leath, None.. C. Washington, None.. K. Moore, None.. K. Bunch, None.. N. Bateman, None.. T. P. Conrads, None.. G. Maxwell, None.. K. M. Darcy, None.

← 返回 AACR 2026 检索