HPV16 E6 Antibody Detection as an Early Marker for Oropharyngeal Cancer Among Men Living with HIV

HPV16 E6 抗体检测作为男性 HIV 感染者口咽癌的早期标志物

• 批准号: 10395618
• 负责人: Krystle A. Kuhs
• 金额: $ 61.43万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-02-05 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10395618
• 关键词: Acquired Immunodeficiency Syndrome; Address; Affect; Age; Antibodies; Behavioral; Biological Markers; Blood; Blood Banks; Blood specimen; Cancer Center; Cancer Etiology; Cancer Prognosis; Clinic; Collection; Comprehensive Health Care; Development; Diagnosis; Early Diagnosis; Eligibility Determination; General Population; HIV; HIV Infections; HIV Seronegativity; HPV oropharyngeal cancer; HPV-High Risk; Head and Neck Cancer; Head and Neck Surgeon; Head and neck structure; High Prevalence; Human Papilloma Virus-Related Malignant Neoplasm; Human Papillomavirus; Human papilloma virus infection; Human papillomavirus 16; Incidence; Individual; Laryngoscopes; Lesion; Life Expectancy; Malignant Neoplasms; Malignant neoplasm of cervix uteri; Methods; Natural History; Oncoproteins; Oral cavity; Oral health; Palpation; Patients; Persons; Population; Positioning Attribute; Prevalence; Quality of life; Questionnaires; Research; Resources; Risk; Risk Estimate; Risk Factors; Screening for cancer; Screening procedure; Seroprevalences; Sex Behavior; Surrogate Markers; Tennessee; Testing; Time; Tonsil; Ultrasonography; Visit; Visual; Work; aged; antibody detection; base; biobank; cancer risk; chemoradiation; clinical examination; cohort; early detection biomarkers; effective therapy; high risk; improved; malignant oropharynx neoplasm; men; middle age; mortality; novel; oral HPV; oral HPV infection; premalignant; rapid detection; screening; screening guidelines; seropositive

People living with HIV (PLWH) have an increased life expectancy due to effective therapies. This has resulted in an increased incidence of non-AIDS defining cancers (NADCs), in particular, cancers caused by human papillomavirus (HPV). The most rapidly increasing HPV-related malignancy in the general US population is HPV-driven oropharyngeal cancer (HPV-OPC), a type of head and neck that has increased in incidence by more than 200% over the past few decades.1, 2 PLWH are 1.5 to 4 times more likely to develop HPV-OPC than the general population.3 They are also more likely to develop HPV-OPC at younger ages (51 versus 60)4 and have a less favorable cancer prognoses.5 Unlike cervical cancer, where the introduction of highly effective screening has significantly reduced the incidence and mortality of cervical cancer, there are no methods for early detection of HPV-OPC. A major barrier for early detection has been the inability to identify PLWH at highest risk for HPV-OPC given that a precancerous precursor lesion for OPC has yet to be identified. Recently, HPV16 E6 antibody positivity has been identified as a promising early biomarker. Previous work from our group showed that HPV16 E6 antibodies are present in up to 90% of HPV-OPC patients6 and appear more than 10 years prior to diagnosis.7-9 Additionally, we have shown that HPV16 E6 antibodies are highly specific for HPV-OPC10 and are not strongly associated with the 5 other cancers caused by HPV.11 The objective of this study is to evaluate the ability of the HPV16 E6 marker to identify a sub-population of PLWH at highest risk for developing HPV-OPC and for which head and neck cancer screening would be most effective. To accomplish this, we will conduct a natural history study of the HPV16 E6 antibody marker. This study will focus on men aged 40+ living with HIV given that ~85% of HPV-OPC cases occur in middle aged men and HIV infection additionally elevates risk by up to 4-fold. Using the Tennessee Center for AIDS Research (TN-CFAR) Biorepository, banked blood samples from men aged 40+ living with HIV (N=3,261) will be tested for HPV16 E6 antibodies. All HPV16 E6 seropositives and a subset of HPV16 E6 seronegatives (1:2 ratio) will be invited to participate in yearly (4 total) comprehensive head and neck cancer screening exams performed by a Vanderbilt Ingram Cancer Center (VICC) head and neck surgeon. Cancer screening visits will include: visual inspection of the mouth and palpation of tonsils, ultrasound imaging, laryngoscope exam, a detailed questionnaire and biospecimen collection. E6 seropositive men will be compared to E6 seronegative men in terms of: a) markers of elevated HPV-OPC risk and b) development of HPV-OPC. The specific aims are: (1) Estimate the prevalence of HPV16 E6 antibodies among men aged 40+ living with HIV; (2) Determine the association between HPV16 E6 seropositivity and markers of HPV-OPC risk; (3) Estimate the risk of developing: a) precancerous markers of HPV-OPC and/or; b) HPV-OPC by HPV16 E6 serostatus. We hypothesize that men with HPV16 E6 antibodies will be more likely to have known risk factors associated with HPV-OPC development [sexual behavior, persistent oral HPV infection] and will be more likely to develop HPV-OPC than men without HPV16 E6 antibodies. These efforts could help to generate evidence for oral health screening guidelines tailored to PLWH. This work is particularly impactful given that HPV-OPC disproportionately affects PLWH.

由于有效的治疗，艾滋病毒感染者 (PLWH) 的预期寿命得以延长。这导致了 非艾滋病定义癌症（NADC）的发病率增加，特别是由人乳头瘤病毒（HPV）引起的癌症。 美国普通人群中增长最快的 HPV 相关恶性肿瘤是 HPV 驱动的口咽癌 (HPV-OPC)，一种头颈部疾病，在过去几十年中发病率增加了 200% 以上。1, 2 PLWH 感染 HPV-OPC 的可能性是一般人群的 1.5 至 4 倍。3 他们也更有可能感染 HPV-OPC。 HPV-OPC 的发病年龄较年轻（51 岁与 60 岁）4，并且癌症预后较差。5 与宫颈癌不同， 高效筛查的引入显着降低了宫颈癌的发病率和死亡率 癌症方面，尚无早期检测 HPV-OPC 的方法。早期检测的一个主要障碍是无法 鉴于尚未确定 OPC 的癌前前体病变，以确定 HPV-OPC 风险最高的 PLWH。 最近，HPV16 E6 抗体阳性已被确定为一种有前途的早期生物标志物。我们之前的工作 研究小组表明，高达 90% 的 HPV-OPC 患者6 中存在 HPV16 E6 抗体，并且出现时间超过 10 年 7-9 此外，我们已经证明 HPV16 E6 抗体对 HPV-OPC10 具有高度特异性，而不是 与 HPV 引起的其他 5 种癌症密切相关。11 本研究的目的是评估 HPV16 E6 标记物可识别感染者中感染 HPV-OPC 风险最高的亚群，以及其头部和 颈部癌症筛查是最有效的。为了实现这一目标，我们将对 HPV16 进行自然史研究 E6 抗体标记。鉴于约 85% 的 HPV-OPC 病例发生在 中年男性和艾滋病毒感染还会使风险增加多达 4 倍。使用田纳西州艾滋病中心 研究 (TN-CFAR) 生物储存库中储存的 40 岁以上艾滋病毒感染者 (N=3,261) 男性的血液样本将进行检测 HPV16 E6 抗体。所有 HPV16 E6 血清阳性者和 HPV16 E6 血清阴性者的子集（1:2 比例）​​将被邀请参加 参加由范德比尔特英格拉姆 (Vanderbilt Ingram) 进行的年度（总共 4 次）综合头颈癌筛查检查 癌症中心 (VICC) 头颈外科医生。癌症筛查就诊将包括： 目视检查口腔和 扁桃体触诊、超声成像、喉镜检查、详细调查问卷和生物样本采集。 E6 血清阳性男性与 E6 血清阴性男性在以下方面进行比较：a) HPV-OPC 风险升高的标志物，b) HPV-OPC的开发。具体目标是： (1) 估计老年男性中 HPV16 E6 抗体的患病率 40+ 艾滋病病毒感染者； (2)确定HPV16 E6血清阳性与HPV-OPC风险标志物之间的关联； (3) 估计出现以下情况的风险： a) HPV-OPC 的癌前标志物和/或； b) 根据 HPV16 E6 血清状态检测 HPV-OPC。我们 假设具有 HPV16 E6 抗体的男性更有可能具有与 HPV-OPC 相关的已知危险因素 发育[性行为、持续口腔 HPV 感染]，并且比男性更容易患 HPV-OPC 没有 HPV16 E6 抗体。这些努力可能有助于为量身定制的口腔健康筛查指南提供证据 感染者。鉴于 HPV-OPC 对 PLWH 的影响尤为严重，这项工作尤其具有影响力。