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: 10616562
• 负责人: Krystle A. Kuhs
• 金额: $ 45.27万
• 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/10616562
• 关键词: Acquired Immunodeficiency Syndrome; Address; Affect; Age; Antibodies; Behavioral; Biological Markers; Blood; Blood Banks; Blood specimen; Cancer Center; Cancer Etiology; Cancer Patient; 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; Tonsil; Ultrasonography; Visit; Visual; Work; aged; antibody detection; 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.

由于有效的疗法，患有艾滋病毒（PLWH）的人的预期寿命会增加。这导致了 尤其是由人乳头瘤病毒（HPV）引起的癌症（HPV）引起的癌症（NADC）的发病率增加。 美国普通人群中与HPV相关的恶性肿瘤最快的是HPV驱动的口咽癌 （HPV-OPC），在过去几十年中，一种头和颈部的发病率增加了200％以上。1、2 PLWH开发HPV-OPC的可能性是一般人群的1.5至4倍。3它们也更有可能 在年轻人（51 ves 60）4中发展HPV-OPC，并且预后不太有利。5与宫颈癌不同， 高效筛查的引入显着降低了宫颈的发病率和死亡率 癌症，没有早期检测HPV-OPC的方法。早期检测的主要障碍是无法 鉴于尚未确定OPC的前癌前体病变，尚未确定HPV-OPC风险最高的PLWH。 最近，HPV16 E6抗体阳性已被确定为有希望的早期生物标志物。我们以前的工作 组表明，HPV16 E6抗体在多达90％的HPV-OPC患者中存在，并且出现超过10年 7-9此外，我们已经表明HPV16 E6抗体对HPV-OPC10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，以确定开发HPV-OPC风险最高的PLWH的子群，以及哪个负责人和 颈癌筛查将是最有效的。为此，我们将对HPV16进行自然史研究 E6抗体标记。鉴于约有85％的HPV-OPC病例发生在40岁以上的HIV患者中，这项研究将集中于40岁以上的男性。 中年男性和艾滋病毒感染还将风险提高多达4倍。使用田纳西州艾滋病中心 研究（TN-CFAR）生物座席，来自40岁以上艾滋病毒（n = 3,261）的男性的储存血液样本（n = 3,261） HPV16 E6抗体。将邀请所有HPV16 E6血清蛋白和HPV16 E6血清剂的子集（1：2） 参加范德比尔特·英格拉姆（Vanderbilt Ingram）进行的年度（总共4个）全面的头颈癌筛查考试 癌症中心（VICC）头颈外科医生。癌症筛查将包括：视觉检查口和 扁桃体的触诊，超声成像，喉镜考试，详细的问卷和生物传播收集。 E6 血清阳性男性将与E6血清质男性相提并论：a）HPV-OPC风险升高的标记和b） HPV-OPC的开发。具体目的是：（1）估计年龄男性HPV16 E6抗体的患病率 40岁以上的艾滋病毒生活； （2）确定HPV16 E6血清阳性与HPV-OPC风险的标记之间的关联； （3） 估计发展的风险：a）HPV-OPC和/或的癌前标记； b）HPV16 E6血清的HPV-OPC。我们 假设患有HPV16 E6抗体的男性更可能具有与HPV-OPC相关的已知危险因素 发展[性行为，持续性口服HPV感染]，并且比男性更有可能发展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 到plwh。考虑到HPV-OPC对PLWH的影响不成比例，这项工作尤其有影响力。