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: 10339080
• 负责人: Krystle A. Kuhs
• 金额: $ 65.06万
• 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/10339080
• 关键词: HPV16; E6; Antibody; Detection; Early

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.

艾滋病毒感染者（PLWH）由于有效的治疗而延长了预期寿命。这导致 非艾滋病定义的癌症（NADC）的发病率增加，特别是由人乳头瘤病毒（HPV）引起的癌症。 在美国普通人群中，HPV相关恶性肿瘤增长最快的是HPV驱动的口咽癌 （HPV-OPC），这是一种头颈部疾病，在过去几十年中发病率增加了200%以上。 PLWH发生HPV-OPC的可能性是普通人群的1.5至4倍。 在较年轻的年龄（51岁对60岁）4发展HPV-OPC，并且具有较不利的癌症预后。5与宫颈癌不同， 采用高效筛查显著降低了宫颈癌的发病率和死亡率， 在癌症中，没有用于早期检测HPV-OPC的方法。早期发现的一个主要障碍是 鉴于尚未确定OPC的癌前前驱病变，确定PLWH中HPV-OPC的最高风险。 最近，HPV 16 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 HPV 16 E6抗体存在于高达90%的HPV-OPC患者6中，并且出现时间超过10年 7 -9此外，我们已经证明HPV 16 E6抗体对HPV-OPC 10具有高度特异性， 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 HPV 16 E6标志物，以鉴定处于发展HPV-OPC的最高风险的PLWH亚群，并且对于该亚群， 颈部癌症检查将是最有效的。为了实现这一目标，我们将对HPV 16进行自然史研究， E6抗体标记物。这项研究将重点关注40岁以上的男性艾滋病毒感染者，因为约85%的HPV-OPC病例发生在 中年男子和艾滋病毒感染的风险增加了4倍。田纳西艾滋病中心（Tennessee Center for AIDS） 研究（TN-CFAR）生物储存库，将对40岁以上男性HIV感染者（N= 3，261）的库存血液样本进行检测， HPV 16 E6抗体。将邀请所有HPV 16 E6血清阳性者和HPV 16 E6血清阴性者亚组（1：2比例）， 参加由范德比尔特英格拉姆进行的年度（共4次）全面头颈癌筛查检查 癌症中心（VICC）头颈外科医生。癌症筛查访视将包括：对口腔进行目视检查， 扁桃体触诊、超声成像、喉镜检查、详细的问卷调查和生物标本收集。E6 血清阳性男性将与E6血清阴性男性在以下方面进行比较：a）HPV-OPC风险升高的标志物和B） HPV-OPC的开发本研究的具体目的是：（1）估计10岁以上男性HPV 16 E6抗体的流行情况， 40+ HIV感染者;（2）确定HPV 16 E6血清阳性与HPV-OPC风险标志物之间的关联;（3） 评估发生以下情况的风险：a）HPV-OPC的癌前标志物和/或; B）HPV 16 E6血清状态的HPV-OPC。我们 假设携带HPV 16 E6抗体男性更可能有已知的与HPV-OPC相关的危险因素 发展[性行为，持续的口腔HPV感染]，并且比男性更有可能发展HPV-OPC 没有HPV 16 E6抗体。这些努力有助于为定制的口腔健康筛查指南提供证据 到PLWH。这项工作特别有影响力，因为HPV-OPC不成比例地影响PLWH。