Novel plasma Human Papillomavirus DNA assay as a predictor of residual disease after chemo-radiotherapy for locally advanced head and neck cancer

新型血浆人乳头瘤病毒 DNA 检测可预测局部晚期头颈癌放化疗后残留疾病

• 批准号: MR/R015589/1
• 负责人: Shreerang Bhide
• 金额: $ 191.64万
• 依托单位: Institute of Cancer Research
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FR015589%2F1
• 关键词: Novel; plasma; Human; Papillomavirus; DNA

We are planning a multicentre biological sample collection study to validate circulating human papilloma virus (HPV) DNA as a marker of residual disease following potentially curative treatment in HPV positive oropharyngeal (throat) cancer.Human papilloma virus (or HPV) affects the skin and the mucosa. The mucosa is the moist membrane that lines the inside of certain body parts eg mouth and throat. HPV infection is very common and over 100 different types of HPV have been identified. Although HPV can increase the risk of developing some types of cancer, most people who have HPV won't develop cancer.Approximately 2000 patients are diagnosed with oropharyngeal (throat) cancer caused by HPV infection every year in the UK. The standard treatment for this type of cancer is up-front chemo-radiotherapy followed by surgical removal of any cancer left behind. The surgery is undertaken based on the results of a scan known as an 18F-FDG PET-CT. However, of the patients who undergo surgery, only 20% have viable residual cancer on microscopic pathological examination.Therefore these patients (300 every year) undergo unnecessary surgical procedures. Approximately 25% of patients proceeding to surgery have severe complications immediately after surgery and all of them suffer with significant permanent side effects such as pain, shoulder dysfunction with altered quality of life. Therefore a more reliable marker of presence of residual cancer after chemo-radiotherapy is required to guide management decisions and avoid unnecessary surgical procedures. Furthermore, patients who develop HPV related throat cancer are young (range 47-65 yrs. Average age 55) and due to the excellent treatment outcomes with the current treatments (>90% 5 year survival) are expected to carry the burden of treatment related toxicity for life.Oropharyngeal cancers caused by HPV release material from the tumour (containing the HPV DNA) in to the blood stream. Presence of HPV DNA in the blood stream can serve as a potential marker of the residual (remaining) cancer. We have developed an ultra-sensitive and specific assay 'HPV-detect', which is a non-invasive way to measure the HPV DNA levels after chemo-radiotherapy using a simple blood test to help guide management decisions and avoid any unnecessary surgical procedures.The HPV-detect test was developed and validated in a pilot study carried out by a team of researchers at the Institute of Cancer Research. The pilot study comprised test and blinded validation groups and demonstrated that the HPV-detect test had a sensitivity and specificity in excess of 90%. The research also showed that the plasma HPV DNA levels correlated with the pathological response (ie no active cancer cells present) as assessed following chemo-radiotherapy.The current proposal is designed to validate the relevance and usefulness of the test in patient care (clinical utility) in a large prospective multi-centre study, in order to establish its potential to predict the absence of residual disease.To prove specificity of at least 85% will require the recruitment of 143 HPV+ oropharyngeal cancer patients undergoing chemo-radiotherapy and 48 HPV negative patients as negative controls.Plasma HPV DNA levels will be measured using HPV-detect and at 12 weeks following treatment will be correlated with the 18F-FDG PET-CT results. Laboratory tests will be blinded to HPV status and clinical data. In parallel with the validation study in collaboration with the NHR-Diagnostic Evidence Cooperative at Imperial College London, we will study barriers to adoption of the test and how to address these. We will also undertake a detailed health economic analysis to study the cost benefits of implementing the test in the UK healthcare system.

我们正在计划进行一项多中心生物样本采集研究，以验证循环中的人乳头瘤病毒 (HPV) DNA 作为 HPV 阳性口咽（喉）癌潜在治愈治疗后残留疾病的标志物。人乳头瘤病毒（或 HPV）影响皮肤和粘膜。粘膜是位于某些身体部位（例如口腔和喉咙）内部的潮湿膜。 HPV 感染非常常见，已鉴定出 100 多种不同类型的 HPV。虽然 HPV 会增加患某些类型癌症的风险，但大多数感染 HPV 的人不会患癌症。在英国，每年约有 2000 名患者被诊断患有由 HPV 感染引起的口咽（喉）癌。此类癌症的标准治疗方法是预先进行化疗放疗，然后通过手术切除残留的癌症。手术是根据 18F-FDG PET-CT 扫描结果进行的。然而，在接受手术的患者中，只有20%的患者在镜下病理检查中有存活的残留癌。因此，这些患者（每年300名）接受了不必要的手术。大约 25% 接受手术的患者在手术后立即出现严重并发症，并且所有患者都会遭受明显的永久性副作用，例如疼痛、肩部功能障碍，从而影响生活质量。因此，需要一种更可靠的放化疗后残留癌症存在的标记来指导管理决策并避免不必要的外科手术。此外，患 HPV 相关咽喉癌的患者很年轻（范围为 47-65 岁，平均年龄为 55 岁），并且由于目前治疗的出色治疗效果（>90% 5 年生存率）预计将终生承受治疗相关毒性的负担。 HPV 引起的口咽癌会将肿瘤物质（含有 HPV DNA）释放到血流中。血流中 HPV DNA 的存在可以作为残留（剩余）癌症的潜在标志。我们开发了一种超灵敏和特异的检测“HPV 检测”，这是一种非侵入性方法，使用简单的血液检测来测量放化疗后的 HPV DNA 水平，以帮助指导管理决策并避免任何不必要的手术程序。HPV 检测检测是在癌症研究所的一组研究人员进行的一项试点研究中开发和验证的。该试点研究由测试组和盲法验证组组成，并证明 HPV 检测测试的敏感性和特异性超过 90%。该研究还表明，血浆 HPV DNA 水平与放化疗后评估的病理反应（即不存在活性癌细胞）相关。目前的提案旨在在一项大型前瞻性多中心研究中验证该测试在患者护理（临床实用性）中的相关性和有用性，以确定其预测是否存在残留疾病的潜力。为了证明至少 85% 的特异性，需要招募 143 例接受放化疗的 HPV+ 口咽癌患者和 48 例 HPV 阴性患者作为阴性对照。将使用 HPV-Detect 测量血浆 HPV DNA 水平，并在治疗后 12 周将其与 18F-FDG PET-CT 结果相关联。实验室检测将不了解 HPV 状态和临床数据。在与伦敦帝国理工学院 NHR 诊断证据合作社合作进行验证研究的同时，我们将研究采用该测试的障碍以及如何解决这些障碍。我们还将进行详细的健康经济分析，以研究在英国医疗保健系统中实施该测试的成本效益。