Prospective validation of ctHPVDNA for detection of minimal residual disease and prediction of recurrence in patients with HPV-associated head and neck cancer treated with surgery.

作者：Shun Hirayama, Yana Al-Inaya, Ling Aye, Michael Bryan, Dipon Das, Julia Mendel, Saskia Naegele, William C. Faquin, Peter M. Sadow, Adam S. Fisch, Derrick T. Lin, Mark A. Varvares, Allen L. Feng, Kevin S. Emerick, Daniel G. Deschler, Michael S. Lawrence, A. John Iafrate, Annie W. Chan, Jeremy D. Richmon, Daniel L. Faden · 发表于：Journal of Clinical Oncology · 年份：2024 · DOI：10.1200/jco.2024.42.16_suppl.6010 · 被引用次数：16 · 研究领域：Molecular Biology Techniques and Applications、Head and Neck Cancer Studies、RNA modifications and cancer

6010 Background: Prediction of minimal residual disease (MRD) following surgery, and thus the need for adjuvant therapy, is currently based on clinicopathologic risk factors which have poor individual prognostic capacity. We previously reported that MRD detection by ctHPVDNA droplet digital (dd)PCR as early as post-operative day (POD) 1 is predictive of recurrence in stage I-II HPV+HNSCC patients. Here, we applied a significantly more sensitive custom whole genome hybrid-capture-based next generation sequencing assay, termed HPV-DeepSeek, to validate the prognostic capacity of ctHPVDNA detection and explore the optimal timing of MRD testing in HPV+HNSCC patients. We tested the primary hypothesis that patients with MRD detection within 6 weeks of surgery would have inferior PFS at 2 years and the secondary hypothesis that patients with ctHPVDNA positivity detected at any point following treatment completion would have inferior PFS at 2 years. Methods: 98 patients with HPV+HNSCC were prospectively enrolled with a mean follow-up of 712 days. All patients underwent surgery as primary treatment and clinicopathologic adjusted adjuvant treatment. 10ml blood samples were collected before surgery, in the post-operative period (POD 1-42), and serially in follow-up. MRD was defined as a lack of ctHPVDNA clearance during the 6 weeks following surgery. Cell free DNA was extracted from plasma and run on HPV-DeepSeek, and on existing ddPCR assays for head to head comparisons. Results: 96/98...