TEST:

SafeSEQ HPV Test

The RaDaR assay but not CAPP-seq may detect MRD in patients who relapse within 1 year. HPV-seq may be more sensitive than dPCR for MRD detection.

Whole viral genome sequencing genotypes and quantifies plasma HPV DNA. Pts with residual HPV DNA had poorer RFS and OS, independent of stage. For HPV16, HPV-seq and dPCR are strongly correlated, but HPV-seq is more sensitive with higher negative predictive value and predicted 2.3x more 3-year recurrences in OPC pts.

The level of HPV16 ctDNA but not HPV16 E6 antibodies in plasma was associated with disease burden. These findings have potential implications for early detection and prognostication.

Persistent HPV ctDNA after CRT is independently associated with inferior PFS. HPV ctDNA testing can identify, as early as at the end of CRT, patients at high risk of recurrence for future treatment intensification trials.

HPV-seq enables HPV genotyping directly from plasma in locally advanced cervical cancer. Persistent HPV ctDNA following CRT is independently associated with inferior PFS in this prospective validation study. HPV ctDNA testing can be used to identify, as early as at the end of CRT, patients at high risk of recurrence in future treatment intensification trials.

HPV-seq enables HPV genotyping directly from plasma in locally advanced cervical cancer. Persistent HPV ctDNA following CRT is independently associated with inferior PFS in this prospective validation study. HPV ctDNA testing can be used to identify, as early as at the end of CRT, patients at high risk of recurrence in future treatment intensification trials.

HPV DNA and ctDNA can be detected in LA-HNSCC before and after definitive therapy. RaDaR but not CAPP-seq may detect MRD in pts who relapse within 1 year after RT/CRT with a significant lead time. HPV-seq may be more sensitive than dPCR to detect HPV DNA in MRD.

P2 | "cfHPV DNA kinetics were more pronounced than radiographic response to systemic therapy in both high and low risk groups. cfHPV DNA was predicted by TV response to chemoimmunotherapy, but was not predicted by traditional RECIST dynamics. We identified potential TV responses to predict cfHPV DNA response."

Serial cfHPV DNA may provide an earlier and more quantitative readout of individualized treatment responsiveness compared with imaging assessment alone in HPV-related HNC. We identify a group of patients with locally advanced disease who had complete or near-complete cfHPV DNA clearance during IC. Rapid and effective clearance of cfHPV DNA may ultimately serve as a preferred metric for identifying “exceptional responders” who are ideal biological candidates for short-course CRT after IC.

Serial cfHPV DNA identifies a group of locally advanced HPV-related HNC patients who have complete/near-complete cfDNA clearance during IC. This may provide an earlier readout of individualized treatment responsiveness compared to radiologic assessment, and may therefore be a preferred metric for CRT de-intensification eligibility. Clearance velocity will be evaluated with our granular biweekly IC and weekly CRT cfHPV DNA dataset to help further elucidate tumor response kinetics with this paradigm.

Dr. Fred Jones discusses the clinical value of SafeSEQ by reviewing therapy de-escalation of HPV+ HNSCC patients and monitoring PIK3CA and ESR1 low-level mutations in breast cancer.

Using an NGS-based liquid biopsy approach in HPV+ OPC patients, we demonstrate that dynamic changes in cfHPV-DNA levels correlate with response to induction therapy. These data support the development of cfHPV-DNA assessment to guide personalized de-escalation in HPV+ OPC. Analyses are ongoing to further evaluate cfHPV-DNA as a reliable blood-based biomarker in the context of an adaptive de-intensification paradigm.

"Sysmex Inostics...announces the use of their HPV-SEQ test in the prospective University of Chicago clinical trial, 'Pilot Study of Chemotherapy for HPV-Associated Oropharyngeal Cancer...HPV-SEQ, Sysmex Inostics ultra-sensitive quantitative, CLIA-validated, blood test for the detection of cell-free HPV 16/18 DNA (cfHPV-DNA), will be used in the trial to monitor personalized treatment and de-escalation of HPV positive oropharyngeal cancer (OPC) patients."