Abstract 788P
Background
Limited data exists to show how HPV cell-free DNA (cfDNA) may be a unique tumour marker in advanced cervical cancer. Our objective was to examine the association between change in HPV cfDNA and clinical outcome.
Methods
HPV cfDNA genotyping and quantification using Illumina NovaSeq was applied to plasma, prospectively-collected at times of change in clinical outcome, from patients with metastatic cervical cancer. Bespoke circulating tumour DNA (ctDNA) analysis was applied, using a panel of likely oncogenic mutations determined from sequencing of archival tumour (PTEN, HRAS, TP53, NFE2L2, CASP8, MAPK1, EP300, PIK3CA, PBXW7, TERT, CDKN2A, NOTCH1, KEAP1, KRAS, STK111).
Results
Treatments received included front-line platinum-based chemotherapy (N=4), with bevacizumab (N=5), bevacizumab monotherapy (N=3), or subsequent therapy (N=5). 4 previously-treated patients were included to study HPV kinetics during observation. Using Fisher's Exact Test, from baseline to first assessment, change in HPV was associated with clinical response or progression on treatment (N=17) (p=0.015), and across all patients on treatment or observation (N=21) (p=0.001) (Table). Across ≥2 time points (59 samples), HPV dynamics remained closely related to outcome in a majority of cases (N=15/21). Custom-designed ctDNA panel detected mutations in 10 cases, consistent with mutations in corresponding tumour (excluding 2 cases with insufficient tissue for profiling). Change in HPV and change in Variant Allele Frequency were correlated (Spearman’s rank correlation; rho=0.83, p=0.006).
Table: 788P
Changes in HPV cfDNA relationship to clinical outcome in advanced cervical cancer across baseline and first subsequent collection timepoint
| Clinical Outcome | Decrease in HPV cfDNA (N) | Increase in HPV cfDNA (N) |
| On Treatment (N=17) Disease progressionStable DiseasePartial Response/Complete Response | 228 | 410 |
| On Treatment or Observation (N=21) Disease progressionStable DiseasePartial Response/Complete Response | 228 | 810 |
Conclusions
In this pilot study, dynamic change in HPV cfDNA is associated with clinical outcome in advanced cervical cancer. This data suggests HPV cfDNA may have application for non-invasive HPV genotyping and treatment monitoring, requiring validation in larger studies.
Clinical trial identification
This study is performed under the auspice of the LIBERATE (NCT03702309) study, which is an institutional liquid biopsy program at the University Health Network supported by the BMO Financial Group Chair in Precision Cancer Genomics (Chair held by Dr. Lillian Siu).
This study is also performed under the auspice of the VENUS (NCT03420118) study.
Editorial acknowledgement
Legal entity responsible for the study
Princess Margaret Cancer Centre.
Funding
Princess Margaret Cancer Centre.
Disclosure
A.M. Oza: Other, Institutional, Research Grant: AstraZeneca; Other, Personal and Institutional, Research Grant: GSK; Other, Personal and Institutional, Research Grant: Clovis; Non-Financial Interests, Personal, Advisory Board: AstraZeneca; Non-Financial Interests, Personal, Advisory Board: GSK; Non-Financial Interests, Personal, Advisory Board: Clovis. S. Lheureux: Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Invited Speaker: GSK; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Invited Speaker: Eisai. All other authors have declared no conflicts of interest.