Hpv-Driven Cancers Show Distinct Methylation Signatures In Cell-Free Dna (Cfdna)

Accurate tissue of origin (TOO) prediction is crucial for effective clinical follow-up in early cancer detection from blood. In the second substudy of the Circulating Cell-free Genome Atlas (CCGA; NCT02889978), we trained logistic regression classifiers under cross-validation to detect and localize cancer. Input features were methylation states from a targeted cfDNA assay of 2023 participants. TOO classification accuracy was 89% across 20 pre-specified prediction classes. We subsequently sought to understand the causes of the remaining TOO errors. 45% of the errors fell into clusters reflecting similarities in developmental biology, histology, or oncological drivers. Here, we analyzed tissues that may be affected by HPV-driven cancers; these accounted for 21% of TOO errors. The original classifier, which used only human epigenetic states as input, demonstrated cross-scoring between likely HPV-driven cancers of the anus (N = 14) and cervix (N = 11), as well as confirmed HPV-positive head \u0026 neck (HN 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2114.