Michael Mints

So that figure had a transparent background.. new version here

This leads to a model where, although the cancer is initiated through HPV infection, some cells can epigenetically repress HPV, allowing them to survive treatment and become persister cells through limiting proliferation. 8/8

Finally, to see if this has a clinical impact, we deconvoluted bulk TCGA data and showed that higher levels of HPV mRNA expression are linked to better prognosis! 7/8

Cell line studies showed that HPVon cells are preferentially killed by chemo/radiation, while HPVoff cells are resistant due to their non-proliferative state. We also showed that HPV DNA copy numbers are not affected, suggesting epigenetic regulation. 6/8

We mapped transcriptional heterogeneity through defining cellular states and found that this novel HPVoff subset was highly enriched in a state characterised by senescence-related genes as opposed to HPV-expressing cells (HPVon) that were largely proliferating. 5/8

Focusing on the malignant cells, we found a high degree of genetic diversity, allowing us to detect distinct subclones. We also noticed that in some cells, called HPVoff, no HPV mRNA could be detected, and that HPV expression was linked to subclonality. 4/8

To do this, we sequenced >70,000 cells from 16 patients and studied HPV gene expression, genetic subclones and cellular signalling states at the single-cell level. 3/8