Although most HPV infections are cleared by the immune system within several months, persistent HPV infections cause certain cancers, e.g. cervix, anogenital sites and oropharynx. This small DNA virus is a major public health burden causing 5% of all cancers worldwide and 7.5% of all female cancer deaths. Viral oncogenes induce cell replication and also interfere with the cellular DNA methylation machinery. Concurring with progression towards malignancy, viral genomes undergo hypermethylation, paralleled by broad epigenetic changes in the human DNA. However, the link between the genomic status of the HPV (episomal or integrated), the aberrant methylation patterns of cancer cells and the disease severity remains poorly understood. In addition, the early stages of HPV infection are less studied and the onset of DNA methylation on the episomal viral genomes is largely unknown.
Here I propose to tackle both problems. In the first workpackage, I will be using the publically available data generated by The Cancer Genome Atlas project to identify a new form of HPV episome in the cervical cancer: HPV-human hybrid episome. Recently identified in oropharynx cancer, the biological impact of those forms of HPVs on cervical cancer development and the clinical outcome of their tumors have never been characterized so far. In a second workpackage, I will be using a novel and original clinical study following young women from the onset of HPV infection to decipher DNA methylation changes occurring during the early stage of the HPV infection. Together, the data and discoveries generated from this project will be answering to clinically-relevant questions that may lead to the development of new diagnostic approaches against HPV-associated cancers.
Josquin Daron, Ignacio Bravo
The METHYVIREVOL has received funding from the European Union’s
Horizon 2020 research and innovation programme under grant agreement No 800489.