Primary Organoid Models and Combined Nucleic Acids Therapeutics for Anti-HPV Treatments

In this project, the investigators want to develop organotypic culture of primary-derived biopsies, and combine them with organ-on-a-chip technology, to better characterize the HPV infection and cancer progression, as well as to screen innovative treatments for cervical and vaginal cancers. Our study will cover cervical dysplasia and cervical cancers HPV induced. The investigators will perform cervical and or vaginal biopsies from patients with oncogenic HPV lesions. A protocol validated to collect biopsies from precancerous cervico-vaginal lesions or cervical cancer patients in CHRO (Orleans, France). The biopsies will be performed during a consultation in the Hospital center of Orleans, or in the theatre room during a conisation or an hysterectomy. The PRIMMO platform is the research platform of Regional hospital center of Orleans (CHRO) dedicated to the promotion of translational research. It will be involved in the collection, analysis and biobank storage setup of the project. Fresh samples will be collected and bring directly to the lab for organoid cell culture development. Detection of HPV in each biopsy will be carried out by the PRIMMO platform. The organoid development from patient biopsies will take place into the lab of the Biophysic Molecular center in Orleans. The organoids will be selected according to three criteria: their ability to grow until a first passage, their doubling time and their ability to be frozen and resuscitated. Such organoids maintain pathogen-host interaction and better model physiopathology of vaginal cervical dysplasia CIN2-3 or cervical cancer and thus allow for the detection of biomarkers for pre-cancerous lesions. In addition, organoids reduce the use of animal models and can be used for drug screening, In a second step, the investigators propose to use mRNA to produce in situ the nanobodies targeting E6 and E7, to inhibit viral replication and tumor growth Socio-epidemiological data will be collected for each patient, in the form of a table. The study could be stopped in case of serious undesirable events. Safety evaluation As this is a category 2 study, no particular vigilance linked to the research protocol will be useful. However, the monitoring and reporting of unexpected events resulting from participation in the study will be declared to the "materiovigilance site" of the CHR of Orleans Given the minimal risks associated with the study, an independent monitoring committee was not considered necessary.