Deciphering the radiosensitivity of HPV-positive tumors

The increased radiosensitivity of HPV positive tumors (compared to HPV negative ones) is widely known in clinical settings. However, the mechanisms by which this phenomenon occurs are still to be elucidated. A few hypotheses have been suggested regarding this differential radiosensitivity like, for example, an altered microtumoral environment or virus-host protein interactions. In this study, we focused on interactions between DNA repair proteins and virus oncoproteins. A large panel of 147 proteins implicated in DNA repair pathways was tested for potential interaction with HPV16 E6 and/or E7 oncoproteins using the GPCA method (Gaussia Princeps Complementation Assay). The proteins highlighted by the screening were validated by co-IP. The functional experiments, realized on HPV negative head and neck cancer (UPCI-SCC-111, FaDu, UPCI-SCC-40), vulva cancer (C33a) and control keratinocytes (HaCaT) stably transduced with E6 and/or E7, are in progress.