Persistent infection with 51 (20 high-risk [HR] and 31 low-risk [LR]) oncogenic genotypes of human papillomavirus (HPVs) promotes the development of cervicovaginal carcinomas (CVCs), one of the most frequent causes of women death. Presently used screening tests (Pap test, genotyping) do not reveal the earliest CVC stages. As 90% of the patients heal spontaneously in 2 years, this causes an excess follow-up tests which weighs heavily on healthcare costs. In the least developed countries HPV-screening tests are rarely done and CVC has a high prevalence. After DNA integration oncoprotein E6 and E7 expression is vital for virus reproduction via apoptosis prevention and cell transformation. Thus, our project aims at identifying novel early biomarkers predicting an active oncoprogression. To this aim anonimized (leftovers) human cervicovaginal epithelium samples of known CIN1/ASCUS/LSIL stage will be used. MALDI-TOF analysis will identify infecting HR- or LR-HPV genotypes. Cell fractionation will be followed by MALDI-TOF analysis of the subproteomes obtained via immunoprecipitations of E6 or E7 proteins. Crossed immunoprecipitations and immunoblotting will validate the identified biomarkers. Next, the suitability of some of the best biomarkers will be assessed via diagnostic statistics methods to set up a prospective prototype kit revealing the initial CVC not only in usual health centres but also "in the field" in difficult hygienic-healthcare places (African and Asian areas). By screening the patients requiring immediate treatment, this kit will provide healthcare, economical, and humanitarian benefits curtailing HR- and LR-HPV-driven CVC prevalence.
