Objective. To determine changes of the cervicovaginal fluid proteomic composition for assessment of the severity of HPV-associated cervical lesions among women of reproductive age. Subject and methods. The study involved 30 volunteers with various forms of HPV-associated cervical lesions (ASCUS, LSIL and HSIL). All samples of cervicovaginal fluid were prepared for further proteomic analysis by tandem mass spectrometry (HPLC-MS/MS). Semi-quantitative data analysis including identification and annotation of proteins was carried out using the software package MaxQuant and Perseus. Results. The protein panels specific to the various forms of HPV-associated cervical lesions (ASCUS, LSIL and HSIL) were identified. The first group of proteins (P4HB, HSPA8, C4BPA and others) characterized the early changes associated with HPV infection and cervical epithelium lesion, including viruspenetration into the cell and its transcription, impaired function of the complement system. The second group of proteins (PRDX5, YWHAE, LRG1 and others) were directly involved in the development and progression of cervical neoplasia and characterized late changes, in particular, reduced apoptosis, impaired differentiation and maturation of the epithelium, and the transformation of atypical cells. Conclusion. The analysis of the proteome of the CVH allows to study the molecular mechanisms of the pathogenesis of HPV-associated cervical diseases and to differentiate epithelial changes at early stages of development.
- Cervical intraepithelial neoplasia
- Cervicovaginal fluid
- Mass spectrometry