The relationship of suppressor gene changes, inflammation and morphological changes in cervical epithelium infections related with HPV types in HİGH risk group

Background: It is known that HR-HPV E6 and E7 oncoproteins cause suppressor gene changes at different levels of the cell cycle. In this study, we aimed to discuss the effects of p16, Rb, p53 and p27 suppressor genes on HR-HPV-related cervical carcinogenesis and to examine the contribution of the expressions of these markers to the morphological diagnosis of preneoplastic lesions. In addition, we aimed to discuss the contribution of inflammation accompanying HR-HPV infection to carcinogenesis. Material-Methods: Colposcopic biopsy, conization and hysterectomy materials of 100 patients infected with any HR-HPV type between 2017-2021 in Bolu Abant İzzet Baysal University Faculty of Medicine, Department of Pathology and whose infection was detected by PCR before biopsy were retrospectively analyzed. The cases were collected in three groups. The first group without dysplasia consisted of 34 cases, the L-SIL group consisted of 32 cases, and the H-SIL group consisted of 34 cases. Appropriate paraffin blocks were extracted from the archives of our department and Rb, p53 and p27 were studied by H&E and immunohistochemistry. The previously applied p16 staining of the cases was also taken from the archive and re-evaluated and included in the study. Results: As the degree of dysplasia increased in the cervical epithelium infected with HR-HPV, an increase in p16 expression and a decrease in Rb, p53 and p27 expressions were observed at varying rates. In p16, it was noted that diffuse staining increased as the degree of dysplasia increased. While Rb and p53 stained predominantly basal/parabasal in the non-dysplastic group, they showed a tendency to stain randomly in H-SIL. Differently, p27 did not show basal/parabasal staining in the non-dysplastic group but showed random staining including basal cells in the H-SIL group. H-SIL was observed at a higher rate in cases with a single type of HR-HPV infection than in cases with multiple HR-HPV infections. Conclusion: It supported that p16, which increased due to the negative feedback mechanism between Rb-p16, could be used as a potential biomarker for HR-HPV infection in dysplastic lesions. It was thought that the random staining increase of Rb and p53 in L-SIL and H-SIL cases, more in H-SIL, would contribute to the diagnosis of L-SIL and H-SIL, which are morphologically in between. Although p27 mostly did not show basal staining in non-dysplastic epithelium, it had a random staining pattern, including basal staining in L-SIL and H-SIL. Considering this staining pattern of p27 when determining the degree of dysplasia or dysplasia will support reaching the correct diagnosis.