Reparative Spheroids in HPV-Associated Chronic Cervicitis

Background: Spheroid cell structures (SCS) described in cell culture are used to study cell-cell and cell-matrix interactions. However, the role of the SCS in the repair process in vivo remains unexplored. The aim of the study was to examine the cellular composition of the spherical structures and their functional significance in the repair of the squamous epithelium in human papilloma virus-associated chronic cervicitis (HPV-CC). Methods and Results: The cytology and biopsy materials from 223 patients with HPV-CC were subjected to molecular testing for HPV DNA by Real-Time Polymerase Chain Reaction (Real-Time PCR) with genotyping and chromogenic in situ hybridization (CISH), as well as immunocytological and immunohistochemical analyses of p16INK4A, Ki67, SMA, Vimentin, CD34, E-cadherin, Oct4, CD44, CKW markers. In the stem cell niche zone, these spheroid structures were discovered having proliferative activity and showing signs of producing stem cells involved in the repair of the cervical mucosa in HPV-CC. Conclusion: The persistence of the HPV in the stem cell niche zone cells in the cervix determines the chronization of inflammation in this area, with the ability to perform pathological repair. The immunophenotype of the spheroid cell structures in the HPV-CC includes cells with signs of stem cells (‘stemness’) and the mesenchymal-epithelial transition