The role of programmed death-ligand 1 (PDL-1) in high-grade cervical intraepithelial neoplasia (CIN2+) development and recurrence: A systematic review of literature about HPV-CIN2+-PDL-1 axis

Background and aims: Cervical intraepithelial neoplasia(CIN)and persistent high-risk human papillomavirus (HRHPV)infection are associated with impaired local cellular immunity; however, the molecular mechanisms underlying these processes are not well understood. The involvement of the programmed death 1/programmed death 1 ligand (PD-1/PD-L1) pathway in the downregulation of T cell function has been demonstrated recently and it is believed to have a role in the onset and persistence of HPV infection and cervical cancer. Our aim is to analyze the role of PD-L1 in the CIN to identify a possible biomarker of HSIL (CIN2+) progression and persistence. Methods: We performed a systematic review, considering papers published from January 2000 to May 2024, according to PRISMA guideline, in order to obtain a Comprehensive analysis of the literature regarding the role of PD-L1 expression in CIN. The most important medical databases, such as PubMed, Cochrane Database of narrative Reviews, EMBASE, and Web of Science, were consulted. Articles documenting the characteristics and clinical implications of PDL-1 expression in cervical dysplasia were given special consideration. Results: HR-HPV lesions show a positive expression of PD-L1, which level increase from LSIL (CIN1) to cervical cancer. The expression of PD-L1 in both mononuclear and cervical epithelial cells also exhibit an elevation with the progression of the lesions followed by a overexpression of pro-inflammatory cytokines IFN-gamma and IL-12 and downregulation of anti-inflammatory cytokine IL-10 indicating a role of PD-1/PD-L1 pathway in cervical immunity. Conclusions: PD-1 and PD-L1 may serve as diagnostic and prognostic biomarkers as well as valuable tools in immunotherapy for treating cancer and CIN.