Comparison of different micrRNA levels in patients diagnosed with cervical ntraepithelial neoplasia (CIN) with and without high-risk HPV persistence

Cervical cancer is the fourth most common gynecological cancer in women. Despite advancements in vaccination and screening programs for early detection and prevention in recent years, it remains a significant cause of mortality. The most common etiological factor for cervical cancer is HPV (Human Papillomavirus). Persistent infection with high-risk HPV types is the primary risk factor for the development of cervical cancer. miRNAs (microRNAs) are short non-coding RNA molecules that regulate gene expression post-transcriptionally. HPV infection exerts its effects on host cells by inducing cellular transformation through modulation of the activity of miRNAs that regulate gene expression. Additionally, miRNAs play a role in regulating cellular processes such as proliferation, apoptosis, metastasis, and cellular immune response, thereby influencing cancer development. Understanding the relationship between HPV infection, cervical cancer, and miRNAs will facilitate the development of diagnostic, prognostic, and therapeutic strategies. Our aim is to identify which patients with a history of persistent HPV infection will progress, and to establish a prognostic marker in this regard. The study included cases diagnosed with high-grade cervical intraepithelial neoplasia (HSIL) at the Department of Obstetrics and Gynecology, Pamukkale University Hospital, who had previously undergone treatment and were under follow-up. These cases were defined as the study group, and they were invited to participate in the study in chronological order during their routine follow-up visits. Among the 100 cases who agreed to participate in the study, they were evaluated in two separate groups: those who were HPV positive (the group with HPV persistence) and those whose HPV status turned negative (the group without HPV persistence). During routine gynecological examinations, cervical smear samples were obtained from consenting individuals, and miRNA levels (miR-125b-5p, miR-125a, miR-21-5p, miR-18a, mi-9-5p, miR-34c-3p, miR-182, miR-148b, miR-34a, miR-29a-5p, miR-375, miR-143-5p, miR-372) were analyzed from these specimens. The study aimed to investigate whether there were differences in miRNA levels between HSIL development and persistent HPV infection by analyzing miRNAs from cervical smear samples. Routine follow-up and necessary treatments of the cases were continued as usual, and no experimental invasive procedures or drug applications were performed on the patients as part of the study. In the study, there were 62 individuals in the group where HPV became negative and 38 individuals in the group where HPV persisted. In the evaluation of miRNA, an increase in expression was observed in miR-125a (p<0.001), miR-34c-3p (p=0.004), and miR-375 (p=0.023) in the group with persistent HPV compared to the group without persistence, while a decrease in expression was observed in miR-143-5p (p=0.027). There was no statistically significant difference in the expression values of other miRNAs. Correlation analysis between miRNA values and demographic data did not reveal a significant relationship. The role of miRNAs in cervical cancer is increasingly understood. A miRNA panel generated from significant miRNA values identified in patients with persistent HPV infection could be used alongside existing screening tests as a prognostic factor in patients with HPV persistence and may even guide treatment decisions. In light of the findings, miRNAs appear to have potential applications in processes such as early diagnosis, treatment, and prognosis prediction. However, more research and standardization are needed for miRNA-based diagnostic studies. Additionally, larger-scale studies involving more patients are required to differentiate miRNA levels in patients with HPV infection, dysplasia, and carcinoma development.