Evaluation of periodontal status in patients with gynecological cancer

Periodontitis is a multifactorial, chronic inflammatory disease initiated by the dental plaque biofilm, sustained by the host response, and characterized by the destruction of the tooth-supporting tissues, including the gingiva, periodontal ligament, cementum, and alveolar bone. Cancer is a complex group of diseases characterized by the dysregulation of cellular proliferation, arising from the accumulation of genetic and epigenetic alterations. Malignant cells acquire capabilities such as evasion of apoptosis, induction of angiogenesis, invasion, and metastasis, thereby infiltrating surrounding tissues and disseminating to distant organs. Recent studies have demonstrated that cancer development and progression are not solely driven by genetic mutations but are also directly influenced by immune system responses, microbial interactions, and the inflammatory microenvironment. In recent years, studies investigating the contribution of inflammation to the pathogenesis of chronic diseases have introduced the concept of "low-grade inflammation" (LGI). LGI is characterized by the persistent, low-intensity production of systemic inflammatory mediators and is currently recognized as a risk factor for cardiovascular, cerebrovascular, and neurodegenerative diseases, as well as cancer. Indeed, as early as 1863, Virchow identified the presence of leukocytes within tumoral tissues, thereby first suggesting that inflammation may contribute to the development of cancer. The aim of this study was to investigate whether severity of periodontal diseases is associated with gynecological cancers including ovarian, endometrial, and cervical cancers. This study included a total of 76 participants, comprising 38 patients with gynecological cancer (GC) and 38 systemically healthy controls (S). Clinical periodontal parameters were obtained from all participants. Participants were categorized according to the severity of periodontal diseases as gingivitis and stage I and II periodontitis (S-GP1/2; GC-GP1/2) and stage III and IV periodontitis (S-P3/4; GC-P3/4). Serum and saliva samples were analyzed for interleukin-1 beta (IL-1β), interleukin-6 (IL-6), interleukin-10 (IL- 10), and the chemokines MCP-1 (Monocyte Chemoattractant Protein-1), RANTES (Regulated upon Activation, Normal T-cell Expressed and Secreted), and ENA-78 (Epithelial Neutrophil-Activating Peptide-78) using ELISA kits. Statistical analyses were performed using R software (version 4.1.2; The R Foundation for Statistical Computing, Vienna, Austria; https://www.r-project.org). Prior to analyses, the distributional properties of the data were assessed using the Shapiro–Wilk normality test and Q–Q plots, while homogeneity of variances across groups was examined with Levene's test. The majority of the variables investigated in the study did not exhibit a normal distribution. Therefore, to ensure analytical consistency, non-parametric methods, including the Kruskal–Wallis and Mann– Whitney U tests, were employed. A significance level of p<0.05 was considered statistically significant. The GC group had higher age and BMI values compared to the S group. GC group exhibited higher DMFT scores, as well as greater numbers of decayed and missing teeth, and higher bleeding on probing percentages (p<0.05), whereas the S group demonstrated higher salivary flow rate, number of filled teeth, and PESA values (p<0.05). In serum samples, IL-1β, IL-6, and ENA-78 levels were higher in the S group compared to the GC group (p<0.05). However, subgroup analysis revealed that xii saliva ENA-78 levels were significantly higher in the GC-P3/4 group compared to the GC-GP1/2 group (p<0.05). Despite the higher number of missing teeth and greater bleeding on probing observed in the JK group, the systemic inflammatory burden of periodontal disease in these patients has not been clearly established. To more precisely elucidate the findings and to better understand the mechanisms underlying the relationship between periodontal inflammation and gynecological