Is Periodontal Disease a Red Flag for Breast Cancer Among Postmenopausal Female Smokers? An Update of the Last Decade

Periodontal disease is characterized by a chronic inflammation produced in response to a disease-associated, multispecies bacterial community in the subgingival region. In recent years, interest has focused on the potential role of periodontal disease in cancer pathogenesis. In this review, we presented a summary showing a strong association between breast cancer and poor oral health, presence of periodontitis-associated bacteria, tooth loss, and clinical signs of periodontitis. Proinflammatory pathways are activated either by mono- or polymicrobial infections, resulting in an increase in the expression of proinflammatory molecules such as interleukin (IL)-6, IL-8, IL-1β, and tumor necrosis factor (TNF)-α. In addition, it has been shown that several periodontitis-associated species induce the expression of genes related to cell proliferation, cell cycle, apoptosis, transport, and immune and inflammatory responses. Intriguingly, many of these pathways are linked to carcinogenesis. Among them, the activation of Toll-like receptors (TLRs) and antiapoptotic pathways (such as the phosphoinositide-3-kinase-protein kinase B/Akt [PI3K-PKB/Akt], Janus kinase/signal transducers and activators of transcription [JAK/STAT], and mitogen-activated protein kinase [MAPK] pathways), the reduction of proapoptotic protein expression, the increase in cell migration and invasion, and the enhancement in metastasis are addressed. Cigarette smoking is one of the major causes of carcinogenesis. The incidence of breast cancer is increasing worldwide, making it the most common type of cancer among women. The etiology of breast cancer is multifactorial and cigarette smoking is one of the risk factors that has recently been shown to be associated with breast cancer. The relationship between cigarette smoking and breast cancer is due to one of the important components of cigarette smoke, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), which is a representative carcinogen of N-nitrosamines that has gained focus in breast cancer carcinogenesis. The purpose of this review is to investigate the relationship between breast cancer and chronic periodontal disease changes that can occur at the oral level, including alterations of the oral microbiome, and pathological conditions among postmenopausal female smokers. Chronic periodontal disease and tooth loss were highly prevalent in postmenopausal breast cancer survivors. Based on this traditional review, the importance of dentists is clear in proposing to patients with breast cancer appropriate therapies and dedicated prevention sessions

Classification of Periodontal Diseases – Old is Gold or New is Bold? A Survey Study in Egypt

Background: A consensus was reached for a new classification system for periodontal and peri-implant diseases and conditions and was proposed by a group of world experts in 2017. Since then, there have been ongoing debates among periodontists regarding the application of the new classification. This study aims to shed light on the current understanding of the new classification among Egyptian periodontists. Methods: This cross-sectional survey study was performed using an anonymous manually distributed questionnaire in various universities in Egypt. The validated questionnaire included 15 questions – 13 multiple choice questions with a Likert scale and two open ended questions, in addition to demographic data of the participant. Qualitative data were presented as frequencies and percentages, and binary and ordinal logistic regression analyses were performed. Results: The clarity of the new classification was the only significant predictor for satisfaction. An increase in clarity scores was directly associated with an increase in satisfaction scores (odds ratio = 5.521, 95% CI = 2.198 – 8.844, P-value = 0.001). Only 24.2% of the participants actually applied the new classification. There was a high approval rate on the introduction of “health on reduced periodontium” and the classification of peri-implant conditions. However, there was a huge dissatisfaction with applying the staging and grading system as well as the omission of aggressive periodontitis. Conclusions: This survey has identified important gaps between theory and practice and bridging these gaps by revising the controversial points would help develop a clearer, simpler system for clinicians to improve patients’ oral health

Influence of Different Decontamination Approaches on Bone Substitute Adhesion to Peri-Implantitis Affected Implant Surfaces: An SEM Proof of Principle Study

Background: During healing, clot blended graft materials may retract away from implant surfaces creating microgaps that compromise re-osseointegration. The present study aimed to evaluate different surface decontamination materials’ effect on adhesion of the graft materials to peri-implantitis affected parts, a factor that can resist clot blended graft retraction improving re-osseointegration. Methods: Eighteen peri-implantitis affected implants diagnosed as hopeless and designated for removal contributed in this prospective, masked trial. Samples were randomly distributed into three groups, each of six implants. Group one (G1) was coated with hydroxyapatite of a micro particle size of 250 to 1000 µm after saline surface decontamination for two minutes. Group two (G2) peri-implantitis affected parts were treated with the graft material following two minutes of chlorhexidine gluconate 0.12% (CHX) surface treatment. Group three (G3) implants were coated with the graft material after citric acid (CA) (pH = 1) surface conditioning for two minutes. Implants in all groups were agitated in phosphate-buffered saline (PBS) by using an automatic tissue processor agitator for three minutes. Implants were prepared for surface scanning evaluation. Results: Scanning electron microscopy (SEM) observation of G1 saline treated control implants were devoid of bone particles adherent to peri-implantitis affected surfaces. The surface area covered by grafted particles in G2 was statistically higher than that of G1 (P<0.01). Group three (CA-treated) showed nearly complete coverage of peri-implantitis affected parts by the graft material covering 88.8% of examined surface areas which was statistically higher than that of G2 (P<0.05). Conclusion: Citric acid implant surface conditioning could improve implant re-osseointegration through enhancement of the graft adhesion to the implant surface. Smear layer barrier effect seemed to be the most important factor that compromised graft adhesion to preri-implantitis affected parts of the implant surfaces

Polymorphisms of IL-17A and IL-17F in Periodontal Disease: A Case-Control Study

Background: Increased interleukin-17 (IL-17) leads to the production of proinflammatory mediators and increases local inflammation. Interleukin-17 may also promote receptor activator of nuclear factor kappa-B ligand (RANKL) expression on gingival fibroblasts, T cells, and B cells, resulting in alveolar bone resorption. Interleukin-17A and IL-17F levels in saliva and gingival crevicular fluid (GCF), were found to be elevated in periodontitis patients. Thus, IL-17A and IL-17F polymorphisms were hypothesized to be associated with a risk of periodontitis. Methods: The present study was conducted on 60 subjects, including 20 stage II grade B periodontitis patients, 20 stage III grade C periodontitis patients, and 20 healthy controls. Blood samples were drawn from the subjects and analyzed for IL-17A G-197A and IL-17F 7488T/C genetic polymorphisms using the TaqMan assay. Results: There was a significant statistical difference between the distribution of the different genotypes and the different alleles in the three groups for IL-17A G-197A with the A allele presence indicating a risk of periodontitis. Conclusions: Interleukin-17A G-197A polymorphism is significantly associated with different clinical forms of periodontitis in the Egyptian population. The A allele could be considered a risk factor for periodontal diseases

Detection and Characterization of Prevotella Intermedia and Its In Vitro Susceptibility to Selected Antimicrobial Agents in Chronic Periodontitis and Acute Myocardial Infarction

Background: Periodontal disease has been reported to play a causative role in acute myocardial infarction (AMI), which may add to the various risk factors associated with coronary heart disease. The objective of the present study was to investigate the presence of Prevotella intermedia – an established periodontal pathogen – in subgingival plaque samples of chronic periodontitis and AMI patients in order to identify a possible association, and to evaluate the susceptibility of Prevotella intermedia to nine antimicrobial agents. Methods: After undergoing screening for eligibility, a total of 50 subjects were included in the present study. Twenty patients were diagnosed with AMI and generalized chronic periodontitis (Group I), 20 patients were diagnosed with only AMI (Group II), and 10 subjects were healthy controls (Group III). The isolated Prevotella intermedia strains were tested for susceptibility to bacitracin, chloramphenicol, penicillin G, polymyxin, gentamycin, neomycin, tetracycline, cefotaxime, and cefoxitin using an antibiotic zonescale to determine minimum inhibitory concentrations (MICs). Results: Periodontal pathogens were identified by phenotypic and enzymatic methods. The mean bacterial load of Prevotella intermedia species was higher in Group I compared to Group II and Group III. It was also found that pencillin G, gentamycin, neomycin, tetracycline, cefotaxime, and cefoxitin inhibited 90% of Prevotella intermedia, whereas bacitracin, chloramphenicol, and polymyxin inhibited 80% of Prevotella intermedia. Thus, only 10% of Prevotella intermedia were resistant to these antibiotics. Conclusion: The present study confirms that Prevotella intermedia is associated with chronic periodontitis and AMI

Effect of Periodontal Surgery on Tissue Plasminogen Activator and Plasminogen Activator Inhibitor Type-1 Gene Expression in Gingival Tissues of Periodontitis Patients: A Controlled Before-And-After Study

Background: Regulation of the plasminogen activation system (PAS) is a vital component in governing proteolytic events within the extracellular matrix (ECM). PAS is believed to play a substantial role in the destruction and healing of periodontal tissues. Thus, the current work aimed to study the histopathological effect of open flap debridement (OFD) on periodontitis, as well as its effect on tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type-1 (PAI-1) gene levels in gingival tissues. Methods: A total of 30 subjects were enrolled in the present study. They were divided into two groups: Group I (control group) included 10 periodontally healthy volunteers and group II (periodontitis group) comprised 20 patients suffering from stage III grade B periodontitis. Gingival tissue samples were collected from all periodontitis patients, before and after OFD, and from healthy controls. Hematoxylin and eosin (H&E) stained slides were subsequently examined and gene expression levels of t-PA and PAI-1 were assessed in the gingiva through quantitative reverse transcription polymerase chain reaction (RT-PCR). Results: Gingival tissue samples from periodontitis patients showed dilated blood vessels, diffuse hemorrhage, areas of edema, and disorganized collagen fibers together with large amounts of inflammatory cells in between.  Following OFD, smaller sized blood vessels, a restored collagen fiber distribution, and an obvious decrease in the inflammatory infiltrate were noted. Gene expression levels of t-PA and PAI-1 were significantly higher in the periodontitis patients compared to the healthy controls. Although their levels showed a significant decrease following OFD in the periodontitis group, they were still significantly higher than the control group. Conclusion: OFD procedures resulted in down regulation of t-PA and PAI-1 expression levels in the gingiva of periodontitis patients, which could signify an important role of these proteins on periodontal disease progression

Evaluation of Local and Systemic Levels of Vitamin D3 and Fibroblast Growth Factor 23 After Non-Surgical Periodontal Therapy

Background: Vitamin D is an important micronutrient possessing valuable and diverse biological effects that are related to periodontal disease pathogenesis. Vitamin D levels are regulated by fibroblast growth factor 23 (FGF23) which is strongly associated with inflammation. The aim of the present study was to explore the relation of vitamin D and FGF23 with periodontal disease through the assessment of their levels in gingival crevicular fluid (GCF) and serum in periodontitis patients before and after non-surgical periodontal therapy and to compare those levels with healthy controls in order to identify any possible correlation between them. Methods: Serum and GCF samples were collected at baseline and 3 months after therapy to evaluate levels of vitamin D3 and FGF23 using enzyme-linked immunosorbent assay (ELISA) in both study groups. Group I consisted of 15 controls who were systematically and periodontally healthy, while group II consisted of 15 subjects who were systematically healthy with stage II periodontitis. Results: A significant elevation in vitamin D3 levels in both GCF and serum were recorded 3 months after therapy with a 25.98% and 39.29% increase respectively. On the contrary, a significant reduction in mean values of FGF23 in both GCF and serum were found after treatment with a 49.75% and 39.28% decrease respectively. Conclusion: The results of the present investigation have shed light on a vital association of both FGF23 and vitamin D3 with periodontitis, where FGF23 is associated with periodontal inflammation and vitamin D3 is associated with periodontal health.

Is Entamoeba Gingivalis a Risk Factor for Periodontal Diseases? A Case-Control Study

Background: Entamoeba gingivalis was the first commensal parasite detected in the oral cavity of humans, and a high incidence has been reported in patients with poor oral hygiene. The current study aimed to investigate the association of Entamoeba gingivalis with gingivitis and periodontitis among Egyptian subjects. Methods: A total of 120 plaque samples were collected for this case-control study and were divided as follows: 40 plaque samples from gingivitis patients (group 1), 40 from stage II grade A and B periodontitis patients (group 2), and 40 samples from healthy volunteers (group 3). Diagnosis of parasitic stages relied on direct microscopic detection using permanent stains, trichrome stain, and hematoxylin and eosin (H&E) stain, in addition to ocular micrometry to confirm the diagnosis. Results: The occurrence of Entamoeba gingivalis within the gingivitis group was significantly higher (40%) than that observed in the control group (22.5%), whereas the occurrence within the periodontitis group was 15%. Samples from diseased subjects, regardless of immune status, were found to be moderately to severely affected with numerous parasitic nests, in contrast to a moderate near mild occurrence that was recorded in the healthy control group. Moreover, Entamoeba gingivalis occurrence was significantly higher (77.4%) in subjects with bad oral hygiene. Conclusion: The results of the present study suggest a potential role for the neglected oral parasitic Entamoeba gingivalis, especially the intensively multiplying forms, in the pathogenesis of periodontal diseases. This certainly needs further elucidation on a larger scale to explore the basis behind such multiplication, which may be related to genetic variation or may be pathophysiological in origin

Interleukin-33 and Osteoprotegerin Levels in Gingival Crevicular Fluid and Saliva in Chronic Periodontitis and Their Correlation to Diabetes Mellitus: A Cross-Sectional Study

Background: This study investigates the presence of interleukin (IL)-33 and osteoprotegerin (OPG) in saliva and gingival crevicular fluid (GCF) samples of patients with chronic periodontitis and whether or not they are correlated with diabetes mellitus. Methods: Sixty subjects were included in this study: 20 chronic periodontitis patients (CP), 20 diabetic chronic periodontitis patients (CPDM) and 20 systemically and periodontally healthy subjects. GCF and saliva samples were collected from all participants. Enzyme linked immunosorbent assay (ELISA) kits were used for assaying IL-33 and OPG levels. Analysis of variance was used to compare means of the CP and CP-DM groups with the control. Correlation analyses were performed to find the value of Spearman's correlation. A receiver operating characteristic (ROC) curve was constructed to determine the cut-off values of the markers to differentiate between the groups. Areas under the ROC curve (AUCs) were compared using z-statistic. Results: IL-33, in both GCF and saliva, was significantly higher in the CP and CP-DM groups compared to the control, and significantly higher in the CP-DM group compared to the CP group in saliva. On the other hand, the level of OPG in GCF and saliva was significantly lower in the CP and CP-DM groups compared to the control, but was of no significance when comparing the CP-DM and CP groups. Conclusion: IL-33 seems to play a role in the pathogenesis of periodontal disease, while OPG may have a protective function. Diabetes may affect and influence the expression of IL-33. Thus, they could be utilized as diagnostic biomarkers for chronic periodontitis either in saliva or GCF

Gingival Crevicular Fluid and Placental Tissue Levels of Interleukin-17 as a Possible Marker for Preterm Labor in Patients with Chronic Periodontitis

Background:  The present study was conducted to evaluate the levels of interleukin (IL)-17 in gingival crevicular fluid (GCF) and placental tissue samples of pregnant females as a possible marker in determining whether or not an association exists between chronic periodontitis and preterm labor. Methods:  This case-control study included a random sample of 40 female patients, aged 18 to 35 years, who were assigned to one of the following four groups (10 subjects each): group 1 included patients who underwent spontaneous preterm birth (PB) and were diagnosed with chronic periodontitis upon clinical examination (preterm/periodontitis); group 2 included patients who underwent spontaneous PB and who had a healthy periodontium upon clinical examination (preterm/healthy periodontium); group 3 included patients who underwent spontaneous normal term birth and were diagnosed with chronic periodontitis upon clinical examination (term/periodontitis); and group 4 included patients who underwent spontaneous normal term birth and who had a healthy periodontium upon clinical examination (term/healthy periodontium). GCF and placental tissue samples were obtained from each patient and IL-17 levels were measured using enzyme-linked immunosorbent assay (ELISA). Results: GCF levels of IL-17 were significantly higher (P=0.010) in patients with chronic periodontitis compared to those with a healthy periodontium. No significant differences were observed in IL-17 levels in placental tissue samples of all study groups. Conclusion: An association between chronic periodontitis and preterm labor could not be established based on IL-17 levels measured in the present study