Strategic approaches in oral squamous cell carcinoma diagnostics using liquid biopsy.

Liquid biopsy is a noninvasive diagnostic technique used for monitoring cancer utilizing specific genetic biomarkers present in bodily fluids, such as blood, saliva, or urine. These analyses employ multiple biomolecular sources including circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and exosomes (that contain DNA fragments) to detect genetic biomarkers that can predict, disclose, and/or monitor cancers. Levels of these biomarkers can inform on the presence of cancer, its genetic characteristics, and its potential treatment response and also provide predictive genetic predisposition information for specific cancers including oral squamous cell carcinomas (OSCC). Liquid biopsies can aid cancer management as they offer real-time dynamic information on the response to say chemotherapy or radiotherapy and recurrence following surgical excision. Unlike traditional tissue biopsies, which are invasive with a degree of morbidity and require specific tumor location sampling, liquid biopsies are noninvasive and can be repeated frequently. For oral squamous cell carcinoma, on which this review focuses, liquid biopsy of blood or saliva can be valuable in predicting susceptibility, providing early detection, and monitoring the disease's progression and response to therapy. This review gives a general narrative overview of the technology, its current medical usage, and advantages and disadvantages compared with current techniques and discusses a range of current potential biomarkers for disclosing OSCC and predicting its risk. Oral squamous cell carcinoma is all too often detected in the late stages. In future, liquid biopsy may provide an effective screening process such that cancers including OSCC will be detected in the early stages rather than later when prognosis is poor and morbidity and debilitation are greater. In this screening process, periodontists and hygienists have a critical role in that they are adept in examining mucosa, they see patients with shared risk factors for periodontitis and OSCC, namely smoking and poor oral hygiene, and they see patients frequently such that OSCC examinations should be a routine part of the recall visit. With this additional screening manpower, oral medicine and oral surgery colleagues will detect OSCC earlier and this coupled with new techniques such as liquid biopsy may greatly decrease global morbidity in OSCC.

Efficacy of type-1 collagen cones in extraction sockets following surgical removal of semi-impacted mandibular third molars: a randomized controlled trial.

OBJECTIVES: Third molar extractions may affect the periodontal health of the adjacent second molars as well as the patient's comfort. The objective of this study was to evaluate the efficacy of type-1 collagen cone (CC) on periodontal health and postoperative sequelae following extraction of third molars with secondary healing. METHOD AND MATERIALS: This was a randomized, controlled, split-mouth clinical trial. Sixty mandibular third molars (30 patients) were subdivided according to side. A collagen cone was randomly inserted into one side and the other side was the control. Pain was evaluated using a visual analog scale. Trismus and facial swelling were determined on postoperative days 2, 7, and 30. The alveolar osteitis (AO) incidence was recorded on days 2 and 7. The Plaque Index, Gingival Index, clinical attachment level, and pocket probing depth of the second molars were evaluated at postoperative months 1, 3, and 6. RESULTS: No significant differences were found between groups regarding postoperative pain, trismus, facial swelling, or the incidence of AO. However, AO developed in 10% of control side cases, while no sign of AO was observed on the experimental side. Plaque Index, Gingival Index, and clinical attachment level were comparable in both groups. Pocket probing depths for the distobuccal surface of the second molar was significantly higher on the control side at 6 months (P = .017). CONCLUSION: Insertion of a type-1 collagen cone into an extraction socket did not show a significant clinical improvement in extraction socket healing and postoperative sequelae after the third molar extraction.

Evaluation of adipokine levels in obese women with periodontitis: A cohort study.

PURPOSE: To evaluate the inflammation-related adipokine levels in the body fluids of obese female participants with and without periodontitis using healthy participants as a control group. METHODS: A cohort design study was carried out at Kocaeli University between December 2014 and June 2015. The study sample comprised 25 obese female participants with periodontitis (Group 1), 31 obese female participants without periodontitis (Group 2), and 15 lean female participants with healthy periodontium (Group 3), from whom body mass index, clinical periodontal parameters were measured, and serum, saliva, and gingival crevicular fluid (GCF) samples were collected. The three groups' periodontal parameters and adipokine levels were evaluated and compared, and the primary outcome was the difference in local and systemic adipokine levels between the study groups. RESULTS: In the participants' serum samples, tumor necrosis factor-α (TNF-α) and leptin levels were lower, whereas adiponectin levels were significantly higher in Group 3 than in the obese groups (P< 0.05). In the participants' saliva samples, interleukin-1ß, TNF-α, and resistin levels were lowest in Group 3, but adiponectin was lowest in Group 2 (P< 0.05). In the participants' GCF samples, interleukin-1ß, resistin, and adiponectin levels were higher in Group 1 (P< 0.05). This study showed that the amounts of the adipokines could differ in serum, saliva, and GCF samples from obese female participants with and without periodontitis and from lean female participants with healthy periodontium. CLINICAL SIGNIFICANCE: Periodontal diseases in different severities can affect overall health by altering the amounts of adipokines (IL-1ß, TNF-α, leptin, resistin, and adiponectin) in serum, saliva, and GCF of obese female patients. Clinicians should be aware that periodontal disease can alter inflammatory adipokine levels and may affect other treatment outcomes in obese female patients.

Genetic evidence for PLASMINOGEN as a shared genetic risk factor of coronary artery disease and periodontitis.

BACKGROUND: Genetic studies demonstrated the presence of risk alleles in the genes ANRIL and CAMTA1/VAMP3 that are shared between coronary artery disease (CAD) and periodontitis. We aimed to identify further shared genetic risk factors to better understand conjoint disease mechanisms. METHODS AND RESULTS: In-depth genotyping of 46 published CAD risk loci of genome-wide significance in the worldwide largest case-control sample of the severe early-onset phenotype aggressive periodontitis (AgP) with the Illumina Immunochip (600 German AgP cases, 1448 controls) and the Affymetrix 500K array set (283 German AgP cases and 972 controls) highlighted ANRIL as the major risk gene and revealed further associations with AgP for the gene PLASMINOGEN (PLG; rs4252120: P=5.9×10(-5); odds ratio, 1.27; 95% confidence interval, 1.3-1.4 [adjusted for smoking and sex]; 818 cases; 5309 controls). Subsequent combined analyses of several genome-wide data sets of CAD and AgP suggested TGFBRAP1 to be associated with AgP (rs2679895: P=0.0016; odds ratio, 1.27 [95% confidence interval, 1.1-1.5]; 703 cases; 2.143 controls) and CAD (P=0.0003; odds ratio, 0.84 [95% confidence interval, 0.8-0.9]; n=4117 cases; 5824 controls). The study further provides evidence that in addition to PLG, the currently known shared susceptibility loci of CAD and periodontitis, ANRIL and CAMTA1/VAMP3, are subjected to transforming growth factor-ß regulation. CONCLUSIONS: PLG is the third replicated shared genetic risk factor of atherosclerosis and periodontitis. All known shared risk genes of CAD and periodontitis are members of transforming growth factor-ß signaling.

Validation of reported genetic risk factors for periodontitis in a large-scale replication study.

AIM: Many studies investigated the role of genetic variants in periodontitis, but few were established as risk factors. We aimed to validate the associations of recent candidate genes in aggressive periodontitis (AgP). MATERIAL AND METHODS: We analysed 23 genes in 600 German AgP patients and 1441 controls on the Illumina custom genotyping array Immunochip. We tested a suggestive association in a Dutch and German/Austrian AgP case-control sample, and a German chronic periodontitis (CP) case-control sample using Sequenom iPlex assays. We additionally tested the common known risk variant rs1333048 of the gene ANRIL for its association in a Turkish and Italian population. RESULTS: None of the analysed genes gave statistical evidence for association. Upon covariate adjustment for smoking and gender, in the pooled German-Austrian AgP sample, IL10 SNP rs6667202 was associated with p = 0.016, OR = 0.77 (95% CI = 0.6-0.95), and in the Dutch AgP sample, adjacent IL10 SNP rs61815643 was associated with p = 0.0009, OR = 2.31 (95% CI = 1.4-3.8). At rs61815643, binding of the transcription factor PPARG was predicted. ANRIL rs1333048 was associated in the Turkish sample (pallelic = 0.026, OR = 1.67 [95% CI = 1.11-2.60]). CONCLUSIONS: Previous candidate genes carry no susceptibility factors for AgP. Association of IL-10 rs61815643 with AgP is suggested. ANRIL is associated with periodontitis across different populations.