Curcumin is effective in managing oral inflammation: An in vitro study.

BACKGROUND: Oral inflammation is among the most prevalent oral pathologies with systemic health implications, necessitating safe and effective treatments. Given curcumin's documented anti-inflammatory and antioxidant properties, this study focuses on the potential of a curcumin-based oral gel in safely managing oral inflammatory conditions. METHODS: This in vitro study utilized four human cell lines: oral keratinocytes (HOKs), immortalized oral keratinocytes (OKF6), periodontal ligament fibroblasts (HPdLF), and dysplastic oral keratinocytes (DOKs). The cells were treated with Lipopolysaccharides (LPS) and curcumin-based oral gel to simulate inflammatory conditions. A panel of cellular assays were performed along with antimicrobial efficacy tests targeting Candida albicans, Streptococcus mutans, and Porphyromonas gingivalis. RESULTS: LPS significantly reduced proliferation and wound healing capacities of HOKs, OKF6, and HPdLF, but not DOKs. Treatment with curcumin-based oral gel mitigated inflammatory responses in HOKs and HPdLF by enhancing proliferation, colony formation, and wound healing, along with reducing apoptosis. However, its impact on OKF6 and DOKs was limited in some assays. Curcumin treatment did not affect the invasive capabilities of any cell line but did modulate cell adhesion in a cell line-specific manner. The curcumin-based oral gel showed significant antimicrobial efficacy against C. albicans and S. mutans, but was ineffective against P. gingivalis. CONCLUSION: This study demonstrates the potential of the curcumin-based oral gel as a safe and effective alternative to conventional antimicrobial treatments for managing cases of oral inflammation. This was achieved by modulating cellular responses under simulated inflammatory conditions. Future clinical-based studies are recommended to exploit curcumin's therapeutic benefits in oral healthcare.

Effect of Photobiomodulation on Salivary Cytokines in Head and Neck Cancer Patients with Oral Mucositis: A Systematic Review.

Background: Oral mucositis is a common and distressing side effect of head and neck oncology treatment. Photobiomodulation therapy can be utilized to prevent and treat oral mucositis. Its impact on salivary cytokines has yet to be thoroughly investigated. This is the first systematic review aiming to evaluate the effect of photobiomodulation on salivary cytokines in patients undergoing anticancer treatment. Methods: Numerous data resources, from the Web of Science, Embase, ScienceDirect, PubMed, Cochrane Library, and Scopus were sought. Articles published up until February 2024 were included if they met the following inclusion criteria: clinical trials reporting the effect on salivary cytokines in patients undergoing anticancer therapy. The methodological quality was assessed using several appraisal tools. Results: Four studies were deemed eligible for inclusion. All the studies were conducted in Brazil and used an InGaAlP diode laser with a wavelength of 660 nm. The included studies had a relatively low risk of bias. The head and neck cancer patients' salivary cytokines that were assessed by the studies, along with photobiomodulation therapy, included IL-12p70, TNF-α, IL-6, IL-8, IL-10, CXCL8, and IL-1ß. The results varied among the studies. Conclusions: Our results show that photobiomodulation demonstrated positive results for reducing the severity of OM in all the included studies. Among the examined salivary cytokines, IL-6 is the most relevant cytokine for oral mucositis development and severity. A variation in the cytokine levels between the studies was noted due to differences in the type of anticancer treatment and saliva sampling.

Epigenetics in the diagnosis and prognosis of head and neck cancer: A systematic review.

BACKGROUND: Aberrant epigenetic modifications significantly develop and progress human malignancies including head and neck squamous cell carcinoma (HNSCC). Taking into account issues of late diagnosis and poor prognosis associated with HNSCC, this systematic review is designed to provide an up-to-date insight of epigenetic changes in the management of HNSCC. METHODS: All studies that assessed the diagnostic and prognostic utilities of epigenetic changes (DNA methylation and histone modifications) among patients diagnosed with HNSCC or oral potentially malignant disorders (OPMDs) were considered for inclusion till June 2023. Pre-defined Medical Subject Headings terms were used to search Web of Science, Pubmed, Scopus and Embase Ovid databases. RESULTS: Twenty-five studies were deemed eligible for inclusion with a total number of 3790 samples (2123 HNSCCs, 334 OPMDs and 1333 as controls). DNA methylation was investigated in 18 studies while the role of histone modifications was assessed in seven studies. The most investigated biomarkers among the studies were H3, DAPK and TIMP3. The diagnostic accuracy of the epigenetic biomarkers in detecting HNSCC was assessed in eight studies where the following biomarkers showed the highest area under the curve values: TIPM3, DCC, DAPK, SEPT9, SHOX9, HOXA9 and TRH. None of the studies assessed the predictability of the epigenetic biomarkers in HNSCC and OPMDs. CONCLUSION: Although initial promising results were seen using the epigenetic biomarkers in the early detection of HNSCC, the limited number of patients and the absence of well-designed longitudinal studies limit the clinical applicability of the outcomes.

Student and clinical supervisor perceptions of community-based dental educational experiences: A scoping review.

PURPOSE: This scoping review was conducted to map the breadth of experiences in community-based dental education (CBDE), as reported by students and clinical supervisors. METHODS: This scoping review was conducted following the structured framework proposed by Arksey and O'Malley and adhering to PRISMA-SCR guidelines for scoping reviews. Applying specified eligibility criteria, a systematic search of four electronic databases (PubMed, Scopus, Embase, and Web of Science) was followed by data extraction and data synthesis of full-text articles. Research was conducted between June 2022 and September 2022. RESULTS: Sixteen articles were identified for the final full-text review. Utilizing a narrative thematic review, the following five domains emerged: preparation for autonomous practice, understanding of primary care dentistry, understanding of health disparities and patient needs, clinical confidence, clinical diversity, and skill development, and perspectives on quality of teaching and assessment. CONCLUSION: Community/outreach dental education effectively supplements traditional dental school-based education from the perspectives of students and community-based clinical supervisors.

Adjunctive aids for the detection of oral squamous cell carcinoma and oral potentially malignant disorders: A systematic review of systematic reviews.

This study presents the results of systematic reviews on adjunctive tools in screening and diagnosis of oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMD) and to determine if the current literature supports their use as either an adjunctive tool or replacement of gold standard techniques. Systemic reviews and meta-analysis that evaluated adjunctive tools including chemiluminescence, tissue autofluorescence, tissue fluorescence spectroscopy, vital staining and cytology techniques were systematically examined using AMSTAR II. Twenty-seven systematic reviews were included. Five studies had a low quality of evidence, and nine studies had a critically low quality of evidence. This review found limited evidence to recommend chemiluminescence, tissue autofluorescence tools and vital staining as diagnostic tools, but only serve as clinical adjuncts to conventional oral examination. Cytology techniques and narrow-band imaging may be utilised as a non-invasive diagnostic adjunctive tool for the detection of OSCC and the malignant transformation of OPMD. In conclusion, this paper provides evidence on several types of adjunctive tools and provides recommendations on their use in clinical practice. These tools are considered useful as clinical adjuncts but there is insufficient evidence for their use as a diagnostic tool to replace gold standard conventional oral examination and surgical biopsy.

Emerging histopathological parameters in the prognosis of oral squamous cell carcinomas.

Oral squamous cell carcinoma (OSCC) is the most common oral malignancy, representing 90% of all malignant neoplasms in the head and neck region. Patients with this aggressive tumor have an overall 5-year survival rate of approximately 50%, which drops to less than 30% when tumors are diagnosed at advanced clinical stages. Over decades, several studies provided high-level evidence of the impact of histopathological features on treatment guidelines and prognosis of OSCC. The 8th American Joint Committee on Cancer (AJCC) TNM staging system recognized the importance of depth of invasion to the T category and extranodal extension to the N category for OSCC. This review provides the current knowledge on emerging histopathological parameters identified as potential biomarkers for OSCC, such as depth of invasion, tumor thickness, the pattern of invasion, inflammatory profile, and tumor-stroma ratio, evaluating their clinical relevance on patient outcomes. Analysis, limitations, and potential biological mechanisms are highlighted and discussed. Assessing and reporting these markers are cost-effective and can be incorporated into daily practice.

Use of oral nutritional supplements in irradiated patients with head and neck cancer.

OBJECTIVES: Malnutrition is common among patients with head and neck cancer (HNC) and associated with poorer outcomes. Oral nutritional supplements (ONS) are often prescribed, with concerns raised about their cariogenicity. This study examined ONS use and caries experience in patients with HNC 12 months post-diagnosis. METHODS: Fifty-four patients with HNC referred for pre-radiotherapy dental assessment were recruited. Data collected included: age, gender, residential postcode, smoking, alcohol use, HNC characteristics, dental history, oral hygiene habits, dietary advice and ONS use. Data was collected at diagnosis, during radiotherapy and 6 weeks, three, six- and 12-months post-treatment completion. RESULTS: Fifty-one subjects completed the study. 76.5% of the participants used ONS for an average of 13.8 weeks. Caries developed in 22.9% of ONS users and 11.1% of non-users (p = 0.6585). The mean overall duration of ONS use was 18.7 weeks for the caries group and 8.5 weeks for the caries-free group (p = 0.1507). Lack of collaboration and disconnection was noted between dietary advice given by dieticians and dentists. CONCLUSIONS: ONS use is common among patients with HNC. Larger studies are needed to establish the reasons for caries development and impacts of ONS use on oral health. Importance of multidisciplinary management of malnutrition is highlighted.

Dental and oral health students' preparedness for the management of deaf patients: A cross-sectional survey.

Background/purpose: The communication barrier that deaf people face when seeking dental care can impact their experience and may potentially lead to exacerbated dental fear or anxiety. This study aimed to investigate the current attitudes and levels of knowledge and confidence of Australian oral and dental health students in treating a deaf patient. Materials and methods: A 33-item cross-sectional questionnaire was distributed to Australian dental, oral health therapy and dental hygiene students across 13 tertiary institutions. The online questionnaire was distributed to students via their respective course coordinators. Results: 271 viable survey responses were received. While 55.7% of participants reported previous exposure to deaf or hard-of-hearing people, 90.8% had never completed or attempted an Auslan class. These participants who answered 'Yes' to having taken a prior Auslan class were reported to have significantly higher mean knowledge scores and confidence self-efficacy ratings than those who had answered 'No' (p = 0.002). There was no statistically significant association between higher knowledge scores and higher confidence self-efficacy ratings. Most of these participants that answered 'Yes' to having taken a prior Auslan class implied or stated that the party responsible for changing their communication behaviour was the dentist rather than the patient, in contrast to the inconsistent responses from the 'No' group. Conclusion: Inadequate knowledge and cultural competency regarding the Deaf population was reported by Australian dental, oral health therapy and hygiene students. Incorporating more training pertinent to dental curricula is warranted to minimise oral health inequalities.

Awareness and practice of dentists in gulf cooperation council countries regarding medication-related osteonecrosis of the jaw - A web-based survey.

Background/purpose: Medication-related osteonecrosis of the jaw (MRONJ) is a serious complication among dental patients undergoing treatment with antiresorptive medications such as bisphosphonate and denosumab. The present survey investigated the awareness and practice of dentists in the Gulf Cooperation Council (GCC) countries regarding MRONJ. Materials and methods: This questionnaire-based study was conducted among dental practitioners in all six GCC countries. A questionnaire was designed and distributed among all potential participants via different social media platforms. SPSS version 22 was used for data analysis, and P-value <0.05 was considered statistically significant. Results: Overall, 1685 dentists from the six GCC countries participated in the present study. The surveyed dentists revealed relatively fair practices and awareness regarding MRONJ and its prevention, with the majority reported asking their patients about history of anti-osteoporotic medications (67.8%), recording name of the medication (73.1%) and duration of treatment (75.5%). However, the majority of the participants were unconfident about the duration of drug holiday prior to dental surgical interventions (70.6%) and the overall good level of knowledge/practice related to MRONJ was just 50.6%. The regression analysis revealed that previous exposure to MRONJ cases and attending a seminar, course, meeting, or conference about osteonecrosis of the jaw were independent predictors for positive awareness/good practice regarding MRONJ (P < 0.05). Conclusion: The results show inadequate awareness and practices of dentists practicing in GCC countries regarding MRONJ, with significant variations among the countries. Therefore, appropriate interventions such as periodic continuous education courses are required to improve dentists' knowledge and practices regarding MRONJ.

Clinical competency of dental health professionals and students in diagnosing oral mucosal lesions.

OBJECTIVE: Proper identification of oral potentially malignant disorders (OPMDs) provides an opportunity for oral cancer prevention. This study aims to assess the competency of dental health professionals in identifying OPMDs and, in turn, reducing the incidence of oral malignancy by early detection. METHODS: A 26-case online questionnaire of oral mucosal lesions was distributed to cohorts of 363 dental health professionals and dental students in Australia. The participants were asked to provide their provisional diagnosis for each case based on the available information. RESULTS: The overall accuracy in identifying oral mucosal lesions was 65.9%. There were no significant differences in the overall diagnostic accuracies between dental specialists, general dental practitioners and final-year dental students (p > 0.05). The lowest diagnostic accuracies were associated with normal mucosal variations and OPMDs. The predoctoral dental curriculum showed statistically significant values in terms of improving skills in diagnosing oral mucosal lesions. CONCLUSIONS: Lack of adequate knowledge in identifying OPMDs was evident among the participants, highlighting a non-promising figure in reducing the incidence of oral cancers in Australia. Comprehensive modifications of the current continuing professional development system are required to ensure adequate knowledge among dental health providers in Australia.

Aesthetic Gingival Melanin Pigmentation Treatment in Smokers and Non-Smokers: A Comparison Study Using Nd:YAG Laser and Ceramic Bur.

Aesthetic concerns are increasing rapidly; thus, several approaches have been suggested for treating gingival melanin pigmentation. Lasers have been reported as an effective new tool, and the Nd:YAG laser beam has an affinity for melanin and haemoglobin. However, ceramic gingival bur is simple and has less bleeding effect during operation than conventional techniques. This study aimed to compare the outcomes of gingival depigmentation using the Nd:YAG laser and ceramic bur in two different groups (smokers and non-smokers). A total of 40 patients presenting with gingival melanin pigmentation were enrolled in this split-mouth study. The sample was divided into two groups: smokers and non-smokers. Treatment was performed using the Nd:YAG laser (3 W, 60 mJ/pulse, and 50 Hz) and ceramic bur with a one-week interval between the two methods. Clinical indices were recorded, including intraoperative bleeding, wound healing, post-operative pain, and the recurrence of pigmentation, and follow-up periods were determined in the 3rd, 6th, and 9th months postoperatively. Both treatments promoted a similar pain experience and recurrence rate of pigmentation (p > 0.489, p = 1.000, respectively). Bleeding during surgery and complete healing recovery after one week were statistically significantly higher when using ceramic bur (p = 0.00, p = 0.041, respectively). Concerning the effect of smoking on the treatment, a higher recurrence rate was observed in SG than N-SG in laser sites (50%, and 95%, respectively) and bur sites (60%, and 85%, respectively), but statistically no significant difference was observed (p > 0.080). In conclusion, both procedures are adequate for aesthetic gingival depigmentation treatment. The Nd:YAG laser showed greater effectiveness in controlling bleeding, while ceramic bur showed a faster clinical recovery. Furthermore, smokers were more likely to have low depigmentation treatment stability.

CO2 laser vaporisation in treating oral lichen planus: A split-mouth randomised clinical trial.

OBJECTIVES: This study aimed to compare the effectiveness of carbon dioxide (CO2 ) laser vaporisation versus intralesional injection of triamcinolone acetonide (TA) in the management of oral lichen planus (OLP). METHODS: A randomised clinical trial with a split-mouth design was conducted on 16 patients with bilateral symptomatic OLP lesions. One side was treated with CO2 laser vaporisation, and the counterpart was treated with TA intralesional injection. The reticular-erythematous-ulcerative (REU) score, Thongprasom sign scoring (TSS), visual analogue scale (VAS) and lesion area were used to evaluate the lesions at weeks 0, 4 and 9. All participants were followed up for 9 months. RESULTS: Reduction in the REU, TSS scores and lesion area from baseline to the end of treatment was significantly greater in the CO2 group than in the TA group (p values were 0.001, 0.002 and 0.048 respectively). However, the reduction in VAS score did not differ between the two groups (p = 0.54). The recurrence rate was significantly higher in the TA group than in the CO2 group (75% vs. 31.1%; p = 0.016). CONCLUSIONS: CO2 laser vaporisation was more effective than TA intralesional injection in managing OLP and decreased recurrence rates.

Evaluation of Antibacterial Efficacy of High-Intensity Focused Ultrasound Versus Photodynamic Therapy Against Enterococcus faecalis-Infected Root Canals.

OBJECTIVE: The high incidence of endodontic failure is associated with the remnants of Enterococcus faecalis present within the intricate anatomies of the root canal system (RCS), often inaccessible by the current endodontic practices. This study was aimed at evaluating the effect of high-intensity focused ultrasound (HIFU) and photodynamic therapy (PDT) on E. faecalis biofilms in artificially infected root canals for the potential application in current endodontic practices. METHODS: Forty-five single-rooted extracted teeth were instrumented using hand files, sterilized in an autoclave, infected with E. faecalis and incubated for 4 wk. The specimens were treated and identified as follows: Control, 4% sodium hypochlorite (NaOCl); riboflavin (1 mg/mL); light only; HIFU (250 kHz, 20 W, 60s); PDT; riboflavin/HIFU; light/HIFU; and riboflavin/HIFU/light. Bactericidal efficacy was determined by colony-forming units (CFU), (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) (MTT) assay, scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). RESULTS: Enterococcus faecalis biofilm exhibited significantly lower metabolic activity when treated with HIFU (250 kHz, 20 W, 60 s) compared with the control (4% NaOCl) and PDT groups. A similar phenomenon was observed with the CFU assay. HIFU remained the most effective treatment modality, with consistent results in CLSM and SEM. CONCLUSION: This study highlighted the potential application of HIFU as an adjunct drug-free, non-destructive root canal disinfection method for endodontic treatment, suggesting an alternative to the current gold standard of 4% NaOCl and PDT.

The therapeutic effect and mechanism of parthenolide in skeletal disease, cancers, and cytokine storm.

Parthenolide (PTL or PAR) was first isolated from Magnolia grandiflora and identified as a small molecule cancer inhibitor. PTL has the chemical structure of C15H20O3 with characteristics of sesquiterpene lactones and exhibits the biological property of inhibiting DNA biosynthesis of cancer cells. In this review, we summarise the recent research progress of medicinal PTL, including the therapeutic effects on skeletal diseases, cancers, and inflammation-induced cytokine storm. Mechanistic investigations reveal that PTL predominantly inhibits NF-κB activation and other signalling pathways, such as reactive oxygen species. As an inhibitor of NF-κB, PTL appears to inhibit several cytokines, including RANKL, TNF-α, IL-1ß, together with LPS induced activation of NF-κB and NF-κB -mediated specific gene expression such as IL-1ß, TNF-α, COX-2, iNOS, IL-8, MCP-1, RANTES, ICAM-1, VCAM-1. It is also proposed that PTL could inhibit cytokine storms or hypercytokinemia triggered by COVID-19 via blocking the activation of NF-κB signalling. Understanding the pharmacologic properties of PTL will assist us in developing its therapeutic application for medical conditions, including arthritis, osteolysis, periodontal disease, cancers, and COVID-19-related disease.

Macrophages CD163+ and Factor XIIIa+ Provide a First-Line Defence against Proliferative Verrucous Leukoplakia Antigens.

This study aimed to evaluate the density of the dendritic cells (DCs) and macrophages in oral leukoplakia (OL) and proliferative verrucous leukoplakia (PVL) by immunohistochemical analysis. We analysed paraffined tissue samples of PVL (n = 27), OL (n = 20), and inflammatory fibrous hyperplasia (n = 20) as the control group using the immunomarkers for DCs (CD1a, CD207, CD83, CD208 and CD123) and macrophages (CD68, CD163, FXIIIa and CD209). A quantitative analysis of positive cells in the epithelial and subepithelial areas was determined. Our results showed a reduction in CD208+ cells in the subepithelial area of the OL and PVL compared to the control. Additionally, we found a higher density of FXIIIa+ and CD163+ cells in the subepithelial area in PVL compared to the OL and control. Four-way MANOVA revealed a relationship between increased CD123+ cell density in the subepithelial area of "high-risk" samples regardless of disease. Macrophages provide the first line of defence against PVL antigens, suggesting a distinct pattern of innate immune system activation in PVL compared to OL, which may contribute to the complexity and the high rate of malignant transformation in the PVL.

Automated immunohistochemical quantification of hypoxia biomarkers shows correlation with dysplastic epithelial changes.

BACKGROUND: Dysregulation of the hypoxia-aerobic system has been postulated in various malignancies. Nonetheless, the contribution of hypoxia to oral carcinogenesis is yet to be elucidated. Understanding this mechanism is important for improving diagnostic tools and targeted therapies. This study aimed to assess the dysregulation of hypoxia-related factors during different stages of oral squamous cell carcinoma (OSCC) development. METHODS: Ninety-two patients diagnosed clinically with oral leukoplakia or OSCC were included and classified according to their histopathological diagnoses. A panel of seven hypoxia-related antibodies were used for immunohistochemical staining of each case. Automated quantification of immunostaining was used for objective reporting. Microvessel density was also assessed. RESULTS: Significant associations were reported for non-dysplastic epithelial changes and malignancy for Glut1, HIF-1α, vascular endothelial growth factor, and signal transducer and activator of transcription 3(p < 0.005). Similarly, microvessel density significantly increased with the severity of epithelial disorders. A multiple regression model including the H-score of HIF-1α and microvessel density could statistically significantly predict the grade of epithelial disorder (p < 0.005). The associated diagnostic accuracy of this approach was 88%. CONCLUSIONS: Hypoxia-associated events are observed during early epithelial dysplastic changes and have a potential role in oral carcinogenesis. The level of hypoxia may assist in stratifying the severity of epithelial changes among patients with oral leukoplakia.

Salivary-Based Cell-Free Mitochondrial DNA Level Is an Independent Prognostic Biomarker for Patients with Head and Neck Squamous Cell Carcinoma.

Changes in the copy numbers of cell-free nuclear DNA (cf-nDNA) and cell-free mitochondrial DNA (cf-mtDNA) have shown promising diagnostic utilities among patients with head and neck squamous cell carcinoma (HNSCC). Considering the absence of objective prognostic tools for HNSCC surveillance, this study aimed to assess the utility of saliva-based cf-nDNA and cf-mtDNA in predicting the overall survival of patients with HNSCC. The study included ninety-four patients with a confirmed HNSCC diagnosis with a mean follow-up time of 32.04 months (±19.1). A saliva-based liquid biopsy was collected from each patient. A multiplex quantitative PCR was used to determine the absolute number of cf-nDNA and cf-mtDNA. The Kaplan-Meier estimator and Cox proportional hazards regression models were used to assess overall survival. The absolute copy numbers of cf-nDNA and cf-mtDNA were statistically significantly higher among the deceased patients than among the censored ones (p < 0.05). Individuals with elevated levels of cf-nDNA or cf-mtDNA were associated with a significantly poorer overall survival (p ≤ 0.05). A univariate analysis showed that only the absolute copy number of cf-mtDNA was the sole predictor of overall survival. However, the multivariate analysis showed that all the absolute copy numbers of cf-nDNA, the absolute copy numbers of cf-mtDNA, and the stage of HNSCC were predictors of overall survival. Our study confirms that saliva is a reliable and non-invasive source of data that can be used to predict the overall survival of patients with HNSCC, where cf-mtDNA levels act as the sole predictor.

Clinicopathological and prognostic value of chemokine receptor CCR7 expression in head and neck squamous cell carcinoma: a systematic review and meta-analysis.

OBJECTIVES: This study aimed to identify the clinicopathological characteristics and prognostic value of CC chemokine receptor 7 (CCR7) expression in patients with head and neck squamous cell carcinoma (HNSSC). METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed in this meta-analysis. Up to the 2nd of July 2022 a search was conducted using five databases: PubMed, Embase, Scopus, ProQuest, and Web of Science. The methodological standards for the epidemiological research scale were used to assess the quality of the included articles, and Stata software was used to synthesize the meta-analysis. RESULTS: We considered 13 of the 615 studies which included 1005 HNSCC patients. High expression of CCR7 increased the pooled odds ratio (OR) of advanced stage, tumor size, metastasis and recurrence by 2.82 [95% confidence interval (CI) 1.84 to 4.33], 2.48 (95% CI 1.68, to 3.67), 3.57, 95% CI 2.25 to 5.05) and 3.93 (95% CI 2.03 to 7.64), respectively. High CCR7 reduced overall patient survival [hazard ratio 2.62 (95% CI 1.59 to 4.32)]. CONCLUSION: This study showed that high expression of CCR7 in HNSCC tumors was significantly associated with worse clinicopathological and survival outcomes, suggesting that CCR7 and its pathway could be potential therapeutic strategies for HNSCC.

Changes in quality of life over time in patients diagnosed with oral leukoplakia: A prospective longitudinal study.

BACKGROUND: Oral leukoplakia (OL) is one of the most prevalent oral potentially malignant disorders (OPMD). Although there is emerging evidence that quality of life (QoL) is impaired in subjects with OL; studies to date are based on single and heterogenous point-in-time assessments. The aim of this study was to ascertain if QoL scores change over time in individuals diagnosed with OL. METHODS: Forty-one individuals with OL were administered the Short Generic Health Questionnaire (SF-12) and the discipline-specific Oral Potentially Malignant Disorder Questionnaire (OPMDQ) at four points in time: at the time of clinical diagnosis, at the post-biopsy review (confirmed diagnosis), and at 3- and 6-month follow-up appointments. Responses were compared between the four time points. RESULTS: No significant differences were observed in the SF-12 questionnaire scores over time. However, a general improvement in the participants' life quality was evident over the 6-month period under investigation in the domains of psychological and social well-being (p = 0.0027) and effect of treatment on daily life (p = 0.0317) as well as in the total score (p = 0.0005) of the OPMDQ. Age, gender, medical status, tobacco/alcohol use, lesion site, size, the presence of dysplasia and treatment did not impact QoL scores over time. CONCLUSIONS: QoL scores of OL subjects may improve with time. Our results suggest that studies examining QoL in individuals with OL should be controlled for time at which the participants are surveyed.

A Novel Preclinical In Vitro 3D Model of Oral Carcinogenesis for Biomarker Discovery and Drug Testing.

This study aimed to develop an in vitro three-dimensional (3D) cell culture model of oral carcinogenesis for the rapid, scalable testing of chemotherapeutic agents. Spheroids of normal (HOK) and dysplastic (DOK) human oral keratinocytes were cultured and treated with 4-nitroquinoline-1-oxide (4NQO). A 3D invasion assay using Matrigel was performed to validate the model. RNA was extracted and subjected to transcriptomic analysis to validate the model and assess carcinogen-induced changes. The VEGF inhibitors pazopanib and lenvatinib were tested in the model and were validated by a 3D invasion assay, which demonstrated that changes induced by the carcinogen in spheroids were consistent with a malignant phenotype. Further validation was obtained by bioinformatic analyses, which showed the enrichment of pathways associated with hallmarks of cancer and VEGF signalling. Overexpression of common genes associated with tobacco-induced oral squamous cell carcinoma (OSCC), such as MMP1, MMP3, MMP9, YAP1, CYP1A1, and CYP1B1, was also observed. Pazopanib and lenvatinib inhibited the invasion of transformed spheroids. In summary, we successfully established a 3D spheroid model of oral carcinogenesis for biomarker discovery and drug testing. This model is a validated preclinical model for OSCC development and would be suitable for testing a range of chemotherapeutic agents.