Downregulation of salivary miR-3928 as a potential biomarker in patients with oral squamous cell carcinoma and oral lichen planus.

OBJECTIVES: Recent studies highlighted the role of miR expressed in saliva as reliable diagnostic and prognostic tools in the long-term monitoring of cancer processes such as oral squamous carcinoma (OSCC). Based on a few previous studies, it seems the miR-3928 can be considered a master regulator in carcinogenesis, and it can be therapeutically exploited. This is the first study that compared oral potentially malignant disorder (OLP) and malignant (OSCC) lesions for miR-3928 expression. MATERIALS AND METHODS: In this cross-sectional study, saliva samples from 30 healthy control individuals, 30 patients with erosive/atrophic oral lichen planus, and 31 patients with OSCC were collected. The evaluation of miR-3928 expression by q-PCR and its correlation with clinicopathological indices were analyzed by Shapiro-Wilk, Kruskal-Wallis, Pearson's χ2 , and Mann-Whitney tests. The p-value less than .05 indicated statistically significant results. RESULTS: Based on nonparametric Kruskal-Wallis test results, there was a statistically significant difference between the ages of three study groups (p < .05). This test demonstrated a statistically significant difference between the average of miR-3928 expression in three study groups (p < .05). The result of the χ2  test showed a statistically significant difference in miR-3928 expression between patients with OLP (p = .01) and also patients with OSCC (p < .0001) in comparison to the control group. CONCLUSIONS: The salivary miR-3928 can play a tumor suppressive role in the pathobiology of OSCC, and it is significantly downregulated in patients. According to the potential tumor suppressive role of miR-3928 in the OSCC process, we can consider this microRNA as a biomarker for future early diagnosis, screening, and potential target therapy.

Association between Vitamin D Receptor Polymorphism and Susceptibility to Oral Lichen Planus and Oral Squamous Cell Carcinoma.

Introduction: Oral squamous cell carcinomas (OSCC) comprise 90-95% of oral cancers. Early diagnosis improved the survival rate of OSCC patients to 80-90%. Oral lichen planus (OLP) is a chorionic inflammatory disease with malignancy potential. The vitamin D receptor (VDR) plays a critical role in the pathogenesis of oral cancer. This study aimed to determine the association between VDR rs7975232 (Apa I) polymorphism and potential susceptibility to OLP and OSCC risks. Materials and Methods: In this prospective case-control study, a total of 120 blood samples were obtained from OSCC patients (n=29), OLP (n=50), and controls (n=40). VDR rs7975232 polymorphism was studied using the Polymerase Chain Reaction Restriction Fragment Length Polymorphism (PCR-RFLP) method. Statistical analysis was performed with SPSS Version 23 software. Data were expressed as means ± standard deviation (SD). Age, sex, allelic frequency, and genotyping were compared using the chi-square test. A p-value of less than 0.05 was regarded as statistically significant. The disease risk was estimated by Odds ratio (OR) with a 95% confidence interval. Results: A significant age difference was observed between the controls and the OSCC group (p=0.001). A significant difference was observed in Aa and aa genotypes compared with AA between OSCCs and controls. Moreover, dominant (p<0.001), additive (p<0.001), and allelic (p=0.001) models were different between groups. Conclusion: There was a positive association between rs7975232 VDR polymorphism and susceptibility to OSCC. More experimental evidence must reveal the possible association between rs7975232 and the risk of OLP in a larger cohort.

Clinical value and potential circulating of miR-99a as tumor suppressor biomarker in serum of oral squamous cell carcinoma and erosive atrophic lichen planus.

OBJECTIVES: Oral squamous cell carcinoma (OSCC) is the most common type of oral neoplasms that consist of more over 90% of oral cancers. It was demonstrated that erosive atrophic oral lichen planus (OLP) has potential of malignancy transformation into OSCC. The microRNAs are non-coding regulator sequences involved in cancer process. The miR-99a involve in growth, proliferation, migration, invasion, and metastasis of tumor cells. Therefore, we evaluated miR-99a expression in serum of OSCC and erosive atrophic OLP patients in comparison to healthy control individuals to more investigate about level of miR-99a expression in potential premalignant disorder (erosive atrophic OLP) in comparison to malignant transformation form (OSCC). Gene ontology (GO) and pathway analyses were performed to better understand the importance of miR-99a in OSCC. MATERIALS AND METHODS: In this cross-sectional study, total 90 serum samples from OSCC patients (n = 30), erosive atrophic OLP (n = 30) and healthy control individuals (n = 30) were collected, and then evaluated for miR-99a expression by qPCR. Pathway analysis and protein-protein interaction were done using STRING (v: 12.0), and (GO) terms and related genes were extracted from the GO online search tool. The statistical analysis was evaluated by Kruskal Wallis, Chi-Square, Kruskal Wallis, Spearman and Mann-Whitney tests. The p-value less than 0.05 was considered statistically significant. RESULTS: miR-99a expression down regulated in OSCC in comparison to erosive atrophic OLP and control groups (p < 0.05). The miR-99a up regulated in grade I more than grades II and III (p < 0.05). We showed upregulation of miR-99a in early stage more than advanced stage (p < 0.05). Expression of miR-99a reduced accordance to the increasing of tumor size and lymph involvement levels (p < 0.05). The 165 determined targets were classified into three domains. The most significant enrichment in biological processes, cellular components, and molecular functions was in the cellular nitrogen compound biosynthetic process, cytosolic ribosome, and protein binding, respectively. CONCLUSIONS: We highlighted tumor suppressive role of miR-99a in OSCC patients. It seems that miR-99a can be considered a valuable biomarker for the early diagnosis of erosive atrophic OLP before transformation. CLINICAL RELEVANCE: Our results may help to better understand the prognostic factor for oral squamous cell carcinoma to evaluate survival and subsequent tumor development. And it may also help to understand the pathogenesis of OSCC.

Unveiling the Potential of Serum MiR-483-5p: A Promising Diagnostic and Prognostic Biomarker in OLP and OSCC Patients by In silico Analysis of Differential Gene Expression.

BACKGROUND: Oral squamous cell carcinoma (OSCC) and oral lichen planus (OLP) are two separate conditions affecting the mouth and result in varying clinical outcomes and levels of malignancy. Achieving early diagnosis and effective therapy planning requires the identification of reliable diagnostic biomarkers for these disorders. MicroRNAs (miRNAs) have recently received attention as powerful biomarkers for various illnesses, including cancer. In particular, miR-483-5p is a promising diagnostic and prognostic biomarker in various cancers. Therefore, this study aimed to investigate the role of serum miR-483-5p in the diagnosis and prognosis of OLP and OSCC patients by in silico analysis of differential gene expression. METHODS: GSE23558 and GSE52130 data sets were selected, and differential gene expression analysis was performed using microarray data from GSE52130 and GSE23558. The analysis focused on comparing OLP and OSCC samples with normal samples. The genes intersected through the differential gene expression analysis were then extracted to determine the overlapping genes among the upregulated or downregulated DEGs. The downregulated genes among the DEGs were subsequently imported into the miRWalk database to search for potential target genes of miRNA 483-5p that lacked validation. To gain insight into the biological pathways associated with the DEGs, we conducted pathway analysis utilizing tools, such as Enrichr. Additionally, the cellular components associated with these DEGs were investigated by analyzing the String database. On the other hand, blood serum samples were collected from 35 OSCC patients, 34 OLP patients, and 34 healthy volunteers. The expression level of miR-483-5p was determined using quantitative reverse transcription polymerase chain reaction (RT-qPCR). The Kruskal-Wallis test was utilized to investigate the considerable correlation. Moreover, this study explored the prognostic value of miR-483-5p through its association with clinicopathological parameters in OSCC patients. RESULTS: The results showed that serum expression of miR-483-5p was considerably higher in OSCC patients compared to OLP patients and healthy controls (p 0.0001) and that this difference was statistically significant. Furthermore, elevated miR-483-5p expression was associated with tumor size, lymph node metastasis, and stage of tumor nodal metastasis in OSCC patients (p 0.001, p 0.038, and p 0.0001, respectively). In silico analysis found 71 upregulated genes at the intersection of upregulated DEGs and 44 downregulated genes at the intersection of downregulated DEGs, offering insight into the potential underlying mechanisms of miR-483-5p's engagement in OSCC and OLP. The majority of these DEGs were found to be involved in autophagy pathways, but DEGs involved in the histidine metabolism pathway showed significant results. Most of these DEGs were located in the extracellular region. After screening for downregulated genes that were invalidated, miRNA 483-5p had 7 target genes. CONCLUSION: This study demonstrates the potential of serum miR-483-5p as a promising diagnostic and prognostic biomarker in OSCC and OLP patients. Its upregulation in OSCC patients and its association with advanced tumor stage and potential metastasis suggest the involvement of miR-483-5p in critical signaling pathways involved in cell proliferation, apoptosis, and cell cycle regulation, making it a reliable indicator of disease progression. Nevertheless, additional experimental studies are essential to validate these findings and establish a foundation for the advancement of targeted therapies and personalized treatment approaches.

The oncogenic role of NOTCH1 as biomarker in oral squamous cell carcinoma and oral lichen planus.

Background: Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer with heterogeneous molecular pathogenesis. Oral lichen planus (OLP) is demonstrated potentially can transfer to OSCC malignant lesions. Unfortunately, there are no definitive prognostic and predictive biomarkers for the clinical management of OSCC patients. The present research is the first study that compared an oral premalignant lesion such as OLP to malignant lesions like OSCC for NOTCH1 expression levels to better understand its oncogenic or tumor suppressive role. Materials and Methods: In this cross-sectional study, mRNA expression of NOTCH1 was evaluated by quantitative polymerase chain reaction in 65 tissue-embedded Paraffin-Block samples, including 32 OSCC and 33 OLP. Furthermore, we collected demographic information and pathological data, including tumor stage and grade. The association between NOTCH1 and GAPDH gene expressions was determined by Chi-squared, Spearman, and Mann-Whitney tests. A P < 0.05 was considered statistically significant for all statistical analyses. Results: Comparison of OSCC and OLP groups showed a statistically significant difference between the quantitative expression of the NOTCH1 gene (P < 0.001). Qualitative gene expression was divided into low expression and high expression. Both study groups demonstrated a statistically significant gene expression difference (P < 0.001). There was a statistically significant difference between age and NOTCH1 expression in the OLP group (P = 0.036). There was no correlation between NOTCH1 expression and age, gender, tumor grade, and stage. Conclusion: Since the OSCC is a malignant lesion and the OLP showed the possible nature of malignancy transformation, we can consider the NOTCH1 as a biomarker for the assessment of the tumorigenesis process with a definition of a standard threshold for potentially malignant lesions and malignant OSCC tumors.

RT-qPCR Analysis of LAMP3 (CD208) Gene Expression in Oral Lichen Planus and Oral Squamous Cell Carcinoma.

Background: Many new studies have been conducted on cellular proteins to use them as prognostic markers or in target therapy through determining the increase or decrease in their expression in the lichen planus and OSCC. LAMP3 protein is one of these proteins which has been recently considered. Thus, considering the unknown etiology of lichen planus, significance of their early diagnosis and treatment and lack of a suitable and final treatment for this disease and oral cancers, and preventing the progression of lichen planus, which can turn into OSCC, we decided to investigate the level of expression of this gene and its effect on the progression, study the connection between these two conditions and the probable factors contributing to their etiopathogenesis. Methods: In this study, ninety-four paraffin blocks tissue samples of patients were obtained together with their demographic documents. LAMP3 expression was measured RT-qPCR method. Results: The results show that there is not any significant difference between age and sex population of our study. in squamous cell carcinoma the amount of expression of LAMP3 was higher than lichen planus and healthy margin. Average LAMP3 Gene expression in grade III was higher than group grade I & II in which considering significant level of 5%, it is statistically significant. Conclusions: According to the findings of this study, it can be concluded that the expression of the LAMP3 gene in SCC lesions is higher than in healthy tissue. Hence, LAMP3 gene expression can be used as a diagnostic biomarker.

Salivary Antiviral and Antibacterial Properties in the Encounter of SARS-CoV-2.

Due to the high mortality rate of COVID-19 and its high variability and mutability, it is essential to know the body's defense mechanisms against this virus. Saliva has numerous functions, such as digestion, protection, and antimicrobial effects. Salivary diagnostic tests for many oral and systemic diseases will be available soon because saliva is a pool of biological markers. The most important antiviral and antibacterial compounds identified in saliva include lysozyme, lactoferrin (LF), mucins, cathelicidin, salivary secretory immunoglobulin (SIgA), chromogranin A, cathelicidin, salivary agglutinin (SAG) (gp340, DMBT1), α, ß defensins, cystatin, histatins, secretory leukocyte protease inhibitor (SLPI), heat shock protein (HSP), adrenomedullin and microRNA (miRNAs). Antimicrobial peptides (AMPs) in saliva could be used in the future as models for designing effective oral microbial antibiotics. The antiviral properties of the peptides in saliva may be one of the future treatments for the COVID-19 virus. In this review, we investigate compounds with antiviral and antibacterial properties in saliva and the importance of these compounds in saliva in exposure to the COVID-19 virus. Due to the transmission route of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) into the oral cavity in the lower and upper respiratory tract, studies of salivary antiviral properties in these patients are very important. Some of the antiviral effects of saliva, especially mucin, α, ß-defensins, IgA, IgG, IgM, lysozyme, SAG, SLPI, and histatins, may play a greater role in neutralizing or eliminating COVID-19.

A Rare Case of Orthokeratinized Odontogenic Cyst (OOC) in the Posterior Mandible of a Young Adult 18-Year-Old Boy.

Orthokeratinized Odontogenic Cyst (OOC) is a rare odontogenic cyst, which is important because it has a low recurrence potential, but it has a percentage of the potential for malignant changes. OOC characteristics can be different from OKC (odontogenic keratocyst), which was once classified in its category. The microscopic view of OOC cyst is the reason for its easy identification from OKC, the orthokeratinized epithelial covering and the clear granular layer, and the hyperplasia of the basal layer, and the smooth surface of this cyst. OOC cyst treatment is conservative and can be usually carried out by enucleation. In terms of gender predominance, it is often reported in men. Furthermore, OOC is more common in the 3rd and 4th decades of life. Hereby, we report a rare case of OOC in the posterior mandible of a young adult 18-year-old boy and its treatment method. The clinical and diagnostic points of view and the treatment options were discussed in this article.

Associations between RORγt and T-bet Expressions, clinicopathological indices and survival rate in oral Squamous cell carcinoma patients.

BACKGROUND: Oral cancers are the sixth most common cancers around the world. According to the pivotal role of immune cells in the pathogenesis of oral squamous cell carcinoma (OSCC), as the frequent form of malignant epithelial neoplasm in the oral cavity, we investigated the association between the expression of RORγt and T-bet genes as two transcription factors, clinicopathologic indices, and survival rate. METHODS AND MATERIALS: Forty-two OSCC paraffin embded-blocks tissue samples and their surgical healthy margins (as a control group) were collected. Demographic information like age and gender, and medical history including tumor stage/grade, and following-up time were registered. The RORγt and T-bet expression were assessed by qPCR. The overall survival (OS) and disease free survival (DFS) were analyzed by SPSS V.23 software. RESULTS: The expression of RORγt and T-bet genes in OSCC patients were significantly higher than in surgical healthy margins (P < 0.001). Both expression demonstrated a significant difference between surgical healthy margins and tumor tissues related to gender and clinicopathological indices including stage and grade (P < 0.05). The expression of both genes in stage I patients was significant compared to stage IV (P < 0.05). The relation between expressions, OS, and DFS with clinical stage and histological grade of tumors was not statistically significant (P > 0.05). CONCLUSION: Overexpression of RORγt and T-bet in OSCC patients with higher grade and stage in compare to surgical healthy margin highlighted their critical role in OSCC pathogenesis including oral epithelial cell differentiation, tumorigenesis process, and malignant transformation. Moreover, both mentioned genes can apply as prognostic biomarkers in OSCC patients. We suggest surgical healthy margin be considered as valuable biological area.

The association between high-risk human papillomavirus and oral lichen planus.

OBJECTIVES: Oral lichen planus (OLP) is a cell-mediated inflammatory mucosal disorder and is classified as an oral potentially malignant disorder. Some research has shown that apoptosis in OLP cells is similar to a viral infection such as human papillomavirus (HPV). So, the aim of this case-control study was to investigate the association of high-risk HPV with OLP. MATERIAL AND METHODS: DNA was extracted from 25 formalin-fixed, paraffin-embedded (FFPE) OLP tissues and 25 FFPE normal oral tissues as case and control groups, respectively. The presence of high-risk HPV16 and HPV18 DNA was investigated by polymerase chain reaction (PCR). p-value<.05 was considered significant. RESULTS: Twelve samples (48%) of OLPs were positive for HPV16, compared with six samples (24%) of controls; although the difference was not significant, it was borderline (p = .07). Three samples (12%) of OLPs were positive for HPV18 compared with one sample (4%) of controls; the difference was not significant (p = .3). The total frequency of both high-risk HPV were 14 samples (56%) of OLPs and 7 samples (28%) of controls; there was a significant association between the high-risk HPV and OLP (p = .04). High-risk HPVs was more prevalent in erosive-atrophic (EA) form of OLP as compared to non-EA form, although the difference was not significant (p = .13). CONCLUSIONS: The results suggest a significant association between high-risk HPVs and OLP.

The XRCC1 Arg194Trp polymorphism was associated with the risk of head and neck squamous cell carcinoma development: Results from a systematic review and meta-analysis.

BACKGROUND: The X-ray repair cross complementing group 1 (XRCC1) is a DNA repair gene. Various studies have examined the association between XRCC1 Arg194Trp polymorphism and head and neck squamous cell carcinoma (HNSCC) susceptibility with contradictory results. So, this systematic review and meta-analysis aimed to assess whether variants of this polymorphism increase the HNSCC risk or not. RECENT FINDINGS: Thirty three studies consisting of 14282 subjects (6012 cases and 8270 controls) were included in this meta-analysis. Variants of XRCC1 Arg194Trp polymorphism were associated with increased HNSCC risk and the associations were significant based on heterozygous and dominant models (heterozygous model: OR = 1.182, 95%CI = 1.015-1.377, P = 0.032; homozygous model: OR = 1.274, 95%CI = 0.940-1.727, P = 0.119; dominant model: OR = 1.194, 95%CI = 1.027-1.388, P = 0.021; recessive model: OR = 1.181, 95%CI = 0.885-1.576, P = 0.119). There were significant associations between variants of this polymorphism and HNSCC risk based on Asian ethnicity under dominant model, hospital control source under different genetic models, PCR-RFLP genotyping method under dominant model and oral cavity tumor site under heterozygous and dominant models. OBJECTIVE: The X-ray repair cross complementing group 1 (XRCC1) is a DNA repair gene. Various studies have examined the association between XRCC1 Arg194Trp polymorphism and head and neck squamous cell carcinoma (HNSCC) susceptibility with contradictory results. So, this systematic review and meta-analysis aimed to assess whether variants of this polymorphism increase the HNSCC risk or not. METHODS: A systematic search of the literatures published till April 2022 was conducted using Google Scholar, Scopus, PubMed, Web of Science, Cochrane Library and Embase databases. The heterogeneity was assessed with the I-Square statistic. A random effects model or fixed effects model was used to analyze the data. Data were reported by odds ratio (OR) and 95% confidence interval (CI). The p value was considered significant if p < .05. RESULTS: Thirty three studies consisting of 14 282 subjects (6012 cases and 8270 controls) were included in this meta-analysis. Variants of XRCC1 Arg194Trp polymorphism were associated with increased HNSCC risk and the associations were significant based on heterozygous and dominant models (heterozygous model: OR = 1.182, 95%CI = 1.015-1.377, p = .032; homozygous model: OR = 1.274, 95%CI = 0.940-1.727, p = .119; dominant model: OR = 1.194, 95%CI = 1.027-1.388, p = .021; recessive model: OR = 1.181, 95%CI = 0.885-1.576, p = .119). There were significant associations between variants of this polymorphism and HNSCC risk based on Asian ethnicity under dominant model, hospital control source under different genetic models, PCR-RFLP genotyping method under dominant model and oral cavity tumor site under heterozygous and dominant models. CONCLUSION: Variants of XRCC1 Arg194Trp polymorphism were significantly associated with increased risk of HNSCC development based on heterozygous and dominant genetic models.

Analyzing the relationship between tissue color observed in VELscope examination and histopathological factors in OSCC patients.

OBJECTIVE: Early detection of OSCC is a crucial step towards improving OSCC prognosis. In recent years, novel diagnostic aids such as light-based detection systems have been introduced for early diagnosis. VELscope is one such light-based device which is used to examine tissue fluorescence. Based on different studies, VELscope has a sensitivity of 90% in the diagnosis of oral premalignant and malignant lesions. Tumor depth of invasion and invasive front have recently been proposed as influential factors in OSCC prognosis. Therefore, the aim of this study was to assess the relationship between tissue color seen through this device and tumor depth of invasion. METHODS & MATERIALS: 20 histopathologically approved OSCCs were included in this study. Conventional oral examination was carried out followed by an assessment of the lesion using VELscope. The H&E slides prepared following the final OSCC surgeries were then examined by an oral pathologist to assess tumor depth of invasion (interpreted as low-risk/high-risk), invasivefront (low-risk/high-risk) and perivascular and perineural invasions. Data was transferred to SPSS 16 software. The association between color changes and histopathological factors was analyzed using the fisher's exact and chi-square tests. RESULTS: The mean age of the patients was 51/5+/-16/74, 60% of which were men. Most lesions were exophytic and the most common color seen during VELscope examination was red. 55% and 50% of the OSCCs showed high-risk tumor depths and high-risk invasive fronts respectively. Perivascular and perineural invasion was seen in 55% and 35% of the samples respectively. Statistical analysis showed that 72/2% of the lesions with high tumor depths and 70% with high-risk invasive fronts were seen as red, although these associations were not significant (P>0/05). Tumor depth was significantly correlated with invasive front (P<0/05). CONCLUSION: There was no significant relationship between the type of color seen through VELscope and tumor depth of invasion, however most cases with high-risk depth of invasions were red.

The organoid as reliable cancer modeling in personalized medicine, does applicable in precision medicine of head and neck squamous cell carcinoma?

Head and neck squamous cell carcinomas (HNSCCs) are introduced as the sixth most common cancer in the world. Detection of predictive biomarkers improve early diagnosis and prognosis. Recent cancer researches provide a new avenue for organoids, known as "mini-organs" in a dish, such as patient-derived organoids (PDOs), for cancer modeling. HNSCC burden, heterogeneity, mutations, and organoid give opportunities for the evaluation of drug sensitivity/resistance response according to the unique genetic profile signature. The Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) nucleases, as an efficient genome engineering technology, can be used for genetic manipulation in three-dimensional (3D) organoids for cancer modeling by targeting oncogenes/tumor suppressor genes. Moreover, single-cell analysis of circulating tumor cells (CTCs) improved understanding of molecular angiogenesis, distance metastasis, and drug screening without the need for tissue biopsy. Organoids allow us to investigate the biopathogenesis of cancer, tumor cell behavior, and drug screening in a living biobank according to the specific genetic profile of patients.

Evaluation of CD4+ tumor-infiltrating lymphocyte association with some clinicopathological indices of oral squamous cell carcinoma.

Background: The delayed diagnosis of oral squamous cell carcinoma (OSCC) affects therapeutic and prognostic strategies, and provides regional recurrence or distant metastasis. The tumor-infiltrating lymphocytes (TILs) are known as a critical diagnostic biomarker in antitumor immune response. We evaluated the association between CD4+ T-lymphocyte marker, some clinicopathological indices, and the impact of TILs on the stage and grade of OSCC. Materials and Methods: In this cross-sectional study, 37 OSCC specimens including 16 early and 21 advanced stages (categorized base-on recent clinical oncology references) and their related healthy surgical margin (as internal control group) were collected. Obtained histochemical data were analyzed by SPSS V.23 software. The expression of CD4+ marker in tumor microenvironment (TME) was compared by nonparametric Mann-Whitney and Kruskal-Wallis as well as Fisher's exact tests. P < 0.05 was remarked statistically significant. Results: The low-grade patients represented more CD4+ TIL that was statistically significant (P = 0.011). However, there was no statistically significant difference in CD4+ TIL between various stages (P = 0.404), tumor size, and lymph node involvement (P > 0.05). Moreover, there was no significant relation between TIL infiltration, age, and tumor localization (P > 0.05), however CD4+ expression in women was more than men (P = 0.008). The CD4+ T-lymphocyte infiltration in TME was more significant than healthy surgical margin (P < 0.001). There was a statistically significant difference between healthy surgical margin and different grades and stages of OSCCs that lower grades demonstrated more CD4+ TIL infiltration (P < 0.001). Conclusion: The CD4+ T-lymphocytes may play important role in differentiation and maturity of epithelial cell, tumorigenesis, and progression of OSCC.

The role of altered microRNA expression in premalignant and malignant head and neck lesions with epithelial origin.

Background and Aims: The premalignant lesions of the oral cavity carry a risk of transformation to malignancy. Hence, early diagnosis followed by timely intervention remarkably affects the prognosis of patients. During tumorigenesis, particular microRNAs (miRNAs) show altered expressions and because of their post transcriptionally regulatory role could provide favorable diagnostic, therapeutic, or prognostic values in head and neck cancers. Methods: In this review, we have demonstrated diagnostic, prognostic, and potential therapeutic roles of some miRNAs associated with oral premalignant and malignant lesions based on previous validate studies. Results: It is previously documented that dysregulation of miRNAs contributes to cancer development and progression. MiRNAs could be tumor suppressors that normally suppress cell proliferation, differentiation, and apoptosis or play as oncogenes that improved tumorigenesis process. Altered expression of miRNAs has also been reported in premalignant oral epithelial lesions such as leukoplakia, oral submucous fibrosis, oral lichen planus and some malignant carcinoma like oral squamous cell, verrucous, spindle cell, Merkel cell carcinoma and basal cell. Conclusion: Some of miRNAs could be new therapeutic candidates in miRNA-based target gene therapy. Although more investigations are required to identify the most favorable miRNA candidate, altered expression of some miRNAs could be used as biomarkers in premalignant lesions and oral cancers with high sensitivity and specificity.

Association between Tissue Expression of Toll-Like Receptor and Some Clinicopathological Indices in Oral Squamous Cell Carcinoma.

Background: The oral squamous cell carcinoma (OSCC) composes about 90% of all head and neck cancers. The toll-like receptor (TLR)+ immune cells have potential of invasion and malignancy transformation. The aim of this study was assessment of possible associations between clinicopathological indices and TLR2 and TLR9 gene expression in OSCC. Methods: Forty-two OSCC samples with related healthy margins including 25 early and 17 advanced stages were gathered. The samples were classified histologically from grade I to II. The expression of TLR2 and TLR2 was evaluated by Real-time PCR. The patient's disease-free survival (DFS) and overall survival (OS) were analyzed using SPSS V.23 software. Results: The expression of TLR2 and TLR9 genes in tumor tissues (especially in grade I and II) were higher than healthy surgical margin tissue (p< 0.001). TLR9 expression in grade II was statistically significant than grade I in tumor tissue (p< 0.001). TLR9 expression in advanced stage was statistically significant in compare to early stage (p= 0.012). In advanced stage both overall survival (p= 0.029) and disease-free survival (p= 0.012) were statistically lower than early stage. The follow-up time to recurrence in advanced stage was statistically lower than early stage (p= 0.007). Conclusion: Overexpression of TLRs 2, 9 play role in the pathogenesis and tumor development of OSCC and can be applied as biomarker in prognostic approaches.

A Giant Case of Complex Odontoma in the Posterior Mandible of a Young Adult Female: A Spectacular Case Report.

Odontomas are the most common odontogenic benign tumors categorized as hamartomas. Odontoma is primarily made up of enamel and dentin, although it may also contain cementum and pulp tissue in various forms. It is known for having slow-growth and non-aggressive nature. It is made up of either dental tissues categorized as a complex or a compound odontoma based on radiological and histological characteristics. Complex odontomas are less prevalent among them, and they usually show as a tiny, silent radiopaque mass enclosed by a radiolucent border, seen on routine radiographic examinations. To avoid tooth eruption disturbances and additional clinical problems, odontomas should be managed and surgically removed once they have been detected. The present study describe a rare case of giant complex odontoma in the posterior mandible with an unusual dimension in a 16-year-old Iranian female patient referred to the Department of Oral and Maxillofacial, Mashhad Dental School, Mashhad, Iran, in May 2021. The case was effectively treated with surgical curettage and tumor enucleation, emphasizing the significance of early detection to minimize complications. Additionally, the clinical, radiological, and histopathological aspects and probable surgical treatments were discussed.

Head and neck cancer organoids as a promising tool for personalized cancer therapy: A literature review.

Background and Aim: Chemotherapy and targeted therapy are used in treating head and neck cancers (HNCs) either alone or in combination with surgery, especially in advanced tumors but these treatments have resulted in variable outcomes in different patients. This, along with the introduction of new therapies to improve the survival of patients makes it necessary to search for models that can predict the response to treatment among different patients. Organoids, as three-dimensional culture models, have been studied more widely in non-HNCs and to a lesser extent in HNCs as tools to predict treatment outcomes. We aimed to conduct a review to validate the use of organoids as a preclinical tool for the treatment of HNCs patients. Methods: A comprehensive literature search was separately performed by both authors in PubMed and google scholar databases, using the following keywords: "organoid," "head and neck cancer," "personalized medicine," "chemotherapy," and "targeted therapy." The articles published up to September 2021 were included in this review and selected according to a quality appraisal method. Results: Examination of HNC-derived organoids made in various studies showed that these organoids had the ability to recapitulate original tumor features, including histopathological properties, functional characteristics, and expression of molecular markers in almost all of the studies. Differential sensitivity to chemotherapy drugs similar to in vivo was observed in sensitivity testing. Epidermal growth factor receptor (EGFR) expression levels were different between organoids from different patients and EGFR expression level was found to correlate with the response to anti-EGFR targeted therapy. A similar result was reported for organoids derived from salivary adenoid cystic carcinoma. Conclusion: Since HNC-derived organoids seem to recapitulate characteristics of original tumors and to show differential responses to different chemotherapy and targeted therapy agents, these organoids might have the potential to be used as preclinical prediction tools for the treatment of HNC patients.

Tumor tissue Helicobacter pylori and human papillomavirus infection in head and neck squamous cell carcinoma patients and association with clinicopathological indices: A cross-sectional medical survey.

Background: The associations between Helicobacter pylori and human papillomavirus (HPV) with head and neck squamous cell carcinomas (HNSCCs) are approved before. However, the association between demographic, clinicopathological, and histologic characteristics of HNSCC patients and molecular detection of HPV and H. pylori has not been enough investigated. Materials and Methods: In this cross-sectional study, 62 patients with HNSCC from January 2016 to February 2020 were entered the study. For H. pylori detection 16S ribosomal RNA and glmM genes and HPV detection, MY09 and MY11 genes were used. P < 0.05 is considered as significant level. Results: There were 34 patients with advanced-stage cancer (54.8%). Grade I patients (61.3%) had the highest frequency. There were 20 (32.25%) and 7 (11.29%) patients with positive H. pylori infection among tumor tissue and healthy tissue margins, respectively. Positive HPV infections were in 8 (12.90%) and 3 (4.83%) patients, respectively, in tumor tissue and healthy tissue margins (P = 0.01). There was a significant difference between histological grade and infection to HPV among HNSCC patients (P = 0.01), and most of the positive HPV cases had well-, moderate-, and poorly-differentiated tumors, respectively. Our study showed a significant increase in HPV infection in the advanced-stage group compared to the early-stage group (P = 0.05). Conclusion: Our study findings concluded a significant relationship between HPV infection in HNSCC patients with age, stage, and grade. In summary, our findings based on polymerase chain reaction analysis concluded remarkably a potential role of HPV infection and to some extent H. pylori infection into the contribution of HNSCC malignancies.

Cathepsin-B and caveolin-1 gene expressions in oral lichen planus and oral squamous cell carcinoma.

BACKGROUND: Given the importance of the role of cellular changes in the prognosis and diagnosis of malignancies of the head and neck, we examined in this study the gene expressions of cathepsin-B (Cat-B) and caveolin-1 (Cav-1) which are in cell membranes structures involved in carcinogenesis, in oral squamous cell carcinoma (OSCC) and oral lichen planus (OLP) and compared them to controls. We also investigated their relationship to clinicopathological indices. METHODS AND RESULTS: In this case-control study, 29 paraffin blocks of OLP patients were compared to 29 paraffin blocks of OSCC samples as well as 28 paraffin blocks of normal oral tissue. Real-time quantitative PCR was performed to determine gene expressions and results were analyzed for their relationship to clinical data using chi-square, Kruskal-Wallis and Mann-Whitney tests. RESULTS: The mean age of OSCC and OLP patients were 59.24 ± 15.04 and 48.79 ± 14.17 years, respectively. The Cat-B and Cav-1 expressions were significantly higher in OSCC and OLP samples compared to control (p < 0.001). The highest expression was found in OSCC samples. The difference between OLP and control samples for Cat-B and Cav-1 expression was significant. There was no association between the gene expression and age, gender, duration of disease, Thongprasom score, smoking and cutaneous lichen planus. However, the expressions were related to the grade and stage of OSCC samples (P = 0.01, P = 0.02). CONCLUSION: The gene expressions of Cat-B and Cav-1 in OSCC were associated with the stage and grade of lesions. Therefore, they appear to be useful in predicting the biological behavior of OSCC and malignant transformation of OLP, although this process is multi factorial and more investigations are needed.