Case Report: Recalcitrant oral lichen planus involving bilaterally buccal mucosae treated with a combination of photodynamic and photobiomodulation therapies.

Background: Managing recalcitrant oral lichen planus (OLP) can be challenging. Laser therapy has been suggested as an alternative to corticosteroids for treatment. Photodynamic therapy (PDT) is a non-invasive technique that enables the removal of lesions without surgery. Photobiomodulation therapy (PBMT) can promote healing and recovery of the lesions. Case presentation: The objective was to treat unresponsive bilateral OLP of the whole buccal mucosae with a combination of PDT and PBMT. Results: A 43-year-old Thai male presented with the severe painful reticular type of OLP of bilateral buccal mucosae involving upper and lower vestibular areas. The lesions were not remitted with either prednisolone systemic steroids or fluocinolone topical corticosteroids. After undergoing ten sessions of PDT with 10% 5-Aminolevulinic acid (5-ALA) in the form of thermoplastic gel and a 635 nm diode laser at 100 to 400 mW with an energy density of 20 to 30 J/cm 2 in continuous wave mode, combined with five interim-sessions of PBMT using a 635 nm diode laser at 200 to 300 mW with an energy density of 6 to 10 J/cm 2 in continuous wave, the patient reported relief of burning sensation beside remission of lesions without any complications. Conclusion: The wide-spreading recalcitrant OLP with burning sensation can be managed by combining PDT and PBMT.

Perceptions of Online Learning Implementation in Dental Education during the COVID-19 Pandemic: A Cross-Sectional Study of Dental School Faculty Members in Southeast Asia.

OBJECTIVE: To assess the perceptions of faculty members from dental schools in Southeast Asian countries regarding the implementation of online learning during the COVID-19 pandemic. METHODS: A previously implemented questionnaire comprising 43 questions was utilized in this study. Lecturers from four universities in Southeast Asia were invited to participate in the study. STATISTICAL ANALYSIS: The data were analyzed using SPSS version 25.0 through several types of comparative and correlation analyses. RESULTS: There were 183 lecturers who participated in the study. The overall responses suggest that the perceived effectiveness of online learning in dentistry was centered on a neutral value. The participants faced challenges when implementing online learning during the COVID-19 pandemic, with the lack of interaction being the most challenging factor. They agreed that online learning had many advantages, specifically in time flexibility and communication. The participants had stronger perceptions relating the advantages and opportunities of online teaching, and recognized that the effectiveness of offline teaching alone was limited. CONCLUSION: The perceptions of Southeast Asian dental school faculty members were inclined toward a positive outlook on blended learning for implementation in dentistry, as a means of providing opportunities to use online learning beyond COVID-19 in the future.

Oral hyperpigmentation as an adverse effect of highly active antiretroviral therapy in HIV patients: A systematic review and pooled prevalence.

Background: Human Immunodeficiency Virus (HIV) infects patients via CD4+ cells which are later be destroyed subsequently causing the deteriotation of immune system. HIV generally manifests in the oral cavity as the first indicating sign and a marker of disease progression. HAART medications are used to reduce the incidence of oral manifestations, however it can also generate adverse effects in the oral cavity including oral hyperpigmentation. This review aimed to estimate the prevalence of oral hyperpigmentation which affect individual quality of life as a side effect of HAART. Material and Methods: This systematic review applied Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) 2020. Literature search was performed in ScienceDirect, PubMed, and Scopus by combining terms such as highly active antiretroviral therapy, oral manifestation, epidemiology or prevalence published between January 1998 to March 2022. Results: Of 108 articles, eleven articles were included for systematic review and meta-analysis. The pooled prevalence of oral hyperpigmentation in HAART patients was 25% (95% CI: 11%, 38%; I2: 99%). Subgroup analysis based on geographical location showed varied result may be due to the type and duration of HAART used in study population. The most widely used type of ARV was from the NRTI group (n=7) and the study with the shortest duration showed the lowest oral hyperpigmentation prevalence (n=7). Conclusions: There is an increased prevalence of oral hyperpigmentation by the use of HAART. Future study should investigate the correlation between HAART duration and the degree of oral hyperpigmentation. Key words:HAART, oral hyperpigmentation; pooled prevalence.

Detection of Human Papillomavirus and p16INK4a Expression in Thai Patients with Oral Squamous Cell Carcinoma.

This study investigated the prevalence of human papillomavirus (HPV) infection in oral squamous cell carcinoma (OSCC) cases, as well as the association between HPV presence and p16INK4a expression, in Thai patients with OSCC. Eighty-one formalin-fixed paraffin-embedded specimens of OSCC were obtained. DNA extraction was performed; this was followed by nested polymerase chain reaction analysis to determine HPV DNA status, using consensus primers for the L1 region of HPV. HPV subtypes were determined by DNA sequencing. HPV-positive specimens and HPV-negative specimens from age- and sex-matched patients were subjected to immunohistochemical analysis to determine p16INK4a expression status. Of the 81 OSCC specimens, eight (9.9%) exhibited HPV DNA; DNA sequencing confirmed that the viral subtype was HPV-18 in all eight specimens. These eight HPV-positive specimens, as well as eight HPV-negative specimens from age- and sex-matched patients, were subjected to immunohistochemical analysis to determine p16INK4a expression status. Three of eight (37.8%) HPV-positive specimens and three of eight (37.8%) HPV-negative specimens showed positive p16INK4a expression findings. However, we did not find a significant association between HPV status and p16INK4a expression status in our OSCC samples. In conclusion, the prevalence of high-risk HPV was low in this group of OSCC patients; no association between HPV status and p16INK4a expression status was identified.

Human Papillomavirus 16 and 18 Infection in Oral Cancer in Thailand: A Multicenter Study.

OBJECTIVES: To identify the prevalence of high-risk human papillomavirus (HPV) genotypes 16 and 18 among patients with oral squamous cell carcinoma (OSCC) in Thailand and investigate the associations of p16 expression and HPV16/18 with the demographic, clinicopathologic, and risk parameters. MATERIALS AND METHODS: A total of 403 formalin-fixed paraffin-embedded OSCC specimens from four centers in four regions were obtained. p16 expression was evaluated by immunohistochemistry. The detection of HPV16/18 DNA was performed by polymerase chain reaction.  Results: Of all, 172 specimens (42.7%) were presented with amplifiable extracted DNA. Among these, 62.8% were positive for p16, 8.1% were positive for HPV16/18, and 5.8% were positive for both methods. Of all HPV-positive specimens, HPV18 was detected in 57.1%; HPV16 in 14.3%; and HPV16 and 18 (co-infection) in 28.6%. The prevalence of HPV16/18 varied between centers, with the highest rate in the northern center (20.0%). There was no significant correlation between p16 expression and HPV16/18. There were no significant associations of p16 expression and/or HPV16/18 with all variables. CONCLUSIONS: The prevalence of HPV16/18 infection in OSCC geographically varied in Thailand, with the highest rate in the northern region. Poor correlation between p16 and HPV16/18 suggests p16 not be used as a surrogate marker for HPV-positive OSCC.
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A Multicenter Study of Tongue Lesions from Thailand.

OBJECTIVE: Tongue lesions constitute a considerable proportion of the oral lesions. Previous studies on tongue lesions were based on clinical studies. There has been a scarcity of the studies which are based on histopathological examination. This study aimed to determine the prevalence, demographic, and pathologic features of tongue lesions from Thailand. MATERIALS AND METHODS: Biopsy records of the participating institutions were reviewed for lesions on the tongue diagnosed during 1998 to 2017. Demographic data were collected from the biopsy records. Locations were arbitrarily classified as dorsal, lateral, and ventral surfaces, tip of the tongue, and the combination of sites. Lesions of the tongue were classified as reactive/inflammatory, developmental, immune-mediated, cystic, benign, premalignant, malignant, infectious, and miscellaneous categories. STATISTICAL ANALYSIS: Data were analyzed by descriptive statistics using SPSS version 20.0. RESULTS: Of the 44,188 accessioned cases, 2,153 cases (4.87%) were diagnosed from the tongue. The age of the patients ranged from 3 to 93 years with the mean ± standard deviation = 45.26 ± 20.48 years. The female-to-male ratio was 1.49:1. The majority of the tongue lesions were encountered at the lateral border of the tongue (47.66%). Most of the tongue lesions in the present study (53.74%) fell into the reactive/inflammatory category. Irritation fibroma was the most prevalent lesion (18.99%) followed by squamous cell carcinoma (16.91%), and mucus extravasation phenomenon (14.26%), respectively. CONCLUSIONS: This study offers new perspective into the study of tongue lesions apart from the clinically based studies. It also demonstrates the difference between the pediatric and the elderly patients. This study provides invaluable database for clinicians when formulating the clinical diagnosis of tongue lesions.

Molecular mechanism of inhibitory effects of bovine lactoferrin on the growth of oral squamous cell carcinoma.

BACKGROUND: Lactoferrin (LF), a member of the transferrin family, recently has been demonstrated to have anticancer effects on various cancers including oral squamous cell carcinoma (OSCC). However, little is known about the underlying mechanisms of its effects on OSCC. Therefore, we aimed to investigate the mechanism of the suppressive effects of bovine LF (bLF) on the growth of OSCC cells. METHODS: In the current study, HSC2, HSC3, HSC4 and normal human oral keratinocytes (RT7) cell lines were tested with bLF 1, 10, and 100 µg/ml. The effects and detail mechanisms of bLF on proliferation and apoptosis of cells were investigated using flow cytometry and western blotting. RESULTS: We found that bLF (1, 10, and 100 µg/ml) induced activation of p53, a tumor suppressor gene, is associated with the induction of cell cycle arrest in G1/S phase and apoptosis in OSCC. Moreover, bLF downregulated the phosphorylation of Akt and activated suppressor of cytokine signaling 3 (SOCS3), thereby attenuating multiple signaling pathways including mTOR/S6K and JAK/STAT3. Interestingly, we revealed that bLF exerted its effect selectively against HSC3 but not on RT7 via different effects on the phosphorylation status of NF-κB and Akt. CONCLUSION: This is the first report showing that bLF selectively suppresses proliferation through mTOR/S6K and JAK/STAT3 pathways and induction of apoptosis in OSCC. This study provides important new findings, which might be useful in the prevention and treatment of OSCC.

Oral cancer: A multicenter study

Background: To determine the prevalence and clinicopathologic features of the oral cancer patients. Material and Methods: Biopsy records of the participating institutions were reviewed for oral cancer cases diagnosed from 2005 to 2014. Demographic data and site of the lesions were collected. Sites of the lesion were subdivided into lip, tongue, floor of the mouth, gingiva, alveolar mucosa, palate, buccal/labial mucosa, maxilla and mandible. Oral cancer was subdivided into 7 categories: epithelial tumors, salivary gland tumors, hematologic tumors, bone tumors, mesenchymal tumors, odontogenic tumors, and others. Data were analyzed by descriptive statistics using SPSS software version 17.0. Results: Of the 474,851 accessioned cases, 6,151 cases (1.30%) were diagnosed in the category of oral cancer. The mean age of the patients was 58.37±15.77 years. A total of 4,238 cases (68.90%) were diagnosed in males, whereas 1911 cases (31.07%) were diagnosed in females. The male-to-female ratio was 2.22:1. The sites of predilection for oral cancer were tongue, labial/buccal mucosa, gingiva, palate, and alveolar mucosa, respectively. The three most common oral cancer in the descending order of frequency were squamous cell carcinoma, non-Hodgkin lymphoma and mucoepidermoid carcinoma. Conclusions: Although the prevalence of oral cancer is not high compared to other entities, oral cancer pose significant mortality and morbidity in the patients, especially when discovered late in the course of the disease. This study highlights some anatomical locations where oral cancers are frequently encountered. As a result, clinicians should pay attention to not only teeth, but oral mucosa especially in the high prevalence area as well since early detection of precancerous lesions or cancers in the early stage increase the chance of patient being cured and greatly reduce the mortality and morbidity. This study also shows some differences between pediatric and elderly oral cancer patients as well as between Asian and non-Asian oral cancer patients (AU)

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Roles of VEGF-Flt-1 signaling in malignant behaviors of oral squamous cell carcinoma.

BACKGROUND: Vascular endothelial growth factor (VEGF) is a highly specific signaling protein for vascular endothelial cells that plays a critical role in tumor growth and invasion through angiogenesis, and may contribute to cell migration and activation of pre-osteoclasts, osteoclasts and some tumor cells. OBJECTIVES: We aimed to clarify the detailed roles of VEGF-Flt-1 signaling in bone invasion of oral squamous cell carcinoma (OSCC) cells. RESULTS: Forty-two (42) of 54 cases with gingival SCC (77.8%) strongly expressed VEGF, and had a significantly increased number of Flt-1+ osteoclasts (p<0.01) and more aggressive bone invasion (p<0.05). PlGF, a ligand of Flt-1, induced osteoclastogenesis in single culture of bone marrow cells (BMCs), and inhibition of Flt-1-signaling by VEGF tyrosine kinase inhibitor and It's down stream (Akt and ERK1/2) inhibitos reduced osteoclastogenesis in PlGF-stimulated BMCs (p<0.01). In molecular level, PlGF stimulation significantly upregulated RANKL expression in Flt-1-expressing HSC2 cells via phosphorylation of Akt and ERK1/2. In the co-culture of VEGF-producing HSC2 cells and BMCs, number of TRAP-positive osteoclasts markedly increased (p<0.01). The osteoclastogenesis was significantly inhibited by RANKL-neutralizing antibody (p<0.01) as well as by VEGF tyrosine kinase inhibitor (p<0.01) and it's downstream (Akt and ERK1/2) inhibitors (p<0.01, p<0.05, respectively). CONCLUSION: VEGF-Flt-1 signaling induces osteoclastogenesis in OSCC through two possible ways: 1) VEGF produced from OSCC cells can directly stimulate the Flt-1 pathway in preosteoclasts to induce migration to future bone resorbing area and differentiation into osteoclasts, and 2) VEGF-Flt-1 signaling upregulates RANKL expression in OSCC cells, which indirectly leads to osteoclast differentiation. Therefore, blocking of the VEGF-Flt-1 signaling may help inhibit bone invasion of OSCC.

N-terminal region of human ameloblastin synthetic peptide promotes bone formation.

The aim of this study was to examine the effect of 16 amino acids of the N-terminal region of human ameloblastin (16N-AMBN) synthetic peptide, on the proliferation and differentiation of MC3T3-E1 cells and bone regeneration. While 16N-AMBN did not affect the proliferation, it induced mRNA expression of type I collagen, alkaline phosphatase (ALP), bone sialoprotein, and osteocalcin. 16N-AMBN also stimulated ALP activity and promoted mineralized nodule formation. On the other hand, these activities were inhibited by anti-16N-AMBN antibody. Treatment of rat calvarial bone defects with 16N-AMBN resulted in almost complete healing compared to that of the control treatments. These findings suggest that 16N-AMBN may be applicable for regeneration therapy of bone defects.

A multicenter study of oral malignant tumors from Thailand.

BACKGROUND: Oral malignant tumors in Thailand have not been extensively studied. Hence the following study was conducted. AIMS: To determine the prevalence and clinicopathologic data of the oral malignant tumors from Thailand. SUBJECTS AND METHODS: Biopsy records of the Oral Pathology Department, Chulalongkorn University; Department of Oral Biology and Diagnostic Sciences, Chiang Mai University; Department of Oral Diagnosis, Khon Kaen University and Department of Stomatology, Prince of Songkla University, were reviewed for lesions diagnosed in the category of oral malignant tumors from 2005-2014. Demographic data and site of the lesions were collected. STATISTICAL ANALYSIS USED: Data were analyzed by descriptive statistics using SPSS software version 17.0. RESULTS: Of the 22,639 accessioned cases, 1411 cases (6.23%) were diagnosed as oral malignant tumors. The mean age of the patients was 59.13 ± 17.32 years. A total of 651 cases (46.14%) were diagnosed in males, whereas 759 cases (53.79%) were diagnosed in females. The male-to-female ratio was 0.86:1. The sites of predilection for oral malignant tumors were the gingiva, followed by tongue and alveolar mucosa. The three most common oral malignant tumors in the descending order of frequency were squamous cell carcinoma, non-Hodgkin lymphoma and mucoepidermoid carcinoma. CONCLUSIONS: This study provides extensive data on the oral malignant tumors from several university biopsy services located in virtually all parts of Thailand. The data from the present study show some similarities with previous studies; however, differences such as gender and site of predilection still exist.

Molar incisor hypomineralization and dental caries in six- to seven-year-old Thai children.

PURPOSE: This study aimed to determine the prevalence of molar incisor hypomineralization (MIH) in Thai children and evaluate the association between MIH and dental caries in the permanent dentition. METHODS: A cross-sectional study was conducted among six- to seven-year-old participants of a birth cohort study in Khon Kaen, Thailand. MIH was examined by one calibrated dentist using European Academy of Pediatric Dentistry criteria. The association between MIH and caries was determined by logistic regression at subject level, and generalized estimating equations at tooth level. RESULTS: Of 484 children who had at least one erupted permanent first molar, the prevalence of MIH was 20 percent, with no difference between genders. Children with MIH had increased odds of having caries in the permanent dentition compared to those without MIH (odds ratio [OR] equals 4.6; 95 percent confidence interval [CI] equals 2.7 to 7.9). MIH molars had approximately 10 times higher odds of developing caries than non-MIH counterparts (OR equals 9.9; 95 percent CI equals 5.7 to 16.9). Caries risk was higher in the upper molars than in the lower molars. CONCLUSIONS: Molar incisor hypomineralization is common and associated with increased risk for dental caries among this group of Thai children.

Increased immunoexpression of trefoil factors in salivary gland tumors.

OBJECTIVE: Very little is known about the role of trefoil factors (TFFs) in salivary gland tumors, and TFF immunoexpression has never been investigated in such tumors. The aim of this study was to evaluate TFF immunoexpression in benign and malignant salivary gland tumors. MATERIALS AND METHODS: Benign (n = 25) and malignant (n = 25) salivary gland tumor specimens were included in this study, using mucocele (n = 25) specimens as a control group. Immunohistochemical staining was performed to evaluate the expression of TFFs (TFF1, TFF2, and TFF3) by semiquantitative means. RESULTS: Expression of TFF1, TFF2, and TFF3 was significantly increased in benign (p = 0.001, p = 0.005, p < 0.001, respectively) and malignant (p < 0.001, p < 0.001, p < 0.001, respectively) groups as compared with the control group. Patterns of co-expression between TFF1/TFF2, TFF2/TFF3, and TFF1/TFF3 were different among the three groups. CONCLUSIONS: The present study provided new information showing that all TFFs were significantly increased in benign and malignant salivary gland tumors, and overexpression of TFFs could be associated with neoplastic transformation in salivary gland tissues. CLINICAL RELEVANCE: Overexpression of TFFs may be useful as biomarkers in terms of differential diagnosis between salivary gland tumors and other oral neoplasms for which clinical manifestations are indistinguishable.

Matrix metalloproteinase-13 (MMP-13) directly and indirectly promotes tumor angiogenesis.

Matrix metalloproteinases (MMPs) are extracellular zinc-dependent endopeptidases involved in the degradation and remodeling of extracellular matrix in physiological and pathological processes. MMPs also have a role in cell proliferation, migration, differentiation, angiogenesis, and apoptosis. We previously identified cancer invasion-related factors by comparing the gene expression profiles between parent and the highly invasive clone of cancer cells. Matrix metalloproteinase-13 (MMP-13) was identified as a common up-regulated gene by cancer invasion-related factors. Although MMP-13 slightly promoted tumor invasion, we found that MMP-13 was involved in tumor angiogenesis. Conditioned medium from MMP-13-overexpressing cells promoted capillary formation of immortalized human umbilical vein endothelial cells. Furthermore, treatment with recombinant MMP-13 protein enhanced capillary tube formation both in vitro and in vivo. MMP-13-promoted capillary tube formation was mediated by activation of focal adhesion kinase and ERK. Interestingly, MMP-13 promoted the secretion of VEGF-A from fibroblasts and endothelial cells. By immunohistochemical analysis, we found a possible correlation between MMP-13 expression and the number of blood vessels in human cancer cases. In summary, these findings suggest that MMP-13 may directly and indirectly promote tumor angiogenesis.

Ameloblastoma: a multicentric study.

OBJECTIVE: The objective of this study was to supplement the current ameloblastoma database by reporting the clinicopathologic features of ameloblastoma from Asia and North America. MATERIALS AND METHODS: Biopsy records of the participating institutes were reviewed for lesions diagnosed as ameloblastoma during the years 1993 to 2009. Slides were reclassified according to the World Health Organization Classification of Odontogenic Tumors in 2005. Clinical information and radiographic features were collected and analyzed. RESULTS: The mean age of the patients ± SD was 38.27 ± 17.78 years; 662 patients (51.36%) were men. Mandible (84.26%) outnumbered maxilla and other locations combined in all countries. The number of multilocular radiolucencies (43.40%) was comparable with that of unilocular radiolucencies (42.04%). Follicular pattern was the most common histopathologic pattern (27.70%), followed by plexiform (21.10%) and unicystic pattern (20.71%), respectively. CONCLUSIONS: The clinicopathologic features of ameloblastomas in the present study show some similarities with previous studies; however, minor differences exist.

Alteration of the expression of CD44 [corrected] isoforms in oral epithelia and saliva from patients with oral lichen planus.

Oral lichen planus (OLP) is a chronic inflammatory mucosal disease that cell-mediated immunological mechanisms are involved in pathogenesis. The objective of this study was to investigate the expression of CD44 isoforms including CD44s, CD44v5, and CD44v6 in biopsy specimens and saliva from OLP patients. Thirty-one OLP patients and 30 healthy subjects were enrolled in this study. Immunohistochemical methods were used to detect the expression of CD44 isoforms in oral epithelia, and enzyme-linked immunosorbent assay (ELISA) was performed to measure levels of salivary CD44 isoforms. Our results demonstrated that expression of CD44v6 in oral epithelia from OLP patients was significantly decreased in comparison to controls (p = 0.021). Levels of salivary CD44s and CD44v5 from OLP patients were significantly higher than those from controls (p = 0.007 and p = 0.002, respectively). In summary, our findings provided additional evidence that the pathological stress, such as chronic inflammation, altered the expression of CD44 isoforms in oral epithelia and saliva of OLP patients.