Expression of PD-L1 is HPV/P16-independent in oral squamous cell carcinoma.

Objectives: This study aimed to investigate the expression of programmed death-ligand 1 (PD-L1) and its associations with human papillomavirus (HPV) 16/18 DNA status, p16 expression, demographic, clinicopathologic and risk parameters in patients with oral squamous cell carcinoma (OSCC). Study design: A total of 85 formalin-fixed, paraffin-embedded OSCC specimens were collected. HPV16/18 DNA was detected by polymerase chain reaction. PD-L1 and p16 expressions were assessed using immunohistochemical technique. The immunostaining scores were calculated by combined positive score (CPS), previously described. The positive scoring value was determined at CPS ≥1, recommended by FDA. The associations between PD-L1 expression and HPV16/18 DNA status, p16 expression, demographic, clinicopathologic, and risk parameters were analyzed by Chi-square, Fisher's exact tests, and multivariate logistic regression. Results: PD-L1 expression was detected in 22 out of 85 cases of OSCC (25.9%). 16.5% of all cases were HPV 16/18-positive and 62.4% were p16-positive. Statistically, there were no significant associations between PD-L1 expression in OSCC and HPV16/18 DNA status, p16 expression, demographic and, clinicopathologic parameters or risk behaviors. Conclusion: Approximately one-fourth of OSCC cases were PD-L1-positive, suggesting candidacy for anti-PD-L1 immunotherapy. Furthermore, HPV infection and p16 expression were not involved with PD-L1 expression. Further clinical trials warrant the benefits of immunotherapy in patients with PD-L1-positive OSCC.

Pigmented Oral Lesions: A Multicenter Study.

OBJECTIVES: The aim of this study was to determine the prevalence and clinical features of pigmented oral lesions from Thailand. MATERIALS AND METHODS: Biopsy records of the Department of Oral Pathology, Chulalongkorn University, Department of Oral Diagnosis, KhonKaen University, Department of Oral Biology and Oral Diagnostic Sciences, Chiangmai University, Department of Stomatology, Prince of Songkla University, and Rangsit University were reviewed for oral pigmented lesions diagnosed during 1999 to 2019. Demographic data were culled from the biopsy records. Ages of the patients were subdivided into 10-year intervals. Locations of the lesions were classified as gingiva, labial/buccal mucosa, palate, floor of the mouth, tongue, as well as the combination of sites. Data were analyzed by descriptive statistics using SPSS version 20.0. RESULTS: Of the 47,175 accessioned cases, 241 cases (0.51%) were diagnosed in the category of pigmented oral lesions. The age of the patients ranged from 1 month to 88 years with the mean ± standard deviation = 38.74 ± 20.96 years. Regarding gender, 172 patients (71.37%) with pigmented lesions were females, while 69 patients (28.63%) were males. The female-to-male ratio was 2.49:1. The majority of the pigmented lesions were encountered at the gingiva (29.88%) followed by labial/buccal mucosa (26.97%), palate (14.94%), lip (10.79%), alveolar mucosa (9.54%), and others (7.88%), respectively. The three most common pigmented oral lesions in the present study were nevus (39.83%), followed by melanotic macule (28.63%) and amalgam tattoo (17.43%), respectively. CONCLUSIONS: The most common pigmented oral lesion in the present study is nevus. Demographic data of the patients in the present study are in accordance with previous studies with minor differences. Even though pigmented lesions of the oral cavity constitute a small portion of the oral pathology biopsies, accurate diagnosis is important since there is an overlap in clinical appearance of benign pigmented lesions and melanoma.

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.

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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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.

Effects of enamel matrix derivative on bioactive glass in rat calvarium defects.

Tissue engineering-based bone grafting has emerged as a viable alternative to biologic and synthetic grafts. The purpose of this study was to evaluate the effect of enamel matrix derivative (EMD; Emdogain gel, Biora AB, Malmö, Sweden) on bioactive glass in enhancing bone formation in rat calvarium defects. Twenty rats were used in the study. In all animals, 2 standardized critical-sized calvarial defects (5.0 mm diameter) were created surgically. The animals were randomly allocated into 4 groups of 5 animals each. Group AI: one calvarial defect was filled with bioactive glass plus EMD, while the contralateral defect was filled with bioactive glass alone. The healing period was 2 weeks. Groups AII and AIII: the animals were treated in the same manner as in group AI, but the healing periods were 4 and 8 weeks, respectively. Group B: one calvarial defect was filled with EMD only, while the contralateral defect was empty (CSD). The healing period was 8 weeks. New bone formation was evaluated by radiomorphometry and histomorphometry. Results of radiomorphometry showed no significant difference in the mean optical density between bioactive glass with EMD and bioactive glass alone; no defect completely regenerated with bone. The histologic analysis revealed that defects filled with bioactive glass plus EMD in all groups contained slightly more percentage of new bone than those filled with bioactive glass alone; however, the difference was not statistically significant. The highest percentage of new bone formation was present at 8 weeks in the bioactive glass plus EMD group. Bioactive glass particles, used with or without EMD, maintained the volume and contour of the area grafted in CSD. However, they did not lead to a significant difference in bone formation when compared with CSD 8 weeks postoperatively.

A recombinant fragment of the fibronectin-binding protein of Staphylococcus aureus inhibits keratinocyte migration.

Staphylococcus aureus is a common wound-infecting organism which can interact with cells via the extracellular matrix protein fibronectin (FN). The aim of this study was to determine the effect of the FN-binding protein (FnBP) of S. aureus on the behaviour of a human skin keratinocytes cell line (UP). FN-coated plates and Transwell membranes were exposed to a recombinant protein encompassing the D1-D4 repeat region of S. aureus FnBPB (rFnBPBD1-D4) before cell adhesion and migration assays. The influence of this protein on migration into a wounded area, cell cycle progression and endogenous cellular FN assembly was also assessed. The rFnBPBD1-D4 protein potently inhibited S. aureus entry into UP keratinocytes but had no effect on cell adhesion to FN substrate. It inhibited UP keratinocyte Transwell migration by 17% (P= 0.04) and 31% (P=0.02) at 10 and 100 microg/ml, respectively. In the wound assay, 100 microg/ml of rFnBPBD1-D4 protein reduced the migration area by approximately 30%. No differences in cell cycle progression were observed. In the presence of rFnBPBD1-D4, most of the cellular FN matrix on the cell surface and along the cell filopodia seen in untreated cells was absent. Interaction of S. aureus FnBPs with FN may influence cell behaviour and thus play a role in delayed epithelial closure in infected healing wounds.

Internalization of Staphylococcus aureus by human keratinocytes.

Staphylococcus aureus is among the most important human pathogens and causes various superficial and systemic infections. The ability of S. aureus to be internalized by, and survive within, host cells, such as keratinocytes, may contribute to the development of persistent or chronic infections and may finally lead to deeper tissue infections or dissemination. To examine the mechanisms of internalization of S. aureus by keratinocytes, isogenic mutants lacking fibronectin-binding proteins (FnBPs), a recombinant protein consisting of the fibronectin-binding domain of S. aureus FnBPs, and an anti-alpha5beta1 antibody were used in cocultures with immortalized keratinocytes and primary keratinocytes. We found that internalization of S. aureus by immortalized keratinocytes requires bacterial FnBPs and is mediated by the major fibronectin-binding integrin alpha5beta1. In contrast to internalization by immortalized keratinocytes, internalization of S. aureus by primary keratinocytes could occur through FnBP-dependent and -independent pathways. S. aureus clumping factor B (ClfB), which was recently determined to bind to epithelial cells, was not involved in the uptake of this bacterium by keratinocytes. The identification of an alternate uptake pathway, which is independent of S. aureus FnBPs and host cell alpha5beta1, has important implications for the design of therapies targeted to bacterial uptake by host cells.