Genetic Variants in the TBC1D2B Gene Are Associated with Ramon Syndrome and Hereditary Gingival Fibromatosis.

Ramon syndrome (MIM 266270) is an extremely rare genetic syndrome, characterized by gingival fibromatosis, cherubism-like lesions, epilepsy, intellectual disability, hypertrichosis, short stature, juvenile rheumatoid arthritis, and ocular abnormalities. Hereditary or non-syndromic gingival fibromatosis (HGF) is also rare and considered to represent a heterogeneous group of disorders characterized by benign, slowly progressive, non-inflammatory gingival overgrowth. To date, two genes, ELMO2 and TBC1D2B, have been linked to Ramon syndrome. The objective of this study was to further investigate the genetic variants associated with Ramon syndrome as well as HGF. Clinical, radiographic, histological, and immunohistochemical examinations were performed on affected individuals. Exome sequencing identified rare variants in TBC1D2B in both conditions: a novel homozygous variant (c.1879_1880del, p.Glu627LysfsTer61) in a Thai patient with Ramon syndrome and a rare heterozygous variant (c.2471A>G, p.Tyr824Cys) in a Cambodian family with HGF. A novel variant (c.892C>T, p.Arg298Cys) in KREMEN2 was also identified in the individuals with HGF. With support from mutant protein modeling, our data suggest that TBC1D2B variants contribute to both Ramon syndrome and HGF, although variants in additional genes might also contribute to the pathogenesis of HGF.

Enamel-renal-gingival syndrome and FAM20A mutations.

The enamel-renal syndrome of amelogenesis imperfecta (AI) and nephrocalcinosis, and the amelogenesis imperfecta-gingival fibromatosis syndrome have both been associated with mutations in FAM20A. We report on two unrelated Thai patients with three novel and one previously reported mutations in FAM20A with findings suggesting both disorders, including hypoplastic AI, gingival fibromatosis, unerupted teeth, aggressive periodontitis, and nephrocalcinosis/nephrolithiasis. Additional findings consisted of a supernumerary premolar, localized aggressive periodontitis, thin alveolar bone, vitamin D deficiency-associated hyperparathyroidism, and heterotopic calcification in other tissues, including lungs, dental pulp, gingiva, dental follicles, and periodontal tissues, and early cessation of limited menstruation. Greater promotory activity of urine on calcium oxalate crystal growth compared to controls may help to explain the pathogenesis, and suggest that FAM20A mutations can contribute to nephrocalcinosis/nephrolithiasis. Our findings expand the phenotypic spectrum of FAM20A mutations. Since both of our patients and a large number of previously reported cases had all the important features of both syndromes, including AI, renal anomalies, and gingival fibromatosis, we are convinced that these two disorders actually are the same entity. The name of enamel-renal-gingival syndrome is suggested.

Cutis laxa with pulmonary emphysema, conjunctivochalasis, nasolacrimal duct obstruction, abnormal hair, and a novel FBLN5 mutation.

We report on a 4-year-old girl with autosomal recessive cutis laxa, type IA, or pulmonary emphysema type (ARCL1A; OMIM #219100), with loose and wrinkled skin, mitral and tricuspid valve prolapse, conjunctivochalasis, obstructed nasolacrimal ducts, hypoplastic maxilla, and early childhood-onset pulmonary emphysema. Mutation analysis of FBLN5 showed a homozygous c.432C>G missense mutation, and heterozygosity in the parents. This is predicted to cause amino acid substitution p.Cys144Trp. Conjunctivochalasis or redundant folds of conjunctiva and obstructed nasolacrimal ducts have not been reported to be associated with FBLN5 mutations. Histopathological study of the conjunctival biopsy showed that most blood vessels had normal elastic fibers. The gingiva appeared normal, but histologically elastic fibers were defective. Scanning electron micrography of scalp hair demonstrated hypoplastic hair follicles. The cuticles appear intact underneath the filamentous meshwork.

Oral manifestations of monkeypox: Brief review.

The current outbreak of monkeypox infection has caught the attention of people worldwide. Updated data showed a dramatic increase in the number of patients in many non-endemic countries. An emergence of monkeypox together with coronavirus disease 2019 (COVID-19) caused a tremendous burden on the healthcare system, globally. The aim of this review was to briefly describe the current situation, transmission, clinical features, diagnosis, and prevention of the disease. Oral manifestations of monkeypox as well as those of similar viral diseases were elaborately delineated. The outbreak of monkeypox in non-endemic regions has expanded to at least 47 countries with more than 4,100 new infections. The clinical features in non-endemic regions are atypical and different from those in central and western Africa. Milder symptoms with no death cases have been observed. The oral mucosa is often involved and oral lesions may initially be manifested before the rash spreads to the face and other parts of the body. The diagnosis of monkeypox is mainly based on clinical presentations and laboratory investigations. Prevention by avoiding close contacts with patients and sick animals and providing vaccination to those who have a primary contact with patients is essential. Oral manifestations may occur prior to skin eruptions, suggesting that dentists and dental personnel should be well aware of the nature of the disease. Prevention and public awareness of the disease are crucial for mitigating further human-to-human transmission.

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.

A German AWMF's S2e/realist synthesis and meta-narrative snapshot of craniomaxillofacial manifestations in COVID-19 patients: Rapid living update on 1 January 2021.

PURPOSES: To execute a review answering the following question: "Among novel coronavirus disease (COVID19) patients, what are craniomaxillofacial (CMF) manifestations?" based on the RAMESES and the German Association of Scientific Medical Societies (AWMF)'s S2e guidelines. METHODS: We performed a realist synthesis and meta-narrative review extracting data in English, French, German and Thai from PubMed/Medline, Embase, Biomed Central, Cochrane Library, and Thai Journals Online, until 1 January 2021. The primary outcome variable was CMF manifestations grouped into 5 categories: (1) mouth and throat, (2) nose, paranasal sinus, and skull base (3) ocular/orbital and periorbital tissue, (4) ear, and (5) craniofacial skin. Appropriate statistics was computed. RESULTS: Thirty-seven original articles meeting the inclusion criteria were analysed; all were in English and indexed in PubMed/Medline. Hand searches of their references yielded a total of 101 articles for the review. Most data were in low level of evidence and focused on smell and taste disturbances and non-specific orofacial lesions. Iatrogenic complications may occur in this body region. Conservative measures remained effective and were usually enough for patient care. CONCLUSION: Because SARS-CoV-2 infection is new and becomes the stringent worldwide pandemic within a short time period, most of the data on CMF symptoms are of low level evidence. Apart from taste and smell dysfunctions, non-specific CMF lesions can be found and treated conservatively. Treatment complications are possible. Dentists and CMF surgeons are privileged to examine the orofacial region and work closely with colleagues in other specialities to combat this pandemic.

High Prevalence of Human Papillomavirus Type 18 in Oral Potentially Malignant Disorders in Thailand.

OBJECTIVES: The main objectives of this study were to investigate the detection rate of high-risk human papillomavirus types 16 and 18 (high-risk HPV16/18) in oral potentially malignant disorders (OPMDs) including oral leukoplakia (OL) and oral lichen planus (OLP) in a Thai population and their associations with demographic, risk habits, and clinicopathologic features. METHODS: Paraffin-embedded formalin-fixed specimens from 101 OL and 59 OLP patients with patients' demographic, risk habits, and clinicopathologic data were collected. Conventional qualitative polymerase chain reaction was used to detect high-risk HPV16/18 DNA. Associations between high-risk HPV type 16/18 and demographic, clinicopathologic, risk factors (tobacco and alcohol uses) of OPMDs were analysed by Chi-square or Fisher's exact test. The results with p value less than 0.05 were considered statistically significant. RESULTS: HPV16/18 DNA was found in both OL and OLP groups with the detection rate of 19.8% and 18.6%, respectively. Approximately 90% of high-risk HPV were HPV18 subtype. Additionally, in OL group, high-risk HPV was found more frequently in patients with moderate/severe dysplasia than that in mild dysplasia. Interestingly, in OLP group, high-risk HPV was only detected in atrophic/ulcerative subtypes. None of risk factors was associated with high-risk HPV. CONCLUSIONS: Approximately 19% of OPMDs were HPV16/18-positive. HPV18 DNA was predominantly detected in both OL and OLP patients (90%). Additionally, the detection rate of high-risk HPV was higher in more severe dysplastic cases of OL and more clinically severe cases of OLP.

Three-Dimensional Prediction of the Nose for Facial Approximation in a Thai Population.

Most of the previous studies about nose prediction were concentrated only some landmarks of the nose. This study aimed to generate prediction equations for ten landmarks of the nose in the midline and alar regions for forensic facial approximation. The six midline landmarks were the sellion, nasion-pronasale posterior, nasion-pronasale anterior, pronasale, nasal drop, and subnasale. The four landmarks of the alar region were the alare, superior alar groove, posterior alar groove, and inferior alar groove. We used the skull landmarks in the nasal, zygomatic, and maxillary bone to predict the landmarks of the nose. Cone-beam computed tomography scans of 108 Thai subjects with normal BMI and age ranging from 21.0 to 50.9 years were obtained in a sitting position. The data were converted into three-dimensional (3-D) images of the skull and face. The Cartesian coordinates of the landmarks of the skull and nose were used to formulate the multiple regression equations. The formulated equations were tested in 24 new subjects. The mean differences in the predicted midline landmarks varied between -0.4 mm and 0.5 mm, whereas those for bilateral landmarks varied between -1.0 mm and 1.4 mm. In conclusion, the prediction equations formulated here will be beneficial for facial approximation of the nose in a Thai population.

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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An anatomical study on locations of the mandibular foramen and the accessory mandibular foramen in the mandible and their clinical implication in a Thai population.

Mandibular foramen (MF) is a structure that inferior alveolar nerve and artery pass through itself which is found on the mandible. The objective of this research aims to locate MF among the Thai population including other MF characteristics. The sampling is conducted in the Thai population of the total number of 220 samples from the Forensic Osteology Research Center, Faculty of Medicine, Chiang Mai University. The MF anteroposterior and superoinferior localizations are similar in both sex which at Q3 of right anteroposterior, Q2 of left anteroposterior and Q2 of left and right superoinferior axis. Otherwise, the prevalence of accessory MF has in 68 samples which are 30.89%. The prevalence of unilateral single accessory MF is 20.45%, bilateral single accessory MF is 6.36%, unilateral double accessory MF is 2.27% and bilateral double accessory MF is 0.45%. This present research results that the Thai population has a difference in MF location while comparing to other populations. Moreover, Thai MF and accessory MF location and localization will be helpful to clinical implications.

Association between hepatitis C infection in Thai patients with oral lichen planus: A case-control study.

AIM: The aim of the present study was to investigate the prevalence of hepatitis C virus (HCV) infection and evaluate liver enzyme levels in patients from upper northern Thailand with oral lichen planus (OLP). METHODS: A case-control study of 101 patients with OLP and 101 patients without OLP was conducted. Peripheral blood was taken from each patient and screened for anti-HCV antibody using immunochromatography. Positive samples were further confirmed using chemiluminescent microparticle immunoassay (CMIA) and reverse transcription-polymerase chain reaction. In addition, liver enzyme levels, alanine transaminase, aspartate transaminase, and alkaline phosphatase were evaluated using spectrophotometry. RESULTS: Immunochromatography and CMIA revealed that nine patients with OLP (8.9%) were positive for anti-HCV antibodies, whereas only one patient without OLP was HCV positive (odds ratio = 9.78). All patients who were HCV positive had significantly higher liver enzyme levels than patients who were HCV negative. CONCLUSIONS: The results of the present study indicated that OLP in certain patients was significantly associated with HCV. This could warrant screening for HCV-infected patients with OLP in Thailand.

Cross-cultural comparison of the attitudes of dental students in three countries.

The aim of this study was to identify and compare the attitudes of dental students toward their career choice and dental education in three different countries. Three hundred thirty-six dental students from the University of British Columbia, Canada; Mahidol University and Chiang Mai University, Thailand; and Nippon Dental University, Japan, participated in this study. Information was derived from a questionnaire consisting of career choice items and dental education items. Significant differences in the responses of the participants from each of the three countries were detected for each of the questionnaire items (P<0.001). Regarding factors that may have served as motivations for career choice, the majority of dental students from each country indicated positive reasons such as interpersonal motives, caring for other people, and academic interest. For future career options, the majority of Japanese and Canadian students planned to work as general dentists. Thai students were more likely than Japanese or Canadian to prefer specialization than practicing general dentistry. Nearly three-quarters of the Canadian and Thai students were satisfied with the teaching faculty of their schools, while only a quarter of the Japanese students indicated satisfaction. The findings from this study enhance our understanding of differences and/or similarities among dental students in three nations; this information may help to define strategies to improve the quality of international student exchange programs.

Akt2 and p-Akt overexpression in oral cancer cells is due to a reduced rate of protein degradation.

OBJECTIVE: To quantitatively measure the increased expression of Akt2 and its phosphorylated form (p-Akt) in oral cancer cell lines and investigate the post-translational mechanism for Akt2 and p-Akt overexpression. METHODS: Three oral cancer cell lines and three cell lines of primary human oral keratinocytes (HOKs) were cultured and the degrees of Akt2 and p-Akt expression was evaluated by immunoblot analysis and flow cytometry. Each cell line was incubated with cycloheximide, an inhibitor of new protein synthesis, for various times to quantitatively determine the remaining expression levels of Akt2 and p-Akt by flow cytometry. The localization of Akt2 and p-Akt was assessed by immunofluorescence. RESULTS: The levels of Akt2 and p-Akt proteins were significantly higher in cancer cell lines than those in HOKs (P < 0.05). When the new protein synthesis was blocked by cycloheximide treatment, the degradation rate of Akt2 and p-Akt in oral cancer cells was significantly lower than that in HOKs (P < 0.05). Both Akt2 and p-Akt were more intensely stained in the cytoplasm of cancer cells, whereas HOKs expressed Akt2 and p-Akt only minimally. CONCLUSION: Both Akt2 and p-Akt were overexpressed in oral cancer cells, which may be partly explained by a reduced rate of protein degradation in order to maintain high cytosolic levels.

Ten-Year Outcome of Different Treatment Modalities for Squamous Cell Carcinoma of Oral Cavity

Objective: This study reports outcomes of squamous cell carcinoma of oral cavity (SCCOC) patients with different treatment modalities. Materials and Methods: We evaluated the treatment outcomes of 775 newly diagnosed SCCOC patients treated in our hospital between 2001 and 2010. Outcome data were obtained from the medical records. Survival rates were estimated by the Kaplan-Meyer method. Cox-proportional-hazard regression models were used to compare the risk of death among all risk factors. Results: The patients were divided into group 1) surgery ± adjuvant radiotherapy (RT) (n = 323) or group 2) RT ± chemotherapy (CT) for curative intent (n = 315) or group 3) RT/CT for palliative intent (n = 137). The overall 10-year survival rate was 17%. Statistically significant difference was noted in 10-year overall survival when SCCOC was managed surgically as compared to curative RT and palliative RT/CT with 25.3 %, 12.9%, 4.7%, respectively. The hazard ratio of cancer death in group 1 was 2.0 (95% CI 1.7-2.4) as compared to group 2. Conclusion: This study suggested that surgery must be the mainstay of treatment in locally advanced stage SCCOC. Palliative RT/CT still offered long term survival in some SCCOC patients.

Aberrant expression of Smad4, a TGF-beta signaling molecule, in oral squamous cell carcinoma.

Although carcinogenesis of oral squamous cell carcinoma (OSCC) has been studied by many investigators in the past decade, the available evidence about its molecular mechanism is inconclusive. The objective of the present study was to compare expression of Smad4, a signaling molecule of the transforming growth factor beta (TGF-beta) pathway, between OSCC and normal oral mucosa. We assayed expression of Smad4 in OSCC and normal oral mucosa by performing immunohistochemistry using paraffin-embedded tissue samples. We also compared expression of Smad4 protein between OSCC lines and normal oral keratinocytes, using Western blot analysis. Smad4 expression was observed in only 60% of OSCC tissue samples, whereas it was observed in 82% of normal oral mucosa samples. Reduced Smad4 expression was clearly observed in all OSCC lines, compared with normal oral keratinocytes. These findings suggest that aberration of the TGF-beta pathway, as indicated by a reduction or absence of Smad4 expression, promotes carcinogenesis of OSCC.

Characterization of oral pemphigus vulgaris in Thai patients.

Pemphigus vulgaris (PV) is a serious mucocutaneous disease that be fatal if left untreated. The oral mucosa is often the first site to be affected by the disease. It is thus important that the dentist is able to recognize oral manifestations of PV and refer appropriately. Although oral PV is a well-characterized condition, the disease characteristics of patients in Thailand have not been previously reported. Here, we describe patient and lesion characteristics of 18 cases of oral PV. For these 18 cases, the mean age was 38 years, and the male:female ratio was 1:2. The most commonly affected sites were the gingiva and buccal mucosa, and the duration of disease was approximately one year. Medications previously used included corticosteroids and interferon, and nine patients reported systemic disease. Histopathologic examination with/without direct immunofluorescence was the method of diagnosis in all cases.

Morphometric study of incisive, greater and lesser palatine foramina: a novel point of maxillary nerve block in a Thai population / Estudio morfométrico del foramen palatino incisivo, mayor y menor: un punto novedoso de bloqueo del nervio maxilar en una población tailandesa

SUMMARY: To study the morphometric location of the incisive, greater, and lesser palatine foramina for maxillary nerve block. Two hundred Thai dry skulls were randomly organized from the Forensic Osteology Research Center. The distances of the parameters were measured via Vernier caliper.: Thedistances from the incisive foramen to the incisive margin of the premaxilla were 10.93?2.42 mm in males and 10.98?2.06 mm in females. From the left side, the incisive foramen to the greater palatine foramen (GPF) was39.07?2.23mm in males and 38.57?2.41 mm in females, and from the right side were 39.81?2.37 mm in males and 38.62?2.53mm in females. From the left side, the incisive foramen to the lesser palatine foramen (LPF) was 43.16?2.23 mm in males and 41.84?2.42mm in females and from the right side were 42.93?2.14 mm in males and 41.76?2.61 mm in females. The GPF found at medial to the maxillary third molar were 94-95 % in males and 84 % in females. These findings suggest that the medial position to the third molar teeth be used as a landmark for a palatine nerve block in Thais. These findings will help dentists to perform local anesthetic procedures, especially the nasopalatine and greater palatine nerve blocks, more effectively.

RESUMEN: El objetivo de este trabajo fue estudiar la localización morfométrica de los forámenes palatinos incisivos, mayores y menores para el bloqueo del nervio maxilar. Se organizaron al azar doscientos cráneos secos tailandeses del Centro de Investigación de Osteología Forense. Las distancias de los parámetros se midieron mediante un calibre Vernier. Las distancias desde el foramen incisivo hasta el margen incisivo de la premaxila fueron 10,93 ? 2,42 mm en hombres y 10,98 ? 2,06 mm en mujeres. Desde el lado izquierdo, el foramen incisivo al foramen palatino mayor (FPM) fue de 39,07 ? 2,23 mm en los hombres y 38,57 ? 2,41 mm en las mujeres, y del lado derecho fue de 39,81 ? 2,37 mm en los hombres y 38,62 ? 2,53 mm en las mujeres. Del lado izquierdo, el foramen incisivo al foramen palatino menor (LPF) fue de 43,16 ? 2,23 mm en hombres y 41,84 ? 2,42 mm en mujeres y del lado derecho 42,93 ? 2,14 mm en hombres y 41,76 ? 2,61 mm en mujeres. El FPM encontrado medial al tercer molar maxilar fue 94-95 % en hombres y 84 % en mujeres. Estos hallazgos sugieren que la posición medial de los terceros molares se utilice como punto de referencia para un bloqueo del nervio palatino en individuos tailandeses. Estos hallazgos ayudarán, de manera más eficaz, a los dentistas a realizar procedimientos anestésicos locales, especialmente los bloqueos nasopalatinos y del nervio palatino mayor.

New prediction models for dental age estimation in Thai children and adolescents.

UNLABELLED: The aims of this study were to develop new prediction models for dental age estimation and to test the accuracy of the resulting models in comparison with the Demirjian et al. and the Willems et al. methods in Thai children and adolescents. Digital panoramic radiographs of 1,134 Thai individuals (487 males and 647 females) aged from 6 to 15 years were selected and evaluated for dental age estimation. Quadratic regression was used to generate new models. The results showed that the new prediction models indicated a strong correlation coefficient between the dental maturity score and the chronological age in both sexes (r=0.951 for males, r=0.945 for females). The new age prediction models were: y=0.006297x(2) - 0.804930x+32.591843 for males and y=0.010677x(2) - 1.538823x+61.955056 for females, where y is the dental age, x is the dental maturity score according to Demirjian et al. METHOD: Moreover, these new models were tested showing the greatest accuracy for estimating the age in Thai samples using the mean difference values between the dental and the chronological ages (-0.04 years for males, 0.02 years for females) when compared with the Demirjian et al. and the Willems et al. METHODS: In addition, the new models revealed a high percentage of accuracy in the absolute difference values between the dental and the chronological ages within 1 year (76.26% and 74.49% for males and females, respectively). Furthermore, our results in mean difference values indicated that the Demirjian et al. method (0.11 and 0.10 years for males and females, respectively) was more accurate than the Willems et al. method (-0.37 and -0.39 years for males and females, respectively) in Thai samples. In conclusion, the new age prediction models in this study provide accurate age estimation in both sexes, suggesting that these models be applied for forensic age estimation, especially in Thai children and adolescents.

p16 - a Possible Surrogate Marker for High-Risk Human Papillomaviruses in Oral Cancer?

BACKGROUND: High-risk human papillomaviruses (HR-HPV), particularly types 16 and 18, have been found to play an important role in head and neck cancer, including oropharyngeal squamous cell carcinoma (OPSCC) and oral squamous cell carcinoma (OSCC). p16, a cell cycle inhibitor, has been postulated as a surrogate marker for HR-HPV, since p16 is aberrantly overexpressed in such lesions, especially in HR-HPV-positive OPSCC. However, p16 as a surrogate marker for HR-HPV infection in cancers of the oral cavity remains controversial. OBJECTIVE: The objectives of the study were to investigate the expression of p16 and the presence of HR-HPV in OSCC and oral verrucous carcinoma (VC) and to determine if p16 could be used as a surrogate marker for HR-HPV. MATERIALS AND METHODS: Forty one formalin-fixed, paraffin-embedded tissues of OSCC (n=37) or VC (n=4) with clinical and histopathologic data of each case were collected. Expression of p16 was determined by immunohistochemistry, focusing on both staining intensity and numbers of positive cells. The presence of HPV types 16 and 18 was detected by polymerase chain reaction (PCR). Descriptive statistics were employed to describe the demographic, clinical, and histopathologic parameters. Associations between p16 overexpression, HR-HPV and all variables were determined by Fisher's exact test, odds ratios (ORs) and corresponding 95% confidence intervals (CIs). In addition, the use of p16 as a surrogate marker for HR-HPV was analyzed by sensitivity and specificity tests. RESULTS: p16 was overexpressed in 8/37 cases (21.6%) of OSCC and 2/4 cases (50%) of VC. HPV-16 was detected in 4/34 OSCC cases (11.8%) and HPV-18 was detected in 1/34 OSCC cases (2.9%). Co-infection of HPV-16/18 was detected in 1/4 VC cases (25%). Both p16 overexpression and HR-HPV were significantly associated with young patients with both OSCC and VC (<0.05, OR 20, 95% CI 1.9-211.8; <0.05, OR 23.3, 95% CI 2.4-229.7, respectively). p16 was able to predict the presence of HPV-16/18 in OSCC with 40% sensitivity and 79.3% specificity and in VC with 100% sensitivity and 66.7% specificity, respectively. CONCLUSIONS: p16 overexpression was found in 24.4% of both OSCC and VC. HR-HPV, regardless of type, was detected in 15.8% in cases of OSCC and VC combined. The results of sensitivity and specificity tests suggest that p16 can be used as a surrogate marker for HR-HPV in OSCC and VC.

Increased cyclooxygenase 2 expression in association with oral lichen planus severity.

BACKGROUND/PURPOSE: Although some studies have shown induction of cyclooxygenase 2 (COX-2) in oral lichen planus (OLP), an association between COX-2 upregulation and OLP clinical severity has not been investigated. Therefore, we aimed to compare COX-2 expression in OLP with that in normal oral tissues, and to determine correlations between COX-2 expression and both clinical criteria and visual analog scale (VAS) scores. MATERIALS AND METHODS: COX-2 expression was studied in 25 OLP and 13 normal oral tissues by immunohistochemistry. Both clinical criteria and VAS scores were used to evaluate the clinical severity of OLP. The differences in COX-2 expression between OLP and normal tissues, and the correlations between COX-2 expression and clinical severity were determined by the nonparametric statistical tests. RESULTS: COX-2 expression was significantly increased in OLP epithelium when compared with normal epithelium (P < 0.001), and intense COX-2 staining in inflammatory infiltrates was observed in the OLP lamina propria. COX-2 expression in OLP epithelium and inflammatory infiltrates was significantly correlated with the clinical criteria score (r = 0.428, P = 0.007, and r = 0.681, P < 0.001, respectively), whereas a significant correlation with the VAS score was observed only in OLP inflammatory infiltrates (r = 0.605, P < 0.001). CONCLUSION: Enhanced COX-2 expression in both OLP epithelium and inflammatory infiltrates correlates well with the clinical severity. An association between VAS score and COX-2 expression in OLP inflammatory infiltrates suggests an important role of additional COX-2 expression from inflammation in causing pain in OLP patients.