Characterization of a Novel Oral Glucocorticoid System and Its Possible Role in Disease

Synthetic corticosteroids are used widely for the treatment of a variety of diseases of the mouth. However, little is known as to whether the oral mucosa is able to modulate the local concentration of active corticosteroids or to produce steroids de novo. This has important clinical implications, because tissue-specific regulation of glucocorticoids is a key determinant of the clinical efficacy of these drugs. In the present study, we show that oral fibroblasts and keratinocytes expressed ACTH receptor (MC2R), glucocorticoid receptor (GR), and 11 beta-hydroxysteroid dehydrogenases (11 beta-HSDs). Unlike keratinocytes, fibroblasts lacked 11 beta-HSD2 and could not effectively deactivate exogenously administered cortisol. However, both cell types were able not only to activate cortisone into the active form cortisol, but also to synthesize cortisol de novo following stimulation with ACTH. 11 beta-HSD2, the enzyme controlling cortisol deactivation, exhibited different patterns of expression in normal (squamous epithelium and salivary glands) and diseased oral mucosa (squamous cell carcinoma and mucoepidermoid carcinoma). Blocking of endogenous cortisol catabolism in keratinocytes with the 11 beta-HSD2 inhibitor 18 beta-glycyrrhetinic acid mimicked the effect of exogenous administration of hydrocortisone and partially prevented the detrimental effects induced by pemphigus vulgaris sera. Analysis of the data demonstrates that a novel, non-adrenal glucocorticoid system is present in the oral mucosa that may play an important role in disease.

Expression of nonclassical molecule human leukocyte antigen-G in oral lesions

Introduction: Human leukocyte antigen (HLA)-G is a nonclassic class I molecule that acts as a modulator of immune responses, and the expression of these molecules in virus-infected cells has been associated with subversion of the immune response. Objective: In this study, we performed a cross-sectional study, systematically comparing the expression of the HLA-G in benign, premalignant, and malignant oral lesions and correlating it with the presence of high-risk and low-risk human papillomavirus (HPV) types. Specimens and Methods: Oral biopsies were collected from 51 patients and analyzed by immunohistochemistry using anti HLA-G antibody. Human papillomavirus detection and typing from oral biopsies were obtained by polymerase chain reaction using GP5+/GP6+ and specific primers. Results: The 51 biopsies were stratified into 3 groups according to lesion grade: oral benign lesions (oral hyperplasia and papilloma, n = 16), oral premalignant lesions (oral leukoplakia with dysplasia and lichen planus, n = 17), and malignant lesions (oral squamous cell carcinoma, n = 18). Human leukocyte antigen G overexpression was mainly observed in benign and premalignant oral lesions but was not related to HPV infection (P>.05). On the other hand, HPV DNA was detected in 24 (47%) oral lesions, mainly in benign and premalignant lesions, with the most frequent type detected being high-risk HPV type. Conclusion: The HLA-G molecule was expressed in a significant number of benign oral lesions and was not correlated with HPV infection or oral cancer. Crown Copyright (C) 2012 Published by Elsevier Inc. All rights reserved.

TWIST and p-Akt immunoexpression in normal oral epithelium, oral dysplasia and in oral squamous cell carcinoma

Objectives: The aim of this study was to evaluate the immunoexpression of TWIST and p-Akt proteins in oral leukoplakia (OL) and oral squamous cell carcinoma (OSCC), correlating their expressions with the histological features of the lesions. Study design: Immunohistochemical studies were carried out on 10 normal oral epithelium, 30 OL and 20 OSCC formalin-fixed, paraffin-embedded tissue samples. Immunoperoxidase reactions for TWIST and p-Akt proteins were applied on the specimens and the positivity of the reactions was calculated for 1000 epithelial cells. Results: Kruskal-Wallis and Dunn's post tests revealed a significant difference in TWIST and p-Akt immunoexpression among normal oral mucosa, OL and OSCC. In addition, a significant positive correlation was found between TWIST and p-Akt expressions according to the Pearson's correlation test. Conclusions: The results obtained in the current study suggest that TWIST and p-Akt may participate of the multi-step process of oral carcinogenesis since its early stages.

Vitamin or mineral supplement intake and the risk of head and neck cancer: pooled analysis in the INHANCE consortium

To investigate the potential role of vitamin or mineral supplementation on the risk of head and neck cancer (HNC), we analyzed individual-level pooled data from 12 casecontrol studies (7,002 HNC cases and 8,383 controls) participating in the International Head and Neck Cancer Epidemiology consortium. There were a total of 2,028 oral cavity cancer, 2,465 pharyngeal cancer, 874 unspecified oral/pharynx cancer, 1,329 laryngeal cancer and 306 overlapping HNC cases. Odds ratios (OR) and 95% confidence intervals (CIs) for self reported ever use of any vitamins, multivitamins, vitamin A, vitamin C, vitamin E, and calcium, beta-carotene, iron, selenium and zinc supplements were assessed. We further examined frequency, duration and cumulative exposure of each vitamin or mineral when possible and stratified by smoking and drinking status. All ORs were adjusted for age, sex, race/ethnicity, study center, education level, pack-years of smoking, frequency of alcohol drinking and fruit/vegetable intake. A decreased risk of HNC was observed with ever use of vitamin C (OR = 0.76, 95% CI = 0.590.96) and with ever use of calcium supplement (OR = 0.64, 95% CI = 0.420.97). The inverse association with HNC risk was also observed for 10 or more years of vitamin C use (OR = 0.72, 95% CI = 0.540.97) and more than 365 tablets of cumulative calcium intake (OR = 0.36, 95% CI = 0.160.83), but linear trends were not observed for the frequency or duration of any supplement intake. We did not observe any strong associations between vitamin or mineral supplement intake and the risk of HNC.

ORAOV1 is amplified in oral squamous cell carcinoma

BACKGROUND: Oral cancer overexpressed 1 (ORAOV1) was found as a candidate oncogene in the 11q13 chromosomal region, based on its amplification and overexpression in oral cancer cell lines. Because gene amplification often leads to increased levels of gene expression, we aimed to verify the relationship between ORAOV1 gene status and mRNA expression primarily in oral squamous cell carcinoma (OSCC) by quantitative assay, correlating with clinical and pathological characteristics in patients. METHODS: Levels of ORAOV1 amplification and expression were evaluated by qPCR and RT-qPCR in OSCC cell lines and in tumor and non-tumoral surgical margins from 33 patients with OSCC. All subjects were smokers and habitual alcohol drinkers, mostly men above 40 years of age and with a single primary tumor. RESULTS: ORAOV1 exhibited increased gene expression levels as well as higher copy number in three OSCC cell lines with 11q13 amplified chromosomal region when compared with the OSCC cell line without the amplification (one-way ANOVA, P < 0.05). Weak correlation between ORAOV1 mRNA levels and DNA copy number was seen in tumor samples (Spearman, P = 0.07). Although ORAOV1 was amplified in tumor (Wilcoxon, P < 0.01), high levels of transcripts in margin did not reveal differences in comparison with tumor (Wilcoxon, P = 0.85). Aggressiveness and survival rate did not demonstrate statistical difference for both events in OSCC. CONCLUSION: The overexpression of ORAOV1 in non-tumoral margin samples can occur in the absence of amplification. The weak correlation between ORAOV1 amplification and expression in OSSC suggests that ORAOV1 expression can be regulated by mechanisms other than gene amplification. J Oral Pathol Med (2012) 41: 5460

Accuracy of Screening for Potentially Malignant Disorders of the Oral Mucosa by Dentists in Primary Care

Purpose: To examine the accuracy of a screening programme for potentially malignant disorders of the oral mucosa by visual inspection in primary health care. Materials and Methods: The study was based on secondary data from the Primary Care Information System maintained by seven units of family health in Sao Paulo City managed by a non-governmental agency. The reference population was composed of 15,072 residents 50 years old or more of both genders. The study population comprised 2,980 individuals. During screening in community settings, the oral mucosa was examined by trained dentists and distributed into two categories: (a) screen negative (b) screen positive. All participants underwent comprehensive clinical exams by a general dental practitioner supervised by a specialist. Individual records were grouped in a working dataset. Point and 95% confidence interval estimates were calculated regarding measures of sensitivity (Se), specificity (Sp) and positive and negative predictive values (PPV and NPV, respectively). Results: 18.0% of the population was considered screen positive. A total of 133 lesions (4.5%) were identified and 8 cases of oral cancer were confirmed, which corresponded to a prevalence rate of 27 cases in 10,000 people, a much higher rate than expected. The measures found were Se: 91.7% (85.3-95.6), Sp: 85.4% (84.1-86.7), PPV: 22.7% (19.3-26.5), NPV: 99.5% (99.2-99.8). The visual screen presented high accuracy. Conclusion: The test presented high sensibility and specificity values. From a public health point of view, the high accuracy levels showed the importance of oral health teams on family health strategy for more comprehensive primary care. Targeting risk groups and delegating the screening to community health agents may improve PPV and coverage.

Do Tobacco and Alcohol Modify Protective Effects of Diet on Oral Carcinogenesis?

Recent systematic reviews concluded that the frequent consumption of fruits and vegetables is inversely associated with the risk of oral cancer. We assessed this association, specifically comparing results obtained to nonsmokers and smokers, as well to nondrinkers and drinkers. We conducted a case-control study involving 296 patients with oral squamous cell carcinoma (cases) attended in 3 major hospitals of Sao Paulo, Brazil, paired with 296 controls, recruited from outpatient units of the same hospitals. Multivariate models assessed the effect of fruits and salads according to smoking and drinking. The intake of fruit was associated with the prevention of the disease in the specific assessment among light [odds ratio (OR) = 0.46; 95% confidence interval (CI) = 0.27-0.78) and heavy (OR = 0.30; 95% CI = 0.14-0.65) smokers. The same was observed for vegetables consumption. For nonsmokers, no fruit (OR = 50; 95% CI = 0.22-1.12) or vegetable (for tomato, OR = 0.53; 95% CI = 0.31-0.93) was associated with reduced risk of oral and oropharyngeal cancer. Similar results were found in the stratified analysis according to drinking status with OR = 0.51 (95% CI = 0.30-0.87) and 0.18 for fruits (95% CI = 0.07-0.45), respectively, for light and heavy drinkers. This observation suggests that the protective effect of fruit and salad intake may modulate the deleterious effects from tobacco and alcohol.

Diet and the risk of head and neck cancer: a pooled analysis in the INHANCE consortium

We investigated the association between diet and head and neck cancer (HNC) risk using data from the International Head and Neck Cancer Epidemiology (INHANCE) consortium. The INHANCE pooled data included 22 case-control studies with 14,520 cases and 22,737 controls. Center-specific quartiles among the controls were used for food groups, and frequencies per week were used for single food items. A dietary pattern score combining high fruit and vegetable intake and low red meat intake was created. Odds ratios (OR) and 95% confidence intervals (CI) for the dietary items on the risk of HNC were estimated with a two-stage random-effects logistic regression model. An inverse association was observed for higher-frequency intake of fruit (4th vs. 1st quartile OR = 0.52, 95% CI = 0.43-0.62, p (trend) < 0.01) and vegetables (OR = 0.66, 95% CI = 0.49-0.90, p (trend) = 0.01). Intake of red meat (OR = 1.40, 95% CI = 1.13-1.74, p (trend) = 0.13) and processed meat (OR = 1.37, 95% CI = 1.14-1.65, p (trend) < 0.01) was positively associated with HNC risk. Higher dietary pattern scores, reflecting high fruit/vegetable and low red meat intake, were associated with reduced HNC risk (per score increment OR = 0.90, 95% CI = 0.84-0.97).

Effects of 3-Dimensional Conformal or Intensity-modulated Radiotherapy on Dental Pulp Sensitivity during and after the Treatment of Oral or Oropharyngeal Malignancies

Introduction: Radiation therapy (RT) of malignant tumors in the head and neck area may have damaging effects on surrounding tissues. The aim of this investigation was to evaluate the effects of RI delivered by 3-dimensional conformal radiotherapy (3D-RT) or intensity-modulated radiotherapy (IMRT) on dental pulp sensitivity. Methods: Twenty patients with oral or oropharyngeal cancer receiving RT with 3D-RT or IMRT underwent cold thermal pulp sensitivity testing (PST) of 2 teeth each at 4 time points: before RT (TP1), the beginning of RT with doses between 30 and 35 Gy (TP2), the end of RT with doses between 60 and 70 Gy (TP3), and 4 to 5 months after the start of RT (TP4). Results: All 40 teeth showed positive responses to PST at TP1 (100%) and 9 at TP2 (22.5%; 3/16 [18.8%] for 3D-RT and 6/24 [25.0%] for IMRT). No tooth responded to PST at TP3 and TP4 (0%). A statistically significant difference existed in the number of positive pulp responses between different time points (TP1 through TP4) for all patients receiving RT (P <= .05), IMRT (P <= .05), and 3D-RT (P <= .05). No statistically significant differences in positive sensitivity responses were found between 3D-RT and IMRT at any time point (TP1, TP3, TP4, P = 1.0; TP2, P = .74). A statistically significant correlation existed between the location of the tumor and PST at TP2 for IMRT (P <= .05) but not for 3D-RT (P = .14). Conclusions: RT decreased the number of teeth responding to PST after doses greater than 30 to 35 Gy. The type of RT (3D-RT or IMRT) had no influence on the pulp responses to PST after the conclusion of RT. (J Endod 2012;38:148-152)

Oral health risks of tobacco use and effects of cessation

The purpose of this paper is to review the epidemiologic evidence for the effects of tobacco use and tobacco use cessation on a variety of oral diseases and conditions. Exposures considered include cigarette and bidi smoking, pipe and cigar smoking, and smokeless tobacco use. Oral diseases and disorders considered include oral cancer and precancer, periodontal disease, caries and tooth loss, gingival recession and other benign mucosal disorders as well as implant failure. Particular attention is given to the impact of tobacco use cessation on oral health outcomes. We conclude that robust epidemiologic evidence exists for adverse oral health effects of tobacco smoking and other types of tobacco use. In addition, there is compelling evidence to support significant benefits of tobacco use cessation with regard to various oral health outcomes. Substantial oral health benefits can be expected from abstention and successful smoking cessation in a variety of populations across all ages.

Oral leukoplakia in China: a review

BACKGROUND: Most prevalence studies on oral leukoplakia (OL) in China have been published in the Chinese language. The present review on the literature in Chinese aimed at making the data available to colleagues who are not familiar with the Chinese language. METHODS: The overall rate and 95% confidence interval of OL were calculated using Excel 2003. RESULTS: Overall prevalence of OL was 9.18% (95%CI = 9.06-9.30%). Gender ratio of prevalence was 8.03:1 (males/females). Prevalence was high in age groups over 40 years with the highest in the group aged 60-69 years (21.04%, 95%CI = 19.95-22.13%). The buccal mucosa was most commonly affected (47.08%, 95%CI = 46.52-47.64%), followed by lip (39.09%), palate (9.85%), gingiva (1.80%), and tongue (1.46%). The prevalence in smokers was 23.43% and in non-smokers 1.93%. Among three variants of smoking, the traditional Hanyan pipe smoking carried the highest risk for the development of OL followed by cigarette and Shuiyan water pipe smoking. The rate of alcohol drinkers with OL was 54.50% and 22.21% in individuals without OL. No case of oral cancer was found in six surveys. CONCLUSIONS: The present data on the prevalence of OL in China are comparable to those in other parts of the world. Some traditional smoking habits, however, are particular to certain regions of China.

Fibula free flap reconstruction of the mandible in cancer patients: Evaluation of a combined surgical and prosthodontic treatment concept

The final goal of mandibular reconstruction following ablative surgery for oral cancer is often considered to be dental implant-supported oral rehabilitation, for which bone grafts should ideally be placed in a suitable position taking subsequent prosthetic restoration into account. The aim of this study was to evaluate the efficacy of a standardized treatment strategy for mandibular reconstruction according to the size of the bony defect and planned subsequent dental prosthetic rehabilitation. Data of 56 patients, who had undergone such a systematic mandibular fibula free flap reconstruction, were retrospectively analyzed. Early complications were observed in 41.5% of the patients but only in those who had been irradiated. Late complications were found in 38.2%. Dental implant survival rate was 92%, and dental prosthetic treatment has been completed in all classes of bony defects with an overall success rate of 42.9%. The main reasons for failure of the complete dental reconstruction were patients' poor cooperation (30.4%) and tumour recurrence (14.3%) followed by surgery-related factors (10.8%) such as implant failure and an unfavourable intermaxillary relationship between the maxilla and the mandible. A comparison of our results with the literature findings revealed no marked differences in the complication rates and implant survival rates. However, a systematic concept for the reconstructive treatment like the method presented here, plays an important role in the successful completion of dental reconstruction. The success rate could still be improved by some technical progress in implant and bone graft positioning.

[Smokeless tobacco: a new risk factor for oral health? A review]

Due to migration of different ethnic groups, mainly from Africa and Asia, into Switzerland, many traditional products and habits that have not been seen before were also introduced. Smokeless tobacco (ST)--as one of those habits--is a product of increased use in Switzerland, although no sound epidemiological data are presently available. Numerous studies from North-America, Sweden, Asia and Africa could verify the carcinogenic potency of smokeless tobacco and its effects in the developement of oral cancer and different systemic disorders. For dental professionals and their team it is important to detect ST-associated lesions, and to tell the patients about the potential harmful sequelae of ST products. The present review focusses on the different types of RT products and their effects on oral health.

Recurrence due to neoplastic seeding in head and neck cancer: report of two cases and review of the literature

AIMS AND BACKGROUND Tumor progression due to seeding of tumor cells after definitive treatment for squamous cell carcinomas of the head and neck is an uncommon condition that can considerably worsen the outcome of patients with head and neck cancer. METHODS AND STUDY DESIGN We report two cases of recurrence due to neoplastic seeding from oropharyngeal and oral cancer, respectively. We performed a literature review with MEDLINE as the main search engine. RESULTS Seeding was found to occur most often in tracheotomy scars and gastrostomy sites. The oral cavity, hypopharynx and oropharynx were the primary sites in most cases, and advanced tumor stage seemed to be a risk factor for seeding. Treatment options include salvage surgery, which requires thorough resections, radiotherapy when possible, and palliative management. The prognosis of such events is poor. CONCLUSION Although neoplastic seeding is a well-known phenomenon in cancer surgery, many questions remain unanswered, especially regarding preventive measures and management strategies.

Incidental detection of an occult oral malignancy with autofluorescence imaging: a case report.

BACKGROUND: Autofluorescence imaging is used widely for diagnostic evaluation of various epithelial malignancies. Cancerous lesions display loss of autofluorescence due to malignant changes in epithelium and subepithelial stroma. Carcinoma of unknown primary site presents with lymph node or distant metastasis, for which the site of primary tumour is not detectable. We describe here the use of autofluorescence imaging for detecting a clinically innocuous appearing occult malignancy of the palate which upon pathological examination was consistent with a metastatic squamous cell carcinoma. CASE DESCRIPTION: A submucosal nodule was noted on the right posterior hard palate of a 59-year-old white female during clinical examination. Examination of this lesion using a multispectral oral cancer screening device revealed loss of autofluorescence at 405 nm illumination. An excisional biopsy of this nodule, confirmed the presence of a metastatic squamous cell carcinoma. Four years ago, this patient was diagnosed with metastatic squamous cell carcinoma of the right mid-jugular lymph node of unknown primary. She was treated with external beam irradiation and remained disease free until current presentation. CONCLUSION: This case illustrates the important role played by autofluorescence tissue imaging in diagnosing a metastatic palatal tumour that appeared clinically innocuous and otherwise would not have been biopsied.