Long-term follow-up of osteoradionecrosis of the mandible.

AIM: Investigating the prevalence of mandibular ORN in a single Swedish Oncology Center. METHODS: A total of 450 patients, treated with radiotherapy for squamous cell carcinoma in the oropharynx between 2004 and 2014 were included. Three different techniques of radiotherapy were studied. ORN diagnosis was set when clinical signs according to Marx were observed, or if radiological signs were staged according to Schwartz and Kagan. RESULTS: Using the staging system, 90 patients (20%) were diagnosed with ORN. The mean age of the ORN patients was 56.6 years, the older the patient the lower the risk of developing ORN (p = .01). The risk of developing ORN for patients receiving Intensity Modulated Radiotherapy was lower compared to patients treated with the other techniques in the multivariable analysis. Brachytherapy significantly increases the risk of ORN. The risk of ORN increased by 8% each year after radiation (p = .04). The mean time to the ORN diagnosis was 3.9 years. In the multivariate analysis, the risk of ORN increased by 13% each year after radiation (p = .0013). CONCLUSION: The mean radiation dose was of greater importance for the risk of ORN than the maximum dose. Elderly people with oropharyngeal cancer were less prone to develop ORN.

Intracellular Toll-Like Receptors Modulate Adaptive Immune Responses in Head and Neck Cancer.

The percentage of head and neck cancer (HNC) positive for human papillomavirus (HPV) is unknown in most parts of India. How toll-like receptors (TLRs) affect the adaptive immune response in HNC is also mainly unknown. We here assessed the expressions of HPV DNA, p16, inflammation, and TLRs in oral squamous cell carcinoma (OC) and oropharyngeal squamous cell carcinoma (OPC). Patients with OC (n = 31) and OPC (n = 41), diagnosed during 2017-2018 at the Malabar Cancer Centre (tertiary cancer center), Kerala, India, were included in the study. Immunohistochemistry was performed on tumor specimens against p16, TLR3, TLR7, TLR8, TLR9, CD4, and CD8. Quantitate polymerase chain reaction for 14 high-risk HPVs (HPV16/18/31/33/35/39/45/51/52/56/58/59/66/68) was performed. Seven out of 31 OC (22.6%) were p16+ but only 3.2% (1/31) of OC were positive for HPV DNA. While 24.4% (10/41) of OPC were p16+, HPV DNA was found in only one P16+ OPC and in no P16- OPC. TLR3, TLR7, TLR8, and TLR9 were expressed both in OC and in OPC. The expression of TLR7 was significantly higher in OPC compared with OC. TLR8 expression was correlated with and TLR7 tended to be correlated with the inflammatory score in OPC (r = 0.56, p < 0.05 and r = 0.52, p = 0.08, respectively). In conclusion, the role of HPV in OC and OPC is minor, and p16 constitutes a poor biomarker for HPV positivity in Kerala, India. Intracellular TLRs are correlated with the degree of inflammation in OPC but not in OC and may potentially constitute a medical target in the therapy of HNC in the future.

Patients' experiences of adverse symptoms, emotions, and coping strategies in connection to treatment of head and neck cancer - an interview study.

PURPOSE: This study aimed to increase the understanding of emotions and coping strategies used by head and neck cancer patients before cancer treatment, and to explore their emotions and coping strategies in relation to symptoms and side effects after treatment. Furthermore, we aimed to investigate the patients' perceptions of received treatment and support. METHODS: Semi-structured in-depth interviews were conducted with 10 patients who had been treated for head and neck cancer, which included radiotherapy, at the Department of Oncology and the Department of Oral and Maxillofacial Surgery at Sahlgrenska University Hospital in Gothenburg. The interviews were analyzed in accordance with the method for Qualitative Content Analysis. RESULTS: The result picture revealed three head themes. The first theme "Management of simultaneously influencing mind-sets before cancer treatment" described the patients experiences of feeling "Scared and worried," "Lonely and disappointed," and "Relieved and confident", and how they tried to handle the diagnosis and preparations for treatment by "Applying a positive mind-set", "Searching for support," and "Trusting the healthcare system". The second theme "Experiences of becoming a pale shadow of oneself", illustrated experiences of affecting post-treatment symptoms and side effects. To which, the last theme "Handling contextual influencing experiences after cancer treatment" displayed post-treatment emotions of being "Shocked and disappointed" and "Concerned and unsupported" but also "Grateful and forward-thinking", where strategies such as "Appreciating Life", "Networking socially," and "Adapting to the new life" were used. CONCLUSIONS: The results indicated the need for a more patient-centered care approach, with clearer structures and improved individual support both before and after treatment and in connection to rehabilitation. Patients' cognitive changes after cancer treatment should be considered in the aftercare, which should also include adaptation to situation and strengthening of patients' self-management as a goal.

Brachytherapy and osteoradionecrosis in patients with base of tongue cancer.

BACKGROUND: Base of tongue cancer incidence and patient survival is increasing why treatment sequelae becomes exceedingly important. Osteoradionecrosis (ORN) is a late adverse effect of radiotherapy and brachytherapy (BT) could be a risk factor. Brachytherapy is used in three out of six health care regions in Sweden. AIMS: Investigate if patients treated in regions using BT show an increased risk for ORN and whether brachytherapy has any impact on overall survival. MATERIAL AND METHODS: We used data from the Swedish Head and Neck Cancer Register between 2008-2014. Due to the nonrandomized nature of the study and possible selection bias we compared the risk for ORN in brachy vs non-brachy regions. RESULTS: Fifty out of 505 patients (9.9%) developed ORN; eight of these were treated in nonbrachy regions (16%), while 42 (84%) were treated in brachy regions. Neither age, sex, TNM-classification/stage, p16, smoking, neck dissection, or chemotherapy differed between ORN and no-ORN patients. The risk for ORN was significantly higher for patients treated in brachy regions compared to non-brachy regions (HR = 2,63, p = .012), whereas overall survival did not differ (HR = 0.95, p = .782). CONCLUSIONS AND SIGNIFICANCE: Brachytherapy ought to be used cautiously for selected patients or within prospective randomized studies.

Recurrent copy number alterations involving EGFR, CDKN2A, and CCND1 in oral premalignant lesions.

BACKGROUND: A major challenge in the management of patients with oral leukoplakia is the difficulty to identify patients at high risk of developing oral squamous cell carcinoma. Our knowledge about genomic alterations in oral leukoplakia, and in particular those that progress to oral squamous cell carcinoma, is scarce and there are no useful biomarkers that can predict the risk of malignant transformation. METHODS: Using a novel, custom-made tissue microarray including 28 high-risk oral leukoplakias and the corresponding oral squamous cell carcinomas from 14 cases that progressed to cancer, we assayed copy number alterations involving the oral squamous cell carcinoma driver genes CDKN2A, CCND1, EGFR, and MYC by fluorescence in situ hybridization. The copy number alterationss were correlated with clinicopathological data from all patients. RESULTS: Copy number alterations were identified in 14/24 oral leukoplakias, analyzable for one or more of the oral squamous cell carcinoma driver genes. EGFR was the most frequently altered gene in oral leukoplakias with amplification/gain in 43.5% followed by loss of CDKN2A (26.1%), gains of CCND1 (26.1%), and MYC (8.3%). Losses of CDKN2A were more common in oral leukoplakias progressing to oral squamous cell carcinoma compared to those that did not. Copy number alterations were more common in oral squamous cell carcinomas than in oral leukoplakias. CONCLUSIONS: Our findings demonstrate that copy number alterations involving the oral squamous cell carcinoma drivers CDKN2A, EGFR, and CCND1 occur in oral leukoplakias and suggest a possible role for these genes in the development and/or progression of subsets of oral leukoplakias.

Langerhans Cells, T Cells, and B Cells in Oral Lichen Planus and Oral Leukoplakia.

Although oral lichen planus (OLP) and oral leukoplakia (LPL) have different pathogenetic profiles, both may involve chronic inflammation. The aim of this observational study was to evaluate the inflammatory cell profiles of OLP and LPL. The inflammatory cell infiltrates in patients with OLP and LPL were analyzed for the presence of Langerhans cells (LCs; CD1a), T cells (CD3), and B cells (CD20), as well as for the proliferation marker Ki-67. Biopsied specimens from patients with OLP (N = 14) and LPL without dysplasia (N = 13) were immunohistochemically stained with antibodies directed against CD1a, CD3, CD20, and Ki-67, followed by quantitative analyses. A significant increase in the number of CD3+ cells and CD20+ cells was found in the submucosa of OLP, as compared to LPL (p < 0.01). Likewise, the number of CD3+ cells was significantly higher in the epithelium of OLP than of LPL (p < 0.05). No differences were found in the expression of Ki-67 and the number of CD1a+ cells between the two groups. Although an immune response is elicited in both conditions, there are differences at the cellular level between OLP and LPL. A more robust immune activation involving T cells and B cells is seen in OLP. The role of B cells in OLP needs to be further elucidated. Although the number of B cells in LPL is low, their role in the inflammatory response cannot be ruled out.

Hyperbaric oxygen treatment of mandibular osteoradionecrosis: Combined data from the two randomized clinical trials DAHANCA-21 and NWHHT2009-1.

PURPOSE: Osteoradionecrosis (ORN) of the mandible is a serious complication of head and neck radiotherapy. This study aims to investigate the effect of hyperbaric oxygen (HBO) treatment on ORN in two randomized, controlled multicentre trials. METHODS AND MATERIALS: Patients with ORN with indication for surgical treatment were randomised to either group 1: surgical removal of necrotic mandibular bone supplemented by 30 pre- and 10 postoperative HBO exposures at 243 kPa for 90 min each, or group 2: surgical removal of necrotic bone only. Primary outcome was healing of ORN one year after surgery evaluated by a clinically adjusted version of the Common Toxicity Criteria of Adverse Events (CTCAE) v 3.0. Secondary outcomes included xerostomia, unstimulated and stimulated whole salivation rates, trismus, dysphagia, pain, Activities of Daily Living (ADL) and quality of life according to EORTC. Data were combined from two separate trials. Ninety-seven were enrolled and 65 were eligible for the intent-to-treat analysis. The 33% drop-out was equally distributed between groups. RESULTS: In group 1, 70% (21/30) healed compared to 51% (18/35) in group 2. HBO was associated with an increased chance of healing independent of baseline ORN grade or smoking status as well as improved xerostomia, unstimulated whole salivary flow rate, and dysphagia. Due to insufficient recruitment, none of the endpoints reached a statistically significant difference between groups. ADL data could only be obtained from 50 patients. CONCLUSION: Hyperbaric oxygen did not significantly improve the healing outcome of osteoradionecrosis after surgical removal of necrotic bone as compared to standard care (70% vs. 51%). This effect is not statistically significant due to the fact that the study was underpowered and is therefore prone to type II error.

The prevalence and symptoms of temporomandibular disorders in head and neck cancer patients.

OBJECTIVES: This retrospective patient survey aimed to assess the prevalence of temporomandibular disorders (TMD) before and after curative oncological treatment and to identify possible risk factors. MATERIALS AND METHODS: Patients with squamous cell carcinoma in the tonsil or base of the tongue were included (n = 217). Medical records were collected to assess TMD prevalence before oncological treatment and at 6- and 12-month follow-up. Fisher's test and Pitman's test were used. RESULTS: Significantly reduced mouth opening was observed after oncological treatment at 6- and 12-month follow-up (p < .001). Symptoms from the temporomandibular joint and jaw muscles plus pain upon palpation (p = .0083, p < .001, respectively) and self-reported pain upon chewing (<0.001) and opening the mouth (<0.001) increased 12 months following radiotherapy. Pain and degree of mouth opening prior to treatment, self-reported depression, overall health status, brachytherapy and jaw exercise during radiotherapy were factors affecting the increase of TMD symptoms. CONCLUSION: All TMD symptoms escalated significantly one year after radiotherapy except self-reported sounds from the temporomandibular joint. Reduction in the degree of mouth opening and pain in the jaw muscles and the temporomandibular joint when opening the mouth and upon chewing were commonly reported symptoms following radiotherapy. Several potential risk factors were identified.

Expression of p53, p63, podoplanin and Ki-67 in recurring versus non-recurring oral leukoplakia.

Oral leukoplakia (OL), a potentially malignant disorder, recurs in 40% of cases after surgical removal. Recurrence is a risk factor for malignant transformation. We aimed to examine the prognostic significance of four biomarkers related to cell proliferation: p53, p63, podoplanin (PDPN) and Ki-67 in predicting recurrence. Formalin-fixed-paraffin-embedded specimens from excised OL (n = 73, 33 recurrent; 40 non-recurrent) were collected in a prospective study. Immunohistochemistry was used to visualise expression of p53, p63, PDPN and Ki-67. Image analysis software was used for quantification of p53-, p63- and Ki-67-expressing cells, while PDPN was analysed visually. The expression of all four proteins were higher in recurrent compared with non-recurrent OL, only expression of p53 was statistically significant. In uni- and multivariable Cox regression analyses of individual markers, expression of p63 was significantly associated with higher recurrence risk (p = 0.047). OL with a combined high expression of both p53 and p63 had a significantly higher risk to recur [Log Rank, p = 0.036; multivariate Cox, HR: 2.48 (1.13-5.44; p = 0.024)]. Combination of p53 and p63 expression may be used as a prognostic biomarker for recurrence of OL.

Patient-reported pain after surgical removal of leukoplakia - an observational 1-year follow-up study.

OBJECTIVE: Oral leukoplakia (OL) presents as a white lesion of the oral mucosa and is not typically associated with the sensation of pain. OL should be surgically removed when possible because it is considered a potentially malignant oral disorder (PMOD). This study assessed the pain sensations experienced by patients in association with the occurrence and surgical treatment of OL. METHODS: Inclusion criteria were: a clinical diagnosis of OL; biopsy excision; and observation for at least 12 months in the ORA-LEU-CAN study. At the first visit, all the patients were asked about the occurrence of symptoms within the lesion. Ninety-four subjects were assessed over a period of 1 year. All patients underwent complete removal of OL. The patient cohort was divided into three sub-groups: (i) no pain before excision and at the 1-year follow-up; (ii) pain before excision; and (iii) pain at the 1-year follow-up. RESULTS: Overall, pain was reported by 21.3% of the patients at the study start whereas 13.8% of the patients reported pain 1 year after surgical treatment. Patient-reported pain from the lesion at study inclusion was significantly associated with lesions found on the lateral side of the tongue (p=.002). Pain reported by patients one year after surgery was significantly related to female gender (p=.038) and the presence of epithelial cell dysplasia (p=.022). CONCLUSION: We conclude that surgical removal of OL results in a low risk of long-term post-surgical pain. However, OL located on the lateral side of the tongue and in OL with dysplasia are more likely to be associated with pain.

Comparison of Immunohistochemistry and DNA Sequencing for BRAF V600E Mutation Detection in Mandibular Ameloblastomas.

This study aimed to investigate the presence of BRAF V600E mutation in mandibular ameloblastoma by comparing the results of molecular detection and immunohistochemical analysis. A 128 cases of mandibular ameloblastoma and 30 cases of dentigerous cyst (control group) were selected for analysis. Detection of BRAF V600E mutation was performed with immunohistochemistry (IHC) and polymerase chain reaction techniques. Clinico-pathologic data were collected in order to investigate possible associations with the mutation. Of the 128 cases submitted to IHC, 81.2% (108 cases) showed positivity for anti-BRAF V600E antibody, whereas 24 were negative (18.8%). Molecular analysis of the BRAF V600E mutation by polymerase chain reaction was possible in 116 cases due to DNA quality. Of these cases, 96 were positive (82.8%) and 20 negative (17.2%). All cases of dentigerous cyst were negative for BRAF V600E mutation in both techniques. Considering the sequencing as a gold standard method, the receiver operating characteristics curve analysis showed sensitivity of 0.99 and specificity of 1 (area under the curve=0.995, standard error=0.006; P<0.001; 95% confidence interval=0.983 to 1). We also tested the agreement between the techniques by using the Cohen's κ coefficient, with κ being 0.97 (P<0.001). IHC is a reliable test for identifying the BRAF V600E mutation in ameloblastomas, presenting advantages such as being more frequently used in surgical pathology laboratories and requiring fewer critical steps for paraffin-embedded tissue compared with molecular biology techniques.

High-risk human papillomavirus in patients with oral leukoplakia and oral squamous cell carcinoma-A multi-centre study in Sweden, Brazil and Romania.

OBJECTIVES: Although causal associations between oral leukoplakia (OL), oral squamous cell carcinoma (OSCC) and high-risk human papillomavirus (HR-HPV) have been speculated upon in several reports, conclusive evidence has not been presented. This study investigates whether the number of cases of HR-HPV in OL has increased over time and whether the prevalence of HR-HPV-positive OL differs in various parts of the world. PATIENTS AND METHODS: A total of 432 patients with OL from Sweden, Brazil and Romania were analysed. Patients were divided into historical (1992-2002) and contemporary (2011-2017) cohorts from the respective countries. Seventeen patients with OL developed oral squamous cell carcinoma (OSCC). A real-time PCR assay, targeting HPV sub-types 6,11,16,18,31,33,35,39,45,52,56,58 and 59, was performed to detect HR-HPV in patients with OL. RESULTS: In the Swedish and Romanian cohorts, none of the investigated HPV sub-types were detected. In the Brazilian cohorts, five patients with OL (3%) were positive for HR-HPV, including four patients from the contemporary cohort (HPV 16, 31, 33) and one from the historical cohort (HPV 11). All the cases of OL that transformed into OSCC were HR-HPV-negative, as were the corresponding tumours. CONCLUSIONS: In summary, the prevalence of HR-HPV in OL is low in all the tested countries, and the incidence has not changed over time. HR-HPV in OL does not seem to be a driver of oncogenesis.

Expression of tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL) in minor salivary glands and saliva.

OBJECTIVE: The aim of this study was to characterize the baseline expression of tumor necrosis factor (tnf)-related apoptosis inducing ligand (TRAIL) in minor salivary glands, gingiva and saliva from healthy individuals. DESIGN: Minor salivary gland and gingival tissues were used in the study for immunohistochemical staining. An enzyme-linked immunosorbent assay was used to measure the levels of TRAIL in unstimulated saliva and parotid saliva collected from non-smoking individuals. The salivary levels of TRAIL are presented as secretory output. RESULTS: Parotid saliva showed higher secretory output (327.8 ±â€¯41.6 pg/min) for TRAIL compared to unstimulated saliva (212.3 ±â€¯32.1 pg/min; p =0.041). For unstimulated saliva, the young female subjects had the lowest secretory output (119 ±â€¯17.2 pg/min) compared to elderly females (275 ±â€¯62.18 pg/min; p =0.046) and young males (294.4 ±â€¯50.2 pg/min; p =0.021). The ductal cells of salivary glands exhibited the strongest positivity for TRAIL, whereas mucous cells showed no staining for TRAIL. Serous cells displayed an intermediate staining. Gingival tissues showed gradually decreasing staining towards the basal layer. CONCLUSIONS: The current study shows that TRAIL is not only expressed by immune cells, but also by the epithelial cells of salivary glands. Saliva contains high concentrations of soluble TRAIL that suggest roles of this protein in the apoptosis of tumor cells.

Three-Dimensional Bioprinting Using a Coaxial Needle with Viscous Inks in Bone Tissue Engineering - An In vitro Study.

INTRODUCTION: Vascularized autologous tissue grafts are considered "gold standard" for the management of larger bony defects in the craniomaxillofacial area. This modality does however carry limitations, such as the absolute requirement for healthy donor tissues and recipient vessels. In addition, the significant morbidity of large bone graft is deterrent to fibula bone flap use. Therefore, less morbid strategies would be beneficial. The purpose of this study was to develop a printing method to manufacture scaffold structure with viable stem cells. MATERIALS AND METHODS: In total, three different combinations of ground beta tri-calcium phosphate and CELLINK (bioinks) were printed with a nozzle to identify a suitable bioink for three-dimensional printing. Subsequently, a coaxial needle, with three different nozzle gauge combinations, was evaluated for printing of the bioinks. Scaffold structures (grids) were then printed alone and with additional adipose stem cells before being transferred into an active medium and incubated overnight. Following incubation, grid stability was evaluated by assessing the degree of maintained grid outline, and cell viability was determined using the live/dead cell assay. RESULTS: Among the three evaluated combinations of bioinks, two resulted in good printability for bioprinting. Adequate printing was obtained with two out of the three nozzle gauge combinations tested. However, due to the smaller total opening, one combination revealed a better stability. Intact grids with maintained stability were obtained using Ink B23 and Ink B42, and approximately 80% of the printed stem cells were viable following 24 hours. DISCUSSION: Using a coaxial needle enables printing of a stable scaffold with viable stem cells. Furthermore, cell viability is maintained after the bioprinting process.

Recurrence rates after surgical removal of oral leukoplakia-A prospective longitudinal multi-centre study.

Oral leukoplakia (OL) is a potentially malignant oral disorder. The Gold Standard treatment is to remove surgically the OL. Despite optimal surgery, the recurrence rates are estimated to be 30%. The reason for this is unknown. The aim of this study was to investigate the clinical factors that correlate with recurrence after surgical removal of OL. In a prospective study data were collected from 226 patients with OL. Forty-six patients were excluded due to incomplete records or concomitant presence of other oral mucosal diseases. Overall, 180 patients proceeded to analysis (94 women and 86 men; mean age, 62 years; age range, 28-92 years). Clinical data, such as gender, diagnosis (homogeneous/non-homogeneous leukoplakia), location, size, tobacco and alcohol use, verified histopathological diagnosis, and clinical photograph, were obtained. In patients who were eligible for surgery, the OL was surgically removed with a margin. To establish recurrence, a healthy mucosa between the surgery and recurrence had to be confirmed in the records or clinical photographs. Statistical analysis was performed with the level of significance set at P<0.05. Of the 180 patients diagnosed with OL, 57% (N = 103) underwent surgical removal in toto. Recurrence was observed in 43 OL. The cumulative incidence of recurrence of OL was 45% after 4 years and 49% after 5 years. Fifty-six percent (N = 23) of the non-homogeneous type recurred. Among snuff-users 73% (N = 8) cases of OL recurred. A non-homogeneous type of OL and the use of snuff were significantly associated with recurrence after surgical excision (P = 0.021 and P = 0.003, respectively). Recurrence was also significantly associated with cancer transformation (P<0.001). No significant differences were found between recurrence and any of the following: dysplasia, site of lesion, size, multiple vs. solitary OL, gender, age, use of alcohol or smoking. In conclusion, clinical factors that predict recurrence of OL are non-homogeneous type and use of snuff.

Mandibular biomechanics after marginal resection: Correspondences of simulated volumetric strain and skeletal resorption.

Serious mandibular diseases such as tumor or osteonecrosis often require segmental or marginal mandibulectomy, the latter with improved outcome thanks to preserved mandibular continuity. Nevertheless, gradual osteolytic and/or osteosclerotic skeletal changes frequently indicate repetitive resections. Based on the fundamental adaptivity of bone to mechanical loads, the question arose whether resection-related anatomical alterations trigger relevant pathological skeletal adaptations. For a clinical case after mandibular box resection due to progressive osteoradionecrosis (ORN), routine biomechanical loading was simulated by finite element method, respecting pathology-related anatomy, tissue properties, and biting capacity. By 3D-visualization of the mandible's pathological development from follow-up-CT's over four years, remarkable correspondences of skeletal resorptions and increased unphysiological strain were revealed. Higher unphysiological load was correlated with more serious and earlier skeletal alterations. Three months post-operatively, serious buccal destruction at the distal resection corner occurred in correspondence with dominant tensile strain. At the resection, elevated strain caused by reduced alveolar height corresponded to skeletal compromise, observed 8-9 months post-operatively. ORN-related lesions, diagnosed before resection, entailed unphysiological strain coinciding with local skeletal alterations. Simulations with "healthy" instead of pathological tissue coefficients induced quantitative improvements of 25-33%, but without fundamental change. These results suggest a decisive contribution of resection-related biomechanical skeletal adaptations to this patient's mandibular decline with hemimandibulectomy about 2.5 years after the first resection. However, mechanical stress concentrations in sharp angles as the distal resection corner and reduced stability due to decreased alveolar height generally bear the danger of pathological biomechanics and severe skeletal adaptations for patients after mandibular box resection.

Combined Testing of p16 Tumour-suppressor Protein and Human Papillomavirus in Patients With Oral Leukoplakia and Oral Squamous Cell Carcinoma.

BACKGROUND: Oral leukoplakia (OL) is a potentially malignant oral mucosal disorder. A casual association between OL, oral squamous cell carcinoma (OSCC) and human papillomavirus (HPV) infection has been suggested, but no conclusive evidence has been presented. p16, a tumour-suppressor protein, is used as a surrogate marker for HPV infection. The aim of this study was to investigate how overexpression of p16 correlates with HPV infection in OL and in OSCC. PATIENTS AND METHODS: Seventy-four patients with OL and 13 with OSCC with p16 overexpressed, were analyzed by immunohistochemistry visualizing p16 and a real-time polymerase chain reaction (PCR) assay targeting HPV types 6, 11, 16, 18, 31, 33, 35, 39, 45, 52, 56, 58 and 59. RESULTS: Overexpression of p16 was observed in 18% of patients with OL. None of the HPV subtypes were detected by PCR analysis in patients with OL. In the p16-positive OSCC specimens, 38% were also HPV16-positive. CONCLUSION: Overexpression of p16 was not found to be a reliable biomarker for HPV infection in patients with OL and OSCC.

Mandible reconstruction with patient-specific implants: Case report of five consecutive patients.

The purpose of this case report was to assess whether patient-specific implants (PSI: Xillocs) and soft tissue flaps contribute in reconstructing large mandibular defects. Five patients with a medical situation and history not suitable for free microvascular bone flaps were operated with PSI and evaluated. The mean follow-up time was 12 months. The excellent fit, convenient surgery, and esthetic outcome were seen as the major advantages. The PSI can, in the authors' experience, be considered as a useful alternative provided they are well embedded by viable tissue and attached to vital resection margins of the recipient bone.

Immunohistochemical analysis of BRAF V600E mutation in ameloblastomas.

OBJECTIVE: This study aimed to investigate the presence of BRAF V600E mutation in mandible ameloblastomas by correlating clinical and imaging data on the cases studied. METHODS: Eighty-four cases diagnosed as mandibular ameloblastoma were selected for analysis. The specimens were submitted to immunohistochemistry for detection of BRAF V600E mutated protein. Clinical-pathological data such as age, gender, tumour size, mandibular location, radiographic aspects, histological type and sub-type, and tumour status were collected. The clinical-pathological parameters were categorised and analysed according to BRAF V600E detection. RESULTS: Of the 84 patients, 78.6% (66 cases) demonstrated positivity for anti-BRAF V600E antibody, whereas 18 were negative (21.4%). The correlation between BRAF expression and variables showed statistical significances for mandibular location (P = 0.0353) and tumour size (P = 0.008), whereas no statistical significance was observed for gender, age, radiographic aspect, histological pattern, histological sub-type and tumour status. Multivariate logistic regression revealed a significant risk for BRAF positivity in tumours with posterior mandibular location (OR = 7.23, P = 0.0451) and size > 4 cm (OR = 7.29, P = 0.0150). CONCLUSION: BRAF V600E mutation is common in mandibular ameloblastomas, especially in cases of tumours larger than 4 cm and in the posterior region of the mandible. In addition, this mutation can occur regardless of histological type of the tumour, age, gender, radiographic aspect and tumour status. CLINICAL SIGNIFICANCE: The association between clinical-pathologic features and BRAF V600E mutation in ameloblastomas may provide directions for the treatment of this neoplasia. The use of BRAF inhibitors for targeted therapy could lead to an establishment of an alternative compared to the resective surgery.

Potentially Malignant Oral Disorders and Cancer Transformation.

Cancer in the oral cavity is often preceded by precursor lesions. Nine oral mucosal disorders are known to have an increased risk of malignant transformation. The etiology varies from disorders caused by exogenous factors such as tobacco and autoimmune inflammation to idiopathic or inherited genetic aberrations. In this review, these potentially malignant disorders (PMDs) are described regarding clinical presentation and histopathological architecture. Special attention is paid to the underlying etiologies of PMDs and the potential pathways leading to cancer. The clinical perspective focuses on the importance of accurate and timely diagnosis.