Sebastian Blatt

The prevalence of human papilloma virus (HPV) infections in oral squamous cell carcinomas: A retrospective analysis of 88 patients and literature overview

In addition to tobacco and alcohol consumption, the two main risk factors for oral squamous cell carcinoma (OSCC), recent studies have revealed infections with human papilloma virus (HPV) as an additional risk factor for OSCC development. In the field of head and neck malignancies, the prevalence of HPV infections in oropharyngeal cancer (OC) ranges in different studies up to 84%. While HPV infection is discussed as an independent risk factor in this region, its distinguished role in carcinogenesis of tumours localized to the oral cavity remains still uncertain. In this study, we analysed the HPV status in 88 consecutive patients with OSCCs localized anterior of the palatoglossal arch who were treated in the Department of Oral and Maxillofacial Surgery at the University Medical Center Mainz. The HPV status analysis was performed using DNA-PCR and immunostaining of p16 protein. The prevalence of HPV-positive OSCCs was about 6% (5 patients). In 3 patients the HPV subtypes 16/18 were found. No significant differences between the HPV positive and negative patients regarding age, gender, smoking and alcohol consumption, localization and TNM level could be detected. Contrary to other studies focussing on cancers of the lingual and palatine tonsil, the prevalence of HPV infections was much lower in the oral cavity. Therefore HPV infection might play a less important role in oral carcinogenesis.

Biomarkers in diagnosis and therapy of oral squamous cell carcinoma: A review of the literature

Oral squamous cell carcinoma (OSCC) represents the sixth most common cancer, accounting for 2-4% of all malignancies worldwide. The overall survival rate of less than 60% remains generally poor, with prognosis heavily relying on the TNM staging system. Tumor size as well as the presence and extent of lymph node metastases are widely recognized as the most important predictors. However, the underlying mechanisms that lead to an aggressive phenotype are not yet fully understood. Therefore, possible biomarkers are much in need to predict prognosis, to help individualize therapy approaches, and to overcome possible resistance mechanisms. Despite a multitude of recently published biomarkers for OSCC, there is still an ongoing debate regarding their implementation in the clinical workflow. Thus, a systematic literature search via PubMed was performed to update the current literature with the latest evidence. In total, 128 studies were included and over 100 different biomarkers evaluated with reference to their influence of survival, tumor recurrence, advanced grading and lymph node metastasis. In this review, we highlight the important molecular mechanism underlying possible markers in tissue, blood or saliva samples for OSCC. As a major result, no clinical trials could be obtained to prove clinical importance of the validated predictors for survival, tumor recurrence, lymph node metastasis and therapy resistance. Therefore, further clinical investigations are much needed.

Diagnosing oral squamous cell carcinoma: How much imaging do we really need? A review of the current literature.

Complementary imaging techniques that round out the clinical examination are fundamentally important in the work-up of patients with oral squamous cell carcinoma (OSCC). Above all, exact determination of primary tumour extent, metastatic spread, and treatment response highly depend on accurate imaging methods. Despite a multitude of recently published reviews, there is still an ongoing debate regarding the best imaging method. In order to update the current literature with the latest evidence, a systematic literature search via Pubmed was performed. In total, 56 studies were enrolled, 4170 patients were analysed, and twenty different imaging methods were evaluated referring to their sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV). In summary, CT (computed tomography) and MRI (magnetic resonance imaging) currently remain the gold standard for evaluating extension of the primary tumour site. No additional evidence could be obtained for functional imaging methods displaying metastatic spread in the cervical lymph nodes, but was found for distant metastases. Furthermore, functional imaging seems to be beneficial in evaluating treatment response. There is further evidence in the accuracy of the different imaging methods found in this update that could possibly be implemented into the revision of the current guidelines and obtain a clear and coherent approach in the clinical set-up.

Comparative metabolic analysis in head and neck cancer and the normal gingiva

ObjectivesChronic accumulation of lactate in malignant tumor tissue is associated with increased malignancy and radioresistance. For this study, biopsies of primary head and neck squamous cell carcinoma (HNSCC) and of the normal gingiva of the same patient were compared via metabolic profiling to the healthy gingiva from cancer-free patients.Materials and methodsCryobiopsies of 140 HNSCC patients were used to determine ATP, lactate, and glucose concentrations of the tumor and normal gingiva via induced metabolic bioluminescence imaging (imBI). Additionally, these metabolites were quantified in a collective of 79 healthy (non-tumor-bearing) patients. Furthermore, tumor samples were analyzed via immunofluorescence imaging and quantitative real-time PCR for the expression of lactate and glucose transporters.ResultsThere were significant differences in ATP concentrations detectable between the tumor, normal gingiva of tumor patients, and gingiva from healthy patients. Lactate concentrations were significantly increased in tumor tissue compared to the normal gingiva of tumor patients as well as the gingiva from healthy patients. Concerning glucose, there was a significant decrease in glucose concentrations detectable in the tumor biopsies compared to the normal gingiva of tumor patients. On the other hand, tumor samples from patients revealed significantly elevated relative expression levels of monocarboxylate transporters (MCT-1 and MCT-4), as well as glucose transporters (GLUT-1 and GLUT-3) compared to the corresponding normal gingiva of each patient.ConclusionsWe could demonstrate that the lactate concentration in HNSCC correlates with primary tumor (T) stage.Clinical relevanceThe aim of this study was to identify metabolic parameters to improve early cancer diagnosis, allow predictions on the degree of malignancy, and contribute to a personalized tumor therapy.

Outcome and cervical metastatic spread of squamous cell cancer of the buccal mucosa, a retrospective analysis of the past 25 years

OBJECTIVES Because of the low proportion of squamous cell carcinomas (SCCs) of the buccal mucosa within the carcinomas of the oral cavity in the Western population, data concerning metastatic pattern are sparse. Therefore, this retrospective study is focusing on the occurrence of cervical metastases (CM) and the overall outcome of this tumor entity. MATERIALS AND METHODS From January 1988 to October 2013, 113 patients were treated in the Department of Oral and Maxillofacial Surgery, Mainz, for an oral SCC of the cheek. Metastatic pattern and clinical parameters that are possibly associated with an increased risk for CM as well as overall outcome were analyzed. RESULTS The average follow-up was 48 months (range: 1-248 months). A total of 55 (49%) patients were female and 58 (51%) male, with an average age of 65 ± 13 years (♀68 ± 14 years; ♂63 ± 11 years). In total, 55% of the patients either smoked and/or consumed alcohol. In total, 34% of the patients had a stage III or IV tumor, with overall 23% having CM at the time of diagnosis. During the follow-up, 50% (n = 56) of the patients developed a relapse after 12 months (median). Tumor size (P = 0.002*) and grading (P < 0.001*) are significantly associated with the occurrence of CM. Metastases (P = 0.008*) and advanced tumor size (P = 0.018) had an influence on the survival, whereas the relapse had no significant influence (P = 0.928). Five-year survival rate was 80%. CONCLUSIONS SCC of the buccal mucosa shows aggressive behavior with a considerably high proportion of relapse. Since overall outcome is significantly decreased by the cervical metastatic pattern, a selective, ipsilateral neck dissection for this patient group is recommended as the primary management.

Impact of Soft Tissue Pathophysiology in the Development and Maintenance of Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ)

Since the first description of bisphosphonate-related osteonecrosis of the jaw (BRONJ), numerous research groups have focused on possible pathological mechanisms including the suppression of the bone turnover of the jaw, antiangiogenic effects and soft tissue toxicity. In our review we focused on summarizing the role of the soft tissues in the development and progression of BRONJ. The biological behavior of fibroblasts can be significantly influenced by bisphosphonates (BP) such as a concentration dependent reduction of cell viability. High concentrations of BP can induce apoptosis and necrosis of the cells. Comparable effects could be detected for keratinocytes. Compared to non-nitrogen containing bisphosphonates, nitrogen-containing BP have worse effects on cell biology by blocking the mevalonate pathway. Further, the cell architecture and expression levels of several genes and proteins are significantly disturbed by BP. These inhibitory effects of BP are in accordance with BP-related reduced angiogenesis and neovascularization and could underline the hypothesis that inhibition of fibroblasts and keratinocytes results in delayed wound healing and can induce and trigger BRONJ.

Coincidence of mandibular fractures with isolated posterior maxillary sinus fractures

BACKGROUND/AIM There are no data available to show whether there is a relationship between mandibular fractures and isolated fractures of the posterior and/or lateral walls of the maxillary sinus. The aim of this study was to determine whether there is a coincidence between these fracture patterns. METHODS Four hundred large volume cone beam computed tomography scans (CBCT) of patients with a fracture of the mandible between 2008 and 2013 were analyzed retrospectively. Patients with multiple midfacial fractures were excluded. The radiographic findings were correlated with epidemiological and clinical data of the patients such as gender, age, treatment methods, or complications. RESULTS The most frequent fracture sites of the mandible were the jaw angle, the parasymphysis region, and the condyle. Nineteen of the 400 patients (4.75%) had an isolated fracture of the lateral and/or posterior maxillary sinus. Odds-ratio analysis revealed a high tendency for significant correlation of condylar process fractures with isolated maxillary sinus fractures. Chi-square test demonstrated a P-value near statistical significance (P=.054). No other fracture site of the mandible could be associated with an isolated fracture of the maxillary sinus. CONCLUSION A condylar process fracture of the mandible after trauma without any further injury of the midface may be associated with an isolated fracture of the lateral and/or posterior maxillary sinus.

Angiogenesis in the Development of Medication-Related Osteonecrosis of the Jaws: An Overview

Medication-related osteonecrosis of the jaws (MR-ONJ) is one of the most relevant side effects of bisphosphonate therapy; it is clinically defined as a non-healing wound in combination with an avascular and necrotic jaw within ongoing bisphosphonate therapy or after completed bisphosphonate therapy. Different theories concerning the development of MR-ONJ have been reported, while the exact pathophysiology is still unknown. Recent studies have increasingly focused on angiogenesis and revascularization concerning MR-ONJ pathophysiology, which seems to be a relevant factor in the development of MR-ONJ and a possible and promising point of action for MR-ONJ prevention and therapy. Therefore, and with respect to the different aspects and specific forms of angiogenesis, the enclosed review summarizes the possible role of angiogenesis and revascularization in the pathophysiology of MR-ONJ. Special focus is given to the strong negative influence of bisphosphonates on progenitor and mature endothelial cells in vitro as well as on microvessel sprouting in vitro and in vivo, which might result in overall reduced wound healing of oral soft and hard tissues, and therefore in an exposed and avascular jaw from a clinical viewpoint. Further, it will be summarized whether and in what way the aspect of angiogenesis might be used for possible MR-ONJ prevention and therapy.