A Comparison of Models for Teaching Suturing and Surgical Skills to Dental Students.

Learning suturing skills is an important area of the undergraduate curriculum and ideally requires realistic and anatomically accurate surgical training models to prepare students for treating patients. Little is currently understood regarding which model might be perceived by students to be the best or which might most effectively facilitate their learning. The aim of this study was to compare four teaching models: a tabletop silicon dental model, a restricted access tabletop model, a traditional phantom head mounted model, and a Thiel cadaver. Student preferences were explored for each of the models. Following lecture and video-based teaching 67 fourth-year students attended a practical suturing teaching session followed by the second session more focused on the experience of cutting and suturing mucoperiosteal flaps. Forty-six students (67%) gave online anonymous feedback on the first session. The majority (95%) felt prepared to place a simple interrupted suture on a patient, and 88% felt confident to do so. Twenty-eight students (40%) provided feedback on the second session with 82% agreeing that they were prepared to cut a mucoperiosteal flap and 48% felt confident to do this for a patient. The cadaver model was rated as the best of the four models for both suturing and mucoperiosteal flap skills. These results support its use for teaching students to suturing and surgical skills. However, despite this teaching student-rated confidence to cut and suture flaps for a patient remains poor.

Development of an intraoral handheld optical coherence tomography-based angiography probe for multi-site oral imaging.

Oral cancer, primarily oral squamous cell carcinomas (OSCC), is a major health concern worldwide. The current gold standard for the diagnosis of OSCC is biopsy and histopathological analysis, which is invasive and can place a huge financial burden on the healthcare system. Optical coherence tomography-based angiography (OCTA) is a non-invasive imaging technique that shows promise as an imaging modality to aid the diagnosis of OSCC. This Letter outlines the development of a handheld intraoral OCT probe applied to a swept-source OCT system with an angiography function for oral applications. The probe has a thin body with a diameter of 17.8 mm and a two-lens system with a working distance that is adjustable from 20.92 mm to 24.08 mm, a field of view 9 mm in diameter, an imaging depth of ∼1.7 mm, and resolutions of 39.38 µm (laterally) and 33.37 µm (axially). This probe was used to scan 14 oral sites to evaluate its ability to scan various sites in the oral cavity. This system has the potential to reduce invasive procedures and aid early OSCC diagnosis.

Interventions for the treatment of oral cavity and oropharyngeal cancers: surgical treatment.

BACKGROUND: Surgery is a common treatment option in oral cavity cancer (and less frequently in oropharyngeal cancer) to remove the primary tumour and sometimes neck lymph nodes. People with early-stage disease may undergo surgery alone or surgery plus radiotherapy, chemotherapy, immunotherapy/biotherapy, or a combination of these. Timing and extent of surgery varies. This is the third update of a review originally published in 2007. OBJECTIVES: To evaluate the relative benefits and harms of different surgical treatment modalities for oral cavity and oropharyngeal cancers. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 9 February 2022. SELECTION CRITERIA: Randomised controlled trials (RCTs) that compared two or more surgical treatment modalities, or surgery versus other treatment modalities, for primary tumours of the oral cavity or oropharynx. DATA COLLECTION AND ANALYSIS: Our primary outcomes were overall survival, disease-free survival, locoregional recurrence, and recurrence; and our secondary outcomes were adverse effects of treatment, quality of life, direct and indirect costs to patients and health services, and participant satisfaction. We used standard Cochrane methods. We reported survival data as hazard ratios (HRs). For overall survival, we reported the HR of mortality, and for disease-free survival, we reported the combined HR of new disease, progression, and mortality; therefore, HRs below 1 indicated improvement in these outcomes. We used GRADE to assess certainty of evidence for each outcome. MAIN RESULTS: We identified four new trials, bringing the total number of included trials to 15 (2820 participants randomised, 2583 participants analysed). For objective outcomes, we assessed four trials at high risk of bias, three at low risk, and eight at unclear risk. The trials evaluated nine comparisons; none compared different surgical approaches for excision of the primary tumour. Five trials evaluated elective neck dissection (ND) versus therapeutic (delayed) ND in people with oral cavity cancer and clinically negative neck nodes. Elective ND compared with therapeutic ND probably improves overall survival (HR 0.64, 95% confidence interval (CI) 0.50 to 0.83; I2 = 0%; 4 trials, 883 participants; moderate certainty) and disease-free survival (HR 0.56, 95% CI 0.45 to 0.70; I2 = 12%; 5 trials, 954 participants; moderate certainty), and probably reduces locoregional recurrence (HR 0.58, 95% CI 0.43 to 0.78; I2 = 0%; 4 trials, 458 participants; moderate certainty) and recurrence (RR 0.58, 95% CI 0.48 to 0.70; I2 = 0%; 3 trials, 633 participants; moderate certainty). Elective ND is probably associated with more adverse events (risk ratio (RR) 1.31, 95% CI 1.11 to 1.54; I2 = 0%; 2 trials, 746 participants; moderate certainty). Two trials evaluated elective radical ND versus elective selective ND in people with oral cavity cancer, but we were unable to pool the data as the trials used different surgical procedures. Neither study found evidence of a difference in overall survival (pooled measure not estimable; very low certainty). We are unsure if there is a difference in effect on disease-free survival (HR 0.57, 95% CI 0.29 to 1.11; 1 trial, 104 participants; very low certainty) or recurrence (RR 1.21, 95% CI 0.63 to 2.33; 1 trial, 143 participants; very low certainty). There may be no difference between the interventions in terms of adverse events (1 trial, 148 participants; low certainty). Two trials evaluated superselective ND versus selective ND, but we were unable to use the data. One trial evaluated supraomohyoid ND versus modified radical ND in 332 participants. We were unable to use any of the primary outcome data. The evidence on adverse events was very uncertain, with more complications, pain, and poorer shoulder function in the modified radical ND group. One trial evaluated sentinel node biopsy versus elective ND in 279 participants. There may be little or no difference between the interventions in overall survival (HR 1.00, 95% CI 0.90 to 1.11; low certainty), disease-free survival (HR 0.98, 95% CI 0.90 to 1.07; low certainty), or locoregional recurrence (HR 1.04, 95% CI 0.91 to 1.19; low certainty). The trial provided no usable data for recurrence, and reported no adverse events (very low certainty). One trial evaluated positron emission tomography-computed tomography (PET-CT) following chemoradiotherapy (with ND only if no or incomplete response) versus planned ND (before or after chemoradiotherapy) in 564 participants. There is probably no difference between the interventions in overall survival (HR 0.92, 95% CI 0.65 to 1.31; moderate certainty) or locoregional recurrence (HR 1.00, 95% CI 0.94 to 1.06; moderate certainty). One trial evaluated surgery plus radiotherapy versus radiotherapy alone and provided very low-certainty evidence of better overall survival in the surgery plus radiotherapy group (HR 0.24, 95% CI 0.10 to 0.59; 35 participants). The data were unreliable because the trial stopped early and had multiple protocol violations. In terms of adverse events, subcutaneous fibrosis was more frequent in the surgery plus radiotherapy group, but there were no differences in other adverse events (very low certainty). One trial evaluated surgery versus radiotherapy alone for oropharyngeal cancer in 68 participants. There may be little or no difference between the interventions for overall survival (HR 0.83, 95% CI 0.09 to 7.46; low certainty) or disease-free survival (HR 1.07, 95% CI 0.27 to 4.22; low certainty). For adverse events, there were too many outcomes to draw reliable conclusions. One trial evaluated surgery plus adjuvant radiotherapy versus chemotherapy. We were unable to use the data for any of the outcomes reported (very low certainty). AUTHORS' CONCLUSIONS: We found moderate-certainty evidence based on five trials that elective neck dissection of clinically negative neck nodes at the time of removal of the primary oral cavity tumour is superior to therapeutic neck dissection, with increased survival and disease-free survival, and reduced locoregional recurrence. There was moderate-certainty evidence from one trial of no difference between positron emission tomography (PET-CT) following chemoradiotherapy versus planned neck dissection in terms of overall survival or locoregional recurrence. The evidence for each of the other seven comparisons came from only one or two studies and was assessed as low or very low-certainty.

The Impact of a 1-Year COVID-19 Extension on Undergraduate Dentistry in Dundee: Final Year Students' Perspectives of Their Training in Oral Surgery.

BACKGROUND: The detrimental impact of the COVID-19 pandemic on dental education prompted the Scottish Government to fund an additional year to the dental course to ensure that the students had the necessary clinical experience. The aim of the study was to better understand the final year student perceptions of this extension on their oral surgery experience at the University of Dundee. METHODS: This mixed methods study consisted of an anonymous online questionnaire and a focus group. RESULTS: Forty-one students (69.3%) completed the questionnaire and ten students participated in the focus group. Thirty-six (88.8%) students agreed that the oral surgery teaching provided sufficient knowledge to undertake independent practice. All of the students felt confident to carry out an extraction, and the majority of them (n = 40, 95%) felt confident to remove a retained root, however, their confidence with surgery was lower. CONCLUSION: The extension gave the students sufficient experience in oral surgery to gain confidence in clinical skills and an appropriate level of knowledge in preparation for the next phase of their career. Most of the students agreed that the extension was necessary and beneficial. This cohort graduated with more oral surgery experience than any of the students did in the previous 4 years from Dundee and with experience that was comparable with the students at other schools in the pre-COVID-19 era.

An Educational Evaluation of Thiel Cadavers as a Model for Teaching Suturing Skills to Dental Students during the COVID-19 Pandemic.

Suturing is an essential skill in dentistry and not one easily acquired. The COVID-19 pandemic prompted a change to the use of Thiel cadavers and online resources with the aim of improving skill acquisition using the best model available. This study investigated the utility of the Thiel cadaver for teaching suturing skills and the potential impact of the lockdown. Fifty-seven year 4 students attended a teaching session. Student views on this teaching were explored via a questionnaire survey and qualitative data collected from a focus group. Data were analysed using an inductive approach. The response rate was 53% (30 students) for the questionnaire with 9 students participating in the focus group. Independent feedback was provided by two members of the teaching staff. Online video resources were very well received by the students with 97% agreeing that it was useful preparation. Ninety percent (90%) thought that the cadaveric model was suitable for this teaching and realistic. Positive emergent themes from the focus group centred on the use of the cadaveric model and the positive and relaxed teaching and learning environment. Staff perceived this model as superior to previously used models. There were no reported negative pandemic impacts and the cadaver model was well received.

Interventions for the treatment of oral cavity and oropharyngeal cancer: chemotherapy.

BACKGROUND: Oral cavity and oropharyngeal cancers are the most common cancers arising in the head and neck. Treatment of oral cavity cancer is generally surgery followed by radiotherapy, whereas oropharyngeal cancers, which are more likely to be advanced at the time of diagnosis, are managed with radiotherapy or chemoradiation. Surgery for oral cancers can be disfiguring and both surgery and radiotherapy have significant functional side effects. The development of new chemotherapy agents, new combinations of agents and changes in the relative timing of surgery, radiotherapy, and chemotherapy treatments may potentially bring about increases in both survival and quality of life for this group of patients. This review updates one last published in 2011. OBJECTIVES: To determine whether chemotherapy, in addition to radiotherapy and/or surgery for oral cavity and oropharyngeal squamous cell carcinoma results in improved overall survival, improved disease-free survival and/or improved locoregional control, when incorporated as either induction therapy given prior to locoregional treatment (i.e. radiotherapy or surgery), concurrent with radiotherapy or in the adjuvant (i.e. after locoregional treatment with radiotherapy or surgery) setting. SEARCH METHODS: An information specialist searched 4 bibliographic databases up to 15 September 2021 and used additional search methods to identify published, unpublished and ongoing studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) where more than 50% of participants had primary tumours in the oral cavity or oropharynx, and that evaluated the addition of chemotherapy to other treatments such as radiotherapy and/or surgery, or compared two or more chemotherapy regimens or modes of administration. DATA COLLECTION AND ANALYSIS: For this update, we assessed the new included trials for their risk of bias and at least two authors extracted data from them. Our primary outcome was overall survival (time to death from any cause). Secondary outcomes were disease-free survival (time to disease recurrence or death from any cause) and locoregional control (response to primary treatment). We contacted trial authors for additional information or clarification when necessary. MAIN RESULTS: We included 100 studies with 18,813 participants. None of the included trials were at low risk of bias.  For induction chemotherapy, we reported the results for contemporary regimens that will be of interest to clinicians and people being treated for oral cavity and oropharyngeal cancers. Overall, there is insufficient evidence to clearly demonstrate a survival benefit from induction chemotherapy with platinum plus 5-fluorouracil prior to radiotherapy (hazard ratio (HR) for death 0.85, 95% confidence interval (CI) 0.70 to 1.04, P = 0.11; 7427 participants, 5 studies; moderate-certainty evidence), prior to surgery (HR for death 1.06, 95% CI 0.71 to 1.60, P = 0.77; 198 participants, 1 study; low-certainty evidence) or prior to concurrent chemoradiation (CRT) with cisplatin (HR for death 0.71, 95% CI 0.37 to 1.35, P = 0.30; 389 participants, 2 studies; low-certainty evidence). There is insufficient evidence to support the use of an induction chemotherapy regimen with cisplatin plus 5-fluorouracil plus docetaxel prior to CRT with cisplatin (HR for death 1.08, 95% CI 0.80 to 1.44, P = 0.63; 760 participants, 3 studies; low-certainty evidence).  There is insufficient evidence to support the use of adjuvant chemotherapy over observation only following surgery (HR for death 0.95, 95% CI 0.73 to 1.22, P = 0.67; 353 participants, 5 studies; moderate-certainty evidence). Among studies that compared post-surgical adjuvant CRT, as compared to post-surgical RT, adjuvant CRT showed a survival benefit (HR 0.84, 95% CI 0.72 to 0.98, P = 0.03; 1097 participants, 4 studies; moderate-certainty evidence). Primary treatment with CRT, as compared to radiotherapy alone,  was associated with a reduction in the risk of death (HR for death 0.74, 95% CI 0.67 to 0.83, P < 0.00001; 2852 participants, 24 studies; moderate-certainty evidence).  AUTHORS' CONCLUSIONS: The results of this review demonstrate that chemotherapy in the curative-intent treatment of oral cavity and oropharyngeal cancers only seems to be of benefit when used in specific circumstances together with locoregional treatment. The  evidence does not show a clear survival benefit from the use of induction chemotherapy prior to radiotherapy, surgery or CRT. Adjuvant CRT reduces the risk of death by 16%, as compared to radiotherapy alone. Concurrent chemoradiation as compared to radiation alone is associated with a greater than 20% improvement in overall survival; however, additional research is required to inform how the specific chemotherapy regimen may influence this benefit.

Comparison of machine learning algorithms for the prediction of five-year survival in oral squamous cell carcinoma.

BACKGROUND/AIM: Machine learning analyses of cancer outcomes for oral cancer remain sparse compared to other types of cancer like breast or lung. The purpose of the present study was to compare the performance of machine learning algorithms in the prediction of global, recurrence-free five-year survival in oral cancer patients based on clinical and histopathological data. METHODS: Data were gathered retrospectively from 416 patients with oral squamous cell carcinoma. The data set was divided into training and test data set (75:25 split). Training performance of five machine learning algorithms (Logistic regression, K-nearest neighbours, Naïve Bayes, Decision tree and Random forest classifiers) for prediction was assessed by k-fold cross-validation. Variables used in the machine learning models were age, sex, pain symptoms, grade of lesion, lymphovascular invasion, extracapsular extension, perineural invasion, bone invasion and type of treatment. Variable importance was assessed and model performance on the testing data was assessed using receiver operating characteristic curves, accuracy, sensitivity, specificity and F1 score. RESULTS: The best performing model was the Decision tree classifier, followed by the Logistic Regression model (accuracy 76% and 60%, respectively). The Naïve Bayes model did not display any predictive value with 0% specificity. CONCLUSIONS: Machine learning presents a promising and accessible toolset for improving prediction of oral cancer outcomes. Our findings add to a growing body of evidence that Decision tree models are useful in models in predicting OSCC outcomes. We would advise that future similar studies explore a variety of machine learning models including Logistic regression to help evaluate model performance.

Perineural invasion in oral squamous cell carcinoma: Incidence, prognostic impact and molecular insight.

BACKGROUND: The objective of this study was to characterise the incidence and prognostic correlation of perineural invasion (PNI) in oral squamous cell carcinoma and determine whether nerve growth factor and its receptor tyrosine Kinase A expression could be used as biological markers for PNI. METHODS: A retrospective review of pathology reports of 430 patients with oral squamous cell carcinoma who were treated from 1992 to 2014 in Tayside, Scotland, was carried out. The expression of nerve growth factor and tyrosine kinase A was assessed with immunohistochemistry in 132 tissue sections of oral squamous cell carcinoma. RESULTS: Perineural invasion was identified in 17.4% of oral squamous cell carcinomas. High expression of nerve growth factor and tyrosine kinase A was seen in 84% and 92% of oral squamous cell carcinoma, respectively. Tumours with PNI expressed nerve growth factor and tyrosine kinase A with a greater frequency than tumours without PNI. PNI and high expression of nerve growth factor were significantly associated with pain. PNI was significantly associated with stage IV tumours and poor disease-specific survival. CONCLUSIONS: A higher level of expression of nerve growth factor and tyrosine kinase A may predict PNI and therefore may be considered as biological markers for PNI in oral squamous cell carcinoma. PNI and nerve growth factor overexpression may contribute to the pain generation in oral cancer patients. PNI and nerve growth factor expression can predict the aggressiveness and prognosis of oral squamous cell carcinoma patients.

Nerve growth factor-induced migration in oral and salivary gland tumour cells utilises the PI3K/Akt signalling pathway: Is there a link to perineural invasion?

OBJECTIVES: The aims of this study were to investigate the role of nerve growth factor on perineural invasion in oral and salivary gland tumour cell lines and whether there is an involvement of PI3K/Akt pathway. MATERIALS AND METHODS: Four cell lines were investigated: HSG and TYS (salivary gland tumours), SAS-H1 (oral squamous cell carcinoma) and HaCaT (human skin keratinocyte). Initially, Boyden chamber assay was done to examine the effect of different concentration of nerve growth factor on cell migration. Western blot/ immunofluorescence techniques were used to investigate the phosphorylation status of the Akt pathway within the cells in response to nerve growth factor. The effect of this growth factor and the addition of an Akt inhibitor on cell morphology and migration were also examined using scatter/scratch assays. RESULTS: Nerve growth factor triggered the PI3K/Akt pathway in oral and salivary tumour cells and induced oral and salivary tumour cell scattering and migration. Inhibitor assays confirmed that oral and salivary gland tumour cell scattering and migration is Akt dependent. CONCLUSIONS: Nerve growth factor can stimulate scattering and migration in cells derived from oral and salivary gland tumours, thereby potentially enhancing perineural invasion. Phosphorylated Akt controls cancer cell migration and scattering. Blocking the Akt pathway may inhibit cell migration and therefore perineural invasion and metastasis.

Ezrin-Radixin-Moesin Binding Phosphoprotein 50: A Potential Novel Biomarker in Human Papilloma Virus-Associated Head and Neck Squamous Cell Carcinomas.

High-risk human papilloma virus (HR-HPV) has increasingly been associated with head and neck squamous cell carcinoma (HNSCC), in particular oropharyngeal cancers. Ezrin-Radixin-Moesin Binding Phosphoprotein 50 (EBP50), a putative tumour suppressor, localises to the plasma membrane in suprabasal epithelium and to the cytoplasm in proliferative basal layers, and is a target for degradation by the HR-HPV E6 oncoprotein. The aim of this study was to investigate EBP50 protein expression patterns in HNSCC in a large Scottish cohort to determine if there was a correlation with HPV status and clinical outcomes. EBP50 expression patterns were assessed in 156 HNSCC including oropharyngeal (37.8%), laryngeal (24%), oral (19%) and other sites (18.5%), which were genotyped for presence of HR-HPV. HNSCC were generally negative for membranous EBP50. EBP50 expression was either cytoplasmic/absent, being 'predominantly cytoplasmic' in 76 (49%), 'weak/negligible cytoplasmic' in 44 (28%), 'strongly cytoplasmic' in 5 (3%), 'heterogeneous' in 26 (17%) and 'other' in 5 (3%) samples. Forty tumours (25%) were positive for HPV DNA, predominantly HR-HPV 16, and 44 (28%) were p16 positive. The majority of tumours (71%) with 'weak/negligible cytoplasmic' EBP50 expression originated in the oropharynx were more likely to have positive neck nodes, overexpression of p16 and positive tumour HR-HPV status (P < 0.001). Differences in EBP50 levels between oropharyngeal and non-oropharyngeal tumours may be linked to degradation of EBP50 by HR-HPV, and loss of EBP50 may therefore be a surrogate biomarker for HR-HPV infection in oropharyngeal tumours.

Interventions for the treatment of oral and oropharyngeal cancers: surgical treatment.

BACKGROUND: Surgery is an important part of the management of oral cavity cancer with regard to both the removal of the primary tumour and removal of lymph nodes in the neck. Surgery is less frequently used in oropharyngeal cancer. Surgery alone may be treatment for early-stage disease or surgery may be used in combination with radiotherapy, chemotherapy and immunotherapy/biotherapy. There is variation in the recommended timing and extent of surgery in the overall treatment regimens of people with these cancers. This is an update of a review originally published in 2007 and first updated in 2011. OBJECTIVES: To determine which surgical treatment modalities for oral and oropharyngeal cancers result in increased overall survival, disease-free survival and locoregional control and reduced recurrence. To determine the implication of treatment modalities in terms of morbidity, quality of life, costs, hospital days of treatment, complications and harms. SEARCH METHODS: Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 20 December 2017), the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 11), MEDLINE Ovid (1946 to 20 December 2017) and Embase Ovid (1980 to 20 December 2017). We searched the US National Institutes of Health Trials Registry (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform for ongoing trials. There were no restrictions on the language or date of publication. SELECTION CRITERIA: Randomised controlled trials where more than 50% of participants had primary tumours of the oral cavity or oropharynx, or where separate data could be extracted for these participants, and that compared two or more surgical treatment modalities, or surgery versus other treatment modalities. DATA COLLECTION AND ANALYSIS: Two or more review authors independently extracted data and assessed risk of bias. We contacted study authors for additional information as required. We collected adverse events data from included studies. MAIN RESULTS: We identified five new trials in this update, bringing the total number of included trials to 12 (2300 participants; 2148 with cancers of the oral cavity). We assessed four trials at high risk of bias, and eight at unclear. None of the included trials compared different surgical approaches for the excision of the primary tumour. We grouped the trials into seven main comparisons.Future research may change the findings as there is only very low-certainty evidence available for all results.Five trials compared elective neck dissection (ND) with therapeutic (delayed) ND in participants with oral cavity cancer and clinically negative neck nodes, but differences in type of surgery and duration of follow-up made meta-analysis inappropriate in most cases. Four of these trials reported overall and disease-free survival. The meta-analyses of two trials found no evidence of either intervention leading to greater overall survival (hazard ratio (HR) 0.84, 95% confidence interval (CI) 0.41 to 1.72; 571 participants), or disease-free survival (HR 0.73, 95% CI 0.25 to 2.11; 571 participants), but one trial found a benefit for elective supraomohyoid ND compared to therapeutic ND in overall survival (RR 0.40, 95% CI 0.19 to 0.84; 67 participants) and disease-free survival (HR 0.32, 95% CI 0.12 to 0.84; 67 participants). Four individual trials assessed locoregional recurrence, but could not be meta-analysed; one trial favoured elective ND over therapeutic delayed ND, while the others were inconclusive.Two trials compared elective radical ND with elective selective ND, but we were unable to pool the data for two outcomes. Neither study found evidence of a difference in overall survival or disease-free survival. A single trial found no evidence of a difference in recurrence.One trial compared surgery plus radiotherapy with radiotherapy alone, but data were unreliable because the trial stopped early and there were multiple protocol violations.One trial comparing positron-emission tomography-computed tomography (PET-CT) following chemoradiotherapy (with ND only if no or incomplete response) versus planned ND (either before or after chemoradiotherapy), showed no evidence of a difference in mortality (HR 0.92, 95% CI 0.65 to 1.31; 564 participants). The trial did not provide usable data for the other outcomes.Three single trials compared: surgery plus adjunctive radiotherapy versus chemoradiotherapy; supraomohyoid ND versus modified radical ND; and super selective ND versus selective ND. There were no useable data from these trials.The reporting of adverse events was poor. Four trials measured adverse events. Only one of the trials reported quality of life as an outcome. AUTHORS' CONCLUSIONS: Twelve randomised controlled trials evaluated ND surgery in people with oral cavity cancers; however, the evidence available for all comparisons and outcomes is very low certainty, therefore we cannot rely on the findings. The evidence is insufficient to draw conclusions about elective ND of clinically negative neck nodes at the time of removal of the primary tumour compared to therapeutic (delayed) ND. Two trials combined in meta-analysis suggested there is no difference between these interventions, while one trial (which evaluated elective supraomohyoid ND) found that it may be associated with increased overall and disease-free survival. One trial found elective ND reduced locoregional recurrence, while three were inconclusive. There is no evidence that radical ND increases overall or disease-free survival compared to more conservative ND surgery, or that there is a difference in mortality between PET-CT surveillance following chemoradiotherapy versus planned ND (before or after chemoradiotherapy). Reporting of adverse events in all trials was poor and it was not possible to compare the quality of life of people undergoing different surgical treatments.

Odontogenic Cysts - An Overview.

This article aims to discuss the clinical features, radiological assessment, histopathology and management of a variety of odontogenic cysts. It also highlights the reclassification of odontogenic keratocysts to keratocystic odontogenic tumours.

Activation of Akt at T308 and S473 in alcohol, tobacco and HPV-induced HNSCC: is there evidence to support a prognostic or diagnostic role?

BACKGROUND: Tobacco, alcohol and HPV infection are associated with increased risk of HNSCC. However, little is known about the underlying signaling events influencing risk. We aimed to investigate the relationship between these risk factors and Akt phosphorylation, to determine prognostic value. METHOD: VEGF-positive HNSCC biopsies, with known HPV status, were analyzed by immunohistochemistry (IHC) for Akt, phosphorylated at residues S473 and T308. Comparisons between the tissues were carried out using a Mann-Whitney U test. Associations between the variables and continuous immunohistochemical parameters were evaluated with general linear models. Patient characteristics and pAkt IHC score were analyzed for possible association with overall survival by Cox proportional hazard models. RESULTS: Immunohistochemistry revealed that cancer patients had significantly higher levels of pAkt T308 than S473 (P < 0.001). Smoking and alcohol were found to be independent risk factors for Akt phosphorylation at T308 (P = 0.022 and 0.027, respectively). Patients with tumors positive for HPV or pAkt S473 had a poorer prognosis (P = 0.005, and 0.004, respectively). Patients who were heavy drinkers were 49 times more likely to die than non-drinkers (P = 0.003). Patients with low pAkt T308 were more likely to be HPV positive (P = 0.028). Non-drinkers were also found to have lower levels of pAkt T308 and were more likely to have tumors positive for HPV than heavy drinkers (P = 0.044 and 0.007, respectively). CONCLUSION: This study suggests different mechanisms of carcinogenesis are initiated by smoking, alcohol and HPV. Our data propose higher phosphorylation of Akt at T308 as a reliable biomarker for smoking and alcohol induced HNSCC progression and higher phosphorylation of Akt at S473 as a prognostic factor for HNSCC.

Is there a pAkt between VEGF and oral cancer cell migration?

The PI3K-Akt signalling pathway is a well-established driver of cancer progression. One key process promoted by Akt phosphorylation is tumour cell motility; however the mechanism of VEGF-induced Akt phosphorylation leading to motility remains poorly understood. Previously, we have shown that Akt phosphorylation induced by different factors causes both stimulation and inhibition of motility in different cell types. However, differential phosphorylation of Akt at T308 and S473 residues by VEGF and its role in head and neck cancer cell motility and progression is unknown. The cell lines investigated in this study exhibited a change in phosphorylation of Akt in response to VEGF. However, in terms of motility, VEGF stimulated oral cancer and its associated cell lines, but not normal keratinocytes or oral mucosal fibroblasts. The addition of a PI3 kinase and mTOR inhibitor, inhibited the phosphorylation of Akt and also effectively blocked VEGF-induced oral cancer cell motility, whereas only the PI3 kinase inhibitor blocked oral cancer associated fibroblast cell motility. This study therefore discloses that two different mechanisms of Akt phosphorylation control the motility potential of different cell lines. Akt phosphorylated at both residues controls oral cancer cell motility. Furthermore, immunohistochemical analysis of VEGF positive human head and neck tumour tissues showed a significant increase in Akt phosphorylation at the T308 residue, suggesting that pAkt T308 may be associated with tumour progression in vivo.

Interventions for the treatment of oral and oropharyngeal cancers: surgical treatment.

BACKGROUND: Surgery is an important part of the management of oral cavity cancer with regard to both the removal of the primary tumour and removal of lymph nodes in the neck. Surgery is less frequently used in oropharyngeal cancer. Surgery alone may be treatment for early stage disease or surgery may be used in combination with radiotherapy, chemotherapy and immunotherapy/biotherapy. There is variation in the recommended timing and extent of surgery in the overall treatment regimens of people with these cancers. OBJECTIVES: To determine which surgical treatment modalities for oral cavity and oropharyngeal cancers result in increased overall survival, disease free survival, progression free survival and reduced recurrence. SEARCH STRATEGY: The following electronic databases were searched: the Cochrane Oral Health Group Trials Register (to 17 February 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 1), MEDLINE via OVID (1950 to 17 February 2011) and EMBASE via OVID (1980 to 17 February 2011). There were no restrictions regarding language or date of publication. SELECTION CRITERIA: Randomised controlled trials where more than 50% of participants had primary tumours of the oral cavity or oropharynx, and which compared two or more surgical treatment modalities or surgery versus other treatment modalities. DATA COLLECTION AND ANALYSIS: Data extraction and assessment of risk of bias was undertaken independently by two or more review authors. Study authors were contacted for additional information as required. Adverse events data were collected from published trials. MAIN RESULTS: Seven trials (n = 669; 667 with cancers of the oral cavity) satisfied the inclusion criteria, but none were assessed as low risk of bias. Trials were grouped into three main comparisons. Four trials compared elective neck dissection (ND) with therapeutic neck dissection in patients with oral cavity cancer and clinically negative neck nodes, but differences in type of surgery and duration of follow-up made meta-analysis inappropriate. Three of these trials reported overall and disease free survival. One trial showed a benefit for elective supraomohyoid neck dissection compared to therapeutic ND in overall and disease free survival. Two trials found no difference between elective radical ND and therapeutic ND for the outcomes of overall survival and disease free survival. All four trials found reduced locoregional recurrence following elective ND.A further two trials compared elective radical ND with elective selective ND and found no difference in overall survival, disease free survival or recurrence. The final trial compared surgery plus radiotherapy to radiotherapy alone but data were unreliable because the trial stopped early and there were multiple protocol violations.None of the trials reported quality of life as an outcome. Two trials, evaluating different comparisons reported adverse effects of treatment. AUTHORS' CONCLUSIONS: Seven included trials evaluated neck dissection surgery in patients with oral cavity cancers. The review found weak evidence that elective neck dissection of clinically negative neck nodes at the time of removal of the primary tumour results in reduced locoregional recurrence, but there is insufficient evidence to conclude that elective neck dissection increases overall survival or disease free survival compared to therapeutic neck dissection. There is very weak evidence from one trial that elective supraomohyoid neck dissection may be associated with increased overall and disease free survival. There is no evidence that radical neck dissection increases overall survival compared to conservative neck dissection surgery. Reporting of adverse events in all trials was poor and it was not possible to compare the quality of life of patients undergoing different surgeries.

Interventions for the treatment of oral cavity and oropharyngeal cancer: chemotherapy.

BACKGROUND: Oral cavity and oropharyngeal cancers are frequently described as part of a group of oral cancers or head and neck cancer. Treatment of oral cavity cancer is generally surgery followed by radiotherapy, whereas oropharyngeal cancers, which are more likely to be advanced at the time of diagnosis, are managed with radiotherapy or chemoradiation. Surgery for oral cancers can be disfiguring and both surgery and radiotherapy have significant functional side effects, notably impaired ability to eat, drink and talk. The development of new chemotherapy agents, new combinations of agents and changes in the relative timing of surgery, radiotherapy, and chemotherapy treatments may potentially bring about increases in both survival and quality of life for this group of patients. OBJECTIVES: To determine whether chemotherapy, in addition to radiotherapy and/or surgery for oral cavity and oropharyngeal cancer results in improved survival, disease free survival, progression free survival, locoregional control and reduced recurrence of disease. To determine which regimen and time of administration (induction, concomitant or adjuvant) is associated with better outcomes. SEARCH STRATEGY: Electronic searches of the Cochrane Oral Health Group's Trials Register, CENTRAL, MEDLINE, EMBASE, AMED were undertaken on 1st December 2010. Reference lists of recent reviews and included studies were also searched to identify further trials. SELECTION CRITERIA: Randomised controlled trials where more than 50% of participants had primary tumours in the oral cavity or oropharynx, and which compared the addition of chemotherapy to other treatments such as radiotherapy and/or surgery, or compared two or more chemotherapy regimens or modes of administration, were included. DATA COLLECTION AND ANALYSIS: Eighty-nine trials which met the inclusion criteria were assessed for risk of bias and data were extracted by two or more review authors. The primary outcome was total mortality. Trial authors were contacted for additional information or for clarification. MAIN RESULTS: There is evidence of a small increase in overall survival associated with induction chemotherapy compared to locoregional treatment alone (25 trials), hazard ratio (HR) of mortality 0.92 (95% confidence interval (CI) 0.84 to 1.00, P = 0.06). Post-surgery adjuvant chemotherapy is associated with improved overall survival compared to surgery ± radiotherapy alone (10 trials), HR of mortality 0.88 (95% CI 0.79 to 0.99, P = 0.03), and there is some evidence that this improvement may be greater with concomitant adjuvant chemoradiotherapy (4 trials), HR of mortality 0.84 (95% CI 0.72 to 0.98, P = 0.03). In patients with unresectable tumours, there is evidence that concomitant or alternating chemoradiotherapy is associated with improved survival compared to radiotherapy alone (26 trials), HR of mortality 0.78 (95% CI 0.73 to 0.83, P < 0.00001). These findings are confirmed by sensitivity analyses based on studies assessed at low risk of bias. There is insufficient evidence to identify which agent(s) and/or regimen(s) are the most effective. The additional toxicity attributable to chemotherapy in the combined regimens remains unquantified. AUTHORS' CONCLUSIONS: Chemotherapy, in addition to radiotherapy and surgery, is associated with improved overall survival in patients with oral cavity and oropharyngeal cancers. Induction chemotherapy may prolong survival by 8 to 20% and adjuvant concomitant chemoradiotherapy may prolong survival by up to 16%. In patients with unresectable tumours, concomitant or alternating chemoradiotherapy may prolong survival by 10 to 22%. There is insufficient evidence as to which agent or regimen is most effective and the additional toxicity associated with chemotherapy given in addition to radiotherapy and/or surgery cannot be quantified.

Interventions for the treatment of oral cavity and oropharyngeal cancer: radiotherapy.

BACKGROUND: The management of advanced oral cavity and oropharyngeal cancers is problematic and has traditionally relied on surgery and radiotherapy, both of which are associated with substantial adverse effects. Radiotherapy has been in use since the 1950s and has traditionally been given as single daily doses. This method of dividing up the total dose, or fractionation, has been modified over the years and a variety of approaches have been developed with the aim of improving survival whilst maintaining acceptable toxicity. OBJECTIVES: To determine which radiotherapy regimens for oral cavity and oropharyngeal cancers result in increased overall survival, disease free survival, progression free survival and locoregional control. SEARCH STRATEGY: The following electronic databases were searched: the Cochrane Oral Health Group's Trials Register (to 28 July 2010), CENTRAL (The Cochrane Library 2010, Issue 3), MEDLINE via OVID (1950 to 28 July 2010) and EMBASE via OVID (1980 to 28 July 2010). There were no restrictions regarding language or date of publication. SELECTION CRITERIA: Randomised controlled trials where more than 50% of participants had primary tumours of the oral cavity or oropharynx, and which compared two or more radiotherapy regimens, radiotherapy versus other treatment modality, or the addition of radiotherapy to other treatment modalities. DATA COLLECTION AND ANALYSIS: Data extraction and assessment of risk of bias was undertaken independently by two or more authors. Study authors were contacted for additional information as required. Adverse events data were collected from published trials. MAIN RESULTS: 30 trials involving 6535 participants were included. Seventeen trials compared some form of altered fractionation (hyperfractionation/accelerated) radiotherapy with conventional radiotherapy; three trials compared different altered fractionation regimens; one trial compared timing of radiotherapy, five trials evaluated neutron therapy and four trials evaluated the addition of pre-operative radiotherapy. Pooling trials of any altered fractionation radiotherapy compared to a conventional schedule showed a statistically significant reduction in total mortality (hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.76 to 0.98). In addition, a statistically significant difference in favour of the altered fractionation was shown for the outcome of locoregional control (HR 0.79, 95% CI 0.70 to 0.89). No statistically significant difference was shown for disease free survival.No statistically significant difference was shown for any other comparison. AUTHORS' CONCLUSIONS: Altered fractionation radiotherapy is associated with an improvement in overall survival and locoregional control in patients with oral cavity and oropharyngeal cancers. More accurate methods of reporting adverse events are needed in order to truly assess the clinical performance of different radiotherapy regimens.

Interventions for the treatment of oral cavity and oropharyngeal cancer: chemotherapy.

BACKGROUND: Oral cavity and oropharyngeal cancers are frequently described as part of a group of oral cancers or head and neck cancer. Treatment of oral cavity cancer is generally surgery followed by radiotherapy, whereas oropharyngeal cancers, which are more likely to be advanced at the time of diagnosis, are managed with radiotherapy or chemoradiation. Surgery for oral cancers can be disfiguring and both surgery and radiotherapy have significant functional side effects, notably impaired ability to eat, drink and talk. The development of new chemotherapy agents, new combinations of agents and changes in the relative timing of surgery, radiotherapy, and chemotherapy treatments may potentially bring about increases in both survival and quality of life for this group of patients. OBJECTIVES: To determine whether chemotherapy, in addition to radiotherapy and/or surgery for oral cavity and oropharyngeal cancer results in improved survival, disease free survival, progression free survival, locoregional control and reduced recurrence of disease. To determine which regimen and time of administration (induction, concomitant or adjuvant) is associated with better outcomes. SEARCH STRATEGY: Electronic searches of the Cochrane Oral Health Group's Trials Register, CENTRAL, MEDLINE, EMBASE, AMED were undertaken on 28th July 2010. Reference lists of recent reviews and included studies were also searched to identify further trials. SELECTION CRITERIA: Randomised controlled trials where more than 50% of participants had primary tumours in the oral cavity or oropharynx, and which compared the addition of chemotherapy to other treatments such as radiotherapy and/or surgery, or compared two or more chemotherapy regimens or modes of administration, were included. DATA COLLECTION AND ANALYSIS: Trials which met the inclusion criteria were assessed for risk of bias using six domains: sequence generation, allocation concealment, blinding, completeness of outcome data, selective reporting and other possible sources of bias. Data were extracted using a specially designed form and entered into the characteristics of included studies table and the analysis sections of the review. The proportion of participants in each trial with oral cavity and oropharyngeal cancers are recorded in Additional Table 1. MAIN RESULTS: There was no statistically significant improvement in overall survival associated with induction chemotherapy compared to locoregional treatment alone in 25 trials (hazard ratio (HR) of mortality 0.92, 95% confidence interval (CI) 0.84 to 1.00). Post-surgery adjuvant chemotherapy was associated with improved overall survival compared to surgery +/- radiotherapy alone in 10 trials (HR of mortality 0.88, 95% CI 0.79 to 0.99), and there was an additional benefit of adjuvant concomitant chemoradiotherapy compared to radiotherapy in 4 of these trials (HR of mortality 0.84, 95% CI 0.72 to 0.98). Concomitant chemoradiotherapy resulted in improved survival compared to radiotherapy alone in patients whose tumours were considered unresectable in 25 trials (HR of mortality 0.79, 95% CI 0.74 to 0.84). However, the additional toxicity attributable to chemotherapy in the combined regimens remains unquantified. AUTHORS' CONCLUSIONS: Chemotherapy, in addition to radiotherapy and surgery, is associated with improved overall survival in patients with oral cavity and oropharyngeal cancers. Induction chemotherapy is associated with a 9% increase in survival and adjuvant concomitant chemoradiotherapy is associated with a 16% increase in overall survival following surgery. In patients with unresectable tumours, concomitant chemoradiotherapy showed a 22% benefit in overall survival compared with radiotherapy alone.