Intermittent PI3Kδ inhibition sustains anti-tumour immunity and curbs irAEs.

Phosphoinositide 3-kinase δ (PI3Kδ) has a key role in lymphocytes, and inhibitors that target this PI3K have been approved for treatment of B cell malignancies1-3. Although studies in mouse models of solid tumours have demonstrated that PI3Kδ inhibitors (PI3Kδi) can induce anti-tumour immunity4,5, its effect on solid tumours in humans remains unclear. Here we assessed the effects of the PI3Kδi AMG319 in human patients with head and neck cancer in a neoadjuvant, double-blind, placebo-controlled randomized phase II trial (EudraCT no. 2014-004388-20). PI3Kδ inhibition decreased the number of tumour-infiltrating regulatory T (Treg) cells and enhanced the cytotoxic potential of tumour-infiltrating T cells. At the tested doses of AMG319, immune-related adverse events (irAEs) required treatment to be discontinued in 12 out of 21 of patients treated with AMG319, suggestive of systemic effects on Treg cells. Accordingly, in mouse models, PI3Kδi decreased the number of Treg cells systemically and caused colitis. Single-cell RNA-sequencing analysis revealed a PI3Kδi-driven loss of tissue-resident colonic ST2 Treg cells, accompanied by expansion of pathogenic T helper 17 (TH17) and type 17 CD8+ T (TC17) cells, which probably contributed to toxicity; this points towards a specific mode of action for the emergence of irAEs. A modified treatment regimen with intermittent dosing of PI3Kδi in mouse models led to a significant decrease in tumour growth without inducing pathogenic T cells in colonic tissue, indicating that alternative dosing regimens might limit toxicity.

Point-of-care Analysis for Non-invasive Diagnosis of Oral cancer (PANDORA): A technology-development proof of concept diagnostic accuracy study of dielectrophoresis in patients with oral squamous cell carcinoma and dysplasia.

BACKGROUND: Delays in the identification and referral of oral cancer remain frequent. An accurate and non-invasive diagnostic test to be performed in primary care may help identifying oral cancer at an early stage and reduce mortality. Point-of-care Analysis for Non-invasive Diagnosis of Oral cancer (PANDORA) was a proof-of-concept prospective diagnostic accuracy study aimed at advancing the development of a dielectrophoresis-based diagnostic platform for oral squamous cell carcinoma (OSCC) and epithelial dysplasia (OED) using a novel automated DEPtech 3DEP analyser. METHODS: The aim of PANDORA was to identify the set-up of the DEPtech 3DEP analyser associated with the highest diagnostic accuracy in identifying OSCC and OED from non-invasive brush biopsy samples, as compared to the gold standard test (histopathology). Measures of accuracy included sensitivity, specificity, positive and negative predictive value. Brush biopsies were collected from individuals with histologically proven OSCC and OED, histologically proven benign mucosal disease, and healthy mucosa (standard test), and analysed via dielectrophoresis (index test). RESULTS: 40 individuals with OSCC/OED and 79 with benign oral mucosal disease/healthy mucosa were recruited. Sensitivity and specificity of the index test was 86.8% (95% confidence interval [CI], 71.9%-95.6%) and 83.6% (95% CI, 73.0%-91.2%). Analysing OSCC samples separately led to higher diagnostic accuracy, with 92.0% (95% CI, 74.0%-99.0%) sensitivity and 94.5% (95% CI, 86.6%-98.5%) specificity. CONCLUSION: The DEPtech 3DEP analyser has the potential to identify OSCC and OED with notable diagnostic accuracy and warrants further investigation as a potential triage test in the primary care setting for patients who may need to progress along the diagnostic pathway and be offered a surgical biopsy.

Salivary Electrostimulation in the Treatment of Radiation Therapy-Induced Xerostomia (LEONIDAS-2): A Multicenter, Randomized, Double-Masked, Sham-Controlled, Phase 3 Trial.

PURPOSE: Radiation therapy-induced xerostomia significantly affects quality of life in head and neck cancer survivors. Neuro-electrostimulation of the salivary glands may safely increase natural salivation and reduce dry mouth symptoms. METHODS AND MATERIALS: This multicenter, double-masked, randomized, sham-controlled clinical trial assessed the long-term effects of a commercially available intraoral neuro-electrostimulating device in lessening xerostomia symptoms, increasing salivary flow, and improving quality of life in individuals with radiation therapy-induced xerostomia. Using a computer-generated randomization list, participants were assigned (1:1) to an active intraoral custom-made removable electrostimulating device or a sham device to be used for 12 months. The primary outcome was the proportion of patients reporting a 30% improvement on the xerostomia visual analog scale at 12 months. A number of secondary and exploratory outcomes were also assessed through validated measurements (sialometry and visual analog scale) and quality-of-life questionnaires (EORTC QLQ-H&N35, OH-QoL16, and SF-36). RESULTS: As per protocol, 86 participants were recruited. Intention-to-treat analyses showed no statistical evidence of a difference between the study groups with respect to the primary outcome or for any of the secondary clinical or quality-of-life outcomes. Exploratory analyses showed a statistically significant difference in the changes over time of the dry mouth subscale score of the EORTC QLQ-H&N35 in favor of the active intervention. CONCLUSIONS: LEONIDAS-2 did not meet the primary and secondary outcomes.

Developing and Validating a Multivariable Prognostic-Predictive Classifier for Treatment Escalation of Oropharyngeal Squamous Cell Carcinoma: The PREDICTR-OPC Study.

PURPOSE: While there are several prognostic classifiers, to date, there are no validated predictive models that inform treatment selection for oropharyngeal squamous cell carcinoma (OPSCC).Our aim was to develop clinical and/or biomarker predictive models for patient outcome and treatment escalation for OPSCC. EXPERIMENTAL DESIGN: We retrospectively collated clinical data and samples from a consecutive cohort of OPSCC cases treated with curative intent at ten secondary care centers in United Kingdom and Poland between 1999 and 2012. We constructed tissue microarrays, which were stained and scored for 10 biomarkers. We then undertook multivariable regression of eight clinical parameters and 10 biomarkers on a development cohort of 600 patients. Models were validated on an independent, retrospectively collected, 385-patient cohort. RESULTS: A total of 985 subjects (median follow-up 5.03 years, range: 4.73-5.21 years) were included. The final biomarker classifier, comprising p16 and survivin immunohistochemistry, high-risk human papillomavirus (HPV) DNA in situ hybridization, and tumor-infiltrating lymphocytes, predicted benefit from combined surgery + adjuvant chemo/radiotherapy over primary chemoradiotherapy in the high-risk group [3-year overall survival (OS) 63.1% vs. 41.1%, respectively, HR = 0.32; 95% confidence interval (CI), 0.16-0.65; P = 0.002], but not in the low-risk group (HR = 0.4; 95% CI, 0.14-1.24; P = 0.114). On further adjustment by propensity scores, the adjusted HR in the high-risk group was 0.34, 95% CI = 0.17-0.67, P = 0.002, and in the low-risk group HR was 0.5, 95% CI = 0.1-2.38, P = 0.384. The concordance index was 0.73. CONCLUSIONS: We have developed a prognostic classifier, which also appears to demonstrate moderate predictive ability. External validation in a prospective setting is now underway to confirm this and prepare for clinical adoption.

Informed consent in clinical research.

Since increasing numbers of patients are asked to take part in clinical trials, nurses need to be aware of the principles of valid, informed consent. This article explores consent, which aims to protect the rights, safety and wellbeing of patients. In particular, the history of consent in research and the elements involved in obtaining informed consent from potential participants in research studies are discussed.

Survival in node-positive early oral squamous cell carcinoma: sentinel node biopsy versus elective neck dissection.

Patients undergoing sentinel node biopsy (SLNB) for early oral squamous cell carcinoma (OSCC) who harbour occult metastases (pN+ve) may be at greater risk of mortality due to prolonged overall treatment times than those identified as pN+ve on elective neck dissection (ELND). A retrospective comparative survival analysis was therefore undertaken to test this hypothesis. Patients were identified from the South Glasgow multidisciplinary team (MDT) database. Group 1 comprised 38 patients identified as pN+ve, or who were false negative, on sentinel lymph node biopsy (SLNB). Group 2 comprised 146 patients staged pN+ve on ELND. The groups were compared with the Kaplan Meier method and Cox proportional hazards model. In addition, a matched-pair analysis was performed. A unique and specifically designed algorithm was deployed to optimise the pairings. No difference in disease-specific or overall survival was found between the groups. Patients undergoing SLNB as the initial neck staging modality in early OSCC and are identified as pN+ve do not appear to be at a survival disadvantage compared with those staged with ELND.

Sentinel lymph node biopsy for early oral cancer - accuracy and considerations in patient selection.

Sentinel lymph node biopsy (SLNB) for staging oral squamous cell carcinoma (OSCC) patients presenting with early (T1 and T2 N0) disease in preference to elective neck dissection (END) remains controversial worldwide. A retrospective analysis of 145 patients who underwent sentinel lymph node biopsy for a previously untreated early oral cancer between 2010 and 2020 was performed. The primary outcome measures were predictors of occult metastases, accuracy of SLNB and disease specific plus overall survival. The negative predictive value, the false negative rate, and sensitivity for SLNB were 97%, 7.8%, and 92%, respectively. Depth of invasion (DOI) was a significant predictor of N status, overall survival, and disease specific survival. There was a significant difference in the incidence of the neck node metastasis in patients with DOI <5mm compared to those with DOI >5mm. For tumours >5mm there was a moderate to good correlation between radiological depth on contrast enhanced computed tomography (CECT) and histopathological DOI. Preoperative estimation of DOI may be a useful tool in the counselling of patients in the selection of either SLNB or END for N staging purposes in early OSCC.

Inpatient Omission of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers Is Associated With Morbidity and Mortality in Coronavirus Disease 2019.

PURPOSE: Due to the affinity of severe acute respiratory syndrome coronavirus 2 for the human angiotensin-converting enzyme 2 (ACE2) receptor, use of ACE inhibitors and angiotensin receptor blockers (ARBs) has been a major concern for clinicians during the 2020 pandemic. Meta-analyses have affirmed that these agents do not worsen clinical outcomes in patients with severe acute respiratory syndrome coronavirus 2 infection. To date, only a limited number of studies have directly evaluated the safety of inpatient prescription of ACE inhibitors/ARBs during acute coronavirus disease 2019 (COVID-19) illness. METHODS: A retrospective cohort analysis was conducted to investigate the impact of inpatient provision of ACE inhibitors/ARBs on morbidity and mortality in patients admitted to the hospital with COVID-19. Relationships were explored by using linear and logistic regression. FINDINGS: A total of 612 adult patients met the inclusion criteria, of whom 151 (24.7%) patients were established on ACE inhibitors/ARBs. Despite correction for known confounders, discontinuation of ACE inhibitors/ARBs was highly predictive of worsened outcomes in COVID-19. The proportion of doses omitted in the hospital was significantly associated with increased mortality (OR, 9.59; 95% CI, 2.55-36.09; P < 0.001), maximum National Early Warning Score 2 (OR, 1.66; 95% CI, 1.27-2.17; P < 0.001), maximum oxygen requirements (OR, 3.00; 95% CI, 1.83-4.91; P < 0.001), and maximum C-reactive protein concentration (OR, 1.83; 95% CI, 1.06-3.17; P = 0.030). IMPLICATIONS: Our data show a strong association between missed ACE inhibitor/ARB doses with increased morbidity and mortality. The available evidence supports continuation of currently accepted practice surrounding ACE inhibitor/ARB therapy in acute illness, which is to limit drug omission to established acute contraindications, to actively monitor such decisions, and to restart therapy as soon as it is safe to do so. (Clin Ther. 2021;43:e97-e110) © 2021 Elsevier HS Journals, Inc.

Pharmacological Predictors of Morbidity and Mortality in COVID-19.

The interaction of coronavirus disease (COVID-19) with the majority of common prescriptions is broadly unknown. The purpose of this study is to identify medications associated with altered disease outcomes in COVID-19. A retrospective cohort composed of all adult inpatient admissions to our center with COVID-19 was analyzed. Data concerning all antecedent prescriptions were collected and agents brought forward for analysis if prescribed to at least 20 patients in our cohort. Forty-two medications and 22 classes of medication were examined. Groups were propensity score matched and analyzed by logistic and linear regression. The majority of medications did not show a statistically significant relationship with altered disease outcomes. Lower mortality was associated with use of pregabalin (hazard ratio [HR], 0.10; 95% confidence interval [CI], 0.01-0.92; P = .049) and inhalers of any type (HR, 0.33; 95%CI, 0.14-0.80; P = .015), specifically beclomethasone (HR, 0.10; 95%CI, 0.01-0.82; P = .032), tiotropium (HR, 0.07; 95%CI, 0.01-0.83; P = .035), and steroid-containing inhalers (HR, 0.35; 95%CI, 0.15-0.79; P = .013). Gliclazide (HR, 4.37; 95%CI, 1.26-15.18; P = .020) and proton pump inhibitor (HR, 1.72; 95%CI, 1.06-2.79; P = .028) use was associated with greater mortality. Diuretic (HR, 0.07; 95%CI, 0.01-0.37; P = .002) and statin (HR, 0.35; 95%CI, 0.17-0.73; P = .006) use was associated with lower rates of critical care admission. Our data lends confidence to observing usual practice in patients with COVID-19 by continuing antecedent prescriptions in the absence of an alternative acute contraindication. We highlight potential benefits in investigation of diuretics, inhalers, pregabalin, and statins as therapeutic agents for COVID-19 and support further assessment of the safety of gliclazide and proton pump inhibitors in the acute illness.

Cytochrome P450 isoforms 1A1, 1B1 AND 2W1 as targets for therapeutic intervention in head and neck cancer.

Epidemiological studies have shown that head and neck cancer (HNC) is a complex multistage process that in part involves exposure to a combination of carcinogens and the capacity of certain drug-metabolising enzymes including cytochrome P450 (CYP) to detoxify or activate such carcinogens. In this study, CYP1A1, CYP1B1 and CYP2W1 expression in HNC was correlated with potential as target for duocarmycin prodrug activation and selective therapy. In the HNC cell lines, elevated expression was shown at the gene level for CYP1A1 and CYP1B1 whereas CYP2W1 was hardly detected. However, CYP2W1 was expressed in FaDu and Detroit-562 xenografts and in a cohort of human HNC samples. Functional activity was measured in Fadu and Detroit-562 cells using P450-Glo™ assay. Antiproliferative results of duocarmycin prodrugs ICT2700 and ICT2706 revealed FaDu and Detroit-562 as the most sensitive HNC cell lines. Administration of ICT2700 in vivo using a single dose of ICT2700 (150 mg/kg) showed preferential inhibition of small tumour growth (mean size of 60 mm3) in mice bearing FaDu xenografts. Significantly, our findings suggest a potential targeted therapeutic approach to manage HNCs by exploiting intratumoural CYP expression for metabolic activation of duocarmycin-based prodrugs such as ICT2700.

Gender differences in patients with severe dental infections presenting to hospital.

Introduction Gender differences have been documented in prevalence and morbidity of caries, gingivitis and oral health, but not previously in cervicofacial infection. Identification and minimisation of gender inequalities is a World Health Organisation priority, and there are physiological, behavioural and cultural reasons to suspect that sex and gender differences may be present.Methods Analysis was carried out of the MTReC National Snapshot audit of cervicofacial infections. This database was created by oral and maxillofacial surgery trainees in 2017 and records over 400 variables in 1,002 individual patients admitted to hospital with severe odontogenic infection.Results Records were available for 1,002 patients with cervicofacial infection (456 females and 546 males). There were significant differences between recorded gender in those presenting with airway compromise (male 7% vs female 2%, p = 0.001), severe inflammatory response syndrome (male 60% vs female 39%, p = 0.007) and requirement for awake fibre-optic intubation on admission (male 4% vs female 1%, p = 0.014).Discussion These results suggest that male patients access healthcare later in their disease than female patients, and with more severe systemic compromise. This may be due to prevalent cultural and behavioural norms. As equality of access is the responsibility of the administrator, we discuss methods which might improve timely presentation in males with cervicofacial infections.

The relevance of surgical margins in clinically early oral squamous cell carcinoma.

OBJECTIVES: There is controversy regarding surgical margins in the management of early oral squamous cell carcinoma (OSCC). The main objectives of this study were to assess the: relevance of the margin independent of tumour variables; threshold for a safe margin; relevance of dysplasia at the margin. MATERIALS & METHODS: UK based retrospective multicenter cohort study of patients with previously untreated and clinically early OSCC between 1998 and 2016. All patients had surgery as the primary modality and had surgical staging of the neck. Minimum follow-up was 2 years. Margins were classified as: clear ≥5.0 mm; close 1.0-4.9 mm; involved not cut-through (INC-T) 0.1-0.9 mm; cut-through (C-T) 0 mm. RESULTS: 669 patients were included. After adjusting for tumour variables Cox multivariate regression analysis demonstrated that close margins had similar survival outcomes to clear margins (Hazard Ratio(HR) 0.99 (95%CI 0.50-1.95) for Local Recurrence Free Survival (LRFS); HR 1.08 (95%CI 0.7-1.66) for Disease Free Survival (DFS); HR 0.74 (95%CI 0.44-1.25) for Disease Specific Survival (DSS); HR 0.80 (95%CI 0.58-1.11) for Overall Survival (OS)). C-T margins had significantly worse LRFS (HR 5.01 (95%CI 2.02-12.39)) and DFS (HR 2.58 (95%CI 1.28-5.20)). INC-T margins had significantly worse DFS (HR 1.98 (95% CI 1.01-3.87)). Time dependent receiver operating characteristic curve analysis did not demonstrate a clear margin threshold for LRFS within 24 months (AUC = 0.53 (95%CI 0.41-0.64)). Dysplasia at the margin did not influence LRFS or DFS. CONCLUSION: Only resection margins <1 mm independently affected survival outcomes. This should be considered when making decisions regarding adjuvant treatment.

'Nasal flossing': A case report of nasopharyngeal stenosis due to severe erosive lichen planus and a novel therapeutic intervention.

INTRODUCTION: We describe a case of severe erosive oral lichen planus that led to nasopharyngeal stenosis. This is a rare clinical presentation that was ultimately, successfully treated by surgery combined with post-operative 'nasal flossing': a novel therapeutic intervention. PRESENTATION OF CASE: A 76-year-old male suffering from a rare case of severe oral lichen planus that was resistant to conservative measures is described. Initial surgery was complicated by recurrence of nasopharyngeal stenosis. Definitive surgery required revision of nasopharyngeal stenosis release combined with a course of post- operative 'nasal flossing'. The technique for 'nasal flossing' is described and demonstrated in photographs. The patient remained asymptomatic at 3 years using this combined approach, with restoration of olfaction, taste perception and voice quality, significantly enhancing quality of life. DISCUSSION: Erosive oral lichen planus is a rare but important presentation in oral medicine. We found 'nasal flossing' to be a successful treatment to maintain nasopharyngeal patency following surgical repair of this uncommon condition. We are not aware that this combined approach has previously been described in the published literature. CONCLUSIONS: Severe erosive oral lichen planus can lead to nasopharyngeal stenosis. Nasopharyngeal stenosis in these patients may be refractive to conventional surgical approaches. 'Nasal flossing' is demonstrated to be both practical and acceptable as a surgical adjunct in these difficult to treat cases of recurrent nasopharyngeal stenosis. This report has relevance for all those practicing oral and maxillofacial surgery, ear nose and throat surgery and oral medicine.

HOPON (Hyperbaric Oxygen for the Prevention of Osteoradionecrosis): A Randomized Controlled Trial of Hyperbaric Oxygen to Prevent Osteoradionecrosis of the Irradiated Mandible After Dentoalveolar Surgery.

PURPOSE: Hyperbaric oxygen (HBO) has been advocated in the prevention and treatment of osteoradionecrosis (ORN) of the jaw after head and neck radiation therapy, but supporting evidence is weak. The aim of this randomized trial was to establish the benefit of HBO in the prevention of ORN after high-risk surgical procedures to the irradiated mandible. METHODS AND MATERIALS: HOPON was a randomized, controlled, phase 3 trial. Participants who required dental extractions or implant placement in the mandible with prior radiation therapy >50 Gy were recruited. Eligible patients were randomly assigned 1:1 to receive or not receive HBO. All patients received chlorhexidine mouthwash and antibiotics. For patients in the HBO arm, oxygen was administered in 30 daily dives at 100% oxygen to a pressure of 2.4 atmospheres absolute for 80 to 90 minutes. The primary outcome measure was the diagnosis of ORN 6 months after surgery, as determined by a blinded central review of clinical photographs and radiographs. The secondary endpoints included grade of ORN, ORN at other time points, acute symptoms, pain, and quality of life. RESULTS: A total of 144 patients were randomized, and data from 100 patients were analyzed for the primary endpoint. The incidence of ORN at 6 months was 6.4% and 5.7% for the HBO and control groups, respectively (odds ratio, 1.13; 95% confidence interval, 0.14-8.92; P = 1). Patients in the hyperbaric arm had fewer acute symptoms but no significant differences in late pain or quality of life. Dropout was higher in the HBO arm, but the baseline characteristics of the groups that completed the trial were comparable between the 2 arms. CONCLUSIONS: The low incidence of ORN makes recommending HBO for dental extractions or implant placement in the irradiated mandible unnecessary. These findings are in contrast with a recently published Cochrane review and previous trials reporting rates of ORN (non-HBO) of 14% to 30% and challenge a long-established standard of care.

Telomere dysfunction is related to the intrinsic radio-resistance of human oral cancer cells.

Evidence from telomerase-deficient mice strongly suggests that dysfunctional short telomeres affect cellular radio-sensitivity but this idea has yet to be extensively tested in relevant human cancer types such as oral squamous cell carcinomas (OSCCs), which are frequently treated by radiotherapy. The OSCC line BICR7 has low levels of telomerase activity, short telomeres and high levels of telomere dysfunction (judged by a high level of anaphase bridges); whereas the BICR6 line has high levels of telomerase and is more radio-resistant. Ectopic expression of the human TElomerase Reverse Transcriptase (hTERT) reduced telomere dysfunction and increased radio-resistance in BICR7 cells, but not BICR6. Furthermore, the radio-resistance of GM847 cells, which use telomerase-independent mechanisms of telomere maintenance, and of telomerase-negative normal human fibroblasts with long telomeres are similarly unaffected by ectopic expression of telomerase. We tested whether telomere function, as measured by the Anaphase Bridge Index (ABI), was found to be a useful predictor of radio-resistance in a panel of OSCC lines. Using inverse regression analysis, we found a strong inverse relationship between the ABI and radio-resistance (P<0.001), as measured by the Surviving Fraction at 4Gy (SF4). These results suggest that telomerase inhibitors could sensitise a subset of oral SCCs with short telomeres to radiotherapy and for the first time demonstrate that the tumour ABI may assist the selection of cancers that would be suitable for such sensitisation therapy.

HOPON (Hyperbaric Oxygen for the Prevention of Osteoradionecrosis): a randomised controlled trial of hyperbaric oxygen to prevent osteoradionecrosis of the irradiated mandible: study protocol for a randomised controlled trial.

BACKGROUND: Osteoradionecrosis of the mandible is the most common serious complication of radiotherapy for head and neck malignancy. For decades, hyperbaric oxygen has been employed in efforts to prevent those cases of osteoradionecrosis that are precipitated by dental extractions or implant placement. The evidence for using hyperbaric oxygen remains poor and current clinical practice varies greatly. We describe a protocol for a clinical trial to assess the benefit of hyperbaric oxygen in the prevention of osteoradionecrosis during surgery on the irradiated mandible. METHODS/DESIGN: The HOPON trial is a phase III, randomised controlled, multi-centre trial. It employs an unblinded trial design, but the assessment of the primary endpoint, i.e. the diagnosis of osteoradionecrosis, is assessed on anonymised clinical photographs and radiographs by a blinded expert panel. Eligibility is through the need for a high-risk dental procedure in the mandible where at least 50-Gy radiotherapy has been received. Patients are randomised 1:1 to hyperbaric oxygen arm (Marx protocol) : control arm, but both groups receive antibiotics and chlorhexidine mouthwash. The primary endpoint is the presence of osteoradionecrosis at 6 months following surgery, but secondary endpoints include other time points, acute symptoms and pain, quality of life, and where implants are placed, their successful retention. DISCUSSION: The protocol presented has evolved through feasibility stages and through analysis of interim data. The classification of osteoradionecrosis has undergone technical refinement to ensure that robust definitions are employed. The HOPON trial is the only multi-centre RCT conducted in this clinical setting despite decades of use of hyperbaric oxygen for the prevention of osteoradionecrosis. TRIAL REGISTRATION: European Clinical Trials Database, ID: EudraCT200700622527 . First registered on 5 November 2007.

Research training for oral and maxillofacial surgery.

The specialty of oral and maxillofacial surgery (OMFS) is unique among UK medical and dental specialties in having clinical and academic training pathways whose entry criteria, curricula and exit examinations are quite different. The Academic Advisory Committee for Oral and Maxillofacial Surgery (AACOMS) pathway offers a formal academic training but with a limited clinical curriculum, while training within the National Health Service (NHS) offers little or no access to research but a more comprehensive clinical curriculum. As a result, there are few doubly qualified consultants in senior university positions, and limited opportunities for dental and medical undergraduates to be exposed to the full scope of the specialty. A further consequence is that research in certain disciplines, such as head and neck oncology and facial trauma, is absent from the majority of universities. Until this situation is corrected, maxillofacial trainees who wish to undergo a comprehensive clinical and research training must find time and funding to support their research training outwith their clinical education. The purpose of this paper is to identify key steps in deciding when, where and how a maxillofacial trainee can gain accomplished research experience in the context of current UK maxillofacial training.