American Association of Oral and Maxillofacial Surgeon's Position Paper on Oral Mucosal Dysplasia.

Oral potentially malignant disorders (OPMDs) of the oral mucosa include leukoplakia, erythroplakia, erythroleukoplakia, lichen planus, and oral lichenoid lesions, each with varying incidences of dysplastic disease at the time of presentation and each with observed incidences of malignant transformation over time. The primary goal of the management of dysplasia, therefore, includes their early detection and treatment prior to malignant transformation. The recognition and management of these OPMDs and an understanding of their potential progression to oral squamous cell carcinoma will reduce the morbidity and mortality associated with these lesions with expedient and properly executed treatment strategies that will have a positive effect on patient survival. It is the purpose of this position paper to discuss oral mucosal dysplasia in terms of its nomenclature, epidemiology, types, natural history, and treatment to acquaint clinicians regarding the timing of biopsy, type of biopsy, and follow-up of patients with these lesions of the oral mucosa. This position paper represents a synthesis of existing literature on this topic with the intention of closing gaps in our understanding of oral mucosal dysplasia while also stimulating new thinking to guide clinicians in the proper diagnosis and management of OPMDs. The fifth edition of the World Health Organization classification of head and neck tumors published in 2022 represents new information regarding this topic and a construct for this position paper.

Practice patterns for initial management of oral leukoplakia amongst otolaryngologists and oral and maxillofacial surgeons.

OBJECTIVE: Oral leukoplakia is encountered frequently by otolaryngologists and oral and maxillofacial surgeons (OMFS). There are no consensus practice management guidelines for oral leukoplakia, resulting in heterogeneity in practice patterns. Characterization of practice patterns of providers who treat oral leukoplakia will be valuable to establish standards of care and future practice guidelines. MATERIAL AND METHODS: A survey was designed by the American Head and Neck Society Cancer Prevention Service collecting demographic and practice management data for treating oral leukoplakia. The survey was approved and distributed to members of the American Academy of Otolaryngology-Head and Neck Surgery and American Association of Oral and Maxillofacial Surgeons. Data analysis was performed using chi square and t-test where appropriate. RESULTS: 396 responses were collected: 83 OMFS, 81 head and neck fellowship-trained providers, and 232 otolaryngologists (non-head and neck fellowship-trained). Providers saw a wide volume of oral leukoplakia (23.0% >30 cases/year, 35.1% 11-30 cases/year, 41.2% 10 or less cases/year), with OMFS seeing more cases of oral leukoplakia. Factors most associated with consideration of initial biopsy included physical exam findings (94.4%), erythroplakia (82.3%), and smoking status (81.6%). The majority of respondents saw patients in follow-up within 1 month (24.8%) or within 1-3 months (46.5%). CONCLUSION: This survey identifies a range of practice patterns in initial management of oral leukoplakia, including indications for biopsy, and time for follow-up. This data provide insight into practice patterns amongst different groups of providers and can potentially lead to consensus guidelines for initial management of oral leukoplakia.

Effect of preradiation dental intervention on incidence of osteoradionecrosis in patients with head and neck cancer: A systematic review and meta-analysis.

BACKGROUND: The purpose of this systematic review was to examine whether dental intervention involving bone or soft-tissue manipulation preradiotherapy (pre-RT) is associated with lower rates of osteoradionecrosis of the jaw (ORNJ) in patients with head and neck cancer (HNC). TYPES OF STUDIES REVIEWED: The authors included relevant studies from MEDLINE, Embase, and Cochrane Library, including observational studies published from 2007 through 2021 and involving adults who underwent dental intervention pre-RT for HNC. Authors assessed evidence certainty by using the Grading of Recommendations Assessment, Development, and Evaluation approach. Random-effects models were used to calculate pooled relative risk estimates and hazard ratios. When meta-analysis was not possible, study-level measures of association and narrative summaries of the evidence were reported. RESULTS: Twenty-two studies were included. From the pooled, unadjusted analysis, patients undergoing pre-RT extractions may have a 55% increased risk of experiencing ORNJ (relative risk, 1.55; 95% CI, 0.85 to 2.86; very low certainty); the unadjusted pooled hazard ratio was 3.19 (95% CI, 0.99 to 10.31; very low certainty), corresponding to a possible increased hazard of developing ORNJ (very low certainty). Findings for other pre-RT procedures manipulating bone or tissue relied on limited, observational studies with low or very low certainty evidence. CONCLUSIONS: Mostly very low certainty evidence suggests that patients with HNC who need pre-RT dental intervention may have an increased risk of developing ORNJ compared with those who do not. PRACTICAL IMPLICATIONS: Maintaining optimal oral health may help reduce the need for urgent pre-RT dental treatment, potentially reducing ORNJ risk and minimizing delay of oncologic treatment in patients with HNC.

American Association of Oral and Maxillofacial Surgeons' Position Paper on Medication-Related Osteonecrosis of the Jaws-2022 Update.

Strategies for management of patients with, or at risk for, medication-related osteonecrosis of the jaws (MRONJ) - formerly referred to as bisphosphonate-related osteonecrosis of the jaws (BRONJ)-were set forth in the American Association of Oral and Maxillofacial Surgeons (AAOMS) position papers in 2007, 2009 and 2014. The position papers were developed by a committee appointed by the AAOMS Board of Trustees and comprising clinicians with extensive experience in caring for these patients, as well as clinical and basic science researchers. The knowledge base and experience in addressing MRONJ continues to evolve and expand, necessitating modifications and refinements to the previous position papers. Three members of the AAOMS Committee on Oral, Head, and Neck Oncologic and Reconstructive Surgery (COHNORS) and three authors of the 2014 position paper were appointed to serve as a working group to analyze the current literature and revise the guidance as indicated to reflect current knowledge in this field. This update contains revisions to diagnosis and management strategies and highlights the current research status. AAOMS maintains that it is vitally important for this information to be disseminated to other relevant healthcare professionals and organizations.

Intracellular calprotectin (S100A8/A9) controls epithelial differentiation and caspase-mediated cleavage of EGFR in head and neck squamous cell carcinoma.

OBJECTIVES: Calprotectin (S100A8/A9) appears to function as a tumor suppressor in head and neck squamous cell carcinoma (HNSCC) and expression in the carcinoma cells and patient survival rates are directly related. We seek to characterize the suppressive role of calprotectin in HNSCC. AIMS: (1) Investigate changes in S100A8/A9 expression as oral carcinogenesis progresses and (2) determine whether intracellular calprotectin can regulate epidermal growth factor receptor (EGFR), a negative prognostic factor, in HNSCC. MATERIALS AND METHODS: Using immunohistochemistry (IHC), S100A8/A9 was analyzed in HNSCC specimens (N = 46), including well-differentiated (WD, N = 19), moderately-differentiated (MD, N = 14), poorly-differentiated (PD, N = 5) and non-keratinizing/basaloid (NK/BAS, N = 8), and premalignant epithelial dysplasias (PED, N = 16). Similarly, EGFR was analyzed in HNSCCs (N = 21). To determine whether calprotectin and EGFR expression are mechanistically linked, TR146 HNSCC cells that are S100A8/A9-expressing or silenced (shRNA) were compared for EGFR levels and caspase-3/7 activity using western blotting and immunofluorescence microscopy. RESULTS: In normal oral mucosal epithelium, S100A8/A9 stained strongly in the cytoplasm and nucleus of suprabasal cells; basal cells were consistently S100A8/A9 negative. In PED and HNSCC, S100A8/A9 expression was lower than in adjacent normal epithelial tissues (NAT) and declined progressively in WD, MD, PD and NK/BAS HNSCCs. S100A8/A9 and EGFR levels appeared inversely related, which was simulated in vitro when S100A8/A9 was silenced in TR146 cells. Silencing S100A8/A9 significantly reduced caspase-3/7 activity, whereas EGFR levels increased. CONCLUSIONS: In HNSCC, S100A8/A9 is directly associated with cellular differentiation and appears to promote caspase-3/7-mediated cleavage of EGFR, which could explain why patients with S100A8/A9-high tumors survive longer.

Evaluation of a Lectin-Based Imaging System for the Chairside Detection of Oral Dysplasia and Malignancy.

PURPOSE: Currently available oral cancer screening adjuncts have not enhanced clinical screening methods because of high false positives and negatives, highlighting the need for a molecularly specific technique for accurate screening of suspicious oral lesions. The purpose of this study was to evaluate the in vivo screening accuracy of an oral lesion identification system that evaluates aberrant glycosylation patterns using a fluorescently labeled lectin (wheat germ agglutinin and fluorescein isothiocyanate [WGA-FITC]). MATERIALS AND METHODS: The authors designed and implemented a prospective cohort study at 3 institutions composed of patients with and without suspicious oral lesions. Oral cavities were screened by clinical examination and with the oral lesion identification system according to a stepwise procedure that included the topical application and fluorescence visualization of a fluorescent nuclear stain and WGA-FITC. Tissue samples were obtained from all enrolled patients for histopathological diagnosis and were used to calculate sensitivity and specificity metrics (primary outcome variable) irrespective of the oral lesion identification system result. RESULTS: The sample was composed of 97 patients; 86 had 100 clinically suspicious lesions and 11 without such lesions were included as a control group. Use of the oral lesion identification system resulted in 100, 100, and 74% sensitivity for cancer, high-grade dysplasia, and low-grade dysplasia, respectively, and a specificity of 80%. Clinical diagnosis yielded similar sensitivity values of 84, 100, and 88% for cancer, high-grade dysplasia, and low-grade dysplasia, respectively, and a specificity of 76%. Use of the oral lesion identification system enhanced the visualization of lesion dimensionality and borders. CONCLUSIONS: The results of this study suggest the oral lesion identification system was a beneficial adjunct to standard clinical examination, because the system provided sensitivity and specificity values similar to or greater than clinical diagnosis.

What Is the Role of Elective Neck Dissection in the Management of Patients With Buccal Squamous Cell Carcinoma and Clinically Negative Neck?

PURPOSE: Buccal squamous cell carcinoma (BSCC) is rare in the United States. Given its location, few anatomic barriers to spread exist and it has been found to have a high locoregional recurrence rate. The role of elective neck dissection (END) in patients with clinically negative neck (N0) is not clear. This study aims to answer the following research question: Among patients with N0 BSCC, does END improve locoregional control rates, distant metastasis rates, and 2- and 5-year survival rates? MATERIALS AND METHODS: A retrospective cohort study was conducted. The sample included patients who received a diagnosis of BSCC. The primary predictor variable was END status (yes or no). Five institutions participated between June 2001 and June 2011: University of Washington, University of Michigan, University of Tennessee, North Memorial Oral and Maxillofacial Surgery in Minnesota, and Head and Neck Surgical Associates (Portland, OR). The primary outcome variable was locoregional recurrence. Secondary outcome variables were distant metastasis and 2- and 5-year survival rates. Other variables collected were demographic characteristics, initial operation, adjuvant therapy, clinical and pathologic data, and staging. Kaplan-Meier and Cox proportional hazards statistics were computed. RESULTS: The sample was composed of 98 patients with clinical N0 BSCC. The mean age was 66 years (range, 30-88 years), and 54% were men. Of the patients, 74 (76%) underwent END. The locoregional recurrence-free rate was 61% for END versus 38% for no END (P = .042). The distant metastasis rate was 4% for END versus 9% for no END. The 2- and 5-year disease-free survival rates were 91% and 75% (P = .042), respectively, for END and 85% and 63% (P = .019), respectively, for no END. CONCLUSIONS: END had a therapeutic effect, as evidenced by a lower locoregional recurrence rate, lower distant metastasis rate, and improved 2- and 5-year survival rates.

Management update of potentially premalignant oral epithelial lesions.

The term oral potentially malignant disorders, proposed at the World Health Organization workshop in 2005, has now been renamed potentially premalignant oral epithelial lesions (PPOELs). It is important to differentiate among PPOELs, which is a broad term to define a wide variety of clinical lesions, and oral epithelial dysplasia, which should be reserved specifically for lesions with biopsy-proven foci of dysplasia. PPOELs encompass lesions that include leukoplakia, erythroplakia, erythroleukoplakia, lichen planus, and oral submucous fibrosis. The primary goal of management of dysplasia includes prevention, early detection, and treatment before malignant transformation. The aim of this article is to inform the clinician about management of PPOELs.

Proceedings of the American Association of Oral and Maxillofacial Surgeon's 2017 Clinical and Scientific Innovations in Oral and Maxillofacial Surgery (CSIOMS).

The sixth biennial Clinical and Scientific Innovations in Oral and Maxillofacial Surgery, formerly the Research Summit, of the American Association of Oral and Maxillofacial Surgeons and its Committee on Research Planning and Technology Assessment was held in Rosemont, Illinois from April 28 to 30, 2017. The goal of the symposium is to provide a forum for the latest clinical and scientific advances to be brought to the specialty. It also nurtures collaboration and the development of relationships between oral and maxillofacial surgeons and researchers to bridge the gap between clinical and basic science. The goal is to improve the care of oral and maxillofacial surgical patients through the advancement of translational and clinical research.

Chairside molecular imaging of aberrant glycosylation in subjects with suspicious oral lesions using fluorescently labeled wheat germ agglutinin.

BACKGROUND: Aberrant sialylation is accepted as a carcinogenic biomarker. In previous work, fluorescently labeled wheat germ agglutinin (WGA) distinguished between cancerous and normal oral biopsies. The purpose of this study was to investigate WGA-fluorescein isothiocyanate (FITC) as a point-of-care tool for detecting oral malignant and dysplastic lesions in vivo. METHODS: Subject recruitment was divided into two groups: (1) the clinically normal oral mucosa group; or (2) the presence of clinically suspicious oral lesion(s) group. A WGA-FITC solution was topically applied to observable lesions or to half the subject's mouth (sagittal plane) if lesions were absent. Fluorescent molecular imaging was used to evaluate WGA-FITC localization. RESULTS: Fluorescent imaging in 55 subjects demonstrated that WGA-FITC could detect histopathologically-confirmed cancerous and dysplastic lesions with high sensitivity (100% and 81%, respectively) and specificity (82%). CONCLUSION: This study supports in vivo fluorescent molecular imaging of WGA-FITC to visualize aberrant sialic acid expression associated with carcinogenesis. This technique resulted in the immediate chairside detection of oral cancerous and dysplastic lesions.

Oral/Head and Neck Oncologic and Reconstructive Surgery Fellowship Training Programs: Transformation of the Specialty From 2005 to 2015: Report from the AAOMS Committee on Maxillofacial Oncology and Reconstructive Surgery.

Oral and Maxillofacial Surgeons have increasing opportunities to train in head and neck oncologic and reconstructive surgery. The development of a fellowship training programs within our speciality has had a transformative effect on the speciality. This survey by the commitee on Maxillofacial Oncology and Reconstructive is aimed to evaluate the impact of fellowship training on the careers of the fellows and speciality from 2005-2015.

Proceedings of the American Association of Oral and Maxillofacial Surgeons 2015 Research Summit.

The Fifth Biennial Research Summit of the American Association of Oral and Maxillofacial Surgeons and its Committee on Research Planning and Technology Assessment was held in Rosemont, Illinois on May 6 and 7, 2015. The goal of the symposium is to provide a forum for the most recent clinical and scientific advances to be brought to the specialty. The proceedings of the events of that summit are presented in this report.

Pectoralis major myocutaneous flap.

There has been a gradual shift of the utilization of pectoralis major myocutaneous (PMMC) pedicled flaps with the current advancements in the successful development of vascularized free flaps. Currently, PMMC flaps are considered a salvage mechanism after failure of a free vascularized flap or used as the reconstructive option for patients who are considered poor candidates for free flaps. This review discusses the PMMC flap for reconstruction of the oral and maxillofacial region, from preoperative considerations and anatomy to surgical technique and possible complications. Advantages and disadvantages for such flaps are also discussed.

Molecular imaging of oral premalignant and malignant lesions using fluorescently labeled lectins.

Aberrant glycosylation during carcinogenesis results in altered glycan expression on oral cancer cells. The objective of this study was to detect this atypical glycosylation via imaging of fluorophore-conjugated lectins. Paired normal and tumor tissue from seven patients with oral squamous cell carcinoma were investigated for sialic acid expression via the legume protein wheat germ agglutinin (WGA). Fluorophore (Alexa Fluor 350 and Alexa Fluor 647) conjugated WGA was topically applied to the tissue samples and imaged using a custom wide-field fluorescence imaging system. All seven patients had histologically confirmed disease with 6/7 exhibiting squamous cell carcinoma and 1/7 exhibiting dysplasia. Fluorescent data collected from all patients demonstrated that fluorophore conjugated WGA could distinguish between pathologically normal and diseased tissue with the average signal-to-noise ratio (SNR) among all patients being 5.88 (P = .00046). This SNR was statistically significantly higher than the SNR from differences in tissue autofluorescence (P = .0049). A lectin inhibitory experiment confirmed that lectin binding is molecularly specific to overexpressed tumor glycans and that fluorescence is not due to tissue optical properties or tissue diffusion differences. These results illustrate that changes in tumor glycan content of oral neoplasms can be detected with optical imaging using topically applied fluorescently labeled WGA. Lectin targeting of oral lesions using optical imaging may provide a new avenue for the early detection of oral cancers.

Proceedings from the 2013 American Association of Oral and Maxillofacial Surgeons Research Summit.

The American Association of Oral and Maxillofacial Surgeons, the Oral and Maxillofacial Surgery Foundation, and the International Association of Oral and Maxillofacial Surgeons sponsored the fifth research summit, which convened on May 2 and 3 in Rosemont, Illinois. The Research Summits are convened biennially to facilitate the discussion and collaboration of oral and maxillofacial surgeons with clinical and basic science researchers in fields affecting the specialty. The goal is to advance the field of oral and maxillofacial surgery through exposure and education in topics that ultimately benefit the oral and maxillofacial surgical patient. This edition of the research summit included the topics of robotic surgery and antiresorptive-related osteonecrosis of the jaws (ARONJ). Most importantly, this research summit saw the development of research interest groups (RIGs) in the fields of anesthesia, maxillofacial oncology and reconstructive surgery, obstructive sleep apnea and orthognathic surgery, temporomandibular joint surgery, and trauma. These RIGs developed specific research goals with a plan to continue working on potential projects at the AAOMS Clinical Trials Course on May 7 to 9, 2013 at the University of Michigan in Ann Arbor. The summit program was developed by the AAOMS Committee on Research Planning and Technology Assessment. The charge of the committee is to encourage and promote research within the specialty and to encourage interdisciplinary collaboration. The research summit serves as a platform for oral and maxillofacial surgeons to lead the goal of advancement of research relevant to the specialty. This article provides an overview of the presentations that were made in the sessions on robotic surgery and ARONJ. The research summit keynote address and two additional presentations on patient registries are summarized and updates from the RIGs that were formed at the 2013 research summit are highlighted.

Comparison between p16 INK4A immunohistochemistry and human papillomavirus polymerase chain reaction assay in oral papillary squamous cell carcinoma.

PURPOSE: Oral papillary squamous cell carcinoma (OPSCC) is a histologic variant of SCC with a growth pattern suggesting human papillomavirus (HPV) infection. The aim of this study was to investigate the presence of HPV genotypes in OPSCC. MATERIALS AND METHODS: All cases with a histologic diagnosis of OPSCC from 1993 through 2008 were retrieved and confirmed. Immunohistochemical evaluation for the surrogate marker p16(INK4A) and HPV polymerase chain reaction were performed in tissue and DNA derived from formalin-fixed paraffin-embedded tissue. RESULTS: Forty-four patients with confirmed OPSCC (mean age, 71.96 yr; female-to-male ratio, 1.75:1) comprised the study population. The most common site of involvement was the gingiva followed by the palate and buccal mucosa. Forty cases exhibited an invasive component, 1 was noninvasive, and in 3 cases invasion could not be confirmed owing to suboptimal thickness of the biopsy. Paraffin tissue blocks were available in 41 cases. Twenty-three cases (56.1%) exhibited positive p16(INK4A) staining, which was primarily weak to moderate with a generally focal pattern. Polymerase chain reaction assays were negative for HPV DNA in all cases. CONCLUSIONS: In this study, there was a clinical predilection of OPSCC in older women, with most cases occurring in the masticatory mucosa. Weak to moderate and focal p16(INK4A) staining was appreciated in contrast to reported staining properties in genital and oropharyngeal PSCC. Failure of the polymerase chain reaction assay to exhibit transcriptionally active HPV genotypes suggests that HPV is not associated with OPSCC tumorigenesis.