Humanitarian Maxillofacial Mission's Success Requires Experienced Surgeons, Careful Planning, and Meeting With the Local's Care Needs.

PURPOSE: Meeting with local needs of low- and middle-income countries during maxillofacial humanitarian mission is not easy. This article aimed to report on 5 years of experience in humanitarian maxillofacial surgery missions. In addition, several key points for best practices and meeting the medical needs of local populations are discussed. METHODS: In this retrospective case series, all medical charts of patients managed during humanitarian maxillofacial surgery missions organized within the department of maxillofacial surgery of Le Dantec Hospital (Senegal) were analyzed. Disease characteristics, treatments modality, and outcomes were reviewed. Moreover, missions planning and costs were studied. RESULTS: Between 2015 and 2018, 5 humanitarian missions were organized totalizing 177 patients, one-third of which were treated surgically. Tumors (35%) and sequelae from previous surgeries, cancrum oris or trauma (24%) were the most frequently treated disorders. Most patients were treated with free flap reconstructions (35%). Postoperative complications were observed for only 3 patients (5%). With a median follow-up of 13 months, no sequelae requiring specific treatment were observed. The estimated total cost for each mission was $39,000. CONCLUSION: In order to benefit both the locals and the volunteers, humanitarian maxillofacial missions should be carefully planned and volunteers appropriately prepared. Other keys to the success of such missions are setting up training and support programs, reflecting upon ethical considerations, understanding local cultural customs and ensuring mutual respect with the locals. Frequent self-evaluation and long-term mission sustainability are critical. Finally, mission costs should be evaluated.

Bilateral hypoglossal nerve stimulation for treatment of adult obstructive sleep apnoea.

BACKGROUND AND AIM: Hypoglossal nerve stimulation (HNS) decreases obstructive sleep apnoea (OSA) severity via genioglossus muscle activation and decreased upper airway collapsibility. This study assessed the safety and effectiveness at 6 months post-implantation of a novel device delivering bilateral HNS via a small implanted electrode activated by a unit worn externally, to treat OSA: the Genio™ system. METHODS: This prospective, open-label, non-randomised, single-arm treatment study was conducted at eight centres in three countries (Australia, France and the UK). Primary outcomes were incidence of device-related serious adverse events and change in the apnoea-hypopnoea index (AHI). The secondary outcome was the change in the 4% oxygen desaturation index (ODI). Additional outcomes included measures of sleepiness, quality of life, snoring and device use. This trial was registered with ClinicalTrials.gov, number NCT03048604. RESULTS: 22 out of 27 implanted participants (63% male, aged 55.9±12.0 years, body mass index (BMI) 27.4±3.0 kg·m-2) completed the protocol. At 6 months BMI was unchanged (p=0.85); AHI decreased from 23.7±12.2 to 12.9±10.1 events·h-1, a mean change of 10.8 events·h-1 (p<0.001); and ODI decreased from 19.1±11.2 to 9.8±6.9 events·h-1, a mean change of 9.3 events·h-1 (p<0.001). Daytime sleepiness (Epworth Sleepiness Scale; p=0.01) and sleep-related quality of life (Functional Outcomes of Sleep Questionnaire-10; p=0.02) both improved significantly. The number of bed partners reporting loud, very intense snoring, or leaving the bedroom due to participant snoring decreased from 96% to 35%. 91% of participants reported device use >5 days per week, and 77% reported use for >5 h per night. No device-related serious adverse events occurred during the 6-month post-implantation period. CONCLUSIONS: Bilateral HNS using the Genio™ system reduces OSA severity and improves quality of life without device-related complications. The results are comparable with previously published HNS systems despite minimal implanted components and a simple stimulation algorithm.

Custom surgical management of invasive malignant tumors of the scalp.

BACKGROUND: There is no universal management protocol concerning invasive malignant tumors of the scalp with bone and dura mater invasion. The aims of this study were to report and discuss our experience in the management of these forms of tumors. METHODS: We retrospectively reviewed all consecutive patients of microsurgical scalp reconstruction performed after resection of invasive cutaneous malignancies of the scalp, calvarium, and dura mater from 2017 to 2019, at Pitié-Salpêtrière University Hospital (Paris, France). RESULTS: Five patients met inclusion criteria. There were three squamous cell carcinomas and two sarcomas. Mean age at surgery was 63.6 years. The sex ratio male/female was 4. Two received radiation prior to resection and two patients had a history of prior scalp tumor surgery. All the patients underwent craniectomy and the mean cranial defect size was 41 cm2. Cranioplasty was performed in one patient. Soft tissue coverage was provided by free tissue transfer of latissimus dorsi muscle in all patients. In four patients, split thickness skin graft was performed in a second surgical stage few weeks later. There were no intraoperative complications and no complications into the donor site for the tissue transfer or the skin graft. Two patients had flap necrosis that healed after a new free flap of latissimus dorsi. CONCLUSIONS: Wide resection with craniectomy and reconstruction with microvascular free tissue transfer provides safe and reliable treatment of recalcitrant invasive scalp skin cancers. The surgical management of these complex patients is a challenge that must be conducted by trained, experienced, and multidisciplinary teams.

Bibliometric analysis of a century of research on oral erythroplakia and leukoplakia.

BACKGROUND: Oral squamous cell carcinoma is a major cause of cancer-associated morbidity and mortality and may develop from oral erythroplakia and leukoplakia (OEL), the most common oral potentially malignant lesions. Our objective was to provide a descriptive overview of the global research activity on OEL over the past decades. METHODS: We performed a systematic bibliometric analysis of articles and reviews on OEL up to December 31st 2016 using the SCOPUS database. Contribution of each country was analyzed by density-equalizing mapping (DEMP). The overall scientific productivity was analyzed for each journal and country. RESULTS: A total of 5098 published items (articles or reviews) were identified. They are expected to double by 2040, with an expected number of 400 items per year. Only 4% of all research on oral oncology is focused on OEL. Together with the increasing number of publications since 1980s, an increasing number of international collaborative studies were observed. Journal of Oral Pathology and Medicine and Oral Oncology are the leading journals in terms of number of published items. The US, India, and the UK were the most prolific countries in terms of publications overtime. CONCLUSIONS: We identified the leading journals as well as the leading authors and countries contributing to the research on OEL. International collaborative studies in the field are to be encouraged to refine strategies of oral cancer prevention.

A 13-gene expression-based radioresistance score highlights the heterogeneity in the response to radiation therapy across HPV-negative HNSCC molecular subtypes.

BACKGROUND: Radiotherapy for head and neck squamous cell carcinomas (HNSCC) is associated with a substantial morbidity and inconsistent efficacy. Human papillomavirus (HPV)-positive status is recognized as a marker of increased radiosensitivity. Our goal was to identify molecular markers associated with benefit to radiotherapy in patients with HPV-negative disease. METHODS: Gene expression profiles from public repositories were downloaded for data mining. Training sets included 421 HPV-negative HNSCC tumors from The Cancer Genome Atlas (TCGA) and 32 HNSCC cell lines with available radiosensitivity data (GSE79368). A radioresistance (RadR) score was computed using the single sample Gene Set Enrichment Analysis tool. The validation sets included two panels of cell lines (NCI-60 and GSE21644) and HPV-negative HNSCC tumor datasets, including 44 (GSE6631), 82 (GSE39366), and 179 (GSE65858) patients, respectively. We finally performed an integrated analysis of the RadR score with known recurrent genomic alterations in HNSCC, patterns of protein expression, biological hallmarks, and patterns of drug sensitivity using TCGA and the E-MTAB-3610 dataset (659 pancancer cell lines, 140 drugs). RESULTS: We identified 13 genes differentially expressed between tumor and normal head and neck mucosa that were associated with radioresistance in vitro and in patients. The 13-gene expression-based RadR score was associated with recurrence in patients treated with surgery and adjuvant radiotherapy but not with surgery alone. It was significantly different among different molecular subtypes of HPV-negative HNSCC and was significantly lower in the "atypical" molecular subtype. An integrated analysis of RadR score with genomic alterations, protein expression, biological hallmarks and patterns of drug sensitivity showed a significant association with CCND1 amplification, fibronectin expression, seven hallmarks (including epithelial-to-mesenchymal transition and unfolded protein response), and increased sensitivity to elesclomol, an HSP90 inhibitor. CONCLUSIONS: Our study highlights the clinical relevance of the molecular classification of HNSCC and the RadR score to refine radiation strategies in HPV-negative disease.

Selective disruption of acetylcholine synthesis in subsets of motor neurons: a new model of late-onset motor neuron disease.

Motor neuron diseases are characterized by the selective chronic dysfunction of a subset of motor neurons and the subsequent impairment of neuromuscular function. To reproduce in the mouse these hallmarks of diseases affecting motor neurons, we generated a mouse line in which ~40% of motor neurons in the spinal cord and the brainstem become unable to sustain neuromuscular transmission. These mice were obtained by conditional knockout of the gene encoding choline acetyltransferase (ChAT), the biosynthetic enzyme for acetylcholine. The mutant mice are viable and spontaneously display abnormal phenotypes that worsen with age including hunched back, reduced lifespan, weight loss, as well as striking deficits in muscle strength and motor function. This slowly progressive neuromuscular dysfunction is accompanied by muscle fiber histopathological features characteristic of neurogenic diseases. Unexpectedly, most changes appeared with a 6-month delay relative to the onset of reduction in ChAT levels, suggesting that compensatory mechanisms preserve muscular function for several months and then are overwhelmed. Deterioration of mouse phenotype after ChAT gene disruption is a specific aging process reminiscent of human pathological situations, particularly among survivors of paralytic poliomyelitis. These mutant mice may represent an invaluable tool to determine the sequence of events that follow the loss of function of a motor neuron subset as the disease progresses, and to evaluate therapeutic strategies. They also offer the opportunity to explore fundamental issues of motor neuron biology.

Three-dimensional reconstructions from computed tomographic scans on smartphones and tablets: a simple tutorial for the ward and operating room using public domain software.

Handling 3-dimensional reconstructions of computed tomographic scans on portable devices is problematic because of the size of the Digital Imaging and Communications in Medicine (DICOM) stacks. The authors provide a user-friendly method allowing the production, transfer, and sharing of good-quality 3-dimensional reconstructions on smartphones and tablets.

Postoperative infections after sinus lifts and onlay grafts in penicillin allergic patients.

INTRODUCTION: The primary objective of this retrospective study was to determine whether patients treated with clindamycin due to a reported allergy to penicillin have an increased risk of postsurgical infections after sinus lifts and onlay grafts. MATERIAL AND METHODS: A retrospective cohort study was performed on patients who underwent bone reconstruction procedures between October 2018 and December 2020. Data from all patients operated at the Pitié Salpêtrière University Hospital for sinus lifts or onlay grafts were collected. All surgical procedures studied were performed under preoperative and postoperative antibiotic prophylaxis with either amoxicillin (+/- clavulanic acid) or clindamycin for patients with reported penicillin allergy. Bone graft-associated infections as well as graft failures were recorded. RESULTS: In this study, 111 patients received bone reconstructions (89 sinus lifts and 148 onlay grafts). In the sinus lifts group, infections occurred in 5 of 89 sites (5.6 %). The infection rate was 28.5 % (7 graft sites) and only 3.9 % (82 graft sites) for clindamycin and for amoxicillin, respectively. In the onlay graft group, infections occurred in 25 of 148 sites (16.8 %). The infection rate was 56 % and only 12 % for clindamycin (18 graft sites) and for amoxicillin, respectively (130 graft sites). Non-Penicillin treated patients had a higher risk of infection with an odd ratio of 7.8 (95 % CI 1.1-54.8, P = 0.04) and 4.8 (95 % CI 1.9-12.3, P = 0.001) compared with patients receiving amoxicillin for onlay grafts and sinus lifts. CONCLUSION: Penicillin allergy and clindamycin use after sinus lift and onlay graft procedures were associated with a higher rate of infection and may be a risk factor for complications related to bone reconstruction surgery.

Geriatric assessment and quality of life for 2 years in older patients with head and neck cancer.

Due to the location and toxicity of treatments, head and neck cancer (HNC) has a major impact on quality of life (QoL). Objective: to assess the effects of geriatric-assessment (GA)-driven interventions on QoL over 2 years in older adults with HNC.EGeSOR was a randomized study of HNC patients aged ≥65, receiving a pretreatment GA, a geriatric intervention and follow-up (intervention) or standard of care (control). The primary endpoint was QoL score using the European Organisation for Research and Treatment of Cancer's (EORTC QLQ-C30) and HNC (QLQ-HN35) QoL questionnaires over 24 months.In total, 475 patients were included (median age: 75.3; women: 31%; oral cancer: 44%). QoL scores improved over 24 months with various trajectories, without significant differences between the groups. A total of 74% of patients (interventional group) did not receive the complete intervention. Cancer characteristics, functional status, and risk of frailty were associated with change in the Global Health Status QoL score.There is a need to develop an alternative model of implementation such as patient-centered health-care pathways. TRIAL REGISTRATION: NCT02025062.

Reliability of gene-expression profiling from tumor biopsy for refining neoadjuvant strategies in patients with head and neck squamous cell carcinoma.

While recent clinical trials evaluating neoadjuvant immune checkpoint inhibitors showed promising results in a subset of patients with head and neck squamous cell carcinomas (HNSCC), there is a need for the identification of robust biomarkers in tumor biopsies to improve patient selection. This context suggests unravelling transcriptomic heterogeneity between untreated paired samples from same patient with HNSCC. Based on previous studies and the analysis of publicly available gene expression profiles of paired tumor biopsies and surgical resection specimens, we discuss the reliability of tumor biopsy to capture the overall activation of targetable biological pathways in patients with HNSCC. Further studies investigating intratumor transcriptomic heterogeneity as well as the effect of sampling methods on gene expression are needed in patients with HNSCC, in order to develop innovative and relevant biomarker-driven neoadjuvant strategies.

Extensive head and neck skin cancers: Carcinologic surgery as a cornerstone of treatment.

BACKGROUND AND OBJECTIVE: The prevalence of extensive skin cancers increases with the aging of the population. Surgical management is the gold standard of curative treatment while morbidity is not negligible. There are few data in the literature concerning extensive head and neck cutaneous cancers. The aim of this article is to report our experience of curative management of head and neck extensive skin cancers. METHOD: In this single-center retrospective observational study, we report a series of 17 patients with extensive skin facial cancers treated by surgery between 2013 and 2022 in the maxillofacial surgery department of the Pitié-Salpêtrière Hospital. We collected clinical, therapeutic, histological, and carcinologic data. RESULTS: The median age of the patients was 66 years [35-94]. There were 9 male and 8 women. Scalp (39 %) and cheek (22 %) locations were the most frequent ones. The most frequent histological types were squamous cell carcinoma (61 %) and basal cell carcinoma (17 %). Three patients received neoadjuvant treatment. The surgical treatment consisted mainly of carcinological resection followed by one-stage reconstruction by free flap for 5 (30 %) patients and without reconstruction for primary for 12 (70 %) patients, of whom 8 benefited from secondary reconstruction. Five patients received adjuvant radiotherapy or radio-chemotherapy. With a median follow-up of 40 months (2-72), the median overall survival was 40 months (12-72). CONCLUSION: We know that extensive skin cancers of the face have a good prognosis on condition that the carcinological and reconstructive requirements are respected. Surgery remains the cornerstone of treatment while the improvement of adjuvant therapies, in particular the rise of immunotherapies or other targeted therapies, may allow to limit recurrences.

Epidemiology of facial skin cancers managed in a French ambulatory surgical center.

INTRODUCTION: Approximately 80,000 cases of skin cancer are diagnosed annually in France. The management of these cancers can occur in both university hospital centers and ambulatory surgery centers. Limited data exist regarding the epidemiology of cutaneous cancers treated through ambulatory surgery centers. The objective of our study is to describe the epidemiological characteristics of cutaneous cancers managed in a tertiary ambulatory surgery center. METHODS: This is a retrospective, single-center observational study. The included patients were those who underwent surgical excision of one or more skin cancers within the maxillofacial department of a tertiary ambulatory surgery center. Clinical, therapeutic, histopathological, and follow-up data (additional surgery if margins were not clear, progression, recurrence, second cancer…) were collected. RESULTS: Among the n = 1931 patients operated for a head and neck skin tumor from September 2018 to July 2022, n = 426 (22 %) were diagnosed with cancer upon histological analysis. The median age was 76 years (31-100), with a male-to-female ratio of 1/1. The most frequent locations were the nose (23 %) and cheek (20 %). Ten percent of patients had dual-site skin cancer at initial diagnosis. The most common histological types were basal cell carcinoma (77 %) and squamous cell carcinoma (18 %). Surgical treatment primarily consisted of "excision-reconstruction with local flap" (51 %) or "excision-suture" (34 %). Resection margins were mostly clear (65 %), and only six patients (2 %) experienced local recurrence or progression during follow-up. CONCLUSIONS: Skin cancers are prevalent in ambulatory practice. Surgical treatment allows for effective control of the cancer. Photoprotection, particularly in immunocompromised patients, remains crucial for prevention.

A Radiomics Approach to Identify Immunologically Active Tumor in Patients with Head and Neck Squamous Cell Carcinomas.

BACKGROUND: We recently developed a gene-expression-based HOT score to identify the hot/cold phenotype of head and neck squamous cell carcinomas (HNSCCs), which is associated with the response to immunotherapy. Our goal was to determine whether radiomic profiling from computed tomography (CT) scans can distinguish hot and cold HNSCC. METHOD: We included 113 patients from The Cancer Genome Atlas (TCGA) and 20 patients from the Groupe Hospitalier Pitié-Salpêtrière (GHPS) with HNSCC, all with available pre-treatment CT scans. The hot/cold phenotype was computed for all patients using the HOT score. The IBEX software (version 4.11.9, accessed on 30 march 2020) was used to extract radiomic features from the delineated tumor region in both datasets, and the intraclass correlation coefficient (ICC) was computed to select robust features. Machine learning classifier models were trained and tested in the TCGA dataset and validated using the area under the receiver operator characteristic curve (AUC) in the GHPS cohort. RESULTS: A total of 144 radiomic features with an ICC >0.9 was selected. An XGBoost model including these selected features showed the best performance prediction of the hot/cold phenotype with AUC = 0.86 in the GHPS validation dataset. CONCLUSIONS AND RELEVANCE: We identified a relevant radiomic model to capture the overall hot/cold phenotype of HNSCC. This non-invasive approach could help with the identification of patients with HNSCC who may benefit from immunotherapy.

Direct laryngoscopy should be procedure of choice in the airway management of patients with dental cellulitis.

CONTEXT: Airway management of patients with dental cellulitis can be difficult due to laryngeal deviation and oedema. Awake fibre-optic intubation has been recommended. OBJECTIVE: The aim of this study was to assess our routine procedure which is based mainly on direct laryngoscopy. DESIGN: This was a prospective observational study. SETTING: In a single centre between February 2008 and February 2009. PATIENTS: All patients suffering from dental cellulitis and requiring emergency surgery were included except pregnant women and patients under 18 years. INTERVENTION: Nasotracheal intubation by direct laryngoscopy under general anaesthesia was performed unless the supine position was not tolerated, or difficult mask ventilation or intubation was anticipated, when awake nasotracheal fibre-optic intubation was indicated. In the case of failure at the first attempt, orotracheal intubation by direct laryngoscopy was attempted. If failure persisted, tracheotomy was then performed. MAIN OUTCOME MEASURES: The principal endpoint was the incidence of difficult mask ventilation which was expected to be less than 5%. Secondary endpoints were the incidence of difficult tracheal intubation and tracheotomy. RESULTS: We included 127 consecutive patients (mouth opening 20±10 mm). One did not tolerate the supine position and was successfully intubated using the fiberscope. Among the 126 remaining, difficult mask ventilation did not occur [0%, 95% confidence interval (CI) 0-3%], 124 (98%) patients were intubated by direct laryngoscopy and two (2%) required tracheotomy. Retrognathia (odds ratio 8.2, 95% CI 1.3-50.1) and extension to oral floor (odds ratio 15.1, 95% CI 1.8-129.5) were significantly associated with the prediction of intubation failure at the first attempt. CONCLUSION: Most patients with dental cellulitis can be safely intubated through direct laryngoscopy even if mouth opening is limited.

A Retrospective Study of 23 Cases: Are Lichenoid Lesions of the Labial Mucosa Induced?

Background Lichen planus (LP) is a pathology that affects the skin and the mucosa. The lips are rarely involved but represent a diagnostic challenge in those cases. Oral lichenoid lesions (OLL) are defined as lesions that resemble oral lichen planus (OLP) but do not fully meet the clinical and/or histologic criteria for OLP. This study aimed to present our case series and to study the correlation between the location of the lesion and the dental factor (resin composite, amalgams, crowns, abrasive teeth, and mandibular crossbite) that could cause the lesion. Methods We conducted a retrospective observational study of 23 patients with LP/OLL of the lips treated in the Department of Oral Mucosal Pathology of the Department of Stomatology and Maxillofacial Surgery of the Pitié-Salpêtrière Hospital in Paris between January 2017 and February 2021. We noted the location of the lesion (upper, lower, or both lips), medical history, treatments, smoking habits, and the aspect of the teeth facing the lesion. Patients received a local corticoid treatment and were monitored via follow-up. Results Sixteen patients had lesions on the upper lip, two on the lower lip, and five on both lips, and most patients (n = 14, 60.1%) had a dental factor facing the lesion (e.g., abrasive teeth, resin composites, dental crowns, and mandibular crossbite). Six patients received clobetasol propionate, and 15 patients received a preparation combining betamethasone and benzocaine (Orabase, ConvaTec, Deeside, UK). Fourteen patients returned for post-treatment follow-up consultations approximately two months after treatment. Seven patients saw clinical improvement, five had partial improvement, and two had no improvement. Conclusions Lesions of the labial mucosa appear to be a rare condition in LP/OLL. The difference between LP and OLL can be difficult, even with histological analysis. Its pathogenesis remains unknown, although some studies found evidence of lichenoid reactions of the lips in contact with dental composite restorations. In our study, 14 of our patients had a dental factor facing the lesions. However, our study failed to show a correlation between the presence of an inducing factor and the lesion. In a future study, the potential effect of dental inducing factor removal could be studied. This topic requires further investigations, particularly regarding the inducing factor and the optimal therapeutic approach.

Maxillofacial free flap surgery outcomes in critical care: a single-center investigation looking for clues to improvement.

BACKGROUND: Maxillofacial surgery for free flap reconstructions is associated with many complications due to technical complexity and comorbidity of patients. With a focus on critical care, the authors studied the impact of complications to highlight predictors of poor postoperative outcomes in order to implement optimization protocols. METHODS: This case-control study analyzed the relationship between perioperative variables and postoperative medical and surgical complications of patients who underwent head and neck surgery using fibular and forearm free flaps. The primary objective was the incidence of prolonged intensive care unit (ICU) length of stay (LOS). Secondary objectives were the incidence of ICU readmissions, postoperative infections, and 1-year mortality. A univariable logistic regression model was used. A study of mortality was performed with survival analysis. Regarding our primary objective, we performed a Benjamini-Hochberg procedure and a multivariable Poisson regression with defined variables of interest. RESULTS: The data of 118 hospital stays were included. Prolonged ICU LOS was observed in 47% of cases and was associated with chronic obstructive pulmonary disease, pneumopathies, intraoperative blood transfusion, and surgical duration. Medical and surgical complications were associated with prolonged ICU LOS. After the Benjamini-Hochberg procedure, infectious complications, complications, major complications, total number of pneumopathies, and operative time remained significant. At least one complication was experienced by 71% of patients during the hospitalization, and 33% of patients suffered from major complications. Infectious complications were the most common (40% of patients) and were mainly caused by pneumonia (25% of patients); these complications were associated with low preoperative hemoglobin level, intraoperative blood transfusion, accumulation of reversible cardiovascular risk factors, chronic alcohol consumption, and duration of surgery. Pneumonia was specifically associated with chronic obstructive pulmonary disease. The ICU readmission rate was 10% and was associated with lower preoperative hemoglobin level, pneumopathies, surgical duration, and use of a fibular flap. The 1-year mortality was 12%, and the survival analysis showed no association with prolonged ICU LOS. Poisson regression showed that ICU LOS was prolonged by smoking history, lower preoperative hemoglobin level, intraoperative blood transfusion, major complication, and pneumopathies. CONCLUSIONS: Practices such as blood management and respiratory prehabilitation could be beneficial and should be evaluated as a part of global improvement strategies.

Identification of a Gene-Expression-Based Surrogate of Genomic Instability during Oral Carcinogenesis.

BACKGROUND: Our goal was to identify a gene-expression-based surrogate of genomic instability (GI) associated with the transformation of oral potentially malignant disorder (OPMD) into oral squamous cell carcinoma (OSCC). METHODS: GI was defined as the fraction of genome altered (FGA). Training sets included the CCLE and TCGA databases. The relevance of the enrichment score of the top correlated genes, referred to as the GIN score, was evaluated in eight independent public datasets from the GEO repository, including a cohort of patients with OPMD with available outcome. RESULTS: A set of 20 genes correlated with FGA in head and neck SCC were identified. A significant correlation was found between the 20-gene based GIN score and FGA in 95 esophagus SCC (r = 0.59) and 501 lung SCC (r = 0.63), and in 33 OPMD/OSCC (r = 0.38). A significantly increased GIN score was observed at different stages of oral carcinogenesis (normal-dysplasia -OSCC) in five independent datasets. The GIN score was higher in 10 OPMD that transformed into oral cancer compared to 10 nontransforming OPMD (p = 0.0288), and was associated with oral-cancer-free survival in 86 patients with OPMD (p = 0.0081). CONCLUSIONS: The GIN score is a gene-expression surrogate of GI, and is associated with oral carcinogenesis and OPMD malignant transformation.

Defining biomarkers in oral cancer according to smoking and drinking status.

Introduction: Oral Squamous Cell Carcinomas (OSCC) are mostly related to tobacco consumption eventually associated to alcohol (Smoker/Drinker patients: SD), but 25-30% of the patients have no identified risk factors (Non-Smoker/Non-Drinker patients: NSND). We hypothesized that these patients have distinguishable immune profiles that could be useful for prognosis. Materials and Methods: Cells present in immune tumor microenvironment (TME) and blood from 87 OSCC HPV-negative patients were analyzed using a multiparameter flow cytometry assay, in a prospective case-control study. Cytokine levels in tumor supernatants and blood were determined by a cytometric bead array (CBA) assay. Results: Normal gingiva and blood from healthy donors (HD) were used as controls. A significant increase of granulocytes (p<0.05 for blood), of monocytes-macrophages (p<0.01 for blood) and of CD4+ T cells expressing CD45RO and CCR6 (p<0.001 for blood; p<0.0001 for TME) as well as higher levels of IL-6 (p<0.01 for sera, p<0.05 for tumor supernatant) were observed in SD patients as compared to NSND OSCC patients and HD. High percentages of CD4+ T cells expressing CD45RO and CCR6 cells in tumor tissue (p=0.05) and blood (p=0.05) of SD OSCC patients were also associated with a poorer prognosis while a high percentage of regulatory T cells (Treg) in tumor tissue was associated with a more favorable prognostic factor (p=0.05). Also, a higher percentage of blood CD8+ T lymphocytes among CD45+ cells in NSND patients was associated with a better disease-free survival (p=0.004). Conclusion: Granulocytes, monocytes-macrophages, and CD4+ T cells expressing CD45RO and CCR6 in blood and TME as well as serum IL-6 can therefore distinguish OSCC SD and NSND patients. Quantifying the proportion of CD4+ T cells expressing CD45RO and CCR6 and of Treg in SD patients and CD8+ T cells in NSND patients could help defining the prognostic of OSCC patients.