We are pleased to introduce the collection Frontiers in Oral Health: Highlights in Oral Cancers 2021/2. This collection will welcome and showcase a selection of high impact articles authored by leaders in the field. The work presented here highlights the broad diversity of research performed across the Oral Cancers section, and aims to put a spotlight on the main areas of interest. This collection aims to further support Frontiers’ strong community by shining a spotlight on our authors' highly impactful research.

University of Western Australia

Exploring impactful research within the field of Oral Cancers

. Research into oral cavity squamous cell carcinoma (OSCC) has revealed a number of important findings: <ul> <li>Gene expression subtyping in HNSCC is associated with poor survival in surgically resected, early-stage, node(-) OCSCC.</li> <li>Young patients with tongue carcinoma have similar overall survival and disease-free survival as older patients, but middle-aged patients have lower recurrence rates.</li> <li>Axin2 and Snail expression at the surgical margin may be potential predictive biomarkers for the risk assessment of surgical margins in OSCC.</li> <li>Quantitative parameters derived from dual-energy computed tomography (DECT) are predictive of the aggressiveness of oral tongue squamous cell carcinoma (OTSCC).</li> <li>Plasma cell myeloma is the most common malignant hematologic neoplasm in the oral cavity in North Carolina, USA.</li> <li>OSCC-associated inflammation is characterized by increased pro-inflammatory cytokines and salivary immune cells.</li> <li>Preoperative immunotherapy has the potential to prime the tumor and associated native immune infiltration.</li> </ul> These findings suggest that further research into OSCC is needed to improve diagnosis, prognosis, and treatment.

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Frontiers in Oral Health

Oral Cancers

Frontiers in Oncology

Head and Neck Cancer

Frontiers in Oral Health: Highlights in Oral Cancers 2021/2

Editorial on the Research Topic <a href="https://www.frontiersin.org/research-topics/32454/frontiers-in-oral-health-highlights-in-oral-cancers-20212">Frontiers in oral health: Highlights in oral cancers 2021/2</a>Oral cancer is a multi-step tumour associated with diverse presentations and unpredictable outcomes. Regardless of advances in technology and research, the prognosis of oral cancer has not improved over the last decades, which makes this condition a significant health burden that warrants urgent attention in a multidisciplinary manner (<a href="#B1">1</a>).This Frontiers Research Topic, Highlights in Oral Cancers 2021/2, aimed to shed light on the latest evidence-based findings to answer historically debatable questions in this field.This Research Topic starts with a review by <a href="https://doi.org/10.3389/fonc.2021.682075">Philips et al.</a> titled Preoperative immunotherapy in the multidisciplinary management of oral cavity cancer to provide insights into current knowledge in the field of oral squamous cell carcinoma (OSCC) immunotherapy. In this review, several hot topics were comprehensively discussed, like immune response, the rationale for preoperative immunotherapy, limitations of immunotherapy, and prospects. A table summarising the results of all relevant clinical trials in the study area was presented to show the latest advances. In conclusion, the authors proposed generating personalised, tumour-specific algorithms based on multiple factors like pathology, response to preoperative immunotherapy, and immune profile to assure optimum oncologic and functional outcomes.To highlight the inflammatory response's critical role in explaining the defective anti-tumour immunological responses in some OSCC patients, <a href="https://doi.org/10.3389/froh.2021.740469">Laliberté et al.</a> conducted a prospective, case-controlled pilot study to characterise OSCC-associated inflammation titled Characterisation of oral squamous cell carcinoma associated inflammation: a pilot study. In this study, inflammatory changes in the saliva of 37 OSCC patients were compared with changes in 32 healthy controls with and without periodontitis. Multi-channel flow cytometry with a panel of 12 antibodies was employed to determine the inflammatory cell profile in saliva. Moreover, 30 cytokines/chemokines were evaluated in the saliva samples. Fluorescent immunohistochemistry was undertaken to validate results using a cohort of cancer specimens. This paper showed an increase in OSCC-associated inflammation characterised by specific cytokines (IL-6, IL-8, TNFa, and GMCSF). These findings can be used to design clinical tests that may aid in treatment decision-making, like identifying patients at higher risk of developing disease adverse events and recurrence.To report the incidence of malignant lymphoid neoplasms in the oral and maxillofacial region, <a href="https://doi.org/10.3389/froh.2022.802555">Flores-Hidalgo et al.</a> retrospectively reviewed records of patients diagnosed with lymphoid neoplasms over ten years in two different institutions. This paper is titled Malignant lymphoproliferative disorders of the oral and maxillofacial region: report of two institutions. Accordingly, a total of 318 records were retrieved and reassessed according to an updated classification version, of which 138 met the inclusion criteria. Most hematolymphoid malignancies are associated with intra-bony locations. Thus, the authors highlighted the significance of microscopic examination of all tissue samples, even if they present features of persistent periapical lesions after failed root canal therapy.Further, a paper titled Preoperative prediction of the aggressiveness of oral tongue squamous cell carcinoma with quantitative parameters from dual-energy computed tomography was conducted by <a href="https://doi.org/10.3389/fonc.2022.904471">Yang et al.</a> to propose a preoperative non-surgical tool that helps clinicians and pathologists while diagnosing tongue OSCC cases. Ninety-three out of 161 were included in this study based on clearly specified inclusion criteria and underwent preoperative dual-energy computed tomography (DECT). Specific DECT quantitative parameters were compared to certain pathological characteristics of tongue OSCC. Accordingly, the inter- and intra-observer agreements in evaluating DECT parameters were excellent. Among several DECT parameters, the slope of the spectral Hounsfield unit curve in the venous phase was associated with the highest accuracy (75.3%) in predicting the overall pathological stage. Likewise, the accuracy of the normalised iodine concentration in the venous phase in predicting the histologic differentiation was 75.3%. In conclusion, DECT shows the potential to be a valuable tool for the preoperative evaluation of tongue OSCC aggressiveness.To answer the controversial question about the concept of resection margins in OSCC surgery, whether adequate or inadequate, <a href="https://doi.org/10.3389/fonc.2022.930988">Pei et al.</a> conducted a molecular study titled Risk factors of microscopically tumor-free surgical margins for recurrence and survival of oral squamous cell carcinoma patients. A total of 235 OSCC patients who underwent surgery over ten years were retrospectively reviewed and included in this study. Two epithelial-to-mesenchymal transition-associated genes (Axin2 and Snail) were immunohistochemically assessed using tissue specimens of surgical margins. The results were validated by developing an in vitro model of a knocked-down Axin2 cell line and injecting this cell line into mice. The significant outcomes of this study found that molecular analysis provides a more accurate and objective assessment of surgical margins. In opposition to the histopathological assessment of surgical margins, Axin2 and Snail expressions had independent impacts on the overall survival and recurrence-free survival rates of OSCC patients.Next, to predict the recurrence of early-stage, HPV-negative head and neck squamous cell carcinoma (HNSCC), a study by <a href="https://doi.org/10.3389/fonc.2022.954037">Mayhew et al.</a> to identify a gene expression classifier for this purpose was conducted. This study, Mesenchymal gene expression subtyping analysis for early-stage human papillomavirus-negative head and neck squamous cell carcinoma reveals prognostic and predictive applications. For training, the authors performed a retrospective genomic analysis of open-source databases, including 418 patients. The classifier was then validated using a different validation cohort. This study demonstrated that mesenchymal subtypes are associated with poor survival rates even in early-stage, lymph node-negative oral cancers. This finding was contrary to the favourable outcomes of the mesenchymal subtype in non-oral cancer cases. The study highlights the significance of gene expression for the treatment decision-making of HNSCC.Interestingly, several studies assessed the prognosis of patients with oral carcinoma using a mixed population of young and old patients, which were associated with wide discrepancies and heterogeneities, mainly because old patients usually suffered poor systemic conditions. To reduce potential bias, <a href="https://doi.org/10.3389/fonc.2022.959749">Baba et al.</a> conducted a study that classified patients into three groups instead of two. This study is titled Comparison between three age-stratified cohorts reveals poor prognosis of young patients with tongue carcinoma. Two hundred fifty-seven eligible OSCC patients were classified into three groups: young, middle-aged, and older. Accordingly, multivariate analyses found that compared to young patients, there were no differences in overall survival and disease-free survival rates for middle-aged or older patients. However, middle patients were associated with a significant low local recurrence rate. The authors emphasised the importance of categorising patients into various groups according to their age, specifically for patients older than 70 years, while this measure should also be applied to future genomic research.The seven studies contained in this Research Topic described many relevant aspects for development, progression and treatment of oral cancers, especially highlighting possible therapeutic developments and biomarkers to fight these very aggressive cancers. Such studies are essential towards the development of more effective and predictable therapeutic strategies.All authors conceived the editorial and drafted and finalised the manuscript. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Editorial: Frontiers in oral health: Highlights in oral cancers 2021/2

Patients with oral cavity squamous cell carcinoma (OCSCC) are predominantly human papillomavirus (HPV)(−), and treatment typically involves surgical resection ± neck dissection, followed by radiation ± chemotherapy. We previously described four mRNA expression patterns (classical, atypical, basal, and mesenchymal), each with unique genomic features and prognosis. Here, we examine the clinical utility of gene expression subtyping in head and neck squamous cell carcinoma (HNSCC) and introduce potentially predictive applications in HPV(−) OCSCC. A retrospective genomic database analysis was performed including 562 HNSCC patients from MD Anderson (MDA-GSE41116) and The Cancer Genome Atlas (TCGA). Samples were assigned molecular subtypes (classical, atypical, basal, and mesenchymal) using an 88-gene classifier. HPV status was determined by gene expression. The clinical endpoint was overall survival censured at 36 months. The Kaplan–Meier plots and log-rank tests were used to investigate associations between clinical variables and survival. Of the 418 TCGA training patients who met analysis criteria, nearly 20% presented as stage I/II. Among node(−) OCSCC patients, the mesenchymal subtype is associated with worse survival (hazard ratio (HR) = 2.4, p = 0.021), offering a potentially actionable biomarker in otherwise early-stage, low-risk disease. This was confirmed in the MDA validation cohort. Node(−) non-mesenchymal OCSCC patients had far better survival compared to node(−) mesenchymal, and all node(+) patients had similarly poor survival. These findings suggest that the mesenchymal subtype is associated with poor survival in surgically resected, early-stage, node(−) OCSCC otherwise expected to have favorable outcomes. These findings highlight the potential value of gene expression subtyping as a pathology adjunct for prognostication and treatment decision-making in OCSCC patients.

Patients with oral cavity squamous cell carcinoma (OCSCC) are predominantly human papillomavirus (HPV)(&#x2212;), and treatment typically involves surgical resection &#xb1; neck dissection, followed by radiation &#xb1; chemotherapy. We previously described four mRNA expression patterns (classical, atypical, basal, and mesenchymal), each with unique genomic features and prognosis. Here, we examine the clinical utility of gene expression subtyping in head and neck squamous cell carcinoma (HNSCC) and introduce potentially predictive applications in HPV(&#x2212;) OCSCC. A retrospective genomic database analysis was performed including 562 HNSCC patients from MD Anderson (MDA-GSE41116) and The Cancer Genome Atlas (TCGA). Samples were assigned molecular subtypes (classical, atypical, basal, and mesenchymal) using an 88-gene classifier. HPV status was determined by gene expression. The clinical endpoint was overall survival censured at 36 months. The Kaplan&#x2013;Meier plots and log-rank tests were used to investigate associations between clinical variables and survival. Of the 418 TCGA training patients who met analysis criteria, nearly 20% presented as stage I/II. Among node(&#x2212;) OCSCC patients, the mesenchymal subtype is associated with worse survival (hazard ratio (HR) = 2.4, p = 0.021), offering a potentially actionable biomarker in otherwise early-stage, low-risk disease. This was confirmed in the MDA validation cohort. Node(&#x2212;) non-mesenchymal OCSCC patients had far better survival compared to node(&#x2212;) mesenchymal, and all node(+) patients had similarly poor survival. These findings suggest that the mesenchymal subtype is associated with poor survival in surgically resected, early-stage, node(&#x2212;) OCSCC otherwise expected to have favorable outcomes. These findings highlight the potential value of gene expression subtyping as a pathology adjunct for prognostication and treatment decision-making in OCSCC patients.

Mesenchymal gene expression subtyping analysis for early-stage human papillomavirus-negative head and neck squamous cell carcinoma reveals prognostic and predictive applications

ObjectivesInvestigation of the prognosis of young patients with tongue carcinoma has been the focus of several recent studies aimed at improving future precision treatment. Most studies have been two-cohort investigations comparing young and older patients, who have wide discrepancies in prognosis. Older patients, especially those aged >70 years, often have a poor general condition. This affects the prognosis of the older cohort and accounts for the discrepancies observed in two-cohort studies. Accordingly, in this study, older patients (aged ≥71 years) were separated and compared to young and middle-aged patients.</sec>MethodsA total of 257 patients with oral tongue carcinoma referred during 2011–2017 were analyzed. Patients were sorted into young (aged ≤40 years), middle-aged (aged ≥41 and ≤70 years), and older (aged ≥71 years) groups. Overall survival (OS) and disease-free survival (DFS) were compared among the groups. Furthermore, patterns of recurrence rates were compared.</sec>ResultsCompared with young patients, there was no difference in OS or DFS for older patients (hazard ratio [HR]: 1.2, 95% confidence interval [CI]: 0.5–2.7 and HR: 0.7, 95% CI: 0.4–1.2, respectively) in a multivariate analysis. There was also no difference in OS (HR: 0.6, 95% CI: 0.3–1.3) for middle-aged patients. However, middle-aged patients had low recurrence rates (HR: 0.5, 95% CI: 0.3–0.8). With respect to the recurrence type, middle-aged patients had a low local recurrence rate (HR: 0.3, 95% CI: 0.1–0.7).</sec>ConclusionThree-cohort studies should be conducted to evaluate whether the prognosis of young patients with tongue carcinoma is truly poor in terms of future precision treatment.</sec>

Objectives: Investigation of the prognosis of young patients with tongue carcinoma has been the focus of several recent studies aimed at improving future precision treatment. Most studies have been two-cohort investigations comparing young and older patients, who have wide discrepancies in prognosis. Older patients, especially those aged &gt;70 years, often have a poor general condition. This affects the prognosis of the older cohort and accounts for the discrepancies observed in two-cohort studies. Accordingly, in this study, older patients (aged ≥71 years) were separated and compared to young and middle-aged patients.Methods: A total of 257 patients with oral tongue carcinoma referred during 2011–2017 were analyzed. Patients were sorted into young (aged ≤40 years), middle-aged (aged ≥41 and ≤70 years), and older (aged ≥71 years) groups. Overall survival (OS) and disease-free survival (DFS) were compared among the groups. Furthermore, patterns of recurrence rates were compared.Results: Compared with young patients, there was no difference in OS or DFS for older patients (hazard ratio [HR]: 1.2, 95% confidence interval [CI]: 0.5–2.7 and HR: 0.7, 95% CI: 0.4–1.2, respectively) in a multivariate analysis. There was also no difference in OS (HR: 0.6, 95% CI: 0.3–1.3) for middle-aged patients. However, middle-aged patients had low recurrence rates (HR: 0.5, 95% CI: 0.3–0.8). With respect to the recurrence type, middle-aged patients had a low local recurrence rate (HR: 0.3, 95% CI: 0.1–0.7).Conclusion: Three-cohort studies should be conducted to evaluate whether the prognosis of young patients with tongue carcinoma is truly poor in terms of future precision treatment.

Comparison between three age-stratified cohorts reveals poor prognosis of young patients with tongue carcinoma

ObjectivesThe concept of adequate surgical margins remains controversial in oral squamous cell carcinoma (OSCC) surgery. This study aimed to identify surgical margin-related indicators that might impact recurrence and survival of OSCC patients.</sec>Materials and MethodsHistopathological examination was performed using hematoxylin-eosin-stained surgical margin tissue sections in 235 OSCC patients. Axin2 and Snail expression at the surgical margin was detected by immunohistochemistry. The impact of the Axin2-Snail cascade on tumorigenesis of the immortalized human oral keratinocyte (IHOK) line was investigated in vivo.</sec>ResultsThe width and dysplasia of surgical margins were not significantly associated with the outcome of OSCC patients. In a multivariate analysis using variable clinicopathologic factors and with Axin2 and Snail expression as cofactors, higher age (hazard ratio [HR]:1.050; P=0.047), Axin2 (HR:6.883; P=0.014), and Snail abundance (HR:5.663; P=0.009) had independent impacts on worsened overall survival. Similarly, lesion site in retromolar trigone (HR:4.077; P=0.010), upper (HR:4.332; P=0.005) and lower gingiva (HR:3.545; P=0.012), presence of extranodal extension (HR:9.967; P<0.001), perineural invasion (HR:3.627; P=0.024), and Snail abundance (HR:3.587; P<0.001) had independent impacts on worsened recurrence-free survival. Furthermore, Axin2 knockdown induced decreased Snail expression and attenuated tumorigenesis in the IHOK line.</sec>ConclusionHistopathological examination of surgical margins may not be reliable to predict OSCC patient outcome. Molecular analysis may provide a more accurate risk assessment of surgical margins in OSCC. In particular, Axin2 and Snail are potential predictive biomarkers for the risk assessment of surgical margins in OSCC.</sec>

Objectives: The concept of adequate surgical margins remains controversial in oral squamous cell carcinoma (OSCC) surgery. This study aimed to identify surgical margin-related indicators that might impact recurrence and survival of OSCC patients.Materials and Methods: Histopathological examination was performed using hematoxylin-eosin-stained surgical margin tissue sections in 235 OSCC patients. Axin2 and Snail expression at the surgical margin was detected by immunohistochemistry. The impact of the Axin2-Snail cascade on tumorigenesis of the immortalized human oral keratinocyte (IHOK) line was investigated in vivo.Results: The width and dysplasia of surgical margins were not significantly associated with the outcome of OSCC patients. In a multivariate analysis using variable clinicopathologic factors and with Axin2 and Snail expression as cofactors, higher age (hazard ratio [HR]:1.050; P=0.047), Axin2 (HR:6.883; P=0.014), and Snail abundance (HR:5.663; P=0.009) had independent impacts on worsened overall survival. Similarly, lesion site in retromolar trigone (HR:4.077; P=0.010), upper (HR:4.332; P=0.005) and lower gingiva (HR:3.545; P=0.012), presence of extranodal extension (HR:9.967; P&lt;0.001), perineural invasion (HR:3.627; P=0.024), and Snail abundance (HR:3.587; P&lt;0.001) had independent impacts on worsened recurrence-free survival. Furthermore, Axin2 knockdown induced decreased Snail expression and attenuated tumorigenesis in the IHOK line.Conclusion: Histopathological examination of surgical margins may not be reliable to predict OSCC patient outcome. Molecular analysis may provide a more accurate risk assessment of surgical margins in OSCC. In particular, Axin2 and Snail are potential predictive biomarkers for the risk assessment of surgical margins in OSCC.

Risk Factors of Microscopically Tumor-Free Surgical Margins for Recurrence and Survival of Oral Squamous Cell Carcinoma Patients

ObjectivesTo determine whether quantitative parameters derived from dual-energy computed tomography (DECT) were predictive of the aggressiveness of oral tongue squamous cell carcinoma (OTSCC) including the pathologic stages, histologic differentiation, lymph node status, and perineural invasion (PNI).</sec>MethodsBetween August 2019 and March 2021, 93 patients (mean age, 54.6 ± 13.8 years; 66 men) with pathologically diagnosed OTSCC were enrolled in this prospective study. Preoperative DECT was performed and quantitative parameters (e.g., slope of the spectral Hounsfield unit curve [λHu], normalized iodine concentration [nIC], normalized effective atomic number [nZeff], and normalized electron density [nRho]) were measured on arterial phase (AP) and venous phase (VP) DECT imaging. Quantitative parameters from DECT were compared between patients with different pathologic stages, histologic differentiation, lymph node statuses, and perineural invasion statuses. Logistic regression analysis was utilized to assess independent parameters and the diagnostic performance was analyzed by the receiver operating characteristic curves (ROC).</sec>ResultsλHu and nIC in AP and λHu, nZeff, and nIC in VP were significantly lower in stage III–IV lesions than in stage I–II lesions (p < 0.001 to 0.024). λHu in VP was an independent predictor of tumor stage with an odds ratio (OR) of 0.29, and area under the curve (AUC) of 0.80. λHu and nIC were higher in well-differentiated lesions than in poorly differentiated lesions (p < 0.001 to 0.021). The nIC in VP was an independent predictor of histologic differentiation with OR of 0.31, and AUC of 0.78. λHu and nIC in VP were lower in OTSCCs with lymph node metastasis than those without metastasis (p < 0.001 to 0.005). λHu in VP was the independent predictor of lymph node status with OR of 0.42, and AUC of 0.74. No significant difference was found between OTSCCs without PNI and those with PNI in terms of the quantitative DECT parameters.</sec>ConclusionDECT can be a complementary means for the preoperative prediction of the aggressiveness of OTSCC.</sec>

Objectives: To determine whether quantitative parameters derived from dual-energy computed tomography (DECT) were predictive of the aggressiveness of oral tongue squamous cell carcinoma (OTSCC) including the pathologic stages, histologic differentiation, lymph node status, and perineural invasion (PNI).Methods: Between August 2019 and March 2021, 93 patients (mean age, 54.6 ± 13.8 years; 66 men) with pathologically diagnosed OTSCC were enrolled in this prospective study. Preoperative DECT was performed and quantitative parameters (e.g., slope of the spectral Hounsfield unit curve [λHu], normalized iodine concentration [nIC], normalized effective atomic number [nZeff], and normalized electron density [nRho]) were measured on arterial phase (AP) and venous phase (VP) DECT imaging. Quantitative parameters from DECT were compared between patients with different pathologic stages, histologic differentiation, lymph node statuses, and perineural invasion statuses. Logistic regression analysis was utilized to assess independent parameters and the diagnostic performance was analyzed by the receiver operating characteristic curves (ROC).Results: λHu and nIC in AP and λHu, nZeff, and nIC in VP were significantly lower in stage III–IV lesions than in stage I–II lesions (p &lt; 0.001 to 0.024). λHu in VP was an independent predictor of tumor stage with an odds ratio (OR) of 0.29, and area under the curve (AUC) of 0.80. λHu and nIC were higher in well-differentiated lesions than in poorly differentiated lesions (p &lt; 0.001 to 0.021). The nIC in VP was an independent predictor of histologic differentiation with OR of 0.31, and AUC of 0.78. λHu and nIC in VP were lower in OTSCCs with lymph node metastasis than those without metastasis (p &lt; 0.001 to 0.005). λHu in VP was the independent predictor of lymph node status with OR of 0.42, and AUC of 0.74. No significant difference was found between OTSCCs without PNI and those with PNI in terms of the quantitative DECT parameters.Conclusion: DECT can be a complementary means for the preoperative prediction of the aggressiveness of OTSCC.

Preoperative Prediction of the Aggressiveness of Oral Tongue Squamous Cell Carcinoma with Quantitative Parameters from Dual-Energy Computed Tomography

BackgroundReport of the incidence of malignant hematologic neoplasms in the oral cavity according to the experience of the two oral and maxillofacial pathology institutions in North Carolina, USA.</sec>MethodsA 10-year retrospective review was carried out in the records of patients at ECU SoDM and UNC Adams SoD. Age, sex, location of the lesion, clinical impression, initial diagnosis, and the expression immunohistochemical and molecular markers were recorded for each subject. All diagnoses were reviewed according to the 2016 revision of the WHO classification of lymphoid neoplasms.</sec>ResultsA total of 318 records from both institutions were reviewed. Seventy males and 68 females with an average age of 60.7 comprised the study population. The most common neoplasm encountered was plasma cell myeloma, followed by diffuse large B-cell lymphoma, B-lymphoblastic lymphoma, and follicular lymphoma. We encountered primarily intraosseous tumors, with the posterior mandible and posterior maxilla being the most common locations. Twelve cases were identified initially as a periapical radiolucency.</sec>ConclusionOur findings are concurrent with the existing literature regarding epidemiologic data. However, the type and location of tumors encountered do not, as the most common lymphoma in the oral cavity is diffuse large B-cell lymphoma, typically present in soft tissue. To aid in diagnosis and treatment, the collection of data should continue over time so that eventually, a more specific diagnostic profile of North Carolina residents with these neoplasms can be made.</sec>

Background: Report of the incidence of malignant hematologic neoplasms in the oral cavity according to the experience of the two oral and maxillofacial pathology institutions in North Carolina, USA.Methods: A 10-year retrospective review was carried out in the records of patients at ECU SoDM and UNC Adams SoD. Age, sex, location of the lesion, clinical impression, initial diagnosis, and the expression immunohistochemical and molecular markers were recorded for each subject. All diagnoses were reviewed according to the 2016 revision of the WHO classification of lymphoid neoplasms.Results: A total of 318 records from both institutions were reviewed. Seventy males and 68 females with an average age of 60.7 comprised the study population. The most common neoplasm encountered was plasma cell myeloma, followed by diffuse large B-cell lymphoma, B-lymphoblastic lymphoma, and follicular lymphoma. We encountered primarily intraosseous tumors, with the posterior mandible and posterior maxilla being the most common locations. Twelve cases were identified initially as a periapical radiolucency.Conclusion: Our findings are concurrent with the existing literature regarding epidemiologic data. However, the type and location of tumors encountered do not, as the most common lymphoma in the oral cavity is diffuse large B-cell lymphoma, typically present in soft tissue. To aid in diagnosis and treatment, the collection of data should continue over time so that eventually, a more specific diagnostic profile of North Carolina residents with these neoplasms can be made.

Malignant Lymphoproliferative Disorders of the Oral and Maxillofacial Region: Report of Two Institutions

Background: Oral squamous cell carcinoma (OSCC) is a devastating disease that is usually associated with a dense associated inflammatory infiltrate. Characterizing tumor-associated inflammation is critical to understand the pathogenies of tumor development and progression.Methods: We have tested a protocol to analyze tissue and salivary immune cells and mediators of 37 patients with OSCC at different stages and compared to eight chronic periodontitis patients and 24 healthy controls. Tissue analysis was based on fluorescent immunohistochemistry (FIHC) and inflammatory mediators were analyzed using a Luminex-based 30-Plex panel. Immune cells were analyzed using multichannel flow cytometry including CD45, CD66b, CD3, CD4, CD8, CD25, CD56, CD68, CD138, PD-1, and PD-L1.Results: We show an increase in OSCC-associated inflammation characterized by increased pro-inflammatory cytokines including IL-6, IL-8, TNFα, and GMCSF and increased salivary immune cells.Conclusion: We described a new method to analyze salivary inflammatory markers that can be used in future studies to monitor disease progression and prognosis.

Background: Oral squamous cell carcinoma (OSCC) is a devastating disease that is usually associated with a dense associated inflammatory infiltrate. Characterizing tumor-associated inflammation is critical to understand the pathogenies of tumor development and progression.Methods: We have tested a protocol to analyze tissue and salivary immune cells and mediators of 37 patients with OSCC at different stages and compared to eight chronic periodontitis patients and 24 healthy controls. Tissue analysis was based on fluorescent immunohistochemistry (FIHC) and inflammatory mediators were analyzed using a Luminex-based 30-Plex panel. Immune cells were analyzed using multichannel flow cytometry including CD45, CD66b, CD3, CD4, CD8, CD25, CD56, CD68, CD138, PD-1, and PD-L1.Results: We show an increase in OSCC-associated inflammation characterized by increased pro-inflammatory cytokines including IL-6, IL-8, TNFα, and GMCSF and increased salivary immune cells.Conclusion: We described a new method to analyze salivary inflammatory markers that can be used in future studies to monitor disease progression and prognosis.

Characterization of Oral Squamous Cell Carcinoma Associated Inflammation: A Pilot Study

Despite advances in multimodal treatment for oral cavity squamous cell carcinoma, recurrence rates remain high, providing an opportunity for new therapeutic modalities that may improve oncologic outcomes. Much recent attention has been paid to the molecular interactions between the tumor cells with the adjacent peritumoral microenvironment, in which immunosuppressive molecular changes create a landscape that promotes tumor progression. The rationale for the introduction of immunotherapy is to reverse the balance of these immune interactions in a way that utilizes the host immune system to attack tumor cells. In the preoperative setting, immunotherapy has the advantage of priming the unresected tumor and the associated native immune infiltration, supercharging the adaptive anti-tumor immune response. It also provides the basis for scientific discovery where the molecular profile of responders can be interrogated to elucidate prognostic markers to aid in future patient selection. Preoperative immunotherapy is not without limitations. The risk of surgical delay due to immune adverse events must be carefully discussed by members of a multidisciplinary treatment team and patient selection will be critical. One day, the discovery of predictive biomarkers may allow for algorithms where pre-surgical immunotherapy decreases the size of surgical defect and impacts the intensity of adjuvant therapy leading to improved patient survival and decreased morbidity. With further study, immunotherapy could become a key component of future treatment algorithm.

Despite advances in multimodal treatment for oral cavity squamous cell carcinoma, recurrence rates remain high, providing an opportunity for new therapeutic modalities that may improve oncologic outcomes. Much recent attention has been paid to the molecular interactions between the tumor cells with the adjacent peritumoral microenvironment, in which immunosuppressive molecular changes create a landscape that promotes tumor progression. The rationale for the introduction of immunotherapy is to reverse the balance of these immune interactions in a way that utilizes the host immune system to attack tumor cells. In the preoperative setting, immunotherapy has the advantage of priming the unresected tumor and the associated native immune infiltration, supercharging the adaptive anti-tumor immune response. It also provides the basis for scientific discovery where the molecular profile of responders can be interrogated to elucidate prognostic markers to aid in future patient selection. Preoperative immunotherapy is not without limitations. The risk of surgical delay due to immune adverse events must be carefully discussed by members of a multidisciplinary treatment team and patient selection will be critical. One day, the discovery of predictive biomarkers may allow for algorithms where pre-surgical immunotherapy decreases the size of surgical defect and impacts the intensity of adjuvant therapy leading to improved patient survival and decreased morbidity. With further study, immunotherapy could become a key component of future treatment algorithm.