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Background: Oral squamous cell carcinoma (OSCC) is a common malignancy worldwide, leading to significant disease-associated social and financial burdens. The investigation of underlying mechanisms involved in carcinogenesis and tumor progression in OSCC might provide new therapeutic perspectives with an impact on disease control and patient survival. Our study aims to investigate the interrelation between metabolic processes, expressed through final catabolism products and clinicopathological characteristics in OSCC. Materials and methods: This is a single cancer comparative retrospective study investigating metabolic byproducts, namely serum urea, creatinine and uric acid, detected at the moment of diagnosis in patients with OSCC, in comparison to healthy controls. Clinical and paraclinical data regarding exposure to risk factors, disease staging and pathological characteristics were collected for all patients. Subjects with co-existing systemic or metabolic diseases, or with a history of malignancy, were excluded from the study. Subsequently, the metabolic byproducts revealing significant changes in OSCC patients were considered for a correlation analysis with the disease clinico-pathological characteristics. Results: Blood levels for urea, creatinine and uric acid were determined in a total of 225 subjects: 145 patients diagnosed with OSCC and 80 healthy control subjects admitted to our hospital between 2016 and 2021. The comparative analysis between groups revealed that the serum urea level was significantly lower in OSCC patients (p = 0.0344). Serum creatinine and uric acid did not reveal significant differences between groups. Furthermore, in advanced stages of the disease (stages III and IV), the blood level of urea was significantly lower compared to incipient OSCC (stages I and II) (p = 0.003). We found a negative correlation of serum urea levels with smoking (p = 0.0004) and cervical lymph node metastasis (p = 0.0070), and a positive correlation with aging (p = 0.0000). We found no significant correlation of serum urea with primary tumor size (p = 0.5061) and patient survival (p = 0.2932). Conclusions: Decreased serum urea levels are detected in patients with advanced OSCC, in correlation with lymph node metastasis. The invasive features of tumor cells in OSCC might be promoted in association with dysregulation of protein catabolism processes, facilitating aggressive behavior in OSCC. [ABSTRACT FROM AUTHOR]

Head and neck squamous cell carcinoma (HNSCC) is a common type of cancer worldwide. Strong connections have been revealed between immune cells and the pathogenesis of HNSCC. Important differences regarding the levels of immune cell subpopulations in both peripheral circulation and tumor microenvironment were emphasized, with some of them having prognostic significance. In our study, we performed an analysis of immune changes in the tumor tissue and the peripheral blood of untreated HNSCC patients, investigating the proportions of different immune cell populations in these two compartments. The local infiltrating lymphocytes were mainly cytotoxic T cells (CD8+). We have also revealed an increased level of B lymphocytes (CD19+) in the tumor microenvironment. In peripheral blood, the most important lymphocyte subtype was represented by the helper T lymphocytes (CD4+). We also found an increased proportion of circulating NK cells (CD56+). Our results showed significant differences between all investigated lymphocyte subtypes in the peripheral blood and the tumor tissue of untreated HNSCC patients, suggesting that the local and systemic expressions of antitumor immune responses are different and that investigation of immune cell proportions in peripheral circulation has different cues that do not reflect the immune infiltrate pattern within the tumor microenvironment. Further studies are necessary to unveil the complex interplay involving local and systemic events in the immune system's fight against cancer. [ABSTRACT FROM AUTHOR]

An early diagnosis is of overwhelming importance for the management and prognosis of mucocutaneous cancer. Actinic cheilitis (AC), defined by the clonal expansion of genomically unstable keratinocytes, is the most common potentially malignant lesion affecting the lips. Squamous cell carcinoma (SCC) is the most frequent oral malignancy, and there is strong evidence that the majority of the SCCs of the lip originate from AC. There is considerable difficulty in discerning between dysplasia and invasive carcinomas solely on a clinical basis. Although dermoscopy has become an essential tool for skin tumor evaluation, reflectance confocal microscopy (RCM) is a non-invasive imaging technology that has proved itself extremely useful in the diagnosis and monitoring of several skin diseases, including AC and SCC. The present study aimed to re-emphasize the usefulness of RCM in the early detection of malignant transformation, using AC and SCC of the lips as working examples. Due to the apparent innocuousness of AC for numerous patients, it is not possible to overstress the importance of a correct and early diagnosis, proper treatment and long-term patient follow-up as being essential for preventing the progression to lip SCC, or for its timely diagnosis. [ABSTRACT FROM AUTHOR]

Squamous cells carcinoma (SCC) is the second most frequent of the keratinocyte-derived malignancies after basal cell carcinoma and is associated with a significant psychosocial and economic burden for both the patient himself and society. Reported risk factors for the malignant transformation of keratinocytes and development of SCC include ultraviolet light exposure, followed by chronic scarring and inflammation, exposure to chemical compounds (arsenic, insecticides, and pesticides), and immune-suppression. Despite various available treatment methods and recent advances in noninvasive or minimal invasive diagnostic techniques, the risk recurrence and metastasis are far from being negligible, even in patients with negative histological margins and lymph nodes. Analyzing normal, dysplastic, and malignant keratinocyte proteome holds special promise for novel biomarker discovery in SCC that could be used in the future for early detection, risk assessment, tumor monitoring, and development of targeted therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: Oral squamous cell carcinoma (OSCC) is a common cancer with high morbidity and mortality. Alterations of antitumor immune responses are involved in the development of this malignancy, and investigation of immune changes in the peripheral blood of OSCC patients has aroused the interest of researchers. Methods: In our study, we assessed the proportions of CD3+ total T lymphocytes, CD3+CD4+ helper T lymphocytes, CD3+CD8+ suppressor/cytotoxic T lymphocytes, CD3−CD19+ total B lymphocytes, and CD3−CD16+CD56+ NK cells in the peripheral blood of OSCC patients. Results: The data obtained both pre- and post-therapy showed a similar level of total CD3+ T lymphocytes in OSCC patients and control subjects, pinpointing the stability of this immune parameter. On the other hand, pre-therapeutic data showed a lower proportion of helper T lymphocytes (CD4+), a significantly higher level of cytotoxic/suppressive T lymphocytes (CD8+), and a much lower CD4+ T lymphocyte/CD8+ T lymphocyte ratio compared to control subjects. Conversely, evaluation of circulating NK (CD16+) cells showed a markedly higher pre-therapeutic level compared to the control group. Conclusions: Our results related to immune changes in the peripheral blood add new information to this complex universe of connections between immuno-inflammatory processes and carcinogenesis. [ABSTRACT FROM AUTHOR]

Simple Summary: In this study, we assess the prognostic potential of immune and inflammatory elements determined preoperatively in the peripheral blood of patients with oral squamous cell carcinoma (OSCC). Preoperative plasma fibrinogen (Fib) and platelet-to-lymphocyte ratio (PLR) show strong correlations with patients' outcomes. Analyzed together, in a new parameter named Fibrinogen-PLR Algorithm (FiPLA), predictive power increases significantly. Clinicians can use this new, easy, cost-effective, and globally available tool for risk stratification of patients with OSCC, as early as from the moment of diagnosis. (1) Background: Oral squamous cell carcinoma (OSCC) is a common malignancy, and the impact of immune and inflammatory mechanisms in its development and progression are of major interest. The aim of our study is to assess the prognostic potential of circulating immune and inflammatory elements determined preoperatively in patients with OSCC, as well as the development of a new compound parameter with predictive value. (2) Methods: We assessed preoperative fibrinogen (Fib) and the platelet-to-lymphocyte ratio (PLR) in 111 OSCC patients. Using a mathematic algorithm, we determined a composite parameter with cumulative information from Fib and PLR, named Fibrinogen-PLR Algorithm (FiPLA). Survival analysis, followed by bivariate and multivariate analyses, was subsequently conducted. (3) Results: Increased preoperative Fib and PLR levels were associated with poor outcome in OSCC (p = 0.0001 and p = 0.0015, respectively). Preoperative FiPLA values were also associated with poor patient survival (p < 0.0001). Multivariate analysis confirmed the independent prognostic role for FiPLA only (CI95% 1.232–67.770, p = 0.03), showing the superior predictive value of FiPLA compared to its individual components. (4) Conclusions: Preoperative assessments of circulating immune and inflammatory elements can provide high-quality prognostic information, and they represent valuable tools in clinical practice, facilitating the early risk stratification of patients with OSCC. [ABSTRACT FROM AUTHOR]

Background: squamous cell carcinoma (SCC) is the second most common type of malignancy worldwide. Skin and mucosa of the head and neck areas are the most frequently affected. An aggressive behavior in SCC is not easily detected, and despite all efforts, mortality in these types of cancer did not show major improvements during recent decades. In this study, we aim to determine the role of histological features available through standard pathology assessment in SCC and their relation with tumor behavior and patients' survival. Method: in a group of one hundred patients diagnosed with SCC involving the head and neck areas, we assessed the presence of four histological features (tumor/stroma ratio, immune infiltration at the front of invasion, tumor-budding activity, and tumor necrosis), their correlations with tumor type (mucosal or cutaneous), tumor clinicopathological characteristics, and their prognostic potential. Results: the comparison between histological features in cutaneous versus mucosal SCC reveals no significant differences for any of the four parameters assessed. We found significant correlations between tumor/stroma ratio and lymphatic metastasis (p = 0.0275), perineural invasion (p = 0.0006), and clinical staging (p = 0.0116). Immune infiltration at the front of invasion revealed similar correlations with lymph node involvement (p = 0.002), perineural invasion (p = 0.0138), and clinical staging (p = 0.0043). Tumor budding and tumor necrosis correlated with the size of the tumor (p = 0.0077 and p = 0.0004) and the clinical staging (p = 0.0039 and p = 0.0143). In addition, tumor budding was significantly correlated with perineural invasion (p = 0.0454). In mucosal SCC, patients with improved outcome revealed high values for the tumor/stroma ratio (p = 0.0159) and immune infiltration at the front of invasion (p = 0.0274). However, the multivariate analysis did not confirm their independent prognostic roles. Conclusions: extended histological assessments that include features such as tumor/stroma ratio, immune infiltration at the front of invasion, tumor budding, and tumor necrosis can be an easy, accessible method to collect additional information on tumor aggressiveness in skin and mucosa SCC affecting the head and neck areas. [ABSTRACT FROM AUTHOR]

Simple Summary: Oral cancer is a common malignancy with high morbidity and mortality. Tumor-infiltrating immune cells play key roles in its pathogenesis, influencing tumor behavior and evolution. The aim of our study was to assess the prognostic character of tumor-infiltrating CD4+, CD8+ and CD56+ cells in oral squamous cell carcinoma. We found major differences in CD4+ and CD8+ lymphocyte density at the front of invasion compared to the intratumor compartment. In addition, intense infiltration with CD8+ lymphocytes in both compartments carried a positive prognostic character. Moreover, we found that a higher intratumor infiltration with CD56+ cells significantly correlated with locoregional disease control and improved survival. Our study confirms the key role of innate and adaptive immune systems in oral squamous cell carcinoma. The predictive characteristics of CD8+ and CD56+ cells can be implemented as independent prognostic tools and can provide important elements in developing individualized therapy in the fight against oral cancer. (1) Background: The immune microenvironment plays an important role in carcinogenesis and has prognostic potential in many types of cancer. In this study we assess the prognostic character of tumor-infiltrating immune cells CD4+, CD8+ and CD56+ in resectable oral squamous cell carcinoma (OSCC); (2) Methods: We have evaluated the densities of CD4+, CD8+ and CD56+ in two distinct compartments, intratumor and invasion front, in 90 patients with OSCC; (3) Results: Significant differences were found between the tumor compartments for the CD4+ and CD8+ lymphocytes. An improved outcome (OS) was seen in patients with high densities of intratumor CD8+ lymphocytes (p = 0.0086), CD8+ lymphocytes at the front of invasion (p = 0.0011) and for intratumor CD56+ cells (p = 0.0016). Multivariate analysis confirmed the independent prognostic role of CD8+ at the front of invasion (OR = 3.75, CI95% 1.17–12.35, p = 0.026) and for intratumor CD56+ cells (OR = 3.669, CI95% 1.09–15.37, p = 0.035); (4) Conclusions: Tumor-infiltrating CD8+ lymphocytes at the front of invasion and CD56+ in the intratumor compartment display predictive traits in OSCC. A reach immune infiltration with these types of cells is associated with an improved patient outcome. [ABSTRACT FROM AUTHOR]