Primary Oral Squamous Cell Carcinoma Research Articles

Extracellular vesicles from Aggregatibacter actinomycetemcomitans exhibit potential antitumorigenic effects in oral cancer: a comparative in vitro study

Aggregatibacter actinomycetemcomitans is an opportunistic Gram-negative periodontopathogen strongly associated with periodontitis and infective endocarditis. Recent evidence suggests that periodontopathogens can influence the initiation and progression of oral squamous cell carcinoma (OSCC). Herein we aimed to investigate the effect of A. actinomycetemcomitans-derived extracellular vesicles (EVs) on OSCC cell behavior compared with EVs from periodontopathogens known to associate with carcinogenesis. EVs were isolated from: A. actinomycetemcomitans and its mutant strains lacking the cytolethal distending toxin (CDT) or lipopolysaccharide (LPS) O-antigen; Porphyromonas gingivalis; Fusobacterium nucleatum; and Parvimonas micra. The effect of EVs on primary and metastatic OSCC cells was assessed using cell proliferation, apoptosis, migration, invasion, and tubulogenesis assays. A. actinomycetemcomitans-derived EVs reduced the metastatic cancer cell proliferation, invasion, tubulogenesis, and increased apoptosis, mostly in CDT- and LPS O-antigen-dependent manner. EVs from F. nucleatum impaired the metastatic cancer cell proliferation and induced the apoptosis rates in all OSCC cell lines. EVs enhanced cancer cell migration regardless of bacterial species. In sum, this is the first study demonstrating the influence of A. actinomycetemcomitans-derived EVs on oral cancer in comparison with other periodontopathogens. Our findings revealed a potential antitumorigenic effect of these EVs on metastatic OSCC cells, which warrants further in vivo investigations.

Expression of CD4+ and CD8+ Tumor-Infiltrating Lymphocytes in Oral Squamous Cell Carcinoma and Their Relationship With Clinicopathological Parameters: A Cross-Sectional Study.

Background Oral squamous cell carcinoma (OSCC) is the most common malignant neoplasm of the oral cavity. The tumor microenvironment (TME) is a dynamic ecosystem composed of components contributed by both the tumor and the host. The immune cells of TME, mainly CD4+ and CD8+ tumor-infiltrating lymphocytes (TILs), suppress the proliferation of cancer cells andplay a crucial role in the progression of OSCC. The present study aims to analyze the immunohistochemical expression of CD4+ and CD8+ TILs in OSCC and to compare and correlate them with clinicopathological parameters. Methodology A total of 75 formalin-fixed paraffin-embedded samples of cases diagnosed with primary OSCC wereimmunostained withCD4+ and CD8+ antibodies and their expression was compared with the clinicopathological parameters. Results There was a significant positive correlation between CD4+ and CD8+ expression (r = 0.655, p = 0.001).Both CD4+ (r = -2.37, p = 0.041) and CD8+ (r = -0.348, p = 0.002) expressions negatively correlated with the TNM stage (r = -2.37, p = 0.041) of OSCC. CD8+ expression positively correlated with histopathological grade (r = 0.288, p = 0.012). Conclusions The study findings suggest that CD4+ cells are essential to maintain and sustain CD8+ TIL-mediated anti-tumor response. CD4+ and CD8+ TILs are key players in cell-mediated adaptive immunity and prevent tumor progression and metastasis. Strikingly, the higher grade of tumors despite heavy CD8+ infiltration may possibly be due to cancer immunoediting.

Improved recurrence rates and progression-free survival in primarily surgically treated oral squamous cell carcinoma – results from a German tertiary medical center

ObjectivesThis study aimed to explore survival and recurrence patterns in patients undergoing primarily surgical treatment for oral squamous cell carcinoma (OSCC) at a high-volume tertiary medical center in Germany.Materials and methodsThe study included 421 patients with primary OSCC who underwent radical tumor resection, neck dissection, and reconstruction with a free flap. Prognostic relevance of clinicopathological characteristics was assessed using Cox proportional-hazards models. Kaplan-Meier method estimated local recurrence-free survival, progression-free survival (PFS), and overall survival (OS), while the log-rank test compared survival outcomes between groups.ResultsRecurrence manifested in 16.63% of the patients (70 patients), encompassing local recurrence in 54 patients (77.14%) and distant metastasis in 24 patients (34.28%). Neck recurrence occurred in only 1 patient (0.24%) on the contralateral side. The majority of recurrences occurred within the initial twelve months following primary tumor surgery (64.29%). Overall, the 5-year OS stood at 58.29%, while the 5-year PFS reached 72.53%. Patients with early recurrence within ≤ 12 months showed the least favorable prognosis (log-rank, all p < 0.001).ConclusionsOur findings show a significant decrease in recurrence rates and enhanced PFS at a high-volume tertiary medical center in Germany compared to previous studies. Local recurrence was the primary form observed, with most recurrences happening within the initial twelve months post-surgery. Opting for treatment at a high-volume center and devising therapy plans in interdisciplinary tumor boards may not only enhance OS but also contribute to improved PFS.Clinical relevanceThese findings offer valuable insights for physicians regarding the post-treatment care of patients with OSCC. The results underscore the importance of frequent follow-up appointments, particularly during the initial year, and highlight the critical need for vigilance in monitoring for local recurrence.

Expression of Toll-like receptors in oral squamous cell carcinoma.

Almost 380,000 new cases of oral cancer were reported worldwide in 2020. Oral squamous cell carcinoma (OSCC) accounts for 90% of all types of oral cancers. Emerging studies have shown association of Toll-like receptors (TLRs) in carcinogenesis. The present study aimed to investigate the expression levels and tissue localization of TRL1 to TRL10 and NF-κB between OSCC and healthy oral mucosa, as well as effect of Candida colonization in TRL expression in OSCC. Full thickness biopsies and microbial samples from 30 newly diagnosed primary OSCC patients and 26 health controls were collected. The expression of TLR1 to TLR10 and NF-κB was analyzed by immunohistochemistry. Microbial samples were collected from oral mucosa to detect Candida. OSCC epithelium showed lower staining intensity of TRL1, TRL2 TRL5, and TRL8 as compared to healthy controls. Similarly, staining intensity of TRL3, TRL4, TRL7, and TRL8 were significantly decreased in basement membrane (BM) zone. Likewise, OSCC endothelium showed lower staining intensity of TLR4, TLR7 and TLR8. Expression of NF-κB was significantly stronger in normal healthy tissue compared to OSCC sample. Positive correlation was found between the expression of NF-κB, TRL9 and TRL10 in basal layer of the infiltrative zone OSCC samples (P = 0.04 and P = 0.002, respectively). Significant increase in TRL4 was seen in BM zone of sample colonized with Candida (P = 0.01). According to the limited number of samples, our data indicates downregulation of TLRs and NF-κB in OSCC, and upregulation of TLR4 expression with presence of Candida.

Second primary squamous cell carcinoma of the oral cavity - a retrospective cohort study of therapeutic procedures and oncological outcome.

In the presented study, the occurrence rates of second primary oral carcinomas and their prognostic relevance were analyzed. All patients with surgically treated oral squamous cell carcinomas within the years 2010 and 2022 in our department were included in this retrospective cohort study. Two groups were designed including patients with second primary carcinomas and patients with local tumor recurrences. Occurrence rates, tumor stages and applied therapies were assessed. Primary outcome was overall survival in dependence of the index tumor. Secondary outcomes were overall survival in dependence of local recurrences or second primary tumors. An overall number of 908 patients was included in the analysis. 98 patients (10.8%) developed a second primary oral squamous cell carcinoma. Patients with second primary tumors presented significantly (p < 0.001) better overall survival in dependence of the index tumor compared to patients suffering from local recurrences. There was no significant difference in overall survival (p = 0.4) in dependence of the date of second primary tumor or local recurrence. Patients with second primary tumors were more likely to receive surgery-based therapy compared to patients with local recurrences who more frequently received definitive radiotherapy. Our data indicates different clinical courses in terms of therapy and survival of patients suffering from second primary tumors compared to patients with local tumor recurrences. This may be due to a more aggressive biology of local recurrences and earlier detection of second primaries due to oncological follow-up of the index tumor. The differentiation of local tumor recurrences and second primary tumors is of clinical relevance, as applicable therapies and resulting prognosis may differ significantly.

Abstract 3795: Possible role of miR-375-3p in cervical lymph node metastasis of oral squamous cell carcinoma

Abstract Latent cervical lymph node metastasis (LNM) is the most important prognostic factor in early oral squamous cell carcinoma (OSCC). However, no clinically useful predictors of LNM in early OSCC are available. In this study, we focused on the microRNAs (miRNAs) involved in the expression of numerous genes and explored those associated with latent cervical LNM in OSCC. Microarray analysis of miRNA expression showed that the expression levels of miR-375-3p were significantly reduced in primary OSCC tissues with latent cervical LNM. Subsequently, we quantified the expression of miR-375-3p by RT-qPCR and digital PCR. Similar to the results of miRNA microarray analysis, miR-375-3p was significantly downregulated in primary OSCC tissues with latent cervical LNM. The results of digital PCR showed a more significant difference than those of RT-qPCR. When the reference value for predicting latent cervical LNM was set to less than 57.85 copies based on the receiver operating characteristic curve, the sensitivity, specificity, accuracy, and area under the curve were 80%, 100%, 90%, and 0.942, respectively. Next, we examined the effects of miR-375-3p mimics on the growth and migration of four human OSCC cell lines (SAS-L1, HSC2, HSC3, and Ca9-22) that do not express miR-375-3p. When an miR-375-3p mimic was introduced into these cells, cell proliferation and migration were significantly suppressed. Total RNA was extracted from these cells reverse-transfected with miR-375-3p mimic for 48 hours. Microarray analysis and Ingenuity Pathway Analysis (IPA) miRNA target filter showed that miR-375-3p overexpression reduced the expression of 266 genes, of which 37 genes had the target sequences of miR-375-3p in their 3’-untranslated region. Among these target genes, CEPT1 and TIMM8A knockdown significantly inhibited the migration of all human OSCC cells, similar to miR-375-3p mimics. Furthermore, IPA core analysis revealed a decrease in expression of genes involved in the activation of PI3K-AKT pathways by miR-375-3p overexpression. These results indicated that downregulating miR-375-3p expression could promote cervical LNM by enhancing cell proliferation and migration in OSCC. We also found that CEPT1 and TIMM8A as novel target genes of miR-375-3p regulated the migration of human OSCC cells. The expression levels of miR-375-3p in primary OSCC tissues appear to be a useful biomarker for predicting latent cervical LNM. Citation Format: Masato Saika, Koh-ichi Nakashiro, Norihiko Tokuzen, Hiroyuki Shirai, Daisuke Uchida. Possible role of miR-375-3p in cervical lymph node metastasis of oral squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3795.

Comparison of the prognostic value of lymph node yield, lymph node ratio, and number of lymph node metastases in patients with oral squamous cell carcinoma.

The aim of this study was to assess the prognostic significance of lymph node yield (LNY), lymph node ratio (LNR), and the number of lymph node metastases (LNMs) in patients affected by oral squamous cell carcinoma (OSCC). The study included patients who underwent surgical treatment for primary OSCC. Receiver operating characteristic curves were generated to determine the optimal threshold values. Kaplan-Meier curves were employed, along with the log-rank test, for the analysis of survival. To compare the performance in terms of model fit, we computed Akaike's information criterion (AIC). This study enrolled 429 patients. Prognostic thresholds were determined at 22 for LNY, 6.6% for LNR, and 3 for the number of LNMs. The log-rank test revealed a significant improvement in both overall survival and progression-free survival for patients with a LNR of ≤6.6% or a number of LNMs of ≤3 (p < 0.05). Interestingly, LNY did not demonstrate prognostic significance. The AIC analyses indicated that the number of LNMs is a superior prognostic indicator compared to LNY and LNR. Incorporating LNR or the number of LNMs into the TNM classification has the potential to improve the prognostic value, as in other types of cancers. Particularly, the inclusion of the number of LNMs should be contemplated for future N staging.

EMT Dynamics in Lymph Node Metastasis of Oral Squamous Cell Carcinoma.

Epithelial-mesenchymal transition (EMT) enables tumor cell invasion and metastasis. Many studies have demonstrated the critical role of EMT in lymph node metastasis in oral squamous cell carcinoma (OSCC). During EMT, epithelial cancer cells lose intercellular adhesion and apical-basal polarity and acquire mesenchymal properties such as motility and invasiveness. A significant feature of EMT is cadherin switching, involving the downregulation of E-cadherin and upregulation of N-cadherin. The TGF-β/SMAD pathway can also induce EMT. We aimed to evaluate EMT markers as predictors of lymph node metastasis in OSCC. We performed genetic profiling of 159 primary OSCCs from TCGA and analyzed the expression of EMT markers, including cadherin switch genes (CDH1, CDH2), and TGF-β/SMAD pathway genes. Samples were divided into advanced (stage III-IV) and early (stage I-II) stage groups. Differential expression analysis was performed, as well as an independent validation study containing fresh OSCC samples. TGF-β/SMAD pathway genes such as SMAD6 were upregulated in advanced stage tumors. N-cadherin and SNAIL2 were overexpressed in node-positive tumors. Keratins were downregulated in these groups. Our findings demonstrate that EMT marker expression correlates with lymph node metastasis in OSCC. Developing therapies targeting regulators such as N-cadherin may prevent metastasis and improve outcomes.

Do we recognize oral cancer? Primary professional delay in diagnosis of oral squamous cell carcinoma.

The occurrence and causes of primary professional delay in diagnosis of oral squamous cell carcinoma (OSCC) were examined. Factors related to initial diagnosis or malignancy suspicion were evaluated in patients with primary OSCC. The outcome variable was primary professional delay for missed suspicion of malignancy or wrong diagnosis or delayed referral. The primary predictor variable was active care-seeking. Secondary predictor variables were patients' symptoms and clinical findings. Primary professional delay was found in 9.5% of the 528 patients included. Professional delay was 6.6 times more likely to occur in patients actively seeking care than in those whose tumor was an incidental finding (95% CI 1.58-27.58, p = 0.010). Pain (OR = 2.0, 95% CI 1.07-3.87, p = 0.031), ulceration (OR = 2.3, 95% CI 1.29-4.19, p = 0.005), denture fit problem (OR = 3.1, 95% CI 1.25-7.56, p = 0.014), and unhealed tooth extraction socket (OR = 29.6, 95% CI 8.89-98.71, p < 0.001) were significant predictors for primary professional delay. OSCC patients seek care actively. Primary professional delay affects the care of every tenth OSCC patient. The role of health care professionals is essential for early OSCC diagnosis, especially in urgent care. Clinicians' knowledge of the typical symptoms and findings of OSCC should be improved.

Occult metastasis is no burden factor in oral squamous cell carcinoma patients when adhering to a standardized approach in neck dissection

ObjectivesManagement of the neck in patients with oral squamous cell carcinoma (OSCC) is pivotal to oncologic control and survival. However, there is controversy regarding necessity of neck dissection (ND) in patients with clinically node-negative neck. We aimed to assess risk factors for occult metastasis and to explore whether the presence of occult lymph node metastases (LNMs) has an impact on recurrence and survival.Material and methodsA retrospective cohort study was performed including patients with primary OSCC who underwent radical tumor resection and ND in a high-volume center adhering to the prevailing German guideline. The ND was performed according to a standardized approach.ResultsFour hundred twenty-one patients with primary surgically treated OSCC were included. The incidence of occult metastasis was 14.49%. A pathological T stage > 1 (multivariate analysis, odds ratio (OR) 3.958, p = 0.042) and the presence of extranodal extension in LNMs (multivariate analysis, OR 0.287, p = 0.020) were identified as independent risk factors for occult metastasis. When comparing patients with and without occult metastasis, there were no significant differences in terms of progression-free survival (log-rank, p = 0.297) and overall survival (log-rank, p = 0.320). There were no cases of ipsilateral neck recurrence. One patient developed contralateral neck metastasis; however, he initially presented with a unilateral pT1 pN0 tumor.ConclusionsOverall, our findings suggest that conducting a standardized approach in ND should be applied in terms of management of the neck in order to maintain survival rates and to prevent neck recurrence in OSCC patients.Clinical relevance.None of the risk factors for occult metastasis can be reliably assessed preoperatively. Although elective ND does not guarantee the complete prevention of neck recurrence, it increases the likelihood of either timely removal of micrometastases or strengthens the justification for adjuvant therapy. Consequently, this approach leads to improvements in clinical outcomes.

Comparison of the 7th and revised 8th UICC editions (2020) for oral squamous cell carcinoma: How does the reclassification impact staging and survival?

Since its introduction in 1968, the TNM (tumor, node, metastasis) classification established by the International Union Against Cancer has provided a consistent framework for staging of oral squamous cell carcinoma (OSCC). The introduction of the 8th edition in 2017 brought about significant modifications, encompassing the integration of depth of invasion (DOI) and extranodal extension (ENE) into the T and N classifications. Further, the UICC the criteria for the T3 and T4a categories were amended in 2020. This study aimed to evaluate the impact of reclassification on staging and, subsequently, the survival of patients with OSCC. Primary OSCCs from 391 patients were classified according to the 7th and revised 8th UICC editions (2020). Stage migration was assessed, and stage-specific progression-free survival (PFS) and overall survival (OS) were evaluated using the Kaplan-Meier method. The log-rank test was used to compare the different stages. Cox-proportional hazard modeling was used to compare the two editions. Incorporating the DOI into the T classification resulted in an upstaging of 77 patients, constituting 19.69% of the cohort. In addition, 49 (12.53%) patients experienced an upstaging when considering ENE in the N classification. Consequently, 103 patients underwent upstaging in UICC staging, accounting for 21.74% of cases. Upstaging mainly occurred from stage III to IVA (26.92%) and from stage IVA to IVB (31.78%). Upon comparing the categories in survival analysis, significant differences in OS and PFS were especially observed between stage IVB and lower stages. When examining the hazard ratios, it became evident that UICC 8 stage IVB is burdened by a 5.59-fold greater risk of disease progression than stage I. Furthermore, UICC 8 stage IVB exhibits a 3.83 times higher likelihood of death than stage I disease. We demonstrated significant stage migration from the 7th to the revised 8th UICC edition. Overall, incorporating DOI and ENE into the T and N classifications represents a substantial clinical advancement, leading to a more accurate staging of OSCC patients. Both staging systems exhibited statistically significant discrimination between stages; however, the 8th UICC edition allowed for a more precise categorization of patients based on their prognosis and led to enhanced hazard discrimination, particularly within higher stages.

Feasibility and diagnostic performance of sentinel node biopsy for staging cN0 oral squamous cell carcinoma in a previously treated neck

AbstractObjectivesStaging of the cN0 neck with sentinel node biopsy (SNB) in early‐stage oral squamous cell carcinoma (OSCC) is validated in patients with a previously untreated neck. We aimed to investigate the feasibility and diagnostic accuracy of SNB and unexpected drainage patterns in patients with cT1‐T2N0 OSCC and a history of previous head and neck cancer comprising treatment of the neck, that is, surgery, radiotherapy, or both.MethodsFifty patients with a previously treated neck diagnosed with a new primary or recurrent cN0 OSCC between 2014 and 2021 were included and retrospectively analyzed. Feasibility was assessed by the rate of successfully performed SNB neck staging procedures. Based on follow‐up data, the diagnostic performance of SNB was evaluated by calculation of negative predictive value (NPV) and false omission rate (FOR).ResultsA SNB staging procedure was successfully performed in 76% (38/50) of the patients. Technical failures were due to the lack of drainage preoperatively or failure in intraoperative SN detection. In patients successfully staged with SNB, the rate of a positive SN was 13% (5/38). In the SNB‐negative group, no patients were diagnosed with a regional node recurrence during follow‐up, and the NPV and FOR were 100% and 0%, respectively. Unexpected lymphatic drainage occurred in 32% (12/38) of the patients.ConclusionSNB is technically feasible in cT1‐2N0 OSCC patients with a previously treated neck with a high diagnostic accuracy. Importantly, SNB enables the detection of individual and unexpected lymphatic drainage patterns.

Primary intraosseous oral squamous cell carcinoma (PIOSCC) of the jaws: two clinical cases

Primary intraosseous oral squamous cell carcinoma (PIOSCC) of the jaws: two clinical cases

Potentially Lethal But Rarely Considered. Risk of Developing Refeeding Syndrome in Primary Oral Squamous Cell Carcinoma

Presurgical preparation and postoperative care are cornerstones of all surgical procedures. Surgeons should be especially vigilant with malnourished cancer patients. Refeeding syn-drome (RFS) is a serious, potentially fatal complication of initiating appropriate nutrition in malnourished patients or after a period of starvation, although no standard precise definition has been proposed. The rarity of its une-quivocally life-threatening course means that its risk may be underestimated in clinical practice.The study's main goal was to assess the degree of malnutrition and the risk of RFS in the presurgical status of patients with oral cavity cancer and to identify risk factors for the occurrence of RFS.This single-center prospective observational study included patients diagnosed with oral squamous cell carcinoma. We investigated the relationship of RFS with age, BMI, features of the malignant tumor process selected internal medicine comorbidities, inflam-matory markers, renal and hepatic parameters, plasma levels of diverse electrolytes, and microelements were assessed. In the work, we utilized the National Institute for Health and Clinical Excellence (NICE) criteria.The study included 90 patients: 35 women and 55 men, aged 64.2±10.5. A robust statistical correlation at a significance level of p < 0.05 was demonstrated between advanced age, lower BMI, lymph node metastases, and a relatively low LDH as positive predictors of the onset of RFS and confirmed the high predictive value of the NRS-2002 scale.This paper seeks to call attention to RFS and identify critical issues that may be useful for its prevention.

Expression of Ubiquitin C-Terminal Hydrolase-L1 in Minor Normal Salivary Gland Tissues in Perilesional Area to OSCC

Ubiquitin C-terminal hydrolase L1 (UCH-L1), is a deubiquitinating enzyme. Certain changes in ubiquitination attribute to uncontrolled growth, leading to oncogenesis. The aim of this study was to characterize UCH-L1 expression patterns in nor mal looking human minor salivary gland tissues in the perilesional area of oral squamous cell carcinoma (OSCC). A retrospective study in which UCH-L1 immunohistochemical staining performed for 27 formalin fixed paraffin embedded blocks of surgically removed primary OSCC containing perilesional minor salivary gland tissues. The expression, subcellular localization, pattern of distribution, and stain intensity were assessed. UCH-L1 was immunopositive in minor salivary gland tissues of all sections. The immunoreactivity was (70.4%) detected in the cytoplasm and (29.6%) as mixed expression (cytoplasm and nucleus). UCH-L1 was predominately expressed in the ductal system (40.7%), followed by the myoepithelial cells (33.35%), while it was weakly expressed in the acinar cells; mucous (14.9%) and serous acini (11.1%). UCH-L1 expression is detectable in minor salivary glands in a perilesional area of OSCC, Although previously approved that it was absolutely absent in normal salivary gland tissues, it may activate during the course of oncogenesis and can be classified as a marker for predicting the future invasion of OSCC to adjacent minor salivary gland tissues. This study provides evidence for additional studies on the UCH-L1 expression in normal salivary glands in patients with maxillofacial tumorigenesis.

Impact of Adjuvant Radiotherapy in Squamous Cell Carcinoma of the Oral Cavity with Perineural Invasion.

Current guidelines indicate postoperative radiotherapy (PORT) in oral squamous cell carcinoma (OSCC) with perineural invasion (PNI), however, its real benefit has never been proven. The aim of our study is to investigate the benefit of PORT in OSCC patients with PNI in terms of survival and disease control. The Pubmed/MEDLINE, Cochrane Library, and Scopus databases. Patients with PNI + OSCC treated with primary surgery were extracted from the included studies. The pooled logHR was calculated by comparing patients who underwent PORT to those who underwent only observation for overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), and locoregional control (LRC). About 690 patients with primary OSCC and PNI were included from nine studies. 374 (54.2%) patients underwent PORT, while 316 (45.8%) underwent observation. Analyses showed non-significant difference between the two groups for OS (HR: 1.01; 95% CI: 0.38-2.69), DSS (HR: 2.03; 95% CI: 0.54-7.56), and LRC (HR: 0.89; 95% CI: 0.53-1.50). They showed a significant difference in terms of DFS (HR: 0.86; 95% CI: 0.77-0.97). The real benefit of PORT in OSCC patients with PNI is still unclear, although it may have a positive impact on DFS. Clinicians should consider individual patient's characteristics, tumor factors, and treatment goals when deciding whether to recommend PORT. Further studies are needed to clarify which entity of PNI really benefits from PORT. NA Laryngoscope, 134:2019-2027, 2024.

Dynamic Up-Regulation of PD-L1 in the Progression of Oral Squamous Cell Carcinoma.

The introduction of immune checkpoint inhibition for recurrent and metastatic head and neck cancer has brought a new treatment option for patients suffering from advanced oral cancers without a chance for curation using surgery or radiotherapy. The application of immune checkpoint inhibitors in most cases is based on the expression levels of PD-L1 in the tumor tissue. To date, there is a lack of data on the dynamic regulation of PD-L1 during disease progression. Therefore, this study aimed to evaluate the expression levels of PD-L1 in a large cohort of patients (n = 222) with oral squamous cell carcinoma including primary and recurrent tumors. Semiautomatic digital pathology scoring was used for the assessment of PD-L1 expression levels in primary and recurrent oral squamous cell carcinoma. Survival analysis was performed to evaluate the prognostic significance of the protein expression at different stages of the disease. We found a significant up-regulation of PD-L1 expression from primary disease to recurrent tumors (mean PD-L1 H-scores: primary tumors: 47.1 ± 31.4; recurrent tumors: 103.5 ± 62.8, p < 0.001). In several cases, a shift from low PD-L1 expression in primary tumors to high PD-L1 expression in recurrent tumors was identified. Multivariate Cox regression analysis did not reveal a significantly higher risk of death (p = 0.078) or recurrence (p = 0.926) in patients with higher PD-L1 expression. Our findings indicate that the exclusive analysis of primary tumor tissue prior to the application of checkpoint blockade may lead to the misjudgment of PD-L1 expression in recurrent tumors.

Autophagy indicators in oral squamous cell carcinoma

Autophagy plays an important role in maintaining cellular homeostasis. Dysregulation of autophagy has been linked to a number of diseases, including cancer. We retrospectively evaluated immunohistochemical expression of the autophagy markers LC3B and p62 and the autophagy regulator mTOR as an indicator of autophagy in 100 surgically resected primary oral squamous cell carcinoma (OSCC) samples and sought associations with various clinicopathological factors. The expression of all three proteins was significantly higher in malignant squamous cells than in benign squamous cells in the free mucosal margin adjacent to the OSCC. Male sex, higher tumour (T) stage, node (N) stage and tumour, node, metastasis (TNM) stage were significantly associated with high marker expression; age and histological grade showed no significant association. LC3B, p62 and mTOR expression were positively correlated with one another in OSCCs, and the correlation was significant for LC3B and mTOR as well as for LC3B and p62. Disease-free survival showed an inverse correlation with high mTOR expression. Our data suggest that autophagy inhibitors and mTOR inhibitors may have a therapeutic role in the treatment of OSCCs.

Diagnostic accuracy of contrast-enhanced computed tomography in assessing cervical lymph node status in patients with oral squamous cell carcinoma

ObjectiveAccurate preoperative prediction of lymph node (LN) status plays a pivotal role in determining the extension of neck dissection (ND) required for patients with oral squamous cell carcinoma (OSCC). This study aims to evaluate the diagnostic accuracy of contrast-enhanced computed tomography (CT) in detecting LN metastases (LNMs) and to explore clinicopathological factors associated with its reliability.MethodsData from 239 patients with primary OSCC who underwent preoperative CT and subsequent radical surgery involving ND were retrospectively reviewed. Suspicious LNs were categorized into three groups: accentuated (< 10 mm), enlarged (≥ 10 mm), and melted. Statistical analysis encompassing correlation and comparative analysis, and determination of sensitivity, specificity, PPV, and NPV were performed.ResultsOverall, sensitivity was significantly higher in the accentuated LNs group (83.54%) compared to the melted LNs group (39.24%, p < 0.05, t test). Conversely, specificity was significantly higher in the melted LNs group (98.19%) compared to the accentuated LNs group (55.15%, p < 0.05, t test). Accentuated LNs exhibited a false negative rate of 13.00%. False positive rates were 51.80%, 30.26% and 8.82%, respectively. Diagnostic accuracy for detecting LNMs in level IIa and IIb exceeded that of level III. Patients with solely accentuated LNs were more likely to have a small, well-differentiated tumor. However, no distinctions emerged in terms of the occurrence of T4 tumors among the three groups.ConclusionCT proves sufficient to predict LNMs in patients with OSCC. Looking ahead, the potential integration of artificial intelligence and deep learning holds promise to further enhance the reliability of CT in LNMs detection. However, this prospect necessitates further investigation.

Bone invasion by oral squamous cell carcinoma—Is there a link to periodontal disease? A retrospective single center cohort study: 2010–2020

ObjectivesThe aim of this study was to clarify if bone invasion by oral squamous cell carcinoma (OSCC) is associated with periodontal disease (PD), dental status, or tumor location in patients with primary OSCC. Additional overall survival (OS) and recurrence-free survival (RFS) were related to bone invasion and PD. Patients and methodsRetrospectively, 278 patients with OSCC between 2010 and 2020 were included. Uni- and multivariate analyses were performed to assess the association between PD, dental status, tumor location, and the presence of bone invasion by OSCC. Kaplan-Meier curves and logrank tests were used to assess differences in 5-year OS and RFS for the presence of bone invasion and PD. ResultsIn dentate patients (n = 168) periodontal disease was more common in patients with bone-invasive OSCC (90%) compared to patients without OSCC bone invasion (70%), (p = 0.009; OR 3.7 (1.4–9.0)). Floor of mouth (FOM) tumors are more frequent when PD was present (41%). No statistically significant difference was seen in dental status and bone invasion (p = 0.10). Moderate periodontitis was associated with worse OS (55%) compared to severe and no periodontitis (67% and 68% respectively) (p = 0.03; mean survival 42.7 months (SD26.5)). Favorable OS and RFS were significantly associated with no bone invasion (p = 0.047 and 0.035 respectively). ConclusionPD is 3.7 times more common in OSCC with bone invasion and tumor location is related to PD (p < 0.0001). Thus, periodontitis could be a risk factor for bone-invasive OSCC. Elimination of PD might lead to higher OS.