Current Review on Nanophytomedicines in the Treatment of Oral Cancer: Recent Trends and Treatment Prospects.

Cancer is one of the major life-threatening diseases in the world and oral cancer is the 8th most common type of deadly cancers in Asian countries. Despite many causes, tobacco is the main causative agent as 90% of oral cancer cases were due to daily consumption of tobacco and its products. The major drawback of the conventional therapies for oral cancer including chemotherapy, surgery and radiotherapy or combination of these is the dose limiting toxicity. Developments in technology and research led to new innovative discoveries in cancer treatments. In the past few decades, increased attention has been given to researches in alternative cancer treatment strategies using plants and plant products. Recently many anticancer drugs from natural products or phytochemicals were approved internationally. Due to the low bioavailability and poor solubility of phytochemicals, various research works on nano-carrier based drug delivery systems were exploited in the recent past to make them as promising anticancer agents. In the current review, an overview of oral cancer and its treatment, risk factors, missing links of conventional therapies, contribution of nanotechnology in cancer treatment and research on phytochemical based drug treatment and different polymeric nanoparticles were discussed briefly. The future prospects for the use of various types of polymeric nanoparticles applied in the diagnosis and treatment of oral cancer were also mentioned. The major concern of this review is to give the reader a better understanding on various types of treatment for oral cancer.

Deep learning-enabled fluorescence imaging for surgical guidance: in silico training for oral cancer depth quantification.

Significance: Oral cancer surgery requires accurate margin delineation to balance complete resection with post-operative functionality. Current in vivo fluorescence imaging systems provide two-dimensional margin assessment yet fail to quantify tumor depth prior to resection. Harnessing structured light in combination with deep learning (DL) may provide near real-time three-dimensional margin detection. Aim: A DL-enabled fluorescence spatial frequency domain imaging (SFDI) system trained with in silico tumor models was developed to quantify the depth of oral tumors. Approach: A convolutional neural network was designed to produce tumor depth and concentration maps from SFDI images. Three in silico representations of oral cancer lesions were developed to train the DL architecture: cylinders, spherical harmonics, and composite spherical harmonics (CSHs). Each model was validated with in silico SFDI images of patient-derived tongue tumors, and the CSH model was further validated with optical phantoms. Results: The performance of the CSH model was superior when presented with patient-derived tumors ( P -value < 0.05 ). The CSH model could predict depth and concentration within 0.4 mm and 0.4 µ g / mL , respectively, for in silico tumors with depths less than 10 mm. Conclusions: A DL-enabled SFDI system trained with in silico CSH demonstrates promise in defining the deep margins of oral tumors.

mRNA-seq-based analysis predicts: AEG-1 is a therapeutic target and immunotherapy biomarker for pan-cancer, including OSCC.

Background: The aberrant expression of AEG-1 is significantly correlated with tumorigenesis, development, neurodegeneration and inflammation. However, the relationship between AEG-1 expression and immune infiltration in OSCC, as well as other tumor types, has yet to be comprehensively analyzed. Methods: The expression levels, prognostic and clinicopathological characteristics, mutation patterns and methylation landscapes of AEG-1 in various tumors were obtained from multiple databases, including TIMER, GEPIA, HPA, TCGA, UALCAN, cBioPortal, SMART and TISIDB, in addition to single-cell RNA-seq data. The integration of these datasets facilitated the elucidation of the relationships among pan-cancer cellular heterogeneity, immune infiltration and AEG-1 expression levels. In vitro experiments created AEG-1 overexpressing cell lines, and mRNA-seq analyzed AEG-1-related differential genes in OSCC. RT-PCR validated these findings in vivo using xenograft tumors. Tumor cell lines were developed to study AEG-1's effects through H&E, Masson, and PAS staining. Immunohistochemistry examined AEG-1-related gene expression patterns. Results: Our analysis demonstrated that AEG-1 is highly expressed across various cancer types and is associated with tumor grade and patient prognosis. Additionally, AEG-1 amplification was observed in multiple cancers. Notably, we identified a significant elevation of AEG-1 expression in OSCC, which strongly correlated with patient prognosis and immune infiltration. Through mRNA-seq analysis of differentially expressed genes and immune-related gene sets, we identified a strong correlation between AEG-1 and immune infiltration markers such as LCP2, CD247, HLA-DPA1, HLA-DRA, HLA-DRB1, CIITA and CD74 in OSCC. Additionally, AEG-1 was found to regulate Th1/Th2 immune homeostasis, promote glycogen accumulation, and contribute to tumor fibrosis. Conclusion: In conclusion, AEG-1 significantly correlates with prognosis and immune infiltration across various cancer types and holds potential as a novel prognostic immune biomarker for OSCC. This finding may facilitate the identification of patients who are most likely to benefit from adjuvant immunotherapy.

Iontophoresis-Enhanced Buccal Delivery of Cisplatin-Encapsulated Chitosan Nanoparticles for Treating Oral Cancer in a Mouse Model.

Introduction: Cisplatin is one of the most effective chemotherapeutic drugs used in oral cancer treatment, but systemic administration has side effects. The purpose of this study was to evaluate the effect of iontophoresis on the enhancement of cisplatin release from cisplatin-encapsulated chitosan nanoparticles. Methods: The effect of different mass ratios of chitosan to tripolyphosphate (TPP) (5:1, 10:1, 15:1, 20:1) on the encapsulation efficiency of cisplatin was investigated. Uptake of cisplatin-encapsulated chitosan by cells was observed using a confocal laser scanning microscope. The cell viability at different cisplatin concentrations was examined using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Three iontophoresis methods, namely constant-current chronopotentiometry (CCCP), cyclic chronopotentiometry (CCP), and differential pulse voltammetry (DPV), were used to enhance cisplatin release from cisplatin-encapsulated chitosan nanoparticles. In addition, mouse oral squamous cell carcinoma cell lines were implanted into the mouse oral mucosa to induce oral cancer. The effects of enhanced cisplatin release by CCCP, CCP, and DPV on tumor suppression in mice were evaluated. Tumors and lymph nodes were isolated for hematoxylin-eosin staining and immunohistochemistry staining including Ki-67 and pan CK after sacrifice. Inductively coupled plasma mass spectrometry was conducted to quantify the platinum content within the tumors. Results: The results showed that nanoparticles with a mass ratio of 15:1 exhibited the highest cisplatin encapsulation efficiency (approximately 15.6%) and longest continued release (up to 35 days) in phosphate buffered saline with a release rate of 100%. Cellular uptake results suggested that chitosan nanoparticles were delivered to the cytoplasm via endocytosis. The results of the MTT assay revealed that the survival rate of cells decreased as the cisplatin concentration increased. The CCP (1 mA, on:off = 1 s: 1 s) and DPV (0-0.06 V) groups were the most effective in inhibiting tumor growth, and both groups exhibited the lowest percentage of Ki-67 positive and pan CK positive. Conclusion: This study is the first to investigate and determine the efficacy of DPV in enhancing in vivo drug release from nanoparticles for the treatment of cancer in animals. The results suggest that the CCP and DPV methods have the potential to be combined with surgery for oral cancer treatment.

Investigating the Anticancer Potential of Biochanin A in KB Oral Cancer Cells Through the NFκB Pathway.

Squamous cell carcinoma (SCC) is a malignancy primarily affecting squamous cells. Its development is linked to multiple risk factors, such as alcohol and tobacco consumption, human papillomavirus (HPV) infection, and Epstein-Barr Virus (EBV) infection. Biochanin A (BCA), a phytoestrogen extracted from red clover, has been extensively researched for its therapeutic properties. It spans antioxidant activity, anti-inflammatory effects, neuroprotection, cardioprotection, and anticancer potential in different bodily systems. However, its impact on oral cancer remains unexplored. Therefore, this investigation aims to assess the potential anticancer effects of BCA, specifically on KB oral cancer cells. This study utilized KB cells to evaluate the impact of BCA on various cellular parameters, including cell viability, apoptosis, intracellular ROS production, mitochondrial membrane potential, and cell migration. BCA treatment induced several notable effects on KB cells, including reduced cell viability, altered morphology suggestive of apoptosis, heightened oxidative stress, and alterations in mitochondrial membrane potential. Moreover, BCA treatment demonstrated an inhibitory effect on cell migration. The study further investigated the impact of BCA on antioxidant enzyme activities and lipid peroxidation, revealing decreased antioxidant enzyme activities and increased lipid peroxidation across different BCA concentrations (IC50 and IC90). Immunocytochemistry and qRT-PCR analyses unveiled that BCA treatment at varying doses (IC50 and IC90) downregulated the expression of nuclear factor-κB (NF-κB) subunits p50 and p65, pivotal players in cancer progression. In summary, this study sheds light on the promising potential of BCA as an anticancer therapeutic agent for treating oral cancer. Its demonstrated ability to induce apoptosis, perturb cellular functions, and modulate gene expression within cancer cells underscores its significance. Nonetheless, further research, particularly following animal studies, is imperative to comprehensively grasp the breadth of BCA's effects and its viability for clinical applications.

Oral sialadenoma papilliferum with kras mutation in a patient with linear nevus sebaceous syndrome.

Linear nevus sebaceous syndrome (LNSS) is a rare neurocutaneous syndrome part of the epidermal nevus syndromes group, characterized by the presence of sebaceous nevi and other extracutaneous lesions genetically related to RAS family gene mutations. Sialadenoma papilliferum (SP) is a rare benign intraoral neoplasm which is usually BRAF or HRAS mutated. We report a case of a young female girl diagnosed with a LNSS who developed a SP which had a KRAS mutation. This is the first case of SP with a KRAS mutation in the context of a LNSS.

Malignant Transformation of Normal Oral Tissue to Dysplasia and Early Oral Squamous Cell Carcinoma: An In Silico Transcriptomics Approach.

Background: Oral squamous cell carcinoma (OSCC) is a prevalent and aggressive form of head and neck cancer, often diagnosed at advanced stages. Elucidating the molecular mechanisms involved in the malignant transformation from normal oral tissue to oral preinvasive lesions (OPL) and primary OSCC could facilitate early diagnosis and improve therapeutic strategies. Methods: Differentially expressed genes (DEGs) were identified from the GSE30784 dataset by comparing normal oral tissue, oral dysplasia, and primary OSCC samples. Cross-validation was performed using an independent RNA-seq dataset, GSE186775. Protein-protein interaction (PPI) network analysis, gene ontology annotation, and pathway enrichment analysis were conducted on the common DEGs. Hub genes were identified, and their prognostic significance was evaluated using survival analysis. Transcription factor (TF) enrichment analysis, cross-validation, and immunohistochemistry analyses were also performed. Results: A total of 226 proteins and 677 interactions were identified in the PPI network, with 34 hub genes, including FN1, SERPINE1, PLAUR, THBS1, and ITGA6. Pathways such as "Formation of the cornified envelope," "Keratinization," and "Developmental biology" were enriched. Overexpression of SERPINE1, PLAUR, THBS1, and ITGA6 correlated with poor prognosis, while upregulation of CALML5 and SPINK5 was associated with favorable outcomes. NFIB emerged as the most significant TF-regulating hub genes. Immunohistochemistry validated ITGA6 overexpression in primary OSCC. Cross-validation using the RNA-seq dataset supported the involvement of critical genes in the malignant transformation process. Conclusion: This study identified vital genes, pathways, and prognostic markers involved in the malignant transformation from normal oral tissue to OPL and primary OSCC, providing insights for early diagnosis and targeted therapy development. Cross-validation with an independent RNA-seq dataset and immunohistochemistry reinforced the findings, supporting the robustness of the identified molecular signatures.

LncRNA PCBP1-AS1 suppresses cell growth in oral squamous cell carcinoma by targeting miR-34c-5p/ZFP36 axis.

Oral squamous cell carcinoma (OSCC) is the most frequently diagnosed oral malignancy and poses a great threat to public health. According to bioinformatics analysis, long noncoding RNA PCBP1-AS1 is downregulated in OSCC. In this work, the functions and mechanism of PCBP1-AS1 in OSCC were further investigated. PCBP1-AS1 expression in OSCC cells was measured by quantitative polymerase chain reaction. Cell viability and proliferation were detected using CCK-8 assays and colony-forming assays. TUNEL assays as well as flow cytometry analyses were carried out to detect OSCC cell apoptosis. Binding relationship between PCBP1-AS1 and miR-34c-5p or that between miR-34c-5p and ZFP36 in OSCC cells was identified using RNA immunoprecipitation assays, RNA pulldown assays, and luciferase reporter assays. Experimental results revealed that PCBP1-AS1 was downregulated in OSCC cells. PCBP1-AS1 overexpression hampered cell proliferation and enhanced cell apoptosis in OSCC. PCBP1-AS1 interacted with miR-34c-5p in OSCC and negatively regulated miR-34c-5p. ZFP36 3'untranslated region was targeted by miR-34c-5p. PCBP1-AS1 positively regulated ZFP36 expression. ZFP36 silencing abrogated the suppressive impact of PCBP1-AS1 on OSCC cell growth. In summary, PCBP1-AS1 suppresses cell growth in OSCC by upregulating ZFP36 through interaction with miR-34c-5p.

PLGA-Loaded Nedaplatin (PLGA-NDP) Inhibits 7,12-Dimethylbenz[a]anthracene (DMBA) Induced Oral Carcinogenesis via Modulating Notch Signaling Pathway and Induces Apoptosis in Experimental Hamster Model.

The present study is designed to evaluate the nanotherapeutic efficacy of prepared PLGA-loaded Nedaplatin (PLGA-NDP) against 7,12-dimethyl benz(a)anthracene (DMBA)-induced experimental oral carcinogenesis in hamster buccal pouch (HBP) model. The buccal pouch of golden Syrian hamsters was painted with 0.5% DMBA in liquid paraffin three times a week for 14 weeks, ultimately leading to the development of oral squamous cell carcinoma (OSCC). Oral administration of PLGA-NDP (preinitiation) and Cisplatin delivery (5 mg/kg b.wt) started 1 week before the carcinogen exposure and continued on alternative days. Post-administration of PLGA-NDP (5 mg/kg b.wt) started 2 days after carcinogen (DMBA) induction until the end of the experiment. After the 14th week, we observed that DMBA-painted hamsters exhibited tumor formation, morphological alterations, and well-differentiated OSSC in addition to the responsive molecular proteins during oral carcinogenesis. Furthermore, immunoblotting analysis demonstrated that PLGA-NDP inhibits Notch signaling, as evidenced by downregulation of Bcl-Xl, Bcl-2, p21, PGE2, HGF, and CXCL12 proteins, and upregulation of p53 and Bax. This apoptotic response is crucial for PLGA-NDP to induce apoptosis. In addition, RT-PCR results showed that PLGA-NDP nanoparticles play a downregulatory role in the therapeutic action of the notch signaling gene (Notch1, Notch 2, Hes1, Hey1, and Jagged1) at the mRNA transcription level in HBP carcinoma. Taken together, these data indicate that PLGA-NDP is a potent inhibitor of oral carcinogenesis and the expansion of cells that specifically target the Notch signaling pathway indicates that obstructing Notch signaling could potentially serve as a new and innovative therapeutic approach for oral squamous cell carcinoma (OSCC).

DETECTION OF ORAL SQUAMOUS CELL CARCINOMA USING PRE-TRAINED DEEP LEARNING MODELS.

BACKGROUND: Oral squamous cell carcinoma (OSCC), the 13th most common type of cancer, claimed 364,339 lives in 2020. Researchers have established a strong correlation between early detection and better prognosis for this type of cancer. Tissue biopsy, the most common diagnostic method used by doctors, is both expensive and time-consuming. The recent growth in using transfer learning methodologies to aid in medical diagnosis, along with the improved 5-year survival rate from early diagnosis serve as motivation for this study. The aim of the study was to evaluate an innovative approach using transfer learning of pre-trained classification models and convolutional neural networks (CNN) for the binary classification of OSCC from histopathological images. MATERIALS AND METHODS: The dataset used for the experiments consisted of 5192 histopathological images in total. The following pre-trained deep learning models were used for feature extraction: ResNet-50, VGG16, and InceptionV3 along with a tuned CNN for classification. RESULTS: The proposed methodologies were evaluated against the current state of the art. A high sensitivity and its importance in the medical field were highlighted. All three models were used in experiments with different hyperparameters and tested on a set of 126 histopathological images. The highest-performance developed model achieved an accuracy of 0.90, a sensitivity of 0.97, and an AUC of 0.94. The visualization of the results was done using ROC curves and confusion matrices. The study further interprets the results obtained and concludes with suggestions for future research. CONCLUSION: The study successfully demonstrated the potential of using transfer learning-based methodologies in the medical field. The interpretation of the results suggests their practical viability and offers directions for future research aimed at improving diagnostic precision and serving as a reliable tool to physicians in the early diagnosis of cancer.

CLINICAL SIGNIFICANCE OF SALIVARY MIR-21, -155, AND -375 IN PATIENTS WITH SQUAMOUS CELL CARCINOMA OF ORAL CAVITY.

BACKGROUND: The current prognostic markers in oral squamous cell carcinoma (OSCC) have limited accuracy sometimes leading to inappropriate treatment decisions. Identifying new markers would help clinicians tailor treatment plans based on the individual patient risk factors leading to improved survival rates and quality of life. AIM: To estimate the value of the miRNA expression indicators in saliva as prognostic and predictive markers of the effectiveness of neoadjuvant chemotherapy (NACT). MATERIALS AND METHODS: The work is based on the results of the examination and treatment of 61 patients with stage II-IV OSCC. The miR-21, miR-155, and miR-375 expression levels in the saliva samples were analyzed by the real-time reverse transcription polymerase chain reaction. RESULTS: The salivary miR-21 and -155 expression levels in healthy volunteers were 2.49 and 2.84 times lower than in OSCС patients (p < 0.05). The positive association of miR-21 and miR-155 expression levels and the negative correlation of miR-375 expression level with T index by TNM (r = 0.68, r = 0.75, and r = -0.67, respectively) (p < 0.05) and the presence of lymph node metastasis (r = 0.78, r = 0.71, and r = ‒0.59, respectively) (p < 0.05) were found. Patients with good response to NACT had lower miR-21 and -155, and higher miR-375 levels in saliva compared to those with resistant tumors. CONCLUSIONS: Our study suggests that salivary miR-21, miR-155, and miR-375 may be potential biomarkers for the prognosis of cancer course and the response to NACT in OSCC patients.

Prevention of perioperative venous thromboembolic complications using pneumatic compression cuffs in oral cancer patients in maxillofacial surgery.

OBJECTIVES: Venous thromboembolism (VTE) is still considered to be a significant medical issue. Physical measures to prevent perioperative venous thrombosis include early mobilization and intermittent pneumatic compression (IPC). The aim of this study was to evaluate whether IPC can reduce the incidence of postoperative thromboembolic events in patients with oral squamous cell carcinoma (OSCC) undergoing maxillofacial surgery. MATERIALS AND METHODS: Between March 2020 and May 2021, 75 patients with OSCC who did not receive perioperative prophylaxis using IPC were retrospectively examined to determine the occurrence of postoperative thromboembolism. Accordingly, 79 patients who received perioperative thrombosis prophylaxis using an IPC system as part of surgical tumor therapy from May 2021 to September 2023 were included in the study. The primary outcome measure was the occurrence of postoperative thromboembolism. RESULTS: In the control group without IPC, thromboembolic events were observed in five out of 75 patients during postoperative hospitalization. In the intervention group, no thromboembolic occurrences were identified among the 79 patients studied (p = 0.02). The mean Caprini score in the control group was 7.72, whereas in the intervention group it averaged 8.30 (p = 0.027). CONCLUSIONS: The implementation of IPC-devices as supplementary perioperative thrombosis prophylaxis resulted in a notable decrease in postoperative venous thromboembolism (Number Needed to Treat = 15), which is why implementation of the system as a regular part of the clinical routine for perioperative management of OSCC patients can be considered a sensible approach. CLINICAL RELEVANCE: The use of IPC enhances patient outcomes and may lead to improved postoperative care protocols in this high-risk patient population.

Estimating Anticancer Effects of Yohimbine in DMBA-Induced Oral Carcinogenesis Hamster Model: Utilizing Biochemical and Immunohistochemical Techniques.

Yohimbine is a potent bioactive indole alkaloid, isolated from a variety of biological sources and has long been used as a natural stimulant and aphrodisiac, particularly to treat erectile dysfunction. However, some literature also points toward its anticancer effect in different experimental models. The current study aimed to address a clinical concern on the therapeutic utilization of yohimbine as a repurposed drug. We employed 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch carcinogenesis model juxtaposed with biochemical investigation of several detoxification and antioxidant markers, such as Cyt p450, Cyt b5, thiobarbituric acid reactive substance (TBARS), glutathione (GSH), glutathione reductase (GR), glutathione S transferase (GST), DT-diaphorase, vitamin C, vitamin E, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). The immunohistochemical assessment of cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), proliferating cell nuclear antigen (PCNA), and cyclin D1 expression were also performed to observe the effect of yohimbine on these markers. The hamsters treated with DMBA presented the growth of tumors in the buccal pouches, accompanied by significant changes in the liver and buccal mucosa levels of Phase I & II detoxification enzymes and lipid peroxidation (LPO). A significant rise in the range of 2- to 3.5-fold was observed in Cyt p450, Cyt b5, and LPO in DMBA-treated animals. However, oral administration of yohimbine significantly restored the LPO, antioxidant, and detoxifying enzyme activities. Additionally, the levels of COX-2, IL-6, PCNA, and cyclin D1 were also found to be downregulated by yohimbine treatment. In conclusion, yohimbine improved the biochemical and immunohistochemical markers of DMBA-induced oral cancer and reverted to near normal values via ameliorating the underlying inflammation and oxidative stress conditions. Our study highlighted the potential of yohimbine as anticancer agent, especially against oral cancer and suggested its possible use as repurposed drug.

Underexplored Areas of Photobiomodulation in Oral Oncology: An Expert Analysis.

Objective: This study aimed to review the current body of literature on underexplored areas of photobiomodulation (PBM) for preventing and/or treating oral adverse events. Background: Recent studies suggest that PBM may offer potential benefits in managing cancer-related toxicities other than oral mucositis. Nevertheless, further research to establish conclusive evidence is still missing. Methods: A panel of specialists conducted a narrative review to evaluate the evidence on PBM therapy for oral mucositis, xerostomia, dysgeusia, dysphagia, and trismus/fibrosis. Each topic was reviewed by two specialists who discussed treatment rationale, summarized current evidence, evaluated risk/benefit ratio, and identified future research directions. Results: The current evidence suggests promising outcomes in nonroutine uses of PBM for xerostomia, dysgeusia, odynophagia, oral mucositis (extraoral PBM and the pediatric population), and trismus/fibrosis. However, the primary studies are often small and may have biases that require further evaluation, particularly regarding treatment safety. Conclusion: Despite the overall positive impression of PBM therapy for oral adverse events of cancer treatment, robust evidence from large multicentered studies is necessary to support its widespread clinical use.

Advances in Raman spectroscopy for characterising oral cancer and oral potentially malignant disorders.

Oral cancer survival rates have seen little improvement over the past few decades. This is mainly due to late detection and a lack of reliable markers to predict disease progression in oral potentially malignant disorders (OPMDs). There is a need for highly specific and sensitive screening tools to enable early detection of malignant transformation. Biochemical alterations to tissues occur as an early response to pathological processes; manifesting as modifications to molecular structure, concentration or conformation. Raman spectroscopy is a powerful analytical technique that can probe these biochemical changes and can be exploited for the generation of novel disease-specific biomarkers. Therefore, Raman spectroscopy has the potential as an adjunct tool that can assist in the early diagnosis of oral cancer and the detection of disease progression in OPMDs. This review describes the use of Raman spectroscopy for the diagnosis of oral cancer and OPMDs based on ex vivo and liquid biopsies as well as in vivo applications that show the potential of this powerful tool to progress from benchtop to chairside.

Tumor Metastasis to the Oral Soft Tissues and Jaw Bones: A Retrospective Study and Review of the Literature.

OBJECTIVES: Metastasis to the oral soft tissues and jaw is rare and accounts for 1%-3% of maxillofacial malignancies. These lesions usually occur in the context of an extensive malignant tumor with a poor prognosis. MATERIALS AND METHODS: Archived cases from the Oral and Maxillofacial Pathology Department of the Faculty of Dentistry and two hospital centers of Mashhad University of Medical Sciences were examined. Inclusion criteria were cases with available records of pathologically confirmed metastatic lesions of the oral cavity with or without diagnosed primary malignancy. RESULTS: Metastatic lesions in the oral cavity and jaw were found in 18 patients, including seven women and 11 men, with a mean age of 49.5 years. Metastatic lesions were more common in the jaw (66%) and particularly in the mandible (38%) than elsewhere. In the case of soft tissue metastases, the gingiva was more affected than other sites. The primary tumor was most commonly in the kidney in men and in the breast in women (36%-28%). In addition, the diagnosis of a metastatic lesion led to the detection of the primary tumor elsewhere in six out of 18 cases (33.3%). CONCLUSIONS: Early diagnosis of the lesions is challenging, given the absence of specific signs or symptoms, which, in some cases, nonetheless resemble inflammatory, benign, reactive lesions. Therefore, dentists play a crucial role in diagnosing such lesions, as they lead to the discovery of hidden distant primary tumors. Biopsy should always be considered for suspicious lesions, even if the probability is very low.

Cancer cell-specific PD-L1 expression is a predictor of poor outcome in patients with locally advanced oral cavity squamous cell carcinoma.

BACKGROUND: Locally advanced oral cavity squamous cell carcinoma (OCSCC) presents a significant clinical challenge despite being partially responsive to standard treatment modalities. This study investigates the prognostic implications of programmed death-ligand 1 (PD-L1) expression in these tumors, focusing on its association with treatment outcomes and the immune microenvironment. METHODS: We assessed tumor-infiltrating lymphocytes (TILs) in 132 patients with OCSCC to evaluate their impact on survival. Multiplex immunohistochemistry staining for CD3, CD68, CD11c, PD-L1, and P40 was used to explore correlations with clinical outcomes in patients with early-stage (n=22) and locally advanced (n=36) OCSCC. These initial findings were validated through differential gene expression analysis, gene set enrichment, and immune cell deconvolution in a The Cancer Genome Atlas cohort of 163 locally advanced OCSCC tumors. Additionally, single-cell RNA sequencing (scRNA-seq) on a smaller cohort (n=10) further characterized the PD-L1hi or PD-L1lo cancer cells in these tumors. RESULTS: Elevated PD-L1 expression was associated with poor outcomes in patients with locally advanced OCSCC undergoing standard adjuvant therapy, irrespective of "hot" or "cold" classification based on TILs assessment. PD-L1hi tumors exhibited an active immune response phenotype, enriched with M1 macrophages, CD8+ T cells and T regulatory cells in the tumor microenvironment. Notably, the negative impact of PD-L1 expression on outcomes was primarily attributed to its expression by cancer cells, rather than immune cells. Furthermore, scRNA-seq revealed that immune interactions were not essential for PD-L1 upregulation in cancer cells, instead, complex regulatory networks were involved. Additionally, PD-L1lo locally advanced tumors exhibited more complex pathway enrichment and diverse T-cell populations compared with those in the early-stage. CONCLUSION: Our findings underscore the prognostic significance of PD-L1 expression in locally advanced OCSCC, and unveil the complex interplay between PD-L1 expression, immune responses, and molecular pathways in the tumor microenvironment. This study provides insights that may inform future therapeutic strategies, including the possibility of tailored immunotherapeutic approaches for patients with PD-L1hi locally advanced OCSCC.

Custom made brachytherapy applicator for squamous cell carcinoma of oral commissures.

ABSTRACT: Primary treatment with brachytherapy for oral cancer is uncommon in large malignant lesions; however, it is preferred by radiation oncologists for initial and smaller-sized lesions in compromised anatomical locations. The purpose of this report is to introduce and discuss the fabrication of a customized brachytherapy applicator for a case of well differentiated squamous cell carcinoma (SCC) of the oral commissures using a radiotherapy thermoplastic mold (RTM). The RTM was molded into the shape of tongs and two acrylic wings were attached to these customized tongs to secure five high-dose radiotherapy catheter tubes. A mouth-stabilizing stent was used to stabilize the oral cavity throughout the brachytherapy process. A total dose of 45.5 Gy was delivered in 13 fractions to the lesion using a Cobalt-60 source over 35 days. At the end of the brachytherapy treatment and a follow-up period of 3 months, the patient responded well, and complete remission of the lesion was observed. The current brachytherapy applicator technique is a simple, viable, and curative option for patients with lesions in difficult -to- access anatomic locations.

Polymorphous adenocarcinoma of the buccal space-Rare, reported case from our institute.

ABSTRACT: Polymorphous adenocarcinoma (PAC) of head and neck tumors is a rare salivary gland neoplasm of indolent course. We reported a 63-year-old female who presented as an asymptomatic mass in buccal space. The patient, after metastatic workup, underwent complete excision of the lesion with a negative margin. Postoperative histopathology and immunohistochemistry (IHC) were suggestive of PAC. Presently patient is on follow-up as per a multidisciplinary team decision. To conclude, PAC diagnosis is challenging due to morphological diversity, which necessities IHC. In addition, presently treatment of choice as per the literature review is complete excision.