Gingival Squamous Cell Carcinoma Research Articles

Prognostic factors and impact of bone invasion in T1/2 size (

The aim of this study was to characterize the clinicopathological features and prognostic factors of T1/2 size (<4 cm) gingival squamous cell carcinoma (SCC) and to verify the impact of bone invasion. This was a single-centre, retrospective cohort study involving 206 patients with gingival SCC (maxilla or mandible), treated between 2000 and 2020. The patients were divided into three subgroups based on tumour size and bone invasion. The 5-year overall survival (OS) and disease-free survival (DFS) were 80.6% and 67.6%, respectively. Histological differentiation, advanced T stage, positive resection margin, bone invasion, and postoperative adjuvant therapy were associated with a poor prognosis (P < 0.05). Multivariate Cox analysis indicated that only histological differentiation (hazard ratio (HR) 2.68, P = 0.007) and bone invasion (HR 2.08, P = 0.036) were significantly associated with DFS. Bone invasion was observed in 145 (70.4%) patients, of whom 43 (20.9%) had a T1/2 size tumour. The subgroup with bone invasion and T1/2 size showed significantly worse OS and DFS when compared to the subgroup without bone invasion and similar or worse survival when compared to the subgroup with bone invasion and T3/T4 size. Histological differentiation and bone invasion were poor prognostic factors for gingival SCC, even in cases with small-sized tumours. For suspected bone invasion in small-sized tumours, an adequate bone margin is necessary and postoperative adjunctive therapy needs to be considered.

Eugenol as a potential adjuvant therapy for gingival squamous cell carcinoma

Adoption of plant-derived compounds for the management of oral cancer is encouraged by the scientific community due to emerging chemoresistance and conventional treatments adverse effects. Considering that very few studies investigated eugenol clinical relevance for gingival carcinoma, we ought to explore its selectivity and performance according to aggressiveness level. For this purpose, non-oncogenic human oral epithelial cells (GMSM-K) were used together with the Tongue (SCC-9) and Gingival (Ca9-22) squamous cell carcinoma lines to assess key tumorigenesis processes. Overall, eugenol inhibited cell proliferation and colony formation while inducing cytotoxicity in cancer cells as compared to normal counterparts. The recorded effect was greater in gingival carcinoma and appears to be mediated through apoptosis induction and promotion of p21/p27/cyclin D1 modulation and subsequent Ca9-22 cell cycle arrest at the G0/G1 phase, in a p53-independent manner. At these levels, distinct genetic profiles were uncovered for both cell lines by QPCR array. Moreover, it seems that our active component limited Ca9-22 and SCC-9 cell migration respectively through MMP1/3 downregulation and stimulation of inactive MMPs complex formation. Finally, Ca9-22 behaviour appears to be mainly modulated by the P38/STAT5/NFkB pathways. In summary, we can disclose that eugenol is cancer selective and that its mediated anti-cancer mechanisms vary according to the cell line with gingival squamous cell carcinoma being more sensitive to this phytotherapy agent.

Prognostic value of a mandibular canal staging system for primary lesions in patients with lower gingival squamous cell carcinoma: a multicenter, retrospective study.

The Union for International Cancer Control and American Joint Committee on Cancer tumor staging system is used globally for treatment planning. As it may be insufficient for tumor staging of lower gingival carcinomas, we proposed the mandibular canal tumor staging system. In this study, we aimed to compare the two systems for such tumor staging and to identify prognostic markers. This multicenter, retrospective study included patients with lower gingival squamous cell carcinoma who underwent radical surgery during 2001-2018. We compared survival rates (Kaplan-Meier estimator) and patient stratification according to the two systems. The proposed system yielded more balanced patient stratification than the existing system. Progression in the tumor grade according to the proposed system was associated with a poorer prognosis. The 5-year overall and disease-specific survival rates for the entire cohort were 74.9% and 81.8%, respectively. Independent factors affecting overall survival were tumor stage according to the proposed system, excision margins, and number of positive nodes, whereas those affecting disease-specific survival were excision margins and number of positive nodes. Subsite-specific tumor classification should be used for patients with oral cancer, and our results suggest that mandibular canal tumor classification may be effective for patients with lower gingival carcinoma.

Gingival squamous cell carcinoma in 2 lions under managed care.

Neoplasia is one of the main causes of euthanasia in geriatric captive nondomestic felids. However, few studies have examined oral tumors in these animals. We describe here the clinicopathologic features of gingival squamous cell carcinoma (SCC) in 2 lions (Panthera leo) from separate zoologic collections. In both cases, the lions had a history of sialorrhea, bloody oral discharge, and anorexia. Autopsy findings in both lions were similar and were characterized by poorly circumscribed, friable, and bloody gingival masses with grossly apparent invasion of the mandibular bone; a pathologic fracture was observed in 1 case. Histologically, the masses consisted of poorly circumscribed, unencapsulated, densely cellular proliferations of neoplastic epithelial cells arranged in irregular islands, cords, and anastomosing trabeculae with formation of keratin pearls, which, coupled with positive immunohistochemistry for pancytokeratin, were diagnostic for SCC. Although no metastases were found in either animal, both lions were ultimately euthanized because of poor prognosis.

Evaluation of bone marrow invasion on the machine learning of 18 F-FDG PET texture analysis in lower gingival squamous cell carcinoma.

Lower gingival squamous cell carcinoma (LGSCC) has the potential to invade the alveolar bone. Traditionally, the diagnosis of LGSCC relied on morphological imaging, but inconsistencies between these assessments and surgical findings have been observed. This study aimed to assess the correlation between LGSCC bone marrow invasion and PET texture features and to enhance diagnostic accuracy by using machine learning. A retrospective analysis of 159 LGSCC patients with pretreatment 18 F-fluorodeoxyglucose (FDG) PET/computed tomography (CT) examination from 2009 to 2017 was performed. We extracted radiomic features from the PET images, focusing on pathologic bone marrow invasion detection. Extracted features underwent the least absolute shrinkage and selection operator algorithm-based selection and were then used for machine learning via the XGBoost package to distinguish bone marrow invasion presence. Receiver operating characteristic curve analysis was performed. From the 159 patients, 88 qualified for further analysis (59 men; average age, 69.2 years), and pathologic bone marrow invasion was identified in 69 (78%) of these patients. Three significant radiological features were identified: Gray level co-occurrence matrix_Correlation, INTENSITY-BASED_IntensityInterquartileRange, and MORPHOLOGICAL_SurfaceToVolumeRatio. An XGBoost machine-learning model, using PET radiomic features to detect bone marrow invasion, yielded an area under the curve value of 0.83. Our findings highlighted the potential of 18 F-FDG PET radiomic features, combined with machine learning, as a promising avenue for improving LGSCC diagnosis and treatment. Using 18 F-FDG PET texture features may provide a robust and accurate method for determining the presence or absence of bone marrow invasion in LGSCC patients.

Clinicopathological analysis of 134 patients with squamous cell carcinoma of the mandibular gingiva

ObjectiveThe accurate assessment of the involvement of mandibular gingival squamous cell carcinoma (SCC) is essential for determining the extent of resection and is also useful for predicting lymph node metastasis and prognosis. The purpose of this study was to investigate the factors for predicting the prognosis. Study designWe reviewed 134 patients with mandibular gingival SCC treated between 2008 and 2017. The clinical findings, TN stage, relationship between radiographical type and histological pattern, and factors affecting the survival rate were investigated. ResultsThe moth-eaten radiographic type was significantly associated with histologically infiltrative pattern. For all 134 cases, the 5-year OS was 89.5 %, and 5-year DSS was 93.9 %. The 5-year DSS was 95.0 % for cN0 and/or pN0 cases and 90.3 % for pN (+) cases, with a significant difference. The significant risk factors for lymph node metastasis were teeth extractions by previous physicians and moth-eaten radiographic type. ConclusionThe risk factor for poor prognosis was lymph node metastasis. In addition, teeth extractions by previous physicians and moth-eaten radiographic type were the risk factors for lymph node metastasis. It is recommended that these cases be treated considering the possibility of cervical lymph node metastasis.

Unusual localized gingival redness: a case report

Inflammation of the gingiva is one of the most common and routine findings in dental practice. These routine appearances of inflammatory gingivae can show peculiarity when associated with an underlying systemic condition or because of reactive, benign, or malignant pathologies. This case highlights minute clinical signs of the gingiva that deviate from the routine presentation and warrant further investigations. A 63-year-old woman presented with a chief complaint of severe pain in relation to the lower front teeth region for 1 month. Intraoral examination revealed a gingival lesion on the labial aspect of 41, 42, and 43, and an intraoral periapical radiograph showed mild bone loss. The lesion persisted despite oral prophylaxis, and a biopsy was advised. The final diagnosis was stage 1 gingival squamous cell carcinoma (GSCC). It is important to note that the non-descript presentation of GSCC in early stages often mimics benign traumatic or inflammatory lesions of the gingiva. Peculiar clinical features of GSCC of note include the lack of traditionally associated risk factors and localized red or ulcerative lesions with increased bleeding tendencies that do not respond to routine periodontal treatment within 2 weeks.

Alcohol consumption modulates Candida albicans-induced oral carcinogenesis and progression

ObjectivesThis study aimed to determine the impact of low levels of alcohol consumption on the interaction of the oral cavity with Candida albicans, a species that is commonly found at higher levels in the oral cavities of regular alcohol consumers, patients with pre-malignant diseases, and patients with existing oral cancer (OC). MethodsThe gingival squamous cell carcinoma cell line, Ca9-22, was subjected to low-level ethanol exposure before co-culture with heat-inactivated C. albicans (HICA). We performed cell viability assays, measured reactive oxygen species, and used Western blot analysis for cell death markers to examine the effect of ethanol and HICA on cells. Scratch assays and anchorage-independent growth assays were used to determine cell behavioral changes. ResultsThe results showed that ethanol in combination with HICA exacerbated cell death and cell cycle disruption, delayed NF-κB signaling, increased TIMP-2 secretion, and subsequently decreased MMP-2 secretion when compared to exposure to HICA alone. Conversely, both ethanol and HICA independently increased proliferation of Ca9-22 cells in scratch assays, and in combination, increased their capacity for anchorage-independent growth. ConclusionLow levels of ethanol may provide protective effects against Candida-induced inflammatory oral carcinogenesis or OC progression.

High-dose-rate mold brachytherapy for mandibular gingival squamous cell carcinoma in outpatient setting – Initial case report

High-dose-rate mold brachytherapy for mandibular gingival squamous cell carcinoma in outpatient setting – Initial case report

One Case of Cervical Lymph Node Metastasis was Reported

Objective: To report a case of cervical lymph node metastatic cancer in order to improve the understanding of this disease. Methods: To analyze the clinical features, clinical manifestations and risk factors of a case of cervical lymph node metastasis after operation of gingival squamous cell carcinoma. Results: Clinical features: The patient had a long clinical course and was diagnosed as "right cervical lymph node metastatic carcinoma", which was consistent with squamous cell carcinoma combined with morphology and history. Tissue: The tumor cells grew into nests and infiltrated, and the cell atypia was obvious, with keratinized beads and pathological mitosis. Immunohistochemistry: P63 (+), P40 (+), CK5/6 (+), P16 (-), Ki-67 hot spot index 40%. Conclusion: Cervical lymph is the aggregation area of the whole-body lymph; the whole-body lymph fluid can be drained through this. Pathology combined with immunohistochemical examination is the gold standard of diagnosis. The main treatment is surgical resection, combined with radiotherapy if necessary, and close follow-up after surgery.

Synergistic Effects of New Curcumin Analog (PAC) and Cisplatin on Oral Cancer Therapy.

Oral cancer has traditionally been treated with surgery, radiotherapy, chemotherapy, or a combination of these therapies. Although cisplatin, a chemotherapy drug, can effectively kill oral cancer cells by forming DNA adducts, its clinical use is limited due to adverse effects and chemo-resistance. Therefore, there is a need to develop new, targeted anticancer drugs to complement chemotherapy, allowing for reduced cisplatin doses and minimizing adverse effects. Recent studies have shown that 3,5-Bis (4-hydroxy-3-methoxybenzylidene)-N-methyl-4-piperidine (PAC), a new curcumin analog, possesses anticancer properties and could be considered a complementary or alternative therapy. In this study, we aimed to assess the potential complementary effects of PAC in combination with cisplatin for treating oral cancer. We conducted experiments using oral cancer cell lines (Ca9-22) treated with different concentrations of cisplatin (ranging from 0.1 μM to 1 μM), either alone or in conjunction with PAC (2.5 and 5 μM). Cell growth was measured using the MTT assay, while cell cytotoxicity was evaluated using an LDH assay. Propidium iodide and annexin V staining were employed to examine the impact on cell apoptosis. Flow cytometry was used to investigate the effects of the PAC/cisplatin combination on cancer cell autophagy, oxidative stress, and DNA damage. Additionally, a Western Blot analysis was performed to assess the influence of this combination on pro-carcinogenic proteins involved in various signaling pathways. The results demonstrated that PAC enhanced the efficacy of cisplatin in a dose-dependent manner, leading to a significant inhibition of oral cancer cell proliferation. Importantly, treatment with PAC (5 μM) alongside different concentrations of cisplatin reduced the IC50 of cisplatin tenfold. Combining these two agents increased apoptosis by further inducing caspase activity. In addition, the concomitant use of PAC and cisplatin enhances oral cancer cell autophagy, ROS, and MitoSOX production. However, combined PAC with cisplatin inhibits the mitochondrial membrane potential (ΔΨm), which is a marker for cell viability. Finally, this combination further enhances the inhibition of oral cancer cell migration via the inhibition of epithelial-to-mesenchymal transition genes, such as E-cadherin. We demonstrated that the combination of PAC and cisplatin markedly enhanced oral cancer cell death by inducing apoptosis, autophagy, and oxidative stress. The data presented indicate that PAC has the potential to serve as a powerful complementary agent to cisplatin in the treatment of gingival squamous cell carcinomas.

Deep learning methods for oral cancer detection using Raman spectroscopy

The Raman spectroscopy analysis has been applied to the detection and research of oral cancer. One of the essential works in this technique is the Raman spectral data analysis method, which is mainly divided into two categories: traditional machine learning and deep learning. Especially, the deep learning method is proved that it could obtain higher accuracy in oral cancer identification than the traditional machine learning method. The purpose of this study is to test, compare, and analyze the performance of existing classical deep neural network models (AlexNet, VGGNet, ResNet50, MobileNetV2, Transformer) that recognize multiple types of oral cancer tissues. To achieve this goal, 16,200 Raman spectra are first collected from 180 tissue samples of 90 patients who have undergone a surgical resection due to tongue squamous cell carcinoma, gingival squamous cell carcinoma, and buccal squamous cell carcinoma. Then, the models are trained and predicted at the patient level. The experimental results demonstrate that the ResNet50 has the best performance in the identification of oral cancer tissue and normal tissue with an overall accuracy rate of 92.81%, an overall precision rate of 92.93%, and an overall recall rate of 92.86%. With this foundation, we further develop a prototype intelligent detection system with above five classical deep neural network models to realize multi-types of oral cancer tissue detection. Hopefully, our work can provide a guide for oral cancer detection using the deep learning method with Raman spectroscopy analysis and promote the development of clinical diagnosis system for oral cancer. The code is available at https://github.com/ISCLab-Bistu/deep-learning-for-OSCC.

Does Gingival Carcinoma in the Elderly Correspond to a Distinct Entity?

Introduction: Age-related processes in the oral mucosa increase the risk of cancer. The gingiva is the most common localization in the upper aerodigestive tract in the elderly. The aim of this study was to compare the patient and the tumor characteristics, treatments, disease-free survival, and overall survival for gingival squamous cell carcinoma in patients less than and older than 70 years of age.

Determination of diagnostic and predictive parameters for vertical mandibular invasion in patients with lower gingival squamous cell carcinoma: A retrospective study.

Vertical mandibular invasion of lower gingival squamous cell carcinoma (LGSCC) determines the method of resection, which significantly affects the patient's quality of life. Therefore, in mandibular invasion by LGSCC, it is extremely important to monitor progression, specifically whether invasion is limited to the cortical bone or has progressed to the bone marrow. This retrospective study aimed to identify the diagnostic and predictive parameters for mandibular invasion, particularly vertical invasion, to enable appropriate selection of the method of mandibular resection. Of the patients who underwent surgery for LGSCC between 2009 and 2017, 64 were eligible for participation in the study based on tissue microarrays (TMA) from surgical specimens. This study analyzed morphological features using computed tomography (CT), and metabolic characteristics using maximum standardized uptake value (SUVmax), peak value of SUV (SUVpeak), metabolic tumor volume (MTV), and total lesion glycolysis (TLG). Moreover, immunohistochemical analysis of proteins, including parathyroid hormone-related protein (PTHrP), interleukin-6 (IL-6), E-cadherin, and programmed cell death-1 ligand 1 (PD-L1), was performed. Statistical analysis was performed using univariate logistic regression analysis with the forward selection method. The present study showed that MTV (≥2.9 cm3) was an independent diagnostic and predictive factor for positivity of mandibular invasion. Additionally, TLG (≥53.9 bw/cm3) was an independent diagnostic and predictive factor for progression to bone marrow invasion. This study demonstrated that in addition to morphological imaging by CT, the volume-based parameters of MTV and TLG on fluorine-18 fluorodeoxyglucose positron emission tomography were important for predicting pathological mandibular invasion in patients with LGSCC. A more accurate preoperative diagnosis of vertical mandibular invasion would enable the selection of appropriate surgical procedure for mandibular resection.

Intraoral ultrasonography for gingival squamous cell carcinoma: Tumor thickness and bone invasion

AbstractPurposeThe aim of this study was to evaluate the accuracy of intraoral ultrasonography (US) for gingival squamous cell carcinoma (SCC) thickness and bone invasion compared with computed tomography (CT).Materials and MethodsThis study assessed eight gingival squamous cell carcinoma patients who underwent US and CT at our hospital from April 2021 to November 2021. Grayscale and color Doppler US were performed using a liner 14 MHz transducer. Computed tomography imaging was undergone with a 16‐multidetector CT scanner using the oral and maxillofacial protocol. The relationship between US and CT on tumor thickness of gingival SCC was assessed by Pearson's rank correlation test. A p value lower than 0.05 was considered as statistically significant.ResultsPresence or absence of bone invasion was consistent in CT and US. We plotted tumor thickness of gingival SCC and observed a significant correlation between tumor thickness using CT and US.ConclusionWe showed the usefulness of to evaluate of tumor thickness and bone invasion using intraoral US is useful with gingival SCC.

Progress in the methods for evaluating depth of bone invasion and bone invasion of lower gingival squamous cell carcinoma

The depth of invasion is a new index in the 8th edition of TNM classification and staging of oral cancer. Currently, there is no standardized evaluation method for the diagnosis of bone invasion and depth of invasion in lower gingival squamous cell carcinoma (LGSCC). The evaluation of LGSCC bone invasion depth not only provides a reference for surgical margin, but also determines the choice of surgical method, and is an independent prognostic factor for predicting cervical lymphatic metastasis. At present, the main evaluation methods of LGSCC bone invasion and invasion depth include X-ray, MRI, CT, positron emission tomography(PET)/CT, PET/MRI, singlephoton emission CT(SPECT)/CT and pathological examination. In this paper, the evaluation methods and effects of LGSCC bone invasion and invasion depth are summarized, and its advantages and disadvantages are analyzed in order to provide reference for clinical application.

Corrigendum to: Gingival Squamous Cell Carcinoma Masquerading as Localized Periodontal Disease in the Maxilla: A Case Report

Corrigendum to: Gingival Squamous Cell Carcinoma Masquerading as Localized Periodontal Disease in the Maxilla: A Case Report

A retrospective study of oral maxillary squamous cell carcinomas treated from 2008-2018

<b>Introduction:</b> Controversy exists regarding the management of the clinically node negative neck (cN0) in maxillary or gingival squamous cell carcinoma (MGSCC). This study reviews cN0 MGSCC patients over a 10-year period to record the method of neck management and outcome. <b>Methods:</b> Theatre and pathology records were searched for patients diagnosed and treated for site specific cN0 MGSCC from 2008-2018. The Fisher's exact test was used for comparative analysis and survival statistics calculated using the Kaplan–Meier method and log-rank test. <b>Results:</b> 15/36 of patients had an END and 21/36 underwent observation following primary surgery. Included in these 21 patients, 5 underwent vessel access for flap anastomosis with node sampling. 13/36 of patients received PORT. The total recurrence rate was 15/36; 5/15 local, 8/15 regional and 2/15 with locoregional. Regional recurrence was similar in observed patients 5/21 compared to those who had an END 3/15. 8/15 of patients with recurrence underwent salvage surgery. Salvage rates were 3/7 in patients who received PORT and 5/8 without, with success in 2/3 and 4/5 respectively. <b>Conclusions:</b> END 5- year disease specific survival (DSS) (67%) was similar to observed patients (65%) although those with vessel access had a 80% DSS (p=0.87). pT4a END patients had a higher 5- year DSS versus observation only patients (56% vs 44%) (p=0.53). Bone invasion was significant to RL (p= 0.05). There was no advantage to having an END for the N0 neck in MGSCC and control was also achieved with a ‘watch and wait' policy followed by salvage if required.

Rare presentation of gingival squamous cell carcinoma of maxillary posterior region mimicking pyogenic granuloma in a non-smoker – A case report

Gingival Squamous cell carcinoma (GSCC) in maxilla is a rare malignant neoplasm especially when compared with mandible. The most common sites of oral carcinoma are being the lateral border of the tongue and the floor of the mouth which is followed by palate, buccal mucosa and rarely in gingiva. The clinical picture of oral carcinoma can be misguided for gingival overgrowth, desquamative lesions, traumatic ulcers or even pyogenic granuloma. Maxillary oral gingival carcinoma is a rare entity especially in a non-smoker. In this case report, a 70-year-old male patient presented with a gingival lesion in maxilla 24,25 region mimicking pyogenic granuloma without having a tobacco history. A thorough clinical, radiographical and histopathological examination was done and led to the diagnosis of GSCC and the treatment was initiated.Creating awareness among practitioners about gingival squamous cell carcinoma mimicking pyogenic granuloma in dental practice.

Is pathological T4a an independent indication of adjuvant therapy in buccal mucosal or gingival squamous cell carcinoma?

Is pathological T4a an independent indication of adjuvant therapy in buccal mucosal or gingival squamous cell carcinoma?