Search Results (28)

Head and neck cancer (HNC), the sixth most common cancer worldwide, is increasing in incidence, with oral squamous cell carcinoma (OSCC) as the predominant subtype. OSCC mainly affects middle-aged to elderly males, often occurring on the posterior lateral border of the tongue, leading to significant disfigurement and functional impairments, such as swallowing and speech difficulties. Despite advancements in understanding OSCC’s genetic and epigenetic variations, survival rates for advanced stages remain low, highlighting the need for new treatment options. Primary treatment includes surgery, often combined with radiotherapy (RT) and chemotherapy (CT). Cetuximab-based chemotherapy, targeting the overexpressed epidermal growth factor receptor (EGFR) in 80–90% of HNCs, is commonly used but correlates with poor prognosis. Additionally, monopolar spindle 1 (MPS1), a spindle assembly checkpoint (SAC) component, is a significant target due to its role in genomic fidelity during mitosis and its overexpression in several cancers. This review explores EGFR and MPS1 as therapeutic targets in HNC, analyzing their molecular mechanisms and the effects of their inhibition on cancer cells. It also highlights the promise of combinatorial approaches, such as microtubule-targeting agents (MTAs) and antimitotic agents, in improving HNC therapies, patient outcomes, and survival rates. Full article

This study investigated the mechanism by which fucoxanthin acts as a novel ferroptosis inducer to inhibit tongue cancer. The MTT assay was used to detect the inhibitory effects of fucoxanthin on SCC−25 human tongue squamous carcinoma cells. The levels of reactive oxygen species (ROS), mitochondrial membrane potential (MMP), glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), and total iron were measured. Reverse transcription–quantitative polymerase chain reaction (RT−qPCR) and Western blotting were used to assess glutathione peroxidase 4 (GPX4), nuclear factor erythroid 2−related factor 2 (Nrf2), Keap1, solute carrier family 7 member 11 (SLC7A11), transferrin receptor protein 1 (TFR1), p53, and heme oxygenase 1 (HO−1) expression. Molecular docking was performed to validate interactions. Compared with the control group, the activity of fucoxanthin−treated SCC−25 cells significantly decreased in a dose− and time−dependent manner. The levels of MMP, GSH, and SOD significantly decreased in fucoxanthin−treated SCC−25 cells; the levels of ROS, MDA, and total iron significantly increased. mRNA and protein expression levels of Keap1, GPX4, Nrf2, and HO−1 in fucoxanthin−treated cells were significantly decreased, whereas levels of TFR1 and p53 were significantly increased, in a concentration−dependent manner. Molecular docking analysis revealed that binding free energies of fucoxanthin with p53, SLC7A11, GPX4, Nrf2, Keap1, HO−1, and TFR1 were below −5 kcal/mol, primarily based on active site hydrogen bonding. Our findings suggest that fucoxanthin can induce ferroptosis in SCC−25 cells, highlighting its potential as a treatment for tongue cancer. Full article

This study protocol for a prospective, multicenter, diagnostic, clinical trial describes the integration of transoral and transcervical ultrasonography (US) in the initial clinical work-up of patients referred to tertiary head and neck cancer centers with suspected oropharyngeal cancer. The study evaluates the blinded detection rate of oropharyngeal tumors and their US-estimated size and T-stage before histopathology and cross-sectional imaging are available. Magnetic resonance imaging (MRI) scans will be prospectively rated while blinded to T-site histopathology and US. The primary outcome measures of diagnostic accuracy, including sensitivity, specificity, positive and negative predictive values, and overall accuracy, will be reported for both US and MRI. A sub-analysis of prospectively rated 18F-Fluorodeoxyglucose (FDG) positron emission tomography/computerized tomography (PET/CT) scans in patients with clinically suspected unknown primary tumors will also be compared to US and MRI. Secondary outcome measures, including a comparison of tumor size estimation between US, MRI, and CT, will also be reported. This prospective multicenter study will provide clinically impactful information regarding the use of transoral and transcervical US for the diagnostic work-up of oropharyngeal cancer. Full article

Oral squamous cell carcinoma (OSCC) accounts for more than 90% of oral malignancies. Despite numerous advancements in understanding its biology, the mean five-year survival rate of OSCC is still very poor at about 50%, with even lower rates when the disease is detected at later stages. We investigate the use of clinical photographic images taken by common smartphones for the automated detection of OSCC cases and for the identification of suspicious cases mimicking cancer that require an urgent biopsy. We perform a retrospective study on a cohort of 1470 patients drawn from both hospital records and online academic sources. We examine various deep learning methods for the early detection of OSCC cases as well as for the detection of suspicious cases. Our results demonstrate the efficacy of these methods in both tasks, providing a comprehensive understanding of the patient’s condition. When evaluated on holdout data, the model to predict OSCC achieved an AUC of 0.96 (CI: 0.91, 0.98), with a sensitivity of 0.91 and specificity of 0.81. When the data are stratified based on lesion location, we find that our models can provide enhanced accuracy (AUC 1.00) in differentiating specific groups of patients that have lesions in the lingual mucosa, floor of mouth, or posterior tongue. These results underscore the potential of leveraging clinical photos for the timely and accurate identification of OSCC. Full article

Background: Radiation therapy (RT) is a mainstay for the treatment of head and neck (HN) cancers, with 80% of patients receiving such treatment. Radiation-induced malignancies represent a life-threatening long-term effect of RT, with an incidence of 0.5% to 15%. Case Description: After 13 years, a 33-year-old woman treated with chemo-radiotherapy for nasopharyngeal carcinoma developed a locally advanced, radiation-induced, p16-negative oropharyngeal squamous cell carcinoma (SCC) at the base of the tongue. Chemo/immunotherapy was administered as a first-line treatment. Given the optimal response and the feasibility of surgery, after three cycles, the patient underwent a total glossectomy, bilateral neck dissection, and reconstruction with a thoraco-dorsal free flap. A histological examination found SCC with a residual cancer burden of 70% and free margins. Discussion: The mechanisms responsible for carcinogenesis after RT are still not completely clear. Diagnosis may be challenging due to the previous treatment; growth patterns are unusual, and lymphotropism is lower. Prognosis is usually poor since surgical resectability is often not achievable. Conclusions: Radiation-induced malignancies are difficult to treat. Patient management should always be discussed at a multidisciplinary level. Future research is needed to assess whether the promising results of clinical studies with pre-operative immunotherapy in locally advanced HN SCC patients may be translated into radiation-induced cancers. Full article

The base of the tongue (BOT) is the second most common site for squamous cell carcinoma (SCC) in the oropharynx. There are currently no clear guidelines for the management of BOT SCC. Our main objective was to compare the oncological outcomes of two minimally invasive approaches, transoral laser microsurgery (TLM) and transoral robot-assisted surgery (TORS). This was a retrospective French GETTEC (Groupe d’Études des Tumeurs de la Tête et du Cou) multicenter study of patients with BOT SCC removed surgically either by TLM or TORS between 2005 and 2021. The study group included 16 patients treated by TLM and 38 by TORS, with median follow-up times of 14.4 and 37.2 months, respectively. The overall survival (OS) rates at 2 and 3 years were 67% in the TLM group and 90% at 2 years and 86% at 3 years in the TORS group (p = 0.42, p = 0.20). There was no significant difference in recurrence-free survival (RFS) between the two techniques after 2 and 3 years. The tumors removed by TORS were significantly larger. Operative times were significantly shorter in the TLM group. There were no differences in feeding resumption; none of the patients in the TLM group required a tracheotomy. Postoperative hemorrhagic complication rates were similar in the two groups (12% for TLM and 13% for TORS). Both TORS and TLM showed encouraging oncological, functional, and safety results in BOT SCC even in recurrence or second primary cancer patients, without a technique being found superior in terms of OS or RFS. Tumors removed by TORS were larger without an increase in postoperative bleeding, extending the possibilities of transoral treatment. Full article

The natural product Kochiae Fructus (KF) is the ripe fruit of Kochia scoparia (L.) Schrad and is renowned for its anti-inflammatory, anticancer, anti-fungal, and anti-pruritic effects. This study examined the anticancer effect of components of KF to assess its potential as an adjuvant for cancer treatment. Network-based pharmacological and docking analyses of KF found associations with oral squamous cell carcinoma. The molecular docking of oleanolic acid (OA) with LC3 and SQSTM1 had high binding scores, and hydrogen binding with amino acids of the receptors suggests that OA is involved in autophagy, rather than the apoptosis pathway. For experimental validation, we exposed SCC-15 squamous carcinoma cells derived from a human tongue lesion to KF extract (KFE), OA, and cisplatin. The KFE caused SCC-15 cell death, and induced an accumulation of the autophagy marker proteins LC3 and p62/SQSTM1. The novelty of this study lies in the discovery that the change in autophagy protein levels can be related to the regulatory death of SCC-15 cells. These findings suggest that KF is a promising candidate for future studies to provide insight into the role of autophagy in cancer cells and advance our understanding of cancer prevention and treatment. Full article

Oropharyngeal squamous cell carcinoma (OPSCC) comprises cancers of the tonsils, tongue base, soft palate, and uvula. The staging of oropharyngeal cancers varies depending upon the presence or absence of human papillomavirus (HPV)-directed pathogenesis. The incidence of HPV-associated oropharyngeal cancer (HPV + OPSCC) is expected to continue to rise over the coming decades. PET/CT is a useful modality for the diagnosis, staging, and follow up of patients with oropharyngeal cancers undergoing treatment and surveillance. Full article

Background: Tongue squamous cell carcinoma (TSCC) represents one of the major subsets of head and neck cancer, which is characterized by unfavorable prognosis, frequent lymph node metastasis, and high mortality rate. The molecular events regulating tongue tumorigenesis remain elusive. In this study, we aimed to identify and evaluate immune-related long non-coding RNAs (lncRNAs) as prognostic biomarkers in TSCC. Methods: The lncRNA expression data for TSCC were obtained from The Cancer Genome Atlas (TCGA) and the immune-related genes were downloaded from the Immunology Database and Analysis Portal (ImmPort). Pearson correlation analysis was performed to identify immune-related lncRNAs. The TCGA TSCC patient cohort was randomly divided into training and testing cohorts. In the training cohort, univariate and multivariate Cox regression analyses were used to determining key immune-related lncRNAs, which were then validated through Cox regression analysis, principal component analysis (PCA), and receiver operating characteristic (ROC) analysis in the testing cohort. Results: Six immune-related signature lncRNAs (MIR4713HG, AC104088.1, LINC00534, NAALADL2-AS2, AC083967.1, FNDC1-IT1) were found to have prognostic value in TSCC. Multivariate and univariate cox regression analyses showed that the risk score based on our six-lncRNA model, when compared to other clinicopathological factors (age, gender, stage, N, T), was an important indicator of survival rate. In addition, Kaplan–Meier survival analysis demonstrated significantly higher overall survival in the low-risk patient group than the high-risk patient group within both training and testing cohorts. The ROC analysis indicated that the AUCs for 5-year overall survival were 0.790, 0.691, and 0.721, respectively, for training, testing, and entire cohorts. Finally, PCA analysis demonstrated that the high-risk and low-risk patient groups presented significant deviation regarding their immune status. Conclusions: A prognostic model based on six immune-related signature lncRNAs was established. This six-lncRNA prognostic model has clinical significance and may be helpful in the development of personalized immunotherapy strategies. Full article

Background: The prevalence and incidence of oropharyngeal squamous cell carcinomas (OPSCCs) driven by human papillomavirus (HPV) infection are increasing worldwide, being higher in high-income countries. However, data from Italy are scanty. p16^INK4a overexpression is the standard in determining HPV-driven carcinogenesis, but disease prevalence impacts on its positive predictive value. Methods: This is a multicenter retrospective study enrolling 390 consecutive patients aged ≥18 years, diagnosed with pathologically confirmed OPSCC in Northeastern Italy between 2000 and 2022. High-risk HPV-DNA and p16^INK4a status were retrieved from medical records or evaluated in formalin-fixed paraffin-embedded specimens. A tumor was defined as HPV-driven when double positive for high-risk HPV-DNA and p16^INK4a overexpression. Results: Overall, 125 cases (32%) were HPV-driven, with a significant upward temporal trend from 12% in 2000–2006 to 50% in 2019–2022. The prevalence of HPV-driven cancer of the tonsil and base of the tongue increased up to 59%, whereas it remained below 10% in other subsites. Consequently, the p16^INK4a positive predictive value was 89% for the former and 29% for the latter. Conclusions: The prevalence of HPV-driven OPSCC continued to increase, even in the most recent period. When using p16^INK4a overexpression as a surrogate marker of transforming HPV infection, each institution should consider the subsite-specific prevalence rates of HPV-driven OPSCC as these significantly impact on its positive predictive value. Full article

Oral squamous cell carcinoma (OSCC) is characterized by poor survival, mostly due to local invasion, loco-regional recurrence, and metastasis. Given that the weakening of cell-to-cell adhesion is a feature associated with the migration and invasion of cancer cells, different studies have explored the prognostic utility of cell adhesion molecules such as E-cadherin (E-cad). This study aims to summarize current evidence in a meta-analysis, focusing on the prognostic role of E-cad in OSCC. To find studies meeting inclusion criteria, Scopus, Web of Science, EMBASE, Medline, and OpenGrey databases were systematically assessed and screened. The selection process led to 25 studies, which were considered eligible for inclusion in the meta-analysis, representing a sample of 2553 patients. E-cad overexpression was strongly associated with longer overall survival (OS) with Hazard Ratio (HR)  = 0.41 95% confidence interval (95% CI) (0.32–0.54); p < 0.001 and disease-free survival with HR 0.47 95% CI (0.37–0.61); p < 0.001. In terms of OS, patients with tongue cancer experienced better survivability when expressing E-cad with HR 0.28 95% CI (0.19–0.43); p < 0.001. Globally, our findings indicate the prognostic role of the immunohistochemical assessment of E-cad in OSCC and its expression might acquire a different role based on the oral cavity subsites. Full article

Oral squamous cell carcinoma (OSCC) is a common human tumor, that originates from buccal mucosa and the tongue, associated with a high mortality rate. Currently, the treatment for OSCC involves surgery, chemotherapy and radiotherapy; however, survival outcomes for OSCC patients remain poor. For this reason, it is necessary to investigate new therapeutic strategies to counteract the progression of OSCC. In this study, we aimed to evaluate the role of dimethyl fumarate (DMF) in modulation of OSCC progression, both in vitro and in an in vivo orthotopic xenograft model. In vitro results revealed that DMF was able to reduce the expression of anti-apoptotic factors as BCL-2 and increased the expression of pro-apoptotic factors as Bax, Caspase-3 and BID. DMF appears to be involved in the modulation of oxidative stress mediators, such as MnSOD and HO-1. Furthermore, DMF showed to reduce the migratory ability of tumor cells and to modulate the expression of markers of epithelial-mesenchymal transition (EMT), as N-cadherin and E-cadherin. The in vivo study confirmed the data obtained in vitro significantly decreasing tumor mass and also reducing oxidative stress and apoptosis. Therefore, based on these results, the use of DMF could be considered a promising strategy to counteract oral cancer progression. Full article

Head and neck squamous cell carcinomas (HNSCC) caused by infections with high-risk human papillomaviruses (HPV) are responsible for an increasing number of head and neck cancers, particularly in the oropharynx. Despite the significant biological differences between HPV-driven and HPV-negative HNSCC, treatment strategies are similar and not HPV targeted. HPV-driven HNSCC are known to be more sensitive to treatment, particularly to radiotherapy, which is at least partially due to HPV-induced immunogenicity. The development of novel therapeutic strategies that are specific for HPV-driven cancers requires tumor models that reflect as closely as possible the characteristics and complexity of human tumors and their response to treatment. Current HPV-positive cancer models lack one or more hallmarks of their human counterpart. This study presents the development of a new HPV16 oncoprotein-dependent tumor model in MHC-humanized mice, modeling the major biologic features of HPV-driven tumors and presenting HLA-A2-restricted HPV16 epitopes. Furthermore, this model was developed to be orthotopic (base of tongue). Thus, it also reflects the correct tumor microenvironment of HPV-driven HNSCC. The cancer cells are implanted in a manner that allows the exact control of the anatomical location of the developing tumor, thereby homogenizing tumor growth. In conclusion, the new model is suited to study HPV16-specific therapeutic vaccinations and other immunotherapies, as well as tumor-targeted interventions, such as surgery or radiotherapy, or a combination of all these modalities. Full article

This study aimed to develop an apparent diffusion coefficient (ADC) ratio-based prognostic model to predict the recurrence and disease-free survival (DFS) of oral tongue squamous cell carcinoma (OTSCC). A total of 188 patients with cT1-2 oral tongue squamous cell carcinoma were enrolled retrospectively. Clinical and laboratory data were extracted from medical records. The ADC values were measured at the regions of interest of the tumor and non-tumor tissues of the MRI images, and the ADC ratio was used for comparison between the patient with recurrence (n = 83 case, 44%) and patients without recurrence (n = 105 cases, 56%). Cox proportional hazards models were generated to analyze the risk factors of cancer recurrence. A nomogram was developed based on significant risk factors to predict 1-, 5- and 10-year DFS. The receiver operator characteristic (ROC) curves of predictors in the multivariable Cox proportional hazards prognostic model were generated to predict the recurrence and DFS. The integrated areas under the ROC curve were calculated to evaluate discrimination of the models. The ADC ratio, tumor thickness and lymph node ratio were reliable predictors in the final prognostic model. The final model had a 71.1% sensitivity and an 81.0% specificity. ADC ratio was the strongest predictor of cancer recurrence in prognostic performance. Discrimination and calibration statistics were satisfactory with C-index above 0.7 for both model development and internal validation. The calibration curve showed that the 5- and 10-year DFS predicted by the nomogram agreed with actual observations. Full article

A growing proportion of oropharyngeal squamous cell carcinomas (OPSCC) are associated with infection by high-risk human papillomavirus (HPV). For reasons that remain largely unknown, HPV+OPSCC is significantly more common in men than in women. This study aims to determine the incidence of OPSCC in male and female HPV16-transgenic mice and to explore the role of female sex hormone receptors in the sexual predisposition for HPV+ OPSCC. The tongues of 30-weeks-old HPV16-transgenic male (n = 80) and female (n = 90) and matched wild-type male (n = 10) and female (n = 10) FVB/n mice were screened histologically for intraepithelial and invasive lesions in 2017 at the Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), Portugal. Expression of estrogen receptors alpha (ERα) and beta (ERβ), progesterone receptors (PR) and matrix metalloproteinase 2 (MMP2) was studied immunohistochemically. Collagen remodeling was studied using picrosirius red. Female mice showed robust ERα and ERβ expression in intraepithelial and invasive lesions, which was accompanied by strong MMP2 expression and marked collagen remodeling. Male mice showed minimal ERα, ERβ and MMP2 expression and unaltered collagen patterns. These results confirm the association of HPV16 with tongue base cancer in both sexes. The higher cancer incidence in female versus male mice contrasts with data from OPSCC patients and is associated with enhanced ER expression via MMP2 upregulation. Full article