Search Results (16)

Head and neck squamous cell carcinomas (HNSCCs) that develop from the mucosal epithelium in the oral cavity, pharynx, and larynx are a heterogeneous group of malignant tumors. A lack of appropriate screening and diagnostic methods leads to late diagnoses, with the majority of patients having locally advanced disease, which is associated with a high risk of local recurrence and a poor prognosis and is usually treated with combination therapies. Biomarkers for predicting the therapy response and risk of recurrence in HNSCC patients are urgently needed. Liquid biopsy, e.g., the profiling of circulating biomarkers in bodily fluids, is a promising approach with increasing utility in the early detection and diagnosis of cancer, monitoring cancer progression, patient stratification and treatment selection, detecting minimal residual disease (MRD), and predicting recurrence across different cancer types, including HNSCC. Among liquid biomarkers, circulating tumor DNA (ctDNA), which is based on detecting tumor-specific mutations, insertions/deletions, copy number alterations, and methylation, is the most promising transformative tool in cancer management and personalized cancer treatment. In this review, we provide an update of recent data on the role of non-viral ctDNA in the management of HNSCC patients. Accumulating data suggests the enormous potential of ctDNA profiling by serial sampling during and after definitive therapy in detecting MRD and predicting recurrence in HNSSC patients treated with a single treatment modality (surgery or radiotherapy) or with combination therapies, including immune-checkpoint-inhibitor-based immunotherapy. By incorporating the latest immunotherapy trials and organizing the data by the treatment modality, this review offers a novel perspective not found in previous surveys. Full article

Background: Head and neck squamous cell carcinoma (HNSC) is the most prevalent cancer in the head and neck region, originating from the mucosal epithelium of the oral cavity, pharynx, and larynx. The solute carrier (SLC) transporter superfamily, consisting of over 400 proteins across 65 families, plays a crucial role in cellular functions and presents promising targets in precision oncology. This study aims to analyze the expression of SLC transporters in HNSC and their potential as biomarkers and therapeutic targets. Methods: We leveraged mRNA and protein expression data from The Cancer Genome Atlas (TCGA) and The Human Protein Atlas (HPA) to examine SLC transporter expression in HNSC. Gene Set Enrichment Analysis (GSEA) was conducted to assess the involvement of SLC transporters in various oncogenic pathways. Results: Significant upregulation of SLC transporters was observed in tumor tissues compared to normal tissues, with notable increases in SLC16A3, SLC53A1, SLC25A32, and SLC2A3. This upregulation correlated with poorer overall survival (OS) and disease-specific survival (DSS). GSEA revealed that these transporters are significantly involved in critical oncogenic pathways, including epithelial-mesenchymal transition (EMT), angiogenesis, and hypoxia, which are vital for cancer progression and metastasis. Conclusions: The study identifies SLC transporters as potential biomarkers and therapeutic targets in HNSC. Targeting these transporters with small molecule inhibitors could disrupt essential supply routes for cancer cells, enhancing treatment efficacy and improving patient outcomes. This study paves the way for developing SLC-based target therapies in precision oncology, with the goal of improving survival rates for patients with HNSC. Full article

Head and neck cancer (HNC) represents a significant global health challenge, with squamous cell carcinomas (SCCs) accounting for approximately 90% of all HNC cases. These malignancies, collectively referred to as head and neck squamous cell carcinoma (HNSCC), originate from the mucosal epithelium lining the larynx, pharynx, and oral cavity. The primary risk factors associated with HNSCC in economically disadvantaged nations have been chronic alcohol consumption and tobacco use. However, in more affluent countries, the landscape of HNSCC has shifted with the identification of human papillomavirus (HPV) infection, particularly HPV-16, as a major risk factor, especially among nonsmokers. Understanding the evolving risk factors and the distinct biological behaviors of HPV-positive and HPV-negative HNSCC is critical for developing targeted treatment strategies and improving patient outcomes in this complex and diverse group of cancers. Accurate diagnosis of HPV-positive HNSCC is essential for developing a comprehensive model that integrates the molecular characteristics, immune microenvironment, and clinical outcomes. The aim of this comprehensive review was to summarize the current knowledge and advances in the identification of DNA, RNA, and protein biomarkers in bodily fluids and tissues that have introduced new possibilities for minimally or non-invasive cancer diagnosis, monitoring, and assessment of therapeutic responses. Full article

Head and neck squamous cell carcinoma (HNSCC) is the most common histological form of head and neck tumors (HNTs), which originate from the epithelium of the lips and oral cavity, pharynx, larynx, salivary glands, nasal cavity, and sinuses. The main risk factors include consumption of tobacco in all forms and alcohol, as well as infections with high-risk human papillomaviruses or the Epstein–Barr virus. Regardless of the etiological agent, the risk of developing different types of HNTs is from two to more than six times higher in males than in females. The reason for such disparities probably lies in a combination of both biological and psychosocial factors. Therefore, it is hypothesized that exposure to female sex hormones, primarily estrogen, provides women with protection against the formation and metastasis of HNTs. In this review, we synthesized available knowledge on the role of estrogen and estrogen receptors (ERs) in the development and progression of HNTs, with special emphasis on membrane ERs, which are much less studied. We can summarize that in addition to epidemiologic studies unequivocally pointing to the protective effect of estrogen in women, an increased expression of both nuclear ERs, ERα, and ERβ, and membrane ERs, ERα36, GPER1, and NaV1.2, was present in different types of HNSCC, for which anti-estrogens could be used as an effective therapeutic approach. Full article

Head and neck squamous cell carcinoma (HNSCC) is a group of malignancies, involving the oral cavity, pharynx, hypopharynx, larynx, nasal cavity, and salivary glands, that together compose the seventh most common cancer diagnosis worldwide. With 890,000 new cases and 450,000 deaths annually per GLOBOCAN estimates, HNSCC accounts for roughly 4.5% of cancer diagnoses and deaths. In the developing world, the incidence of HNSCC is growing with increasing consumption of tobacco (smoked or chewed), alcohol, and areca nut (betel quid). Alcohol and tobacco have a synergistic effect, with the heavy consumption of both increasing HNSCC risk 40-fold. In developed nations, HPV-related HNSCC surpasses tobacco- and alcohol-related disease. HPV-related HNSCC more commonly affects the oropharynx, hypopharynx, and larynx than the oral cavity, and is associated with a significantly longer median survival (130 months vs. 20 months). Discrepancies in etiology as well as disparities in lifestyle choices and access to healthcare may account for the greater incidence and poorer survival of HNSCC among minority and lower-socioeconomic-status communities in developed nations. Pharmacotherapy and counseling together have been shown to be effective in promoting smoking and alcohol cessation. Education on cancer risk and community engagement have reduced areca nut consumption in Asia as well as in diaspora communities. HPV vaccination, starting at age 11–12 for both sexes, has been shown to reduce the prevalence of high-risk HPV serologies and prevent pre-cancerous lesions of the cervix, vagina, and vulva. As of 2020, 58.6% of eligible adolescents in the US have received the full two-vaccine series. Increased adoption of vaccination, education on safe sex practices, and routine visual oral screening for high-risk patients would curb growing HNSCC incidence in developed nations. Full article

Head and neck (HN) squamous cell carcinomas (SCCs) originate from the epithelial cells of the mucosal linings of the upper aerodigestive tract, which includes the oral cavity, the pharynx, the larynx, and the sinonasal cavities. There are many associated risk factors, including alcohol drinking coupled with tobacco use, which accounts for 70% to 80% of HNSCCs. Human papilloma virus (HPV) is another independent risk factor for oropharyngeal SCC, but it is only a minor contributor to oral cavity SCC (OSCC). Betel quid chewing is also an established risk factor in southeast Asian countries. However, OSCC, and especially oral tongue cancer, incidence has been reported to be increasing in several countries, suggesting risk factors that have not been identified yet. This review summarizes the established risk factors for oral cavity squamous cell carcinomas and examines other undemonstrated risk factors for HNSCC. Full article

Head and neck squamous cell carcinoma (HNSCC) is a term collectively used to describe all cancers that develop in the oral and nasal cavities, the paranasal sinuses, the salivary glands, the pharynx, and the larynx. The majority (75%) of all newly diagnosed cases are observed in patients with locally advanced and aggressive disease, associated with significant relapse rates (30%) and poor prognostic outcomes, despite advances in multimodal treatment. Consequently, there is an unmet need for the identification and application of tools that would enable diagnosis at the earliest possible stage, accurately predict prognostic outcomes, contribute to the timely detection of relapses, and aid in the decision for therapy selection. Recent evidence suggests that DNA methylation can alter the expression of genes in a way that it favors tumorigenesis and tumor progression in HNSCC, and therefore represents a potential source for biomarker identification. This study summarizes the current knowledge on how abnormally methylated DNA profiles in HNSCC patients may contribute to the pathogenesis of HNSCC and designate the methylation patterns that have the potential to constitute clinically valuable biomarkers for achieving significant advances in the management of the disease and for improving survival outcomes in these patients. Full article

Head and neck squamous cell carcinoma (HNSCC) arises from the mucosal epithelium in the oral cavity, pharynx, sino-nasal region, and larynx. Laryngeal squamous cell carcinoma (LSCC) represents one-third of all head and neck cancers. Dysregulated RNA-related pathways define an important molecular signature in this aggressive carcinoma. The Survival Motor Neuron (SMN) protein regulates fundamental aspects of the RNA metabolism but, curiously, its role in cancer is virtually unknown. For the first time, here, we focus on the SMN in the cancer context. We conducted a pilot study in a total of 20 patients with LSCC where the SMN was found overexpressed at both the protein and transcript levels. By a cellular model of human laryngeal carcinoma, we demonstrated that the SMN impacts cancer-relevant behaviors and perturbs key players of cell migration, invasion, and adhesion. Furthermore, in LSCC we showed a physical interaction between the SMN and the epidermal growth factor receptor (EGFR), whose overexpression is an important feature in these tumors. This study proposes the SMN protein as a novel therapeutic target in LSSC and likely in the whole spectrum of HNSCC. Overall, we provide the first analysis of the SMN in human cancer. Full article

The “Cellular Dissociation Grade” (CDG) is based on tumor cell budding and cell nest size. Many studies have examined the CDG in squamous cell carcinomas of other organs such as the lungs, oral cavity, pharynx, larynx, cervix and esophagus. In this study, the CDG was examined in 109 cases of invasive penile squamous cell carcinoma that were treated at the University Medicine Rostock between 2014 and 2022. Furthermore, its correlation with the pathologic status of regional lymph nodes (pN) as the main prognostic factor was verified. Finally, cellular dissociation grading was compared with classic WHO grading. The results showed that pN in penile squamous cell carcinoma showed a highly significant association with the CDG and no statistically significant association with WHO grading. These results support the notion that cellular dissociation grading is an important prognostic factor for squamous cell carcinoma. Full article

Head and neck squamous cell carcinoma (HNSCC) represents a heterogeneous malignant disease of the oral cavity, pharynx, and larynx. Although cigarette smoking, alcohol abuse, and aging are well-established associated factors for HNSCC, their respective influence on immunologic alterations of monocyte subsets or T-cell compositions in the peripheral blood has not yet been fully unveiled. Using flow cytometry, whole blood measurements of CD14/CD16 monocyte subsets and analyses of T-cell subsets in isolated PBMC fractions were carried out in 64 HNSCC patients in view of their tobacco and alcohol consumption, as well as their age, in comparison to healthy volunteers. Flow cytometric analysis revealed significantly increased expression of monocytic CD11b, as well as significantly decreased expression levels of CX3CR1 on classical and intermediate monocyte subsets in smoking-related and in alcohol-related HNSCC patients compared to healthy donors. Peripheral monocytes revealed an age-correlated significant decrease in PD-L1 within the entirety of the HNSCC cohort. Furthermore, we observed significantly decreased abundances of CD8⁺ effector memory T cells in active-smoking HNSCC patients and significantly increased percentages of CD8⁺ effector T cells in alcohol-abusing patients compared to the non-smoking/non-drinking patient cohort. Our data indicate an enhanced influence of smoking and alcohol abuse on the dynamics and characteristics of circulating monocyte subsets and CD4/CD8 T-cell subset proportions, as well as an age-related weakened immunosuppression in head and neck cancer patients. Full article

The anti-PD1 monoclonal antibody pembrolizumab improves survival in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). Patients with locoregional, pathologically high-risk HNSCC recur frequently despite adjuvant cisplatin–radiation therapy (CRT). Targeting PD1 may reverse immunosuppression induced by HNSCC and CRT. We conducted a phase I trial with an expansion cohort (n = 20) to determine the recommended phase II schedule (RP2S) for adding fixed-dose pembrolizumab to standard adjuvant CRT. Eligible patients had resected HPV-negative, stage III–IV oral cavity, pharynx, or larynx HNSCC with extracapsular nodal extension or positive margin. RP2S was declared if three or fewer dose-limiting toxicities (DLT) occurred in a cohort of 12. DLT was defined as grade 3 or higher non-hematologic adverse event (AE) related to pembrolizumab, immune-related AE requiring over 2 weeks of systemic steroids, or unacceptable RT delay. A total of 34 patients enrolled at 23 NRG institutions. During the first cohort, only one DLT was observed (fever), thus RP2S was declared as pembrolizumab 200 mg every 3 weeks for eight doses, starting one week before CRT. During expansion, three additional DLTs were observed (wound infection, diverticulitis, nausea). Of the 34 patients, 28 (82%) received five or more doses of pembrolizumab. This regimen was safe and feasible in a cooperative group setting. Further development is warranted. Full article

Melissa officinalis is a medicinal herb with an extensive pharmacological profile that has been proven to have beneficial effects in oral and gastrointestinal disorders. However, the effects of this plant in oral, pharyngeal, and colorectal malignancies, types of cancer with an increased incidence in recent years, are less investigated. The present study aims to evaluate the pharmacological profile of a Melissa officinalis total extract for potential benefits in oral, pharynx and colorectal carcinoma. The LC-MS profile of MO total extract (MOte) indicated a rich content in polyphenols, data that support the potent antioxidant capacity exhibited and the antimicrobial activity against both Gram-negative and Gram-positive bacteria. In addition, MOte triggered a dose-dependent and selective decrease in the viability of tumor cells (tongue and pharynx squamous cell carcinomas, and colorectal adenocarcinoma), with the most significant effect being recorded at 100 μg/mL. At the same concentration, MOte exhibited an antiangiogenic effect by inhibiting the process of angiogenesis in ovo. Overall, our findings support the potential benefits of Melissa officinalis leaf total extract as a valuable candidate for the prophylaxis of oral, pharyngeal and colorectal neoplasms. Full article

Head and neck squamous cell carcinomas (HNSCC) are among the most common and lethal tumors worldwide, occurring mostly in oral cavity, pharynx, and larynx tissues. The squamous epithelia homeostasis is supported by the extracellular matrix (ECM), and alterations in this compartment are crucial for cancer development and progression. Laminin is a fundamental component of ECM, where it represents one of the main components of basement membrane (BM), and data supporting its contribution to HNSCC genesis and progression has been vastly explored in oral cavity squamous cell carcinoma. Laminin subtypes 111 (LN-111) and 332 (LN-332) are the main isoforms associated with malignant transformation, contributing to proliferation, adhesion, migration, invasion, and metastasis, due to its involvement in the regulation of several pathways associated with HNSCC carcinogenesis, including the activation of the EGFR/MAPK signaling pathway. Therefore, it draws attention to the possibility that laminin may represent a convergence point in HNSCC natural history, and an attractive potential therapeutic target for these tumors. Full article

Head and neck cancers are the seventh most frequent malignancy worldwide, consisting of a heterogeneous group of cancers that develop in the oral cavity, pharynx, and larynx, with head and neck squamous cell carcinoma (HNSCC) being the most common pathology. Due to limitations with screening and physical examination, HNSCC often presents in advanced disease states and is thus associated with poor survival. In this setting, liquid biopsies, or obtaining patient bodily fluid samples for cancer diagnosis and prognosis, may play a dramatic role in optimizing care for HNSCC patients. In recent years, there have been dramatic advancements in investigations focused on optimizing and implementing liquid biopsies in general, and specifically for HNSCC patients. Moving forward, there remain significant challenges in liquid biopsy technological development, as well as opportunities for the development of HNSCC liquid biopsy clinical trials and treatment paradigms. In this review, we discuss the current state of liquid biopsy technologies via circulating tumor cells, circulating tumor DNA and exosomes, approaches in head and neck cancer, challenges to optimization and application of liquid biopsies for clinical study, and future prospects for this field of research as it applies to head and neck cancer. Full article

This retrospective multi-center analysis aimed to assess the clinical response and stabilizing effects of palliative radiotherapy (RT) for spinal bone metastases (SBM) in head and neck cancer (HNC), and to establish potential predictive factors for stability and overall survival (OS). Patients included in this analysis were treated at the University Hospitals of Mainz, Freiburg, and Heidelberg between 2001 and 2019. Clinical information was taken from the medical records. The stability of affected vertebral bodies was assessed according to the validated spine instability neoplastic score (SINS) based on CT-imaging before RT, as well as 3 and 6 months after RT. OS was quantified as the time between the start of palliative RT and death from any cause or last follow-up. Potential predictive factors for stability and OS were analyzed using generalized estimating equations and Cox regression for time-varying covariates to take into account multiple observations per patient. The mean follow-up time of 66 included patients after the first palliative RT was 8.1 months (range 0.3–85.0 months). The majority of patients (70%; n = 46) had squamous cell carcinomas (SCC) originating from the pharynx, larynx and oral cavity, while most of the remaining patients (26%; n = 17) suffered from salivary glands tumors. A total of 95 target volumes including 178 SBM were evaluated that received a total of 81 irradiation series. In patients with more than one metastasis per irradiated region, only the most critical bone metastasis was analyzed according to the SINS system. Prior to RT, pain and neurologic deficits were present in 76% (n = 72) and 22% (n = 21) of irradiated lesions, respectively, and 68% of the irradiated lesions (n = 65) were assessed as unstable or potentially unstable prior to RT. SBM-related pain symptoms and neurologic deficits responded to RT in 63% and 47% of the treated lesions, respectively. Among patients still alive at 3 and 6 months after RT with potentially unstable or unstable SBM, a shift to a better stability class according to the SINS was observed in 20% and 33% of the irradiated SBM, respectively. Pathological fractures of SBM were frequently detected before the start of irradiation (43%; n = 41), but after RT, new fractures or increasing vertebral body sintering within the irradiated region occurred rarely (8%; n = 8). A pathological fracture before RT was negatively associated with stabilization 6 months after RT (OR 0.1, 95% CI 0.02–0.49, p = 0.004), while a Karnofsky performance score (KPS) ≥ 70% was associated positively with a stabilization effect through irradiation (OR 6.09, 95% CI 1.68–22.05, p = 0.006). Mean OS following first palliative RT was 10.7 months, and the KPS (≥70% vs. <70%) was shown to be a strong predictive factor for OS after RT (HR 0.197, 95% CI 0.11–0.35, p < 0.001). There was no significant difference in OS between patients with SCC and non-SCC. Palliative RT in symptomatic SBM of HNC provides sufficient symptom relief in the majority of patients, while only about one third of initially unstable SBM show re-stabilization after RT. Since patients in our multi-center cohort exhibited very limited OS, fractionation schemes should be determined depending on the patients’ performance status. Full article