Search Results (20)

Background and Objectives: Despite the distinct entity of both p16-positive and p16-negative squamous cell carcinoma unknown primary in the head and neck (HNSCCUP), the diagnostic workup did not differ. The aim of the study was to determine the effectiveness of palatine tonsillectomy in the identification of primary tumours in two groups of p16-positive and p16-negative HNSCCUP. Materials and Methods: Patients with HNSCCUP managed in two tertiary care referral centres from 1 January 2014 to 31 December 2020 were analysed retrospectively. Results: Sixty-six patients with HNSCCUP diagnosis were included consecutively. HPV status of metastatic cervical lymph nodes using immunohistochemistry with p16 protein was available for all patients. The proportion of both p16-positive and p16-negative groups was not significantly different (p = 0.242). Of the 39 patients who underwent palatine tonsillectomy, tonsillar cancers were revealed histologically in 6 (15.4%) patients, and all these patients were p16-positive. No primary tonsillar tumour was found in the p16-negative group (0 of 17). The primary tumour identification rate in p16-positive HNSCCUP patients using palatine tonsillectomy was 27% (6 of 22). Conclusions: The diagnostic workup of HNSCCUP should be guided according to HPV/p16 status. Palatine tonsillectomy is a useful procedure in identifying primary cancer in p16-positive SCCUP patients, however, its effectiveness in p16-negative patients is debatable. Full article

Oropharyngeal squamous-cell carcinoma (OPSCC) poses significant challenges in diagnosis, treatment, and management and has important medico-legal and forensic implications. In particular, the management of OPSCC and its treatment-related complications can often be challenging. In cases with advanced OPSCC, a loco-regional extension of the tumor can contribute to the destruction of oral cavity tissues, while the radiotherapy treatment can induce profound changes in tissue morphology and structure. These changes, which resemble tumor neoplasms and endovascular effects, are related to a higher risk of fatal bleeding, as reported in the case study illustrated, in which a hemorrhage occurred from a lingual artery, originating from an ulcerative, necrotic, hemorrhagic lesion on the tongue. Bleeding complications in OPSCC and prolonged radiotherapy are associated with high mortality and require comprehensive management strategies to improve survival and quality of life. Autopsy investigations, contributing to the definition of post-mortem diagnosis, can provide valuable insights into the pathogenetic mechanisms underlying bleeding and guide therapeutic decisions and preventive measures. The integration of autopsy and histopathological investigation into clinical practice should be considered as a necessary support to optimize the management of complications in advanced OPSCC patients, emphasizing the importance of a patient-centered approach and continued research. Full article

Introduction: Oropharyngeal cancer requires a comprehensive evaluation of treatment options, including surgery, radiation therapy, and chemotherapy. It is crucial to customize these treatments based on the stage of the tumor and the overall health of the patient, enabling personalized or combined approaches. Transoral surgical techniques have regained popularity due to the advancements and limitations of non-surgical strategies. The potential influence of surgical procedures on patients’ quality of life highlights the need for careful intervention selection; among them, the transoral approach has proven to be especially beneficial for early-stage oropharyngeal neoplasms. Methods: To explore potential treatments for early-stage oropharyngeal malignancies, this study carefully reviews the literature, using information from papers, current research, and global databases. The review protocol commenced on November 2023. A comprehensive search of the PUBMED database was undertaken, employing pertinent terms associated with oropharyngeal, transoral surgery or radiotherapy, robotic surgery, and chemotherapy. Results: Treating early-stage oropharyngeal neoplasms is particularly intriguing due to the multitude of variables influencing treatment decisions, leading to ongoing debates in specialized literature. Regardless of the chosen approach, maintaining a high quality of life is crucial. To assess this, standardized questionnaires from the European Organization for Research and Treatment of Cancer were employed, revealing superior outcomes for patients solely undergoing surgical intervention. Additionally, in the realm of specialized literature, cases of HPV-positive oropharyngeal neoplasms are recognized for their heightened radiosensitivity and more favorable long-term prognosis. Conclusions: Surgical intervention and radiotherapy are the main treatment options for oropharyngeal cancer, and they can be used separately or together for maximum effectiveness. Amid ongoing discussions, determining the superior effectiveness between the two options continues to be a matter of debate. This study provides a comprehensive analysis, offering valuable perspectives for future discussions. Neoplasm in the oropharynx can be effectively treated using transoral microsurgery. Full article

High-risk human papillomavirus (HPV) infection is one of the leading causes of oropharyngeal squamous cell carcinoma (OPSCC), while the correlation between HPV and oral squamous cell carcinoma (OSCC) remains controversial. The inflammatory infiltrate involved in these epithelial neoplasms differs based on their association with HPV. HPV− tumors show higher tumor-associated neutrophil (TAN) infiltration. It is believed that TANs can play a dual role in cancer by exerting either anti-tumorigenic or pro-tumorigenic effects. However, the impact of HPV status on neutrophil polarization remains unknown. Therefore, this study aimed to investigate the effect of OSCC cells, both HPV− and HPV16+, on the functional phenotype of neutrophils. Peripheral blood neutrophils were stimulated with supernatants from OSCC cell lines and non-tumorigenic HaCaT keratinocytes transduced with HPV16 E6/E7 oncogenes. Subsequently, cytokine production, cell viability, metabolism, expression of degranulation markers, and PD-L1 expression were evaluated. Our findings demonstrate that in contrast to UPCI:SCC154 (HPV+ OSCC) cells, the SCC-9 (HPV− OSCC) cell line induced a highly activated functional state in neutrophils, which is potentially associated with a pro-tumorigenic effect. The HaCaT 16-E7 supernatant only stimulated the activation of some neutrophil functions. Understanding the complex interplay between neutrophils and their microenvironment has the potential to identify TANs as viable therapeutic targets. Full article

Introductions: The global prevalence of obstructive sleep apnea shows that this disease appears in 1 billion people, with the prevalence exceeding 50% in some countries. Treatment is necessary to minimize negative health impacts. Obstructive sleep apnea (OSA) is defined as a cause of daytime sleepiness, as well as a clinical manifestation of sleep-disordered breathing. In the literature, there are numerous controversial studies regarding the etiology of this condition, but it is universally accepted that reduced activity in the upper airway muscles plays a significant role in its onset. Additionally, OSA has been associated with a series of comorbidities, such as type II diabetes, metabolic syndrome, and cardiovascular and pulmonary conditions, as well as head and neck tumors, especially oropharyngeal and laryngeal tumors. This is a review of the subject of OSA that considers several aspects: an analysis of the comorbidities associated with OSA, the involvement of tumor pathology in the onset of OSA, and the association of OSA with various types of laryngeal cancers. Additionally, it includes an evaluation of postoperative and medical outcomes for patients with OSA and laryngeal tumors treated surgically and medically, including chemotherapy. Relevant Sections: By taking into consideration the stated objective, a systematic analysis of the available literature was conducted, encompassing the PubMed, Medline, and Scopus databases. The evaluation was based on several keywords, including head and neck cancer, diabetes, diabetic, overlap syndrome, cardiovascular conditions, laryngeal neoplasm, radiotherapy, and chemotherapy, as well as the concept of quality of life in laryngectomized patients and patients with OSA. Discussions: The review evaluates the involvement of OSA in the presence of comorbidities, as well as the increased incidence of OSA in patients with laryngeal cancer. It is important to note that surgical and post-surgical treatment can play a significant role in triggering OSA in these patients. Conclusions: The studies regarding the correlations between OSA, comorbidities, and head and neck tumors indicate a significantly increased risk of OSA in association with conditions such as diabetes, metabolic syndrome, cardiovascular diseases, and head and neck tumors, particularly laryngeal tumors. This association has a physio-pathological basis. The various surgical methods followed by radiation and chemotherapy for tumor treatment do not exclude an increased risk of developing OSA after treatment. This significantly influences the quality of life of patients who survive these types of tumors. Future directions: Due to the multiple comorbidities associated with OSA, the extension of polysomnography associated with investigations during sleep, such as drug-induced sleep endoscopy, represents a tendency for the early diagnosis of this pathology, which affects the quality of life of these patients. Patients with head and neck cancer are at high risk of developing obstructive sleep apnea; this is why it is necessary to expand the polysomnographic investigation of these patients after surgical procedures or after radiotherapy and chemotherapy. Full article

HPV-associated oropharynx carcinoma (HPVOPC) tumors have a relatively low mutational burden. Elucidating the relative contributions of other tumor alterations, such as DNA methylation alterations, alternative splicing events (ASE), and copy number variation (CNV), could provide a deeper understanding of carcinogenesis drivers in this disease. We applied network propagation analysis to multiple classes of tumor alterations in a discovery cohort of 46 primary HPVOPC tumors and 25 cancer-unaffected controls and validated our findings with TCGA data. We identified significant overlap between differential gene expression networks and all alteration classes, and this association was highest for methylation and lowest for CNV. Significant overlap was seen for gene clusters of G protein-coupled receptor (GPCR) pathways. HPV16–human protein interaction analysis identified an enriched cluster defined by an immune-mediated GPCR signal, including CXCR3 cytokines CXCL9, CXCL10, and CXCL11. CXCR3 was found to be expressed in primary HPVOPC, and scRNA-seq analysis demonstrated CXCR3 ligands to be highly expressed in M2 macrophages. In vivo models demonstrated decreased tumor growth with antagonism of the CXCR3 receptor in immunodeficient but not immunocompetent mice, suggesting that the CXCR3 axis can drive tumor proliferation in an autocrine fashion, but the effect is tempered by an intact immune system. In conclusion, methylation, ASE, and SNV alterations are highly associated with network gene expression changes in HPVOPC, suggesting that ASE and methylation alterations have an important role in driving the oncogenic phenotype. Network analysis identifies GPCR networks, specifically the CXCR3 chemokine axis, as modulators of tumor–immune interactions that may have proliferative effects on primary tumors as well as a role for immunosurveillance; however, CXCR3 inhibition should be used with caution, as these agents may both inhibit and stimulate tumor growth considering the competing effects of this cytokine axis. Further investigation is needed to explore opportunities for targeted therapy in this setting. Full article

Epstein-Barr virus (EBV) has a well-documented association with head and neck neoplasms, including nasopharyngeal carcinoma (NPC). In the last few years, research aimed at elucidating the role of the miRs in the pathogenesis of head and neck cancer (HNC) has gained importance. The study of miRs expression has set new directions in the search for biomarkers with diagnostic and prognostic value, and even in the search for new therapeutic targets for various tumors, including HNC. The aim of current study was to approximate the importance of miR-31-5p and miR-let 7a in the pathogenesis of EBV associated oropharyngeal cancer. For this purpose, experiments were carried out to determine the level of mentioned miRs in serum among patients diagnosed with oropharyngeal cancer linked to EBV infection, depending on histological differentiation-grading (G1–G3) and TNM classification. All clinical specimens stratified by HPV status were HPV negative. The level of antibodies EBNA and EBVCA was also assessed. The obtained results showed a significantly increased serum level of miR-31-5p but decreased level of miR-let 7a in EBV positive oropharyngeal cancer patients. We demonstrated association between the level of tested miRs and clinical stage. Our findings showed that miR-31-5p and miR-let-7a may be involved in development and progression of EBV associated oropharyngeal cancer. Therefore, it seems important to further study these molecules, as well as to determine whether they could be important biomarkers in the diagnosis of oropharyngeal cancer associated with EBV infection. Full article

Celiac disease (CD) is a multiorgan autoimmune disorder of the chronic intestinal disease group characterized by duodenal inflammation in genetically predisposed individuals, precipitated by gluten ingestion. The pathogenesis of celiac disease is now widely studied, overcoming the limits of the purely autoimmune concept and explaining its hereditability. The genomic profiling of this condition has led to the discovery of numerous genes involved in interleukin signaling and immune-related pathways. The spectrum of disease manifestations is not limited to the gastrointestinal tract, and a significant number of studies have considered the possible association between CD and neoplasms. Patients with CD are found to be at increased risk of developing malignancies, with a particular predisposition of certain types of intestinal cancer, lymphomas, and oropharyngeal cancers. This can be partially explained by common cancer hallmarks present in these patients. The study of gut microbiota, microRNAs, and DNA methylation is evolving to find the any possible missing links between CD and cancer incidence in these patients. However, the literature is extremely mixed and, therefore, our understanding of the biological interplay between CD and cancer remains limited, with significant implications in terms of clinical management and screening protocols. In this review article, we seek to provide a comprehensive overview of the genomics, epigenomics, and transcriptomics data on CD and its relation to the most frequent types of neoplasms that may occur in these patients. Full article

Background and Objectives: The research aimed at evaluating the capacity of salivary exosomal miR-10b-5p and miR-486-5p for oral and oropharyngeal cancer detection. Materials and Methods: The saliva samples were harvested from histopathological diagnosed oral and oropharyngeal squamous cell carcinoma patients and healthy volunteer subjects. The exosomes were isolated by differential ultracentrifugation and quantified by Nano Track Analysis. The microRNAs were extracted and quantified from salivary exosomes by quantitative Real-Time Polymerase Chain Reaction. Results: This research comprised fifty participants. When compared to healthy controls, salivary exosomal miR-486-5p was elevated and miR-10b-5p was reduced in oral and oropharyngeal squamous cell carcinoma. Moreover, miR-486-5p had a high expression level in stage II of cancer in comparison to the other cancer stages. The cancer samples presented an increased exosome dimension compared to the control samples. Conclusions: Salivary exosomal miR-10b-5p and miR-486-5p have an altered expression in oral and oropharyngeal cancer. Full article

To investigate the association between sociodemographic factors and variables related to oral health services in oral and oropharyngeal cancer mortality in Brazil, between 2000 and 2019. This study had an ecological design. Standardized mortality rates were compared between age group, sex, and regions. Age–Period–Cohort analysis was applied. Oral health services variables were analyzed in correlation tests. Survival analysis included Kaplan–Meier estimators, log-rank tests, and Cox regression. The mortality rate increased with age and was higher in men. Southeast and south regions had the highest rates for men, and the northeast and southeast had it for women. Age–Period–Cohort analysis showed a slight increase in female deaths and an increasing trend in the annual percent change in mortality for men over age 55. In survival analysis, males, Black individuals and southern residents were more strongly associated with death. The correlation between oral health teams’ coverage was high and negative, while the number of dental specialty centers and soft tissue biopsies had a high and positive correlation. Mortality and survival patterns were dependent on sex, age, geographic region and race/ethnicity. It was observed that preventive and diagnostic procedures were not being performed, which may be related to the increase in mortality. Full article

Human papillomavirus (HPV) is associated with both benign lesions and with neoplastic diseases, such as oropharyngeal cancer. Due to the increasing occurrence of these neoplasms on a global scale, it seems important to estimate the risk factors in the population. So far, data on the presence of oral HPV in the European population are scarce. Oral HPV was detected in 53 out of 461 healthy subjects (11.5%) in south-eastern Poland. Among the most common oncogenic types, HPV 16 was reported in four subjects (0.87%) and HPV 18 in three subjects (0.65%). Another high-risk type, HPV 45, was detected in nine subjects (1.95%). Low risk types (HPV 6, 11, 54) were detected in 25 cases, which constituted 5.4% of all tested samples. In adults and children, statistically more HPV positive cases have been reported in males than in females. A positive relationship was demonstrated between age and the amount of positive oral HPV. The presence of HPV was statistically more frequent in the population living in urban rather than in rural areas in all studied age groups (p < 0.05). Full article

Introduction: Human papilloma virus (HPV)-related oropharyngeal carcinoma (OPC) can be considered a new subtype of cancer with different clinical characteristics and prognosis than that related to tobacco. Its incidence is increasing worldwide. Its epidemiology has been widely studied in areas such as North America and Northern Europe, but less is known in Southern Europe. Methods: We analyzed the epidemiology of OPC using the database from Girona’s population-based Cancer Registry, in the North-East of Spain, from 1994 to 2018. To analyze differences between neoplasms related to human papillomavirus or not, we determined the immunohistochemical expression of p16 in cases within four time periods: 1997–1999, 2003–2005, 2009–2011, and 2016–2018. Results: Oropharyngeal cancer incidence increased significantly from 2001 to 2018 with an Annual Percentage of Change (APC) of 4.1. OPC p16-positive cases increased with an APC of 11.1. In the most recent period, 2016–2018, 38.5% of OPC cases were p16-positive. European age-standardized incidence rate was 4.18 cases/100.000 inhabitants-year for OPC cancer and 1.58 for those p16-positive. Five-year observed survival was 66.3% for p16-positive OPC and 37.7% for p16-negative. Conclusions: Although with lower burden than in other regions, p16-positive oropharyngeal cancer is increasing in our area and has a better prognosis than p16-negative OPC. Full article

The relationship between viral infections and cancer is well known and has been established for decades. Multiple tumours are generated from alterations secondary to viral infections 2 resulting from a dysregulation of the immune system in many cases. Certain causal relationships, such as that between the Epstein–Barr virus (EBV) in nasopharyngeal cancer or hepatitis C and B viruses in hepatocarcinoma, have been clearly established, and their implications for the prognosis and treatment of solid tumours are currently unknown. Multiple studies have evaluated the role that these infections may have in the treatment of solid tumours using immunotherapy. A possible relationship between viral infections and an increased response to immune checkpoint inhibitors (ICIs) has been established at a theoretical level in solid neoplasms, such as EBV-positive cavum cancer and human papillomavirus (HPV)-positive and oropharyngeal cancer. These could yield a greater response associated with the activation of the immune system secondary to viral infection, the consequence of which is an increase in survival in these patients. That is why the objective of this review is to assess the different studies or clinical trials carried out in patients with solid tumours secondary to viral infections and their relationship to the response to ICIs. Full article

Head and neck cancers are largely squamous cell carcinomas derived from the epithelial lining of the structures in the region, and are often classified anatomically into oral, oropharyngeal, nasopharyngeal and laryngeal carcinomas. The region’s component structures serve complex and intricate functions, such as speaking, swallowing and breathing, which are often compromised by these neoplasms. Such lesions may also cause disfigurement, leading to distressing social and psychological issues. Conventional treatments of these neoplasms usually involve surgical intervention with or without chemoradiotherapy. These have shown to be efficacious; however, they can also cause damage to healthy as well as diseased tissue, exacerbating the aforementioned problems. Access to a given region to deliver the treatments is also often a problem, due to the complex anatomical structures involved. The use of photodynamic therapy in the head and neck region has been established for about two decades. In this review, we looked at the basic mechanisms of this intervention, examined its use in common head and neck malignancies and vascular anomalies, and reported on the most recent clinical studies. We further included a clinical guide which can help replicate the use of this technology by any unit. Based on this review, photodynamic therapy has been shown to be efficacious in the treatment of head and neck malignancies and vascular tumours. This therapy can be targeted to the diseased tissue and causes no damage to underlying structures. Recent studies have shown this therapy to be as effective as conventional therapies, without causing major adverse effects. Full article

We reviewed the indications, peroperative feasibility, and postoperative clinical outcomes of our first 50 consecutive patients who underwent free flap reconstruction after TORS for complex pharyngeal defects at our institution. We analyzed indications according to previous radiotherapy, the size of the resection, and the transoral exposure of critical structures. We reviewed surgical data, postoperative complications, and functional outcomes comprising tracheostomy and alimentation management. Indications were upfront surgery (34%), a second primary surgery after radiotherapy (28%), or salvage surgery after chemoradiotherapy failure (38%). Localizations were the tongue base (44%), tonsillar fossa (28%), pharyngeal wall (22%), and soft palate (6%). T-classifications were T1 (6%), T2 (52%), T3 (20%), and T4 (22%). The mean length of the surgery was 574 min. Two patients were intraoperatively converted to a conventional approach at the beginning of the learning curve. In conclusion, TORS and free flap reconstruction in complex situations were associated with low rates of postoperative complications and satisfactory functional outcomes. They were, however, associated with a renewed learning curve. Full article