Frontiers in Inflammation

Head and neck cancer is on the rise around the globe. At present, the disease affects both the elderly and younger patient populations. This type of cancer is significant as it involves crucial anatomic regions of the head and neck, which are vital for breathing, mastication, swallowing, speech, and olfaction. The treatment options for head and neck malignancies are mainly surgery and chemoradiation, depending on the stage of the tumors. Inflammation plays an important role, and it has a strong relationship with the risk factors, assessment, and treatment of head and neck cancer. Multiple risk factors for head and neck squamous cell carcinoma like smoking, alcohol, viruses, chemicals, and foods have some elements of inflammation that play a dominant role in promoting and sustaining carcinogenesis. The inflammation cascades are complex, and multiple factors cohesively interact within the microenvironment that eventually leads to carcinogenesis, tumor recurrence, and metastasis. Recent evidence suggests that numerous anti-inflammatory biomarkers have effective therapeutic roles in the management of head and neck cancer. This chapter highlights the prominent relationship and interaction that exists between head and neck cancer and inflammation, not only in its etiopathogenesis but also in the assessment and overall management approaches. The significant focus is on the role of inflammatory agents that contribute to the process of carcinogenesis, as well as discussion on several significant inflammatory markers and molecules which may serve as a potential effective target for personalized treatment in head and neck cancer management armamentarium in the near future.

Head and neck cancer (HNC) is a heterogeneous group of malignant neoplasms, and its classification is a challenge. Based on the primary site, most literature comprehends five types of HNCs: laryngeal, pharyngeal, oral cavity, nasal cavity, and salivary gland cancer. More than 90% of HCNs are of epithelial origin, making squamous cell carcinoma the most common histological type. The prototypic HNC is a moderately differentiated squamous cell carcinoma associated with tobacco and alcohol consumption that affects older men more frequently. They are usually treated in a similar fashion. Currently, the human papillomavirus epidemic and a shift in tobacco consumption patterns are changing this trend. HNCs have a high rate of genetic heterogeneity, and molecular profiling has gained importance in the classification and future treatment of HNCs.

Head and neck constituency tumor display many types of cell depending on the lineages, which can develop in a variety of tumor types. Nodaway, all these types and variants of tumor have been recognized based on histomorphological features and their molecular behavior. The most updated and receptive classification is provided by the World Health Organization (WHO) and the American Joint Committee on Cancer (AJCC). In the chapter, the discussion will include the common neoplasm, which can occur in oropharynx, nasopharynx, sinonasal region, salivary gland, thyroid gland and other adjacent structures. A brief overview, clinical presentation, histomorphology, genetic profile and outcome/prognosis will be highlighted.

Head and neck malignancy is a critical disease across the globe as its incidence is on the rise. This malignancy comprises the oral cavity, oropharynx, larynx, nasal cavity, paranasal sinus, nasopharynx, salivary glands, and thyroid malignancies. Multiple known risk factors have been strongly associated with the majority of these malignancies. Importantly, the majority of these known risk factors are intricately involved in the inflammation and its ecosystem. Of note, inflammation cascades and inflammatory markers play a dominant role in the pathogenesis of head and neck malignancy. Thus, it is crucial to understand the true process of each identified risk factor and its related inflammation process in the etiopathogenesis of head and neck malignancy. This can serve as an effective platform for the future development of potential agents for screening, prevention, and treatment of head and neck malignancy. This chapter will discuss the significant risk factors of head and neck malignancy and highlight the spectrum of inflammation process that governs the basis of carcinogenesis and its etiopathogenesis.

Diagnosis plays a key role in overall patient assessment and accurate staging of the malignancy. Diagnosis is the starting point to choose treatment strategies for the disease, as well as the basis upon which therapy success, prognosis and the patient’s quality of life will vary. Considering a high level of clinical suspicion of any mucosal alteration or laterocervical swelling is important until medical examinations provide evidence of the contrary. Diagnosis investigation continues with the search, among data collected on the patient's history, of objective signs on which clinical suspicions will focus through further medical and instrumental examinations. Imaging techniques that can be used are ultrasound scan, computerised tomography, magnetic resonance and, in the most complex cases, positron emission computerised tomography. Ultrasonography is the most commonly used imaging technique for head and neck mass, especially for the assessment of lymph nodes, thyroid glands and salivary glands. Magnetic resonance is also considered an important examination in the diagnosis of head and neck tumours, especially for lesions involving the oral cavity, oropharynx, nasopharynx and larynx. Computerised tomography (CT) scan is especially useful when assessing the skull base involvement and the morphology of laryngeal malignancies, for example when the tumour extends over the perichondrium of cartilage structures, as well as when assessing function, i.e. evaluating the degree of chordal motility. In head and neck cancers (HNC), predictive factors namely biological characteristics that can be used to predict tumor response to a specific treatment, are currently remarkably lacking. Conversely, some bio-molecular parameters are recognized as prognostic factors of the disease, since they indicate tumor characteristics that inform about cancer outcome, independently of treatment the patients will undergo. The most prominent prognostic factor for head and neck cancers is viral etiology, specifically HPV-mediated disease for oropharyngeal carcinomas and EBV-mediated disease for nasopharyngeal carcinoma.

Inflammation plays a critical role in the process of carcinogenesis as well as in modulating treatment effects of many therapeutic agents for head and neck malignancy. Current research indicates that a myriad of new diagnostic tools and treatment modality works in harmony in producing a desired effective cancer treatment regime. Imperatively, multiple inflammatory markers have surged in the genomic and molecular ecospheres as highly potential agents that can be used in screening, diagnosis, treatment as well as follow up of head and neck cancer patients. These markers include arrays of cytokines, peptides, macrophages, acute phase proteins, growth factors, and many more. The tumor microenvironment is a complex ecosystem and has an intricate relationship with its surrounding biosphere. The multiple interactions within the molecules in the cancer microenvironment play significant roles in mediating and promoting carcinogenesis as well as mitigating the treatment response. These complex ecosystems are also responsible for the occurrence of metastatic diseases, recurrences, and residual diseases. This chapter highlights some of the critical inflammatory markers that can be potentially used as a potent theranostic approach for head and neck tumors in the near future.

Head and neck malignancy is on the rise, where the majority of the tumors are squamous cell carcinoma (HNSCC). Previously, alcohol and tobacco are reported to be the well-established risk factors for HNSCC development. Currently, the HPV driven HNSCC has shown an increase in incidence globally, with oropharyngeal and oral cavity carcinoma predominating at certain geographic locations. HPV associated oropharyngeal squamous cell carcinoma commonly occurs in Europe and certain Western countries. They have different biological profiles compared to HPV-negative HNSCC. HPV-positive HNSCC patients have different characteristics and prognosis, which remarkably affect the management of this subset of patients. HPV is a significant inflammatory agent that can promote carcinogenesis via multiple critical mechanisms that are discussed in the chapters. Targeting HPV for future research is a great promising avenue for the discovery of novel screening, diagnostic, and therapeutic targets.

Over the past decades, the survival rate of head and neck cancers has not significantly changed. Recently, the importance of the inflammatory responses in head and neck cancer has been a hot topic and of increasing interest. There has been suspicion about the relationship between inflammation and carcinogenesis, and thus, many works had proven these relations. Manipulation of the inflammatory mediators has been experimented with, to reduce the tumor burden, treat as well as prevent the cancer occurrence or second primary. This chapter summarizes the relationship between inflammation and cancer, emphasizing epidemiological and clinical evidence and proposing the current potential targets of anti-inflammatory agents for the therapeutic approach of head and neck cancer (HNC). We hope this knowledge will help us combat carcinogenesis and reduce the morbidity of the current conventional treatment for a better quality of life.

Head & Neck Squamous Cell Carcinoma (HNSCC) is a heterogeneous group of malignancies that collectively constitute a significant group of cancer worldwide. It affects not only the elderly patients but more so the middle age and the pediatric patient population. Around 90% of these tumors develop from the mucosal lining of the head and neck region i.e. Head & Neck Squamous Cell Carcinoma (HNSCC). These mainly include oral cavity carcinoma, oropharyngeal carcinoma, hypopharyngeal carcinoma, laryngeal carcinoma, sinonasal carcinoma, nasopharyngeal carcinoma, and salivary glands carcinomas. Different types of these carcinomas are prevalent at some geographic locations due to various environmental, dietary, social, and genetic factors. Head and neck cancers are critical as these affect many vital functions of the human being, such as breathing, eating, smell, hearing, and vision. Clinical and epidemiologic studies show aetio-pathological relation between chronic inflammation and cancer in several organs, including the Head and Neck region. A huge number of inflammatory mediators and markers have been identified and investigated in the current genomic era. Significant inflammatory biomarkers have a potential role not only in screening and prevention but also in treatment and assessing the prognosis of HNSCC. This chapter will highlight the recent facts, the discovery of evidence of the inflammation, and biomarkers for HNSCC.

Inflammation is a hallmark of cancer. Inflammation is closely linked to head and neck malignancy and other solid tumors. Arrays of inflammation cascades and markers have been identified and proven to play significant roles in carcinogenesis. Many substances and molecules are secreted in response to the inflammation and its ecosystem and can be effectively measured and quantified at various stages of the carcinogenesis process. A spectrum of available inflammatory biomarkers can be a potentially effective therapeutic approach in the management armamentarium of head and neck malignancy. However, the cost, practicality, and availability are some of the major obstacles that need to be counteracted in order to progress in this challenging oncologic arena. Together with the continuous commitment from scientists, clinicians, laboratory personnel, and other related health staff, with the combination of technology updates, this new treatment approach and strategy are coming to reality. This chapter will discuss selected inflammatory biomarkers of significance critical for the armamentarium management of head and neck malignancy. Hopefully, this will escalate the treatment response of head and neck cancer patients. Hence, this ensures the patient’s survival with the best quality of life.