Chapter 1
Introduction
1.1 Head and Neck Cancer
Head and neck squamous cell carcinoma (HNSCC) is a widespread heterogeneous malignancy that accounts for 500,000 new cases globally per year and involves cancers of the oral cavity, oropharynx, nasopharynx, hypopharynx, and larynx [1,2]. HNSCC traditional treatment involves surgery, radiotherapy and chemotherapy, used alone or in combination, depending on the level of the tumour and the main site [3]. Clinical treatment responses differ greatly among patients with HNSCC and remain disappointing, especially in advanced stage disease [4]. Chemotherapy and radiation, in comparison, also confer major toxicity [3].
Therefore, defining biomarkers from which to choose the right care plan for each condition is important. Several studies showed a causal correlation between the growth of HNSCC cancer and human papilla virus infection (HPV) more than a decade ago [5,6,7]. HPV positive (HPV+) HNSCC has been associated with a stronger prognosis and reaction to treatments, including immunotherapy, compared to HPV negative (HPV-). Present efforts are based on explicitly designing therapeutic options for this subtype. For example, for de-intensifying treatment methods, HPV+ oropharyngeal cancers are now being considered [7].
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Worldwide, head-and-neck squamous cell carcinoma (HNSCC) accounts for about 300,000 deaths per year [8]. The key risk factors for the growth of Head-and-Neck Squamous Cell Carcinoma are smoking, alcohol, and high-risk human papillomavirus (HPV) infections. The prevalence of HPV-associated HNSCC is about 25% of the worldwide cases recorded, with an even higher proportion of oropharyngeal cancer, and among those cases, the predominance of HPV-16 and HPV-18 forms of infection.
Historically, squamous cell carcinoma of the head and neck has been linked with tobacco and alcohol use, with a growing proportion of tumours of the head and neck, especially in oropharynx, also associated with human papilloma virus (HPV). Bad prognosis is characterized by recurrent/metastatic illness and there is an unmet requirement for the development of biomarkers for early disease detection, specific prognosis assessment, and efficient collection of therapy.
Furthermore, epidemiological, molecular pathology and cell line evidence suggest that a large percentage of oropharyngeal cancers are sexually transmitted diseases and are causally associated with high-risk human papillomavirus (HPV), especially type 16 [9,10,11]. A distinct biological and clinical species, HPV-associated oropharyngeal cancers (HPV-OSCCs) have a distinct mutation environment and are distinguished by significantly enhanced survival [12]. The majority of patients with HNSCC present with locoregionally advanced (LA) disease using a multimodality clinical approach. The 5-year progression-free survival (PFS) of HPV negative patients with LA disease is ~40-50 percent, despite improvements in diagnosis, care and monitoring, and the survival rates for recurrent/metastatic (R/M) disease have not improved substantially in recent years.
Low HNSCC-related survival rates are attributed in part to early diagnostic failure. In fact, only one-third of HNSCC patients are diagnosed early on [13]; early diagnosis is lacking primarily
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due to a lack of proper screening. As per the National Cancer Institute (NCI), biomarkers are defined as "a biological molecule found in the blood, other body fluids, or tissues that is a symbol of a normal or abnormal process, or of a medical condition." How well the body responds to a treatment for a disease or disorder, a biomarker can be used [14].
Basically, biomarkers are valuable instruments that lead to the diagnosis, determine the likely path of the disease, and predict therapeutic response. Thus, finding a biomarker for head and neck squamous cell carcinoma (HNSCC) comprising of a heterogeneous category of malignancies that arise in the oral cavity, larynx and pharynx is required [15]. Regarding HNSCC, although it has been proposed that certain biomarkers have a potential effect on diagnosis and prognosis, few have been confirmed for use in clinical practice [16].
Cancer is a disorder that develops as a result of genetic and epigenetic changes. Recently, epigenetics has become a rapidly growing biological field. Existing research shows that epigenetic modification has a major impact in gene expression as it is reversible change on DNA or Histones that affects gene expression without changing the sequence of DNA. DNA methylation and Histone modification are two of the most well-known epigenetic changes where DNA methylation is a biological process of adding methyl groups to the DNA molecule and a post-translational modification (PTM) of histone proteins is known as a Histone modification. By modifying chromatin structure or recruiting histone modifiers, PTMs to histones can have an effect on gene expression [17]. When gene/DNA expresses itself to form proteins, this process is called gene expression. DNA can control the activity of cell by forming proteins in two major steps which are transcription and translation. Here, transcription means a process in which coded message from DNA is copied to mRNA while translation is a process in which mRNA is decoded and form proteins. We discovered that computational models that use epigenetic data to predict gene
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expression with high accuracy are uncommon. Therefore, some experiments are required to build a model which can help finding important features that affect the HNSCC.
The Cancer Genome Atlas (TCGA) contains some large-scale genomic profiling experiments. For data collection for more than 30 types of cancer, the TCGA (The Cancer Genome Atlas) is paramount. In various ways, including statistical simulations, statistics and machine learning, the diversity of omics layers, such as RNA sequencing, methylation, miRNA, proteomic, therapeutic, copy number variance and mutation, can be studied.