Molecular Biology of Head and Neck Cancers: Introduction, Risk Factors, Genetic Cancer Syndromes
INTRODUCTION
Head and neck cancers constitute a real challenge for oncologists across the globe, with one person dying every hour of every day. He can lose his voice, have his face distorted and disfigured, and lose his fundamental ability to swallow, eat, and drink. When Sigmund Freud, the father of modern psychiatry, was diagnosed with oral cavity cancer in the 1930s, he endured 30 surgeries before dying at his doctor’s request. The emotional impact can be so terrible. Head and neck cancer is appropriately referred to as “Head and neck cancers.”
MOLECULAR BASIS OF RISK FACTORS
Carcinogenesis risk is increased by genetic factors. Due to its effects on p53 alterations, tobacco use is the most significant risk factor for head and neck cancer.
Chewing betel nut and alcohol together has a synergistic impact on tobacco. Benzo[a] pyrenediol epoxide, one of the numerous recognized carcinogens found in tobacco smoke, causes DNA adducts throughout the genome. The human DNA repair system, which consists of the nucleotide excision repair (NER) and base excision repair (BER) pathways, fixes this DNA damage.
Genetic variations in NER-related genes like ERCC-1 and XPD and BER-related genes like XRCC-1 and ADPRT may raise the risk and vulnerability to head and neck squamous cell cancer (HNSCC).
Infections: Squamous cell carcinoma of the head and neck caused by the human papillomavirus A double-stranded DNA virus that is exclusively epitheliotropic, the human papillomavirus (HPV) has been investigated the etiopathogenesis of HNSCC since the 1980s.
HPV-positive and HPV-negative cancers are distinct genetic/molecular and clinicopathological entities. This subgroup is distinct because of its favourable prognosis, tendency to affect younger people, and preference for the tonsils and oropharynx. The rise in oropharyngeal cancer started in the late 1970s and is linked to rising rates of high-risk HPV infection as a result of shifting sexual behaviours, which can be linked to increased use of oral contraceptives, decreased condom use, and the ability to have more sexual partners without worrying about getting pregnant. The virus has two oncogenes, E6 and E7, whose expression inactivates retinoblastoma (RB) and p53, respectively, altering the control of the cell cycle in infected cells.
The concern of whether we are overtreating patients and subjecting them to needless long-term treatment-related harm arises because HPV-related cancers appear to react well to both chemotherapy and radiation. To find the most effective way to treat these individuals while minimizing treatment-related toxicities, trials are still being conducted. Only time will tell if immunizations are effective in preventing HPV-related HNSCC-like cervical malignancies.
Genetic cancer syndromes
Many genetic cancer syndromes, including Fanconi’s anaemia, Bloom syndrome, Ataxia-Telangiectasia, and Xeroderma Pigmentosa, have been hypothesized to increase the risk of HNSCC. These syndromes are typically characterized by an early age at which cancer first appears, unique and unusual patterns of clinical presentation, and multiple malignancies in the same person, occasionally of different histologies. Familial head and neck cancers are linked to hereditary abnormalities in the hMDM2 regulator p14ARF and the CDKN2A locus, also referred to as the multiple tumour suppressor gene. Young patients without recognized risk factors make up this relatively uncommon yet enigmatic class of patients, offering a rich and useful area for molecular research.
FIELD CANCERIZATION
The concept of field cancerization was initially clarified by Slaughter et al. in their seminal work from 1953. The rationale for second primary tumours and local recurrences was based on this idea. In the molecular era, many years later, the idea was brought back to life, and the molecular underpinnings of the multi-step carcinogenesis process were investigated.
HALLMARKS OF CANCER
The biological capabilities that human tumours acquire during their multi-step carcinogenesis process are known as hallmarks of cancer. It serves as the foundation for making sense of the intricacies of neoplasia.
EPIGENETIC MODIFICATION
Direct harm to the DNA is not usually the cause of tumorigenesis. Without changing the gene sequence, it can be the result of variations in gene expression. Base sequence methylation or histone protein modification by acetylation, ubiquitination, or methylation may be the cause. Without changing the genetic makeup or DNA sequence, hypermethylation of tumour suppressor genes has been investigated as a potential mechanism of HNSCC development.