Inquiry Basket
Loading ......
Head and neck cancers are a broad category of cancers that occur in the head and neck region, not including brain cancers or cancers of the eye. head and neck cancers usually begin in the squamous cells that line the mucosal surfaces of the head and neck (for example, those inside the mouth, throat, and voice box). These cancers are referred to as squamous cell carcinomas of the head and neck. Head and neck cancers can also begin in the salivary glands, sinuses, or muscles or nerves in the head and neck, but these types of cancer are much less common than squamous cell carcinomas.
Symptoms of Head and Neck Cancers vary from the different parts where cancer starts.
Fig. 1 Head and Neck Cancer Regions
The exact cause of head and neck cancer is unknown. However, there are a number of risk factors related to head and neck cancers. Alcohol and tobacco are major risk factors for cancers of the head and neck. About 70% of cancers in the oropharynx are linked to human papillomavirus (HPV). UV light exposure is a major cause of cancer on the lips. Exposure to substances like wood dust, formaldehyde, asbestos, and nickel may increase the risk of getting cancers in the nasopharynx. Radiation therapy history to the head and neck may cause head and neck cancers. In addition, about twice as many men as women get head and neck cancers. They are more likely to be diagnosed in people who are over 50 years of age.
Head and neck squamous cell carcinoma (NSCLC) is the leading type of head and neck cancer. Signaling pathways involving p53, pRb, EGFR, P13-kinase, mTOR, DNA repair, angiogenesis, genetic instability, dissociation, invasion, cellular adhesion, migration and metastasis are commonly affected in HNSCC. EGFR overexpression is an early and very frequent molecular change in HNSCC, the intensity of its expression is associated with reduced survival. The PI3K-AKT pathway is downstream of EGFR. PIK3CA is the most frequently mutated oncogene for HNSCC (approximately 20%). PI3K mutations may confer increased resistance to EGFR inhibition. HRAS is mutated and overexpressed in certain HNSCC tumors, and was identified in up to 20% high-grade histologic subtypes, such as mucoepidermoid carcinoma, adenocarcinoma, and salivary duct carcinoma. Additionally, NOTCH1 is a key tumor suppressor gene and its genetic alterations lead to abnormal pathway activation. ALK1 is a novel target involved in angiogenesis. The hedgehog pathway modulates EGFR dependence and epithelial to mesenchymal transition (EMT), a key invasion and drug-resistance mechanism in HNSCC. Moreover, a contribution of multiple tumor suppressor pathways including p53, Rb/INK4/ARF, and Notch, have been commonly seen, in tumor initiation, progression, and maintenance.
During the diagnosis of head and neck cancer, physical examination will be performed for any lumps on the neck, lips, gums, and cheeks, also inspect the nose, mouth, throat, and tongue for abnormalities. Blood tests and urine tests may be done to help diagnose cancer. In addition, endoscopy, biopsy, biomarker testing, imaging tests (X-ray/barium swallow, CT scan, Ultrasound, MRI, PET), etc., are common methods used in the diagnosis of head and neck cancer. In the detection of biomarkers, early detection of cancer p53 mutation, Loss of heterozygosity (LOH) on chromosomes 3p, 9p, 17p, 18q, and promoter hypermethylation detected in saliva, could be markers useful for early detection of HNSCC. Salivary Interleukin-8(IL-8) and melanoma associated antigens (MAGE) showed good sensitivity, specificity, in the early detection of HNSCC. Cytokeratin and E48 expression are biomarkers for the detection of distant metastasis. eIF4E overexpression, hypermethylation of p16 and O6-methylguanine- DNA-methyl transferase (MGMT) genes in negative surgical margins are reliable prognosticators.
Head and neck cancer treatment can include surgery, radiation therapy, chemotherapy, targeted therapy, immunotherapy, or a combination of treatments. The treatment plan for an individual patient depends on a number of factors, including the location of the tumor, the stage of cancer, and the person’s age and general health. In targeted therapy, Cetuximab (Anti EGFR IgG1 monoclonal antibody, competitively inhibits the binding of EGFR ligands to EGFR receptors) is the only U.S. Food and Drug Administration (FDA)-approved targeted therapy available for HNSCC. Additionally, two anti-Programmed Cell Death-1 (PD-1) antibodies, pembrolizumab and nivolumab have been approved for HNSCC by FDA and EMEA in the recurrent/metastatic setting. Other potential targets include the widespread deletion of TP53 and CDKN2A in HPV-negative HNSCC patients; and the deletion and mutation of TRAF3, PIK3CA, and E2F1 in HPV-positive HNSCC. Overall, the most promising targets in HNSCC include PI3K signaling pathway proteins, VEGF and VEGFR, and cyclin-dependent kinases 4/6.
Fig. 2 New therapies in head and neck cancer
Loading ......
