Head and neck cancers are a group of cancers that affect the mouth, lips, nasopharynx, pharynx, larynx and sinuses. Common risk factors associated with head and neck cancers are alcohol and tobacco consumption, however recent studies have demonstrated a causal link between human papillomavirus (HPV) and oropharyngeal squamous cell carcinoma (OSCC). HPV has been shown to cause cancers in other head and neck subsites but current data on this is limited.
HPV is most commonly linked with cervical cancer as it is responsible for 90% of cases, however the tonsillar crypts in the oropharynx are reminiscent of squamocolumnar junction cells in the cervix in the way that they are arranged into a discontinuous single-layer epithelium.
This arrangement of these cells provides a microenvironment that allows the survival of many bacterial infections and foreign material. This promotes expression of programmed death ligand 1 (PD-L1) which binds to PD-1 on immune cells. PD-1 on immune cells such as T helper cells dampens the immune response when it binds to its complimentary ligand expressed on body cells. This prevents autoimmune responses and is also importance in pregnancy. However, one of the hallmarks of cancer is to evade immune destruction, and so PD-L1 is often overexpressed on cancer cells to protect them from the host immune system. This PD-L1 overexpression in the tonsillar crypts facilitates HPV infection to thrive in the tonsillar crypts.
In this environment, the HPV virus can infect cells and this can lead to integration of the viral genome into the host cell’s DNA at regions of genomic instability. This leads to production of its viral proteins E6 and E7 withing the host cell. E6 causes degradation of p53 and E7 causes degradation of Rb. P53 and Rb are both tumour suppressor proteins which prevent cell cycle entry. Degradation of these by viral proteins allows cell cycle entry regardless of DNA damage or signalling and therefore facilitates uncontrolled proliferation of cells. This leads to cancer.
Please help The Swallows Head and Neck Cancer Group to raise awareness of head and neck cancers in young people and ethnic minority groups by taking this short survey:
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