Oral squamous cell carcinoma (OSCC) is one of the leading presentations of head and neck cancer (HNC). The first part of this review will describe the highlights of the oral microbiome in health and normal development while demonstrating how both the oral and gut microbiome can map OSCC development, progression, treatment and the potential side effects associated with its management. We then scope the dynamics of the various microorganisms of the oral cavity, including bacteria, mycoplasma, fungi, archaea and viruses, and describe the characteristic roles they may play in OSCC development. We also highlight how the human immunodeficiency viruses (HIV) may impinge on the host microbiome and increase the burden of oral premalignant lesions and OSCC in patients with HIV. Finally, we summarise current insights into the microbiome-treatment axis pertaining to OSCC, and show how the microbiome is affected by radiotherapy, chemotherapy, immunotherapy and also how these therapies are affected by the state of the microbiome, potentially determining the success or failure of some of these treatments.
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