In this review, a summary of our current understanding of squamous cell carcinoma of the anus (SCCA) and the advances in our knowledge of SCCA regarding screening, prevention, the role of the immune system, current treatment and the potential for novel targets are discussed. The present standard of care in terms of treatment is 5-fluorouracil (5-FU) and mitomycin C (MMC) concurrently with radiation, which results in a high level of disease control for small early cancers. Preservation of the anal sphincter is achieved in the majority, although anorectal function is often impaired. Although evidence from prospective studies to support a change in the treatment strategy is lacking, patients with HPV-negative SCCA appear to be less responsive to chemoradiation (CRT) and relapse more frequently. In contrast, HPV-positive tumours usually fare better, but oncological outcomes are modified by smoking and immune incompetence. There is current interest in escalating the radiotherapy dose for larger, more advanced tumours, and de-escalating treatment for HPV-positive tumours. The use of novel immunological treatments to target the underlying different molecular pathways of HPV-positive cancers is exciting.
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