Since the 1990s, combination antiretroviral therapy (cART) has markedly reduced HIV-related opportunistic infections and mortality, and increased the life expectancy of people living with HIV. While AIDS-defining malignancies have declined non-AIDS defining malignancies continue at higher rates in HIV-infected persons than in the general population. Amongst these are cancers associated with HPV which is responsible for 90% of SCC of the anal canal. The incidence of anal SCC is increasing in the cART era, and as such, there is an urgent need to find effective ways of preventing anal SCC in those living with HIV. This includes screening for anal cancer precursors and ablative treatment of these lesions.