Anal Squamous Cell Carcinoma (ASCC) is a rare cancer that has a rapidly increasing incidence in areas with highly developed economies. ASCC is strongly associated with HIV and there appears to be increasing numbers of younger male persons living with HIV (PLWH) diagnosed with ASCC in Greater London. This is a retrospective cohort study of HIV positive and HIV negative patients diagnosed with primary ASCC between January 2000 and January 2020 in a demographic group with high prevalence rates of HIV. 176 patients were included, and clinical data was retrieved from multiple, prospective databases. A clinical subgroup was identified in this cohort of younger HIV positive males who were more likely to have had a prior diagnosis of Anal Intraepithelial Neoplasia (AIN). Gender and HIV status had no effect on staging or disease-free survival. PLWH were more likely to develop a recurrence (p < 0.000) but had a longer time to recurrence than HIV negative patients, however this was not statistically significant (46.1 months vs. 17.5 months; p = 0.077). Patients known to have a previous diagnosis of AIN were more likely to have earlier staging and local tumour excision but there was no identifiable survival benefit in this cohort. Five-year Disease-Free Survival was associated with tumour size and the absence of nodal or metastatic disease (p < 0.000).