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This review will discuss current and future anal cytology screening programs to detect anal dysplasia in HIV-positive men who have sex with men (MSM), in addition to other interventions aimed at early detection of anal cancer in this population.Evidence of progression from high-grade anal dysplasia to anal cancer has been recently demonstrated and strengthens the clinical imperative to diagnose and treat this lesion in at-risk populations. The use of adjunct molecular techniques that improve specificity of anal cytology screening may have the potential to rationalize current screening referral pathways and focus resources on those at highest risk of progressing to cancer. Candidate biomarkers that are currently being investigated include protein surrogates of cell cycle deregulation (such as p16ink4a and minichromosomal maintenance proteins), DNA damage biomarkers (53BP1) in addition to testing for human papillomavirus genotype, gamma tubulin and beta defensin levels.Anal cytology, although sensitive for the detection of any anal dysplastic abnormality, has poor specificity to detect high-grade anal dysplasia. As new molecular techniques are evolving, the most important immediate clinical intervention is to educate HIV-positive MSM in order to increase awareness of both risk and clinical symptoms suggestive of progression to anal cancer. In the absence of high-resolution anoscopic expertise, it is recommended that regular digital rectal examinations are performed as most early cancers are palpable even in the absence of clinical symptoms.