Although human papillomavirus (HPV)-related anal squamous cell cancer (ASCC) is rare, its incidence has been rising and in high-risk populations exceeds the incidence of cancers for which screening programs are implemented. Therefore, targeted screening techniques are being evaluated with high-resolution anoscopy (HRA) as the current gold standard because of its ability to detect anal intraepithelial dysplasia (AIN) and premalignant high-grade squamous intraepithelial lesions (HSILs). However, a scarcity of trained providers presents a barrier to screening.ASCC incidence is rising especially in elderly women and young black men. Premalignant HSIL may not only progress to ASCC but also regress. Biomarkers such as HPV type, p16 immunostaining and DNA methylation markers may emerge as predictors of disease progression.HRA with acetic acid and Lugol's iodine staining can be used to detect HSIL and ASCC. Recent studies suggest that anal cancer screening may have an impact on the stage of ASCC at diagnosis and the incidence of anal cancer.The Anal Cancer HSIL Outcomes Research (ANCHOR) study is underway to determine whether treating HSIL effects ASCC incidence.Although there are no consensus screening guidelines for anal cancer, it is reasonable to screen high-risk populations with physical examination, anal cytology and HRA. Gastroenterologists can support anal cancer screening programmes through identifying patients at risk, performing noninvasive screening and considering to incorporate endoscopic techniques to examine the anal canal. VIDEO ABSTRACT: http://links.lww.com/COG/A32.