Human papillomavirus is associated with several anogenital and oropharyngeal lesions, including warts, premalignant lesions, and cancer. There are specific groups that were identified as high-risk groups for anal squamous cell carcinoma and anal human papillomavirus infection, namely HIV-positive patients, men who have sex with men, women with genital tract neoplasia, and solid organ transplant recipients. Condylomas have classically been considered to be a benign lesion, with an exception made for the Buschke-Loewenstein tumor, but several publications have shown that a high percentage of condylomas harbor high-grade lesions. Due to the similarities between anal and cervical carcinogenesis, anal cancer screening based on anal cytology and referral to high-resolution anoscopy, in case of abnormalities, have been advocated. Testing for anal human papillomavirus is not routinely done in anal cancer screening, because of the very high prevalence in high-risk populations. The large majority of anal cancers are squamous cell carcinomas (SCC), and around 90% are attributed to human papillomavirus. Human papillomavirus positivity in anal SCC seems to have a prognostic value, with better survival in those patients with positive tumors. Prophylactic vaccination has been shown to be important for prevention of anal human papillomavirus-related lesions.