[1] Risk factors include human papillomavirus (HPV), HIV/AIDS, receptive anal sex,[4] smoking, and many sexual partners.

[22] In 2010, Gardasil was approved in the US to prevent anal cancer and pre-cancerous lesions in males and females aged 9 to 26 years.

The vaccine has been used before to help prevent cervical, vulvar, and vaginal cancer, and associated lesions caused by HPV types 6, 11, 16, and 18 in women.

[25] In 2011, an HIV clinic implemented a program to enhance access to anal cancer screening for HIV-positive men.

Nurse practitioners perform anal Papanicolaou screening, and men with abnormal results receive further evaluation with high-resolution anoscopy.

The difficulty with surgery has been the necessity of removing the internal and external anal sphincter, with concomitant fecal incontinence.

[17] Current gold-standard therapy is the combination of chemotherapy and radiation treatment to reduce the necessity of debilitating surgery.

[29] This "combined modality" approach has led to the increased preservation of an intact anal sphincter, and therefore improved quality of life after definitive treatment.

Biopsies to document disease regression after chemotherapy and radiation were commonly advised, but are not as frequent any longer.

Current chemotherapy consists of continuous infusion 5-FU over four days with bolus mitomycin given concurrently with radiation.

Although cisplatin might cause fewer blood-related side effects, 5-FU combined with MMC is still the preferred treatment for nonmetastatic anal cancer.

[31] A 2024 systematic review found that chemoradiation therapy (CRT) with 5-FU and Mitomycin C improves locoregional control and colostomy-free survival compared to radiation alone, though with increased acute hematologic toxicity.

Chemotherapy commonly used is similar to other squamous cell epithelial neoplasms, such as platinum analogues, anthracyclines such as doxorubicin, and antimetabolites such as 5-FU and capecitabine.