The anal canal is the most distal portion of the lower digestive tract and is approximately 2-3 inches long. It is enclosed by the internal and external sphincter muscles. The proximal portion of the anus is connected to the rectum, which is the final section of the large intestine. The anal canal terminates at the anal verge, where stool exits the body.

The rectum is lined by columnar epithelial cells while the anal canal is lined by squamous epithelial cells. The transition from columnar to squamous epithelial cells at the start of the anal canal is known as the squamo-columnar junction, or SCJ. HPV preferentially infects squamous epithelial cells that are near the SCJ, such that many anal cancers arise from this area. HPV does not infect columnar epithelial cells and is therefore not typically associated with colorectal cancers. 

Distal to the SCJ and closer to the verge is an irregular line formed by anal folds called the dentate (or pectinate line). The innervation of the anal canal differs relative to the dentate line; while pain receptors are largely absent between the SCJ and the dentate line, the anal canal is exquisitely tender closer to the anal verge.

The perianus or anal margin extends 5cm from the anal verge and is characterized by the presence of squamous epithelial cells with hair follicles and glands. In addition to infecting the anal canal, HPV can also infect the perianus, which can lead to perianal cancer.