The anal canal is defined as extending from the anorectal ring to the intersphincteric groove corresponding to the length of the internal sphincter. The anal verge is the junction of the keratinized hair-bearing squamous epithelium and the anoderm. The mucosa of the anal canal varies from rectal columnar to the anal transitional zone (extending variably above the dentate line, usually 5 to 10 mm) to squamous nonkeratinized anoderm without hair or other skin appendages. The anal transitional zone has the most varied epithelium including basal, columnar, cuboidal, and squamous cells in four to nine layers. In addition, this zone may have endocrine cells and melanocytes. It is this layer that is most susceptible to human papilloma virus (HPV) infection and is where most anal canal cancers arise.

Anal canal squamous cell carcinoma is defined as a tumor between the intersphincteric groove and the anorectal ring. It accounts for about 1.5% of all
gastrointestinal tract tumors; however, it has been rising in incidence over the past 25 years, especially in HIV-positive male homosexuals.

Current major known etiological factors are HPV infection and smoking. Smoking increases the risk (relative risk 7 to 9) of anal cancer, and patients with anal cancer have a higher risk of cervical, vulvar, and other smoking-related cancers (i.e., oral cavity, larynx, lung, bladder, and breast cancers). HPV is important in the etiology of anal cancer. There is a strong association among genital warts known to be caused by HPV, low-grade and high-grade squamous intraepithelial lesions and anal cancer, and sexual promiscuity and anal-receptive intercourse. Patients with HIV disease, especially those with CD4 counts less than 200/mm3, have a higher incidence of HPV infection that is more likely to be persistent compared with patients who do not have HIV disease. HIV infection may also predispose to a greater progression of low-grade to high-grade dysplasia. The incidence of anal cancer has increased in both men and women, but especially in HIV-positive male homosexuals. The relative risk in patients with acquired immunodeficiency syndrome (AIDS) may be as high as 84 for homosexual patients compared with 37 for nonhomosexual patients. Transplant patients have been shown to have a tenfold to 100-fold increased risk of HPV infection, anal intraepithelial neoplasia (AIN 1-3), and anogenital cancer. Benign anal disease (e.g., fistulas) is more often a complication of the neoplasm rather than the cause, though very rarely a long-standing fistula in ano can develop adenocarcinoma.

Size, location of the anal cancer, depth of penetration, and lymph node involvement are important prognostic factors. In a study comparing endoanal ultrasound (EAUS) with clinical staging in 50 patients, two thirds of patients with clinical stage 1 and 2 had evidence of muscle penetration ultrasound T staging (UT) 3-4. Overall, there was good correlation among tumor size, depth of penetration, and tumor volume. Depth of penetration has not been incorporated in
the recent tumor, node, metastasis (TNM) staging system. In a multicenter study, EAUS staging of anal cancer was more accurate in predicting tumor recurrence and survival after treatment than traditional clinical staging using tumor height. The ultrasonic T stage was the only significant factor in survival using multivariate analysis. In the presence of nodal metastasis, invasion and grade do not influence survival. Staging the tumor has no therapeutic value because most patients are treated with chemoradiation irrespective of stage. Chemoradiation successfully treats 90% of groin disease; therefore, inguinal node staging is more useful for prognosis rather than for change in therapy.