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The anal canal is lined from its proximal to distal extent by columnar, transitional, and non-keratinized squamous epithelium, which merges at the anal verge with the keratinized perianal skin.Cancers arising from the mucosa of the anal canal are relatively rare, comprising only 2% of all GI malignancies. Anal carcinoma occurred in an estimated 8590 patients in the United States in 2020, more commonly in women than men (2:1 ratio). Squamous cell carcinomas (SCC) make up the majority of anal cancers; adenocarcinomas account for the remainder but are uncommon.

Over 90% of anal cancers are associated with HPV infections (most commonly, HPV-16 and -18). HPV vaccination in adolescents prior to sexual activity appears reduces the incidence of anal HPV-16 and -18 infections. Anal cancer is increased among women with HPV-associated cervical, vulvar or vaginal squamous intraepithelial lesions (CIN grade 3) or cancer, among men who are having sex with men, and among women and men who have HIV or have received a solid organ transplant.

Identification and screening of high-risk individuals with HPV testing and anal cytology facilitates detection of anal low- and high-grade squamous intraepithelial lesions (LSIL and HSIL, respectively) and early-stage cancers. Anoscopy (preferably high-resolution) with biopsy is warranted in patients with positive cytology. It is hypothesized that early detection and treatment of HSIL with either topical treatment or surgical ablation may reduce progression to advanced cancer. However, this has not yet been shown in prospective randomized studies and topical therapies are not yet FDA-approved. Testing for high-risk HPV has high sensitivity for anal intraepithelial neoplasia (AIN) but low specificity; anal cytology has high sensitivity (~74-87%) but lower specificity (~44–66%) for identifying high-grade AIN.

The most common symptoms of anal carcinoma are bleeding, pain, and local mass. The lesion is often confused with hemorrhoids or other common anal disorders. These tumors tend to become annular, invade the sphincter, and spread upward via the lymphatics into the perirectal mesenteric lymphatic nodes. CT or MRI scans of the abdomen and pelvis are required to identify regional lymphadenopathy or metastatic disease at diagnosis; PET imaging may be used in conjunction.

Treatment depends on the tumor location, histology, and stage. Well-differentiated and small (less than 2 cm) superficial lesions of the perianal skin may be treated with wide local excision.

squamous cell carcinoma of the anal canal as well as large perianal tumors invading the sphincter or rectum are treated with combined-modality external radiation with simultaneous chemotherapy (5-fluorouracil plus mitomycin). Local control is achieved in approximately 80% of patients. Radical surgery (abdominoperineal resection) is reserved for patients who fail chemotherapy and radiation therapy. Following completion of chemoradiation therapy, tumors may continue to regress for up to 26 weeks. Surveillance includes DRE, anoscopy, and inguinal lymph node palpation every 3–6 months for 5 years as well as CT scans of the chest, abdomen, and pelvis annually for 3 years.

The 5-year survival rate ...

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