Anal cancer is a malignant tumor of the anal canal (the region from the perianal skin to the rectoanal junction). It should not be confused with colorectal cancer, as biology, pathology, and treatment differ markedly. Around 80-90% of anal cancers are squamous cell carcinomas; rarer types include adenocarcinoma, malignant melanoma, basal cell carcinoma, and neuroendocrine carcinoma. Annual incidence is low (1-2 per 100,000) but has increased steadily over recent decades, driven by rising HPV prevalence, growth of the HIV population, and limitations in screening. The highest-risk groups are HIV-positive men (particularly men who have sex with men), organ transplant recipients on immunosuppression, and women with chronic HPV infection (especially those with a history of cervical cancer).
Human papillomavirus (HPV) — particularly HPV-16 and HPV-18 — is detected in more than 90% of anal cancers and is considered the definitive etiologic agent. HPV infection drives precursor lesions such as anal intraepithelial neoplasia (AIN) and progresses over time to invasive cancer. High-risk HPV strains inactivate the p53 and Rb tumor suppressors via the E6 and E7 oncoproteins. Anal cytology screening (anal Pap smear) and high-resolution anoscopy (HRA) are recommended for high-risk populations (HIV-positive, organ transplant recipients, prior cervical cancer) to detect precursor lesions. The ANCHOR trial (2022) showed that active treatment of high-risk HSIL (high-grade squamous intraepithelial lesion) prevented progression to cancer compared with observation. HPV vaccination (Gardasil-9) prevents anal cancer when delivered at a young age (9-26).
Clinical features and treatment: Symptoms are often non-specific and mistaken for hemorrhoids, leading to delays — rectal bleeding, anal pain, itching, palpable mass, defecation problems, incontinence, fistula. Diagnosis is established by physical examination (digital rectal exam plus anoscopy) and biopsy. Staging includes pelvic MRI (primary tumor extent and lymph nodes), thoracoabdominal CT (distant metastases), and PET/CT (advanced cases). The standard since 1974 has been the Nigro protocol — concurrent chemoradiotherapy — which delivers cure rates above 80%. The standard regimen is radiotherapy (45-59 Gy with IMRT) plus concurrent 5-FU and mitomycin C, or 5-FU and cisplatin. For residual or recurrent disease, salvage abdominoperineal resection (APR — permanent colostomy) is used. Advanced or metastatic disease is treated with chemotherapy (DCF — docetaxel + cisplatin + 5-FU, or carboplatin + paclitaxel) with or without nivolumab or retifanlimab (anti-PD-1 — FDA approved). Immunotherapy is promising in HPV-positive anal cancer.