Aetiology
Human papillomavirus (HPV) infections are common, affecting 50% of people at least once during their lifetime. HPV is transmitted by skin-to-skin or mucosa-to-mucosa contact. The infection is typically transient and asymptomatic, and is cleared by the host immune system via a cell-mediated immune response. In some people, particularly those with impaired cell-mediated immunity (e.g., people living with HIV, solid organ transplant recipients), the virus persists and viral DNA integrates into the host genome. Expression of the viral oncoproteins E6 (which binds p53) and E7 (which interacts with retinoblastoma protein Rb) eventually causes oncogenic transformation.[16]
More than 200 types of HPV exist, with differing oncogenic potential. HPV 16 and HPV 18 are high-risk types, because of their association with anal dysplasia and squamous cell carcinoma of the anus (SCCA).[16] HPV genotyping of anal squamous cell carcinoma histologic samples have shown that 95% of SCCAs are HPV positive and that HPV 16 accounted for 89% of the positive samples.[11]
Pathophysiology
The primary route of spread of anal canal cancer is direct extension into soft tissues and lymphatic pathways. Lymph from tumours at and proximal to the dentate (or pectinate) line drains to the anorectal, perirectal, paravertebral, and internal iliac nodes. Lymph from tumours distal to the dentate line drains mainly to the superficial inguinal nodes.[8] Haematogenous spread is less common.
At the time of presentation, 47% of anal carcinomas are localised, 33% have spread to regional lymph nodes, and 12.5% have distant metastases; the remainder are unstaged.[17] The para-aortic nodes and the liver are the most common sites of metastatic spread. Lungs, bones, skin, and peritoneum are less frequently affected.[4] The prevalence of metachronous inguinal node metastasis in patients who initially present with clinically negative nodes and do not receive treatment to the inguinal nodes is 6.4% for patients with T1-T2 tumours, and 16% for patients with T3-T4 tumours.[18]
Classification
American Joint Committee on Cancer TNM staging system (version 9)[2]
The American Joint Committee on Cancer staging system describes the extent of disease based on the following anatomical factors: size and extent of the primary tumour (T); regional lymph node involvement (N); and presence or absence of distant metastases (M). Non-anatomical prognostic factors (e.g., tumour grade, biomarkers) may be used to supplement the staging of certain cancers.
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