Cancer screening aims to detect malignancy at an early, presymptomatic stage when treatment is more effective and survival is improved. Effective screening requires a disease with a detectable preclinical phase, a test with adequate sensitivity and specificity, and evidence that early detection improves outcomes (not just lead-time bias). Cancer develops through a multi-step process of genetic mutations: oncogene activation (gain of function - RAS, MYC, HER2) and tumor suppressor gene inactivation (loss of function - p53, RB, APC, BRCA1/2). The adenoma-carcinoma sequence in colorectal cancer illustrates stepwise progression: normal epithelium → aberrant crypt foci → adenomatous polyp → dysplasia → invasive carcinoma over 10-15 years, providing a window for screening and polypectomy to interrupt cancer development. USPSTF grading: Grade A and B recommendations have sufficient evidence of net benefit and should be implemented as routine care. Grade C requires shared decision-making based on individual patient factors. Grade D recommendations have evidence of no benefit or net harm and should not be performed. Grade I indicates insufficient evidence to make a recommendation. Key screening metrics: sensitivity (proportion of diseased correctly identified...