Abstract: Objective To compare the efficacy of the high⁃risk factor questionnaire (HRFQ) and the immune fecal occult blood test (iFOBT) in colorectal cancer screening, and to provide evidence for optimizing early screening strategies. Methods A cross⁃sectional study design was adopted, involving participants scheduled for colonoscopy from Beijing between June 2024 and March 2025. The diagnostic efficacy of HRFQ and iFOBT, both individually and in combination, for detecting colorectal tumors was assessed, using colonoscopy and pathological results serving as the gold standard for evaluation.  Results A total of  920 participants were recruited, with 655 completing the HRFQ，and the high⁃risk rate was 41.98% (275/655). Among these, 557 underwent colonoscopy, resulting in an overall colorectal tumor detection rate of 47.22% (263/557). The HRFQ high⁃risk group (n=243) demonstrated a higher colorectal tumor detection rate than the low⁃risk group (n=314) (54.73% vs 41.40%, P=0.002), the non⁃advanced adenoma detection rate was also higher in the high⁃risk group (35.80% vs 27.07%， P=0.027), whereas no significant differences were observed in the detection rates of advanced adenoma or colorectal cancer. Among the 571 participants who completed iFOBT testing, the positive rate was 25.74% (147/571). Among these, 517 underwent colonoscopy，and the iFOBT⁃positive group （n=133） showed significantly higher detection rates for overall colorectal tumor (60.90% vs 42.96%，  P<0.001) , advanced adenoma （22.56% vs 8.60% ， P<0.001） and colorectal cancer （18.05% vs 0.78%， P<0.001） compared to the iFOBT⁃negative group （n=384）. In serial testing (HRFQ high⁃risk and iFOBT positive), the colorectal cancer detection rate reached 16.92%（11/65）. In parallel testing , the detection rates for both colorectal cancer and non⁃advanced adenoma in the HRFQ high⁃risk or iFOBT positive screening mode were elevated compared to the HRFQ low⁃risk or iFOBT negative screening mode (8.94% vs 0， 31.79% vs 9.77%， P<0.001), while the detection rate of non⁃neoplastic lesions decreased (45.36% vs 80.46%, P<0.001). The sensitivity, specificity and overall accuracy of HRFQ in the diagnosis of colorectal tumors were 50.57%, 62.59% and 56.91%, respectively; and those of iFOBT were 32.93%, 80.81% and 50.03%, respectively; the parallel screening (HRFQ high⁃risk or iFOBT positive) yielded 79.71%, 55.81% and 65.38%, respectively. The sensitivity of HRFQ or iFOBT individually and in combination (HRFQ high⁃risk or iFOBT positive) for colorectal cancer screening was 50.00%, 88.89% and 100.00%, respectively. Conclusions HRFQ is suitable for initial screening of non⁃advanced adenomas, while iFOBT demonstrates greater advantage in detecting advanced lesions. The integration  of both methods significantly enhances the sensitivity of colorectal tumor screening, particularly for advanced lesions, thereby optimizing optimizes screening efficiency and providing a new strategy for early colorectal cancer screening.

Key words: Colorectal neoplasms, Advanced adenomas, Screening, High?risk factor questionnaire, Immune fecal occult blood test