Sporadic hyperplastic polyp associated with above-average risk of developing metachronous colorectal cancer

Post-colonoscopy surveillance interval for colorectal polyps depends on the size, number, and pathological classification of removed polyps. The risk of sporadic hyperplastic polyps (HPs) for developing colorectal adenocarcinoma remains debatable due to limited data. We aimed to evaluate the risk of metachronous colorectal cancer (CRC) in patients with sporadic HPs. A total of 249 patients with historical HP(s) diagnosed in 2003 were included as the disease group, and 393 patients without any polyp as the control group. All historical HPs were reclassified into SSA or true HP based on the recent 2010 and 2019 World Health Organization (WHO) criteria. Polyp size was measured under light microscope. Patients developed CRC were identified from the Tumor Registry database. Each tumor was tested for DNA mismatch repair proteins (MMR) by immunohistochemistry. Results showed that 21 (8%) and 48 (19%) historical HPs were reclassified as SSAs based on the 2010 and 2019 WHO criteria, respectively. The mean polyp size of SSAs (6.7 mm) was significantly larger than HPs (3.3 mm) (P<0.0001). For polyp size ≥5 mm, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for diagnosing SSA was 90%, 90%, 46%, and 99%, respectively. Left-sided polyps with size <5 mm were 100% of HPs. Five of 249 (2%) patients developed metachronous CRC during the 14-year follow-up from 2003 to 2017, including 2 of 21 (9.5%) patients with SSA diagnosed at intervals of 2.5 and 7 years, and 3 of 228 (1.3%) patients with HP(s) at 7, 10.3, and 11.9 years. Two of 5 cancers showed MMR deficiency with concurrent loss of MLH1/PMS2. Based on the 2019 WHO criteria, the rate of developing metachronous CRC in patients with SSA (P=0.0116) and HP (P=0.0384) was significantly higher than the control group, and no significant difference was observed between patients with SSA and with HP (P=0.241) in this cohort. Patients with either SSA or HP also had higher risk of CRC than average-risk US population (P=0.0002 and 0.0001, respectively). Our data add a new line of evidence that patients with sporadic HP are associated with above-average risk of developing metachronous CRC. Post-polypectomy surveillance for sporadic HP may be adjusted in future practice given the low but increased risk of developing CRC.