Jinlei Zhao

Potential Protective Effect of Statins against High-Grade Squamous Intraepithelial Lesions in Women with Metabolic Comorbidities

Abstract Background: Although human papillomavirus vaccination and Papanicolaou screening have advanced cervical cancer prevention, high-grade squamous intraepithelial lesions (HSIL) remain common, particularly among individuals with metabolic comorbidities such as diabetes and hypercholesterolemia. Statins, commonly used for lipid control, possess anti-inflammatory and antiproliferative properties that may offer protective effects against cervical dysplasia. We explored the association between statin use and lesion grade in a population of patients with dysplasia and whether effects vary by comorbidity and race. Methods: Cross-sectional, observational retrospective analysis of electronic health records and billing data for 2,378 non-Latina/e (nL) Black (nLB) and nL White patients diagnosed with low-grade squamous intraepithelial lesions or HSIL between 2014 and 2021 at a large academic medical center. Logistic regression assessed associations between statin use, comorbidity profiles (diabetes, hypercholesterolemia), race, and HSIL versus low-grade squamous intraepithelial lesions, adjusting for potential confounders. Interaction terms were tested to evaluate effect modification. Results: Statin users had significantly lower odds of HSIL than nonusers (adjusted OR = 0.48, P < 0.0001), despite being older, and having higher comorbidity rates. Predicted HSIL probabilities ranged from 4% to 20% in statin users versus 13% to 29% in nonusers. The lowest risk was observed among patients with diabetes on statins, particularly among nLB patients, suggesting a possible synergistic protective effect in metabolically vulnerable populations. Only 35% of patients with a hypercholesterolemia diagnosis listed were on statins. Conclusions: Statin use was associated with substantially lower HSIL risk, particularly among nLB patients with diabetes. Impact: These findings support further investigation of statins as a potential low-cost chemopreventive tool for cervical dysplasia, especially in populations with metabolic dysfunction.