Association of common variable immunodeficiency with NMSC: A retrospective case-control study using the trinetx dataset

Summary: Abstract Body: Common Variable Immunodeficiency (CVID) is a primary immunodeficiency that is characterized by hypogammaglobulinemia and immune dysfunction, as well as an increased risk of certain cancers. Of these, non-melanoma skin cancers (NMSC) have had conflicting evidence. It has been suggested to occur at elevated rates in certain cohorts, but also had a lack of association in others. Given these differences, this study aimed to explore such an association. This retrospective case-control study utilized the TriNetX (Cambridge, MA) United States network. Of 119,333,537 patients, 30,327 met CVID diagnosis criteria. The case group was defined using the ICD-10 code for individuals diagnosed with CVID. The control population included patients who had undergone at least one general outpatient annual physical examination and had no documented history of CVID, as identified using ICD-10 codes. An adjusted analysis with 1:1 propensity score matching between cohorts for age at index, sex, black and white ethnicity, and race was conducted. 29,529 patients were included after matching to controls. Individuals with CVID were more likely to have a diagnosis of SCC and BCC than those without CVID (SCC: OR: 3.817; 95% CI: 2.926,4.979; p<0.0001) (BCC: OR: 1.515; 95% CI: 1.228,1.868; p<0.0001). The findings suggest an increased risk of NMSC, specifically both SCC and BCC, in CVID patients. It is possible that such an increased risk could be due to the condition’s impaired T-cell-mediated immunity. Such patients have a reduced immune surveillance and thus, the body’s ability to eliminate pre-malignant cells may be impaired. The finding of increased SCC risk may mimic risks in iatrogenically immunosuppressed patients, such as organ transplant recipients. Additionally, the chronic inflammation, genetic mutations, autoimmune conditions, and infection in CVID may possibly contribute to a carcinogenic environment. Our findings underscore the need to investigate underlying physiology and enhance early detection to improve outcomes in CVID patients. Ruhi Kanwar^{1, 2}, Thomas Rohan², Vinod Nambudiri² 1. Harvard Medical School, Boston, MA, United States. 2. Dermatology, Brigham and Women's Hospital, Boston, MA, United States. UV Biology/Injury and Non-melanoma Cancers