Lung cancer is the leading cause of cancer-related mortality in the US, with more lives lost due to lung cancer than to breast, prostate, and colorectal cancers combined. Based on the National LungScreening Trial, which showed that low-dose computed tomography (lung screening) vs. chest X-ray reduced mortality due to lung cancer by 20%, the US Preventive Services Task Force recommends annual lung screening for asymptomatic high risk individuals. Despite this recommendation, utilization is poor (3%-20%). Lung screening may be particularly beneficial for people with HIV (PWH), because they are more likely to have higher incidence, advanced disease, lower survival, and lower screening rates compared to the general population. The causes of these disparities are multifactorial due to smoking induced DNA-damage, immune dysregulation and chronic inflammation and lung cancer risk, and finally, the effects of structural factors that affect lung cancer in PWH.
Current lung cancer screening risk assessment tools do not consider HIV status despite it being an independent risk factor for lung cancer after adjusting for age and smoking status. The screening guidelines recommend lung screening initiation at age 50, older than the ages at presentation of most PWH. This situation is confounded by low rates of lung cancer screening among PHW. The proposed study will evaluate current lung cancer risk assessment tools for accuracy in predicting lung cancer and modify and evaluate an adapted risk tool that includes HIV-related factors.
Dr. Williams and her team will leverage extant real-world data from the DC Cohort and the Women's Interagency HIV Study and the Multicenter AIDS Cohort Study (MWCCS) to achieve the following aims: Aim 1: Modify the PLCOm2012 model to include HIV-related parameters (e.g., Nadir CD4, viral load) and evaluate the performance characteristics (AUC, sensitivity, and specificity) of the PLCOm2012 HIV-adapted model vs. the PLCOm2012 model vs. the 2021 USPSTF criteria in the DC Cohort. They will conduct a secondary data analysis using the DC Cohort of PWH (N=12,079) with (cases: N=96) and without lung cancer (non-cases). Aim 2: Perform preliminary validation of the PLCOm2012 HIV-adapted model using the MWCCS study samples of lung cancer cases (N=71) and non-cases (N=3,549).
The potential of this project to inform lung screening guidelines, future decision tools, and personalize strategies to the unique risks for lung cancer among PWH is highly innovative and needed to reduce lung cancer mortality in this priority population.
Project Summary provided by the investigator