PRECISION CANCER SCREENING IN HIGH-RISK POPULATIONS: APPLICATIONS IN CERVICAL, ANAL, AND LUNG CANCERS
Robbins, Hilary A
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Cancer screening can prevent mortality and morbidity from cancer, but it also causes harms. Recently, precision (i.e. risk-based, personalized) screening approaches have emerged as a way to better balance these benefits and harms. The purpose of this dissertation was to identify opportunities for precision screening among two U.S. populations at high risk for cancer: people living with HIV and people with a history of heavy smoking. The first aim (Chapter 2) analyzed data from the Women’s Interagency HIV Study to compare cervical precancer risks between women living with HIV (WLHIV) and general population women. We used a risk benchmarking framework to draw conclusions regarding appropriate cervical cancer screening and management strategies for WLHIV. We show that current guidelines are largely appropriate, but that in some instances, considering CD4 cell count (immunosuppression status) could inform risk-tailored strategies. The second aim (Chapter 3) analyzed data from the Multicenter AIDS Cohort Study (MACS) to describe patterns of repeated anal cytology testing among HIV-positive and HIV-negative men who have sex with men (MSM). We show that approximately one-third of HIV-positive MSM have consistently negative anal cytology over 3 years, which may identify men for whom high-resolution anoscopy is unlikely to be beneficial. Following abnormal anal cytology, the next cytology is commonly negative in HIV-negative or immunocompetent HIV-positive MSM, while persistent cytological abnormality is more likely among immunosuppressed HIV-positive MSM. Finally, the third aim (Chapter 4) develops a risk model to describe how individual lung cancer risk evolved based on screening CT findings during the National Lung Screening Trial. We show that those with a negative CT screen and no emphysema or consolidation maintained reduced lung cancer risk at the next annual screen and thus might be candidates for longer screening intervals. In contrast, most false-positives experienced substantially increased lung cancer detection at the next screen, which could be stratified by accounting for specific features of lung nodules. In sum, this dissertation describes three settings in which precision cancer screening could achieve a better balance of benefits and harms for two high-risk populations. Success in implementing these approaches will require interdisciplinary efforts that engage clinicians, patients, and researchers.
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