Abstract
Social isolation is a growing public health concern, particularly among cancer survivors who face persistent challenges in maintaining social connections following treatment. While its impact on mental health is increasingly recognized, the underlying pathways and contextual differences across rural and urban settings remain underexplored. This study aimed to identify the psychosocial and personal factors that contribute to perceived social isolation among U.S. cancer survivors and to assess how isolation mediates the relationship between these factors and mental health. We also examined whether these associations differ between rural and urban populations. Data were drawn from the 2022 Health Information National Trends Survey (HINTS 6), with a subsample of cancer survivors (n = 926). A conceptual framework was developed using constructs from the Biopsychosocial Model, the Stress Process Model, the Transactional Model of Stress and Coping, and the Andersen Behavioral Model of Health Services Use. Partial Least Squares Structural Equation Modeling (PLS-SEM) was used to evaluate the relationships among personal factors (age, BMI, time since diagnosis, inability of self-care), psychosocial perceptions (perceived care quality, cancer information comprehension, negative life perception), social isolation, and mental health (PHQ-4). Multigroup analysis compared rural and urban survivors. Social isolation was a strong predictor of mental health, with key antecedents including cancer information access, inability of self-care, time since diagnosis, negative life perception, and perception of care quality. Several pathways varied by geography; for instance, the effects of self-care difficulty and care perception on isolation and mental health were significant only in urban settings. This study highlights the central role of social isolation in shaping mental health outcomes among cancer survivors and underscores the importance of targeted, context-sensitive interventions to reduce isolation and promote psychosocial well-being, particularly in underserved rural communities.