Appalachia, a region that spans 420 counties in 13 states from New York to Mississippi, has a greater proportion of residents with low socioeconomic status (SES), including lower household incomes, higher unemployment, and deficits in education compared to the United States (U.S.) as a whole. These factors contribute to disparities such as access to quality healthcare and an increased cancer burden. Cervical cancer incidence and mortality rates in Appalachia are significantly higher than among other women in the U.S. In order to understand and intervene on cancer health disparities, the Centers for Population Health and Health Disparities (CPHHD) initiative developed and tested a multi-level socio-ecological framework (Warnecke model) which included social, behavioral, environmental and biological variables as contributing and interacting factors. The Ohio State University Comprehensive Cancer Center's CPHHD (P50CA015632) used this framework to better understand why cervical cancer disparities exist and to attempt to reduce the cervical cancer burden within Appalachian Ohio.

Four studies, that spanned the Warnecke model levels of influence, were conducted to address important factors causing cervical cancer: 1) the genetic contributions to invasive cervical cancer; 2) the influence of social networks on smoking behaviors; 3) the biological effects of stress on immunity to the HPV vaccine; 4) and the effects of a multi-level intervention on uptake of the HPV vaccine among adolescent girls. The results of each study were examined on a multi-level basis and then the significant factors from each study were included in an overall multi-level model to explain the disparity of cervical cancer in Appalachian Ohio. In all, a total of 1340 participants were included in these studies.

Results from the multi-level models from each study revealed that 1) the interaction of individual risk factors and genetic mechanisms is related to cervical cancer in non-smokers; 2) in terms of tobacco use, individual factors such as age and depression as well as an individual's social network and social influence and social cohesion are relevant factors; 3) poverty, discrimination, social cohesion, neighborhood disadvantage, social support, age, SES, and depression were associated with the immune response to the HPV vaccine; and 4) the interplay of institutional structures such as healthcare systems and families, social influences, as well as SES were associated with HPV vaccine uptake among adolescent girls. Taken together, these results suggest that upstream (poverty, discrimination, health care systems, families, social cohesion, social networks, social support, social influences, and neighborhood factors) as well as downstream factors (tobacco use, age, SES, education, depression, genetics and immune function) together contribute to cervical cancer disparities in Appalachian Ohio. Interventions must now be developed and implemented across these multiple levels to reduce disparities.

Citation Format: Electra D. Paskett, Ryan Baltic, Cecilia R. DeGraffinreid, Mary Ellen Wewers, Mack T. Ruffin, IV, Christopher M. Weghorst, Thomas J. Knobloch, Mira L. Katz, Cathy M. Tatum, Michael L. Pennell, Bo Lu, Erinn M. Hade, Amy K. Ferketich. Multi-level research designs for understanding the determinants of cervical cancer disparities. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr PR03.