CARE

Community Access Resources and Education (CARE) 

A team of investigators from The Ohio State University and the University of Michigan will collaborate on Ohio State’s Center for Population Health and Health Disparities, which focuses on an important health disparity – cancer – among an underserved Appalachian population. The Center (CARE II) builds upon results of CARE I and continues to focus on the goal of understanding why cervical cancer incidence and mortality rates are higher in Appalachia Ohio and West Virginia. This goal will be accomplished using four core principles:

1. The social determinants of health framework
2. Community-based participatory research
3. Multi-level framework (“from cells to society”)
4. Transdisciplinary team of researchers and community members

Four inter-related projects, an Administrative Core and a Shared Resources Core will support the work of the Center and will examine factors related to the high rates of cervical cancer from genetic to policy/access issues using a range of studies from observational to randomized designs. A Training and Career Development Program will train the next generation of transdisciplinary health disparities researchers. All studies will be conducted in community-based settings which represent the more underserved population of women in the region. We will utilize the Center’s advisory committees, community partners and participating clinics to facilitate the accomplishment of the Center’s goals.

Projects

Projects will use a “core” set of survey measures and directly address results found in CARE I. The Center has an institutional commitment (personnel, funds and space) and is dedicated to focusing on the problem of health disparities in the Appalachian region. Team members have worked together in CARE I and have an established relationship with Appalachian communities for the purpose of fulfilling the vision of the Center: to reduce cancer health disparities in Appalachia.

Project 1 – Inherited and Somatic Alterations of the TGF-ß Ligand and Receptor Complex in Cervical Cancer

PI: Chris Weghorst, PhD

Invasive cervical cancer (ICC) is the most common cause of cancer death worldwide, and while decreasing in prevalence in the majority of the developed world, this disease continues to disproportionately affect certain populations in the United States (US). In particular, the rate of ICC incidence and mortality in Appalachian women is the highest in the US. While many risk factors are known to influence ICC development, little is known about the role of hereditary and genetic susceptibility factors. The transforming growth factor beta (TGF-ß) is a universal critical regulator of various cellular functions, including cell proliferation, via its binding with a receptor’s complex on the cell surface. Cancer cells frequently avoid the inhibitory influence of TGF-ß on cell proliferation via somatic inactivation of key components of the signaling pathway, including the ligand and receptor complex.  Additionally, germline polymorphisms in the ligand and receptors have been associated with cancer development and increased cancer susceptibility. In this proposal, we hypothesize that the increased incidence of ICC observed in Appalachian women over their non-Appalachian counterparts is due in part to inherited and somatic alteration of the TGF-ß ligand and receptor complex that can be further potentiated in association with various environmental, behavioral and socioeconomic risk factors. Specifically, we will determine prevalence of inherited polymorphic and somatically-acquired variants of key TGF-ß pathway components in a large cohort of Appalachian ICC patients compared to healthy Appalachian women. Furthermore, we will determine whether these genetic alterations contribute individually or in combination with other known environmental (Human Papillomavirus, Epstein-Barr Virus), behavioral (smoking) and social (stress, social networks) risk factors, to the increased susceptibility of Appalachian women to ICC development.

Project 2 – Social Networks and Tobacco Use Among Ohio Appalachian Women

PI: Mary Ellen Wewers, RN, PhD, MPH 

Tobacco use remains a significant public health problem and is increasingly prevalent among vulnerable groups. Appalachian women have a high prevalence of tobacco use and are at increased risk for tobacco-attributable diseases, including cervical cancer. Little is known about the association of social-contextual factors that may modify or mediate the success of a cessation intervention, including the social network of a woman smoker. A social network may play a critical role in persistent tobacco use, or conversely, during attempts to quit smoking. These factors may be of particular relevance among disadvantaged smokers, especially in regions where tobacco use is normative. The purposes of this application are to:

1. Characterize the social networks of women (never, former and current smokers) in Ohio Appalachian counties
2. Determine the association between selected individual, interpersonal, workplace and neighborhood/community-related characteristics and social networks among women in Ohio Appalachian counties
3. Determine the association between selected individual, interpersonal, workplace andneighborhood/community-related characteristics and smoking status within the social networks among women in Ohio Appalachian counties

A fourth exploratory aim will develop and test the feasibility of a social network-based cessation intervention among Ohio Appalachian women who smoke. Using a cross-sectional design, 400 female residents from four Appalachian health clinics will be randomly selected and invited to participate in a face-to-face interview. Their social network will be characterized and data about individual, interpersonal, workplace and neighborhood/community-related characteristics and smoking status within the social networks will be obtained. Networks will be analyzed for size, including effective size; relationships among members, including maximum numbers; density; redundancy or constraint; percentage of smokers in network; ratio of smokers to non-smokers; and the structural equivalence with the ego (woman participant). Separate regression analyses will be performed to determine the association between individual, interpersonal, workplace and neighborhood/community-related characteristics and each dimension of the social network and smoking status of the participants. In the exploratory aim, focus groups will be conducted to assist in the development of a social network-based cessation intervention. A feasibility test of the intervention will be completed with 12 participants and their social network members. 

Project 3 – HPV Immunization Response and Stress (HIRS)

PI: Mack Ruffin, MD

A quadrivalent HPV 6, 11, 16, 18 vaccine (Gardasil®) has been approved for use among women age 9-26 years to prevent cervical/vaginal/vulvar cancer and genital warts. The efficacy of the vaccine has been demonstrated in clinical trial settings, but the effectiveness of this vaccine has not been tested in clinical practice settings. Patients experiencing greater stress have a reduced capacity to mount an immune response to other types of vaccine. The same phenomenon is likely to exist for Gardasil®, but there are no data. The impact of psychological stress on the immune response to a vaccine is proposed to act via health behaviors (multiple lifetime sexual partners, never using condoms, prior abnormal Pap smear, smoking and HPV infection) or by direct dysregulation of the immune system. We have found higher rates of cervical HPV in Appalachian Ohio women, higher rates of abnormal cervical cytology, and very high rates of psychological stress compared to urban and suburban women. The goal of this study is to determine if, in women age 18-26 years given Gardasil® vaccine, serum HPV 6/11/16/18 antibody response is altered by stress. This will be accomplished by a study of 438 women age 18-26 years who report full range of life stressors recruited from Appalachian Ohio. All participants will receive the Gardasil® vaccine at baseline, two months and six months. Prior to vaccination, questionnaire data related to HPV exposure risk behaviors and psychological stressors will be collected. Cervical samples will be collected for cytology and HPV testing. Serum samples will be collected for HPV 6, 11, 16 and 18 antibody assays at baseline and month 12. The questionnaire data and serum samples will be repeated at 12 months. The primary outcome measure is the difference in serum antibodies to HPV 6, 11, 16 and 18 at baseline and month 12. The variables of interest are perceived stress, sexual behaviors, socioeconomic status, access to health care (health insurance yes/no), smoking, Appalachian self-identity, HPV cervical status at baseline and past history abnormal cervical cytology, as proposed in a psychoneuroimmunology model. In this model, Appalachian Self-Identity, socioeconomic status, loneliness, health care access and coping are proposed to contribute to a woman’s perceived stress. The impact of perceived stress on  immune response to Gardasil® vaccination can be by health behaviors such as multiple lifetime sexual partners (>4), never using condoms, prior abnormal Pap smear, smoking and HPV status at the time of vaccination. Perceived stress can have a direct physiologic impact on the immune response by creating immune dysregulation as measured by increased EBV VCA-IgG titers. Depressive symptoms can mediate the impact of perceived stress on immune function. If psychological stress is found to modulate the immune response to Gardasil®, then we can determine if the modulation reduces the clinical effectiveness of the vaccine and examine methods to limit the impact of stress.

Project 4 – Study to Examine Patient/Provider Systems (STEPS)

PI: Electra Paskett, PhD

Certain segments of the population have persistent increased cervical cancer incidence and mortality rates because women living in the US have not benefited equally from cervical cancer screening, follow-up of abnormal Pap smears, and HPV vaccination. One example of a population group still experiencing elevated cervical cancer rates is women living in the Appalachian region of the US. The Ohio State University (OSU) Center for Population Health and Health Disparities (CPHHD), Community Awareness, Resources, and Education (CARE I) was focused on why women living in Ohio Appalachia have an elevated burden from cervical cancer. From CARE I, we learned that Ohio Appalachian women have a high prevalence of HPV types 6,11,16,18 compared to US rates, respectively (12.0 percent vs. 3.4 percent). Thus, HPV is a major problem in this population, and ways to address elevated HPV rates are needed.

A transdisciplinary health disparities research team at Ohio State and community partners from Ohio Appalachia propose to conduct “STEPS” (Study to Examine Parent/Provider Systems). “STEPS to prevent cervical cancer” will address the cervical cancer burden in Ohio Appalachia by focusing on improving HPV vaccination rates among young girls and female adolescents by using a multi-level intervention approach delivered in health departments. The goal of this proposal is to develop and test a culturally appropriate multi-level educational intervention intended for parents (level 1) of young girls living in Ohio Appalachia who seek care at participating health departments, health care providers (level 2) practicing at these health departments, and health departments (level 3) in Ohio Appalachia to increase HPV vaccination rates among young girls and female adolescents.

The specific aims are to: 

1. Develop the multi-level HPV vaccine educational intervention directed at three levels within participating health departments that includes information about cervical cancer, cervical cancer screening, HPV, the HPV vaccine, communication skills training to improve parent-health care provider conversations about the HPV vaccine and organizational level components
2. Evaluate the effectiveness of the multi-level HPV vaccine educational intervention in a group randomized controlled trial in 12 Ohio Appalachia public health departments. Specific aims will be carried out using community-based participatory research (CBPR) principles and in partnership with parents, health care providers and health departments in Ohio Appalachia

If effective, this multi-level intervention could be disseminated and used to improve the delivery of the HPV vaccine in other Appalachian locations and address the elevated cervical cancer rates in Appalachia. This project is in line with the theme of the renewal of the Ohio State CPHHD, reducing cervical cancer in Appalachia, using a Social Determinants of Health conceptual model and building upon the results of CARE I.

Cores

Administrative Core

The overall role of the Administrative Core (AC) is to ensure that the theme of the Center, reducing cervical cancer in Appalachia, and the goals of the projects, core and the training program are accomplished. The AC is structured into two groups, the Steering Committee (SC) and the Administrative Services (AS) Team, to accomplish the following specific aims:

1. Provide research direction by setting the research agenda focused on addressing cervical cancer disparities in Appalachia, promoting transdisciplinary research and increasing student trainee, post-doctoral, and faculty involvement in research
2. Promote integration of the Center projects, cores and the training program as well as promoting interaction among the investigators, the Appalachian communities and participating community clinics
3. Ensure operational efficiency for all projects and cores of the Center, including assuring Data and Safety Monitoring Board (DSMB) reviews
4. Foster dissemination of research findings, including data sharing and caBIG participation
5. Collaborate with NIH funding agencies and other funded centers to exchange, evaluate and develop data items, strategies, cross-center research initiatives and manuscripts as appropriate

The AC in this center builds upon the successful experience of the Administrative Core for the previous Ohio State Center for Population Health and Health Disparities (CPHHD) which was named Community Awareness Resources and Education (CAREI).

Shared Resources Core

The Shared Resources Core for this Center consists of two sections: the Measurement and Analysis Core (MAC) and the Clinical Correlates Core (CCC). Each section is described below, including how each interacts with the other components of the Center to support the goal of the Center: reducing cervical cancer in Appalachia. This Core builds upon and continues the work of the Cores in the prior Ohio State University (OSU) Center for Population Health and Health Disparities (CPHHD).

Measurement and Analysis CORE (MAC)

The MAC plays a pivotal role of ensuring that all individual projects achieve their research goals and objectives. The MAC provides project investigators with a centralized resource for recruitment, survey design, data collection, data management and statistical expertise and support. Specific study aims include:

1. Providing recruitment and accrual assistance and consultation to all projects
2. Providing guidance and assistance in developing, testing and implementing data collection tools, including hiring, training and supervising interviewers; designing and conducting surveys and focus groups; and monitoring the data collection process, as well as quality control
3. Developing, testing and maintaining data management systems to allow investigators to effectively and efficiently manage, store and analyze their data
4. Overseeing and conducting statistical analysis of data generated by the projects, including both descriptive summary statistics and inferential methods, as well as modification and/or development of new statistical methodologies, when/if the need arises, to directly support the research projects relevant to the Center

The MAC works with the Administrative Core (AC) to provide necessary information for all Data and Safety Monitoring Board (DSMB) meetings, such as accrual rates, analysis plans and results. And the MAC works with Ohio State’s Comprehensive Cancer Center (OSUCCC) Recruitment, Intervention and Survey Shared Resource (RISSR) to assist all projects with participant recruitment and development of data collection tools.

Clinical Correlates Core

The Clinical Correlates Core (CCC) provides a centralized laboratory collection/distribution unit to support the work of the projects within this Center. In addition, core laboratories at Ohio State receive specimens for analysis. The primary functions of the CCC are to collect, catalog, track and analyze specimens and provide data to the MAC on results of the analysis of specimens in order to accomplish the objectives of Center projects. The use of this core is beneficial in regards to reducing cost and increasing efficiency of analyses. The reproducibility of each analysis is enhanced by the use of this core. Detailed tracking of specimens is included to ensure the integrity of the specimens and reduce loss. The overall goal of the CCC is to maintain a centralized specimen repository. The specific aims are to:

1. Obtain and preserve the integrity of the specimens collected in Projects 1 (Dr. Chris Weghorst, PI) and Project 3 (Dr. Mack Ruffin, PI)
2. Ensure accurate collection, cataloging, tracking and analysis of the specimens
3. Submit data from analysis of specimens to the MAC for integration into the Center database
4. Facilitate the ability of the projects of the Center to complete their specified aims

Training and Development Core

This component of the Ohio State Center for Population Health and Health Disparities (CPHHD) develops, implements and evaluates a Training and Career Development Program (TCDP) in cancer health disparities. The overall goal of the TCDP is to help prepare the next generation of health disparities researchers by offering training that emphasizes transdisciplinary science and multi-level approaches to address cervical cancer health disparities among Appalachian populations. The TCDP is open to students, postdoctoral trainees and junior faculty in behavioral sciences, public health, nursing, basic sciences and related disciplines. Postdoctoral trainees will be supported by the TCDP while students and junior faculty will have opportunities to participate in program initiatives and the Center’s research projects.

This transdisciplinary training program will prepare trainees for work in collaborative teams. The Center investigators have extensive experience with research in Appalachia and the expertise to provide this focused training.

This training program expands training capacity, and helps to fill a void in training focused on cancer health disparities. This program builds on the solid foundation established over the last five years of the Ohio State CPHHD and will provide additional capacity for training the next generation of health disparities researchers with expertise in issues related to cancer prevention and control among Appalachian populations.

The specific aims of the training program are to:

1. Recruit postdoctoral trainees to a transdisciplinary training program in health disparities research that includes: a) a specialized curriculum of instruction, b) mentored research experiences, and c) development of an NIH grant proposal
2. Provide opportunities for students and junior faculty at Ohio State to participate in the Center’s research projects and special program initiatives
3. Conduct continuous process evaluation and annual outcome evaluation of the training program and provide feedback to Center leadership