Abstract B52: Promoter methylation, stage at presentation, and neighborhood-level effects are linked to survival disparities in HNSCC patients
Authors: Lawson Fahcina P. , Folawiyo Oluwasina , Valle Blanca L. , Pirini Francesca , Turaga Nitesh , Sidransky David , Guerrero-Preston Rafael E. 
Published: May 2016

Introduction: Head and neck squamous cell carcinoma (HNSCC) survival has steadily increased over the last 50 years, but the survival gap between African Americans (AAs) and Non-Latino Whites (NLWs) has remained practically unchanged. Most of the survival differences in HNSCC survival are due to HPV infection among oropharyngeal patients, which is mostly seen in younger white males and has better prognosis than HPV-negative disease. HPV-negative HNSCC survival among AAs is associated with stage at presentation, treatment compliance, and other health services related factors. Little is known about how molecular and neighborhood-level effects are linked to HNSCC survival. Our objective is to determine the extent to which molecular alterations; clinical factors and neighborhood-level interactions are linked with HNSCC survival. We hypothesize that HNSCC survival is associated with promoter methylation and neighborhood zip code level measures of education, income, health insurance and housing variables.

Methods: We conducted a retrospective analysis in specimens collected between 1985 and 2010 from the Johns Hopkins Head and Neck Cancer tumor bank. Neighborhood-level characteristics at the zip code level were collected from the US Census Bureau. We estimated HNSCC survival linked to molecular, clinical, and neighborhood variables using the Kaplan-Meier method. The log-rank test was used to test the significance of the association between survival and the following categorical variables: promoter methylation of EDNRB, NID2, PAX5, PAX1 and tumor stage; and the following determinants of health at the zip code level: high school diploma, median family income, health insurance, home ownership rate and home vacancy rate. Cox proportional hazard regression was used to test the significance of the association between survival and the following continuous variables: promoter methylation of EDNRB, NID2, PAX5, PAX1 and the following determinants of health at the zip code level: high school diploma, median family income, health insurance, home ownership rate and home vacancy rate. We then used Cox proportional hazard models for univariate and multivariate analyses. Multiple regression models were developed to describe the relationship between HNSCC survival and differential promoter methylation, clinical factors and neighborhood-level interactions within the entire study population and among racial strata. Analyses were performed using STATA version 13.

Results: Of 117 patients, 63 AAs and 56 NLWs, AAs had significantly lower 5-year HNSCC cancer survival rates compared to NLWs (57% versus 67%). Within racial strata, multivariate analysis revealed that at the molecular level promoter methylation of EDNRB, NID2 and PAX5 are significant. At the individual level, tumor stage is a significantly strong predictor of HNSCC survival and has an increased HR for tumors that are at stage I (HR 4.3; 95% CI .94, 20) and II (HR 6.0; 95% CI 1.4, 26). At the neighborhood-level, health insurance, home ownership rate and home vacancy rate displayed an association with survival (P&lt;0.05) though hazard ratios are modest.

Conclusion: We conclude that HNSCC survival is driven by differences in promoter methylation of EDNRB, NID2 and PAX5 at the molecular-level, tumor stage at the individual-level and neighborhood-level effects such as health insurance, home ownership rate and home vacancy rate. Iterations of this work will improve our understanding of how molecular, individual and neighborhood-level factors influence cancer risk and survival, potentially leading to improved prevention and treatment strategies and the elimination of cancer health disparities.

Citation Format: Fahcina P. Lawson, Oluwasina Folawiyo, Blanca L. Valle, Francesca Pirini, Nitesh Turaga, David Sidransky, Rafael E. Guerrero-Preston. Promoter methylation, stage at presentation, and neighborhood-level effects are linked to survival disparities in HNSCC patients. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr B52.