Environmental exposure and prevalence of papillary thyroid cancer in West Virginia: An ecological analysis of per and polyfluoroalkyl substances (PFAS)–impacted regions.

6073 Background: Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants with widespread exposure through contaminated surface water, groundwater, and drinking water systems. In West Virginia, PFAS contamination has been documented across counties within the Ohio River basin and inland regions affected by industrial activity, waste disposal, and groundwater contamination. This project aimed to study the prevalence of papillary thyroid cancer at a county-level to assess geographic clustering in relation to PFAS-impacted regions and compare statewide incidence with national benchmarks. Methods: We conducted a statewide, county-level ecological analysis using Epic electronic health record-driven data to identify papillary thyroid cancer cases diagnosed between 2015 and 2025. County specific prevalence rates were calculated using averaged county population denominators. Relative risks (RR) with 95% confidence intervals were calculated for each county relative to the statewide thyroid cancer prevalence using Poisson-based methods. Spatial patterns were evaluated in relation to counties within the Ohio River basin, including the Monongahela and Kanawha sub-basins, as well as counties with documented or suspected PFAS-related groundwater contamination. Statewide thyroid cancer incidence was contextualized using U.S. Cancer Statistics (1999-2022). Results: Papillary thyroid cancer prevalence demonstrated marked geographic heterogeneity across WV, with spatial clustering observed in multiple PFAS-impacted counties. Counties with elevated prevalence demonstrated RRs ranging from approximately 1.75 to 2.75, with the highest RR observed in Harrison (RR 2.75 CI 2.35-3.22), Marion (RR 2.33 CI 1.94-2.79), Braxton (RR 2.30 CI 1.58-3.33), Barbour (RR 2.13 CI 1.50-3.00) and Webster (RR 1.98 CI 1.21-3.24) counties. All associations were statistically significant (p <0.05). Many counties outside PFAS-impacted regions demonstrated RR approximating or below 1.0. At the population level, WV demonstrated a higher thyroid cancer incidence than the U.S. overall (20.5 vs 17.4 per 100,000, age-adjusted). Conclusions: Papillary thyroid cancer in West Virginia has a spatial clustering pattern in PFAS-impacted counties and a higher statewide incidence compared with national benchmarks. Experimental evidence provides biologic plausibility, as perfluorooctanoic acid disrupts thyroid-stimulating hormone receptor signaling, impairs N-glycosylation, and promotes pro-tumorigenic cellular pathways. Although causal inference is limited by the ecologic design, the convergence of geographic clustering and elevated statewide incidence warrants further investigation of PFAS-related papillary thyroid cancer risk using exposure-resolved individual-level analytic approaches.