Temporal Associations Between Thyroid Cancer Epidemiological Trends and Classification Revisions
4 affiliations
- 1Department of Clinical and Experimental Medicine, University of Messina, 98122 Messina, Italy
- 2Department of Mathematics, University of Wisconsin-Whitewater, 800 W. Main Street, Whitewater, WI 53190-1790, USA
- 3Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy
- 4Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, 98122 Messina, Italy
Abstract
Background/Objectives: This study evaluated potential temporal associations between international histopathological classifications, staging updates, and the long-term divergence observed between papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC) incidence trends. Applying an advanced statistical protocol comprising the recursive Supremum Chow Test, Piecewise Segmented Regression with Regime Switching (PSR-RS), and a non-linear Markov-Switching Intercept and Slope (MSIA) model, we analyzed population-level annual incidence rates (AIR) in the United States from 1975 to 2023. Methods: We implemented a two-pronged approach to identify and validate structural trend changes in incidence trends. Approach 1 tracked endogenous, data-driven incidence shifts, while Approach 2 tested the fixed calendar milestones corresponding to the official publication dates of major classifications. Crucially, this multistage analytical protocol was applied directly to the individual PTC and FTC series, as well as to the scale-independent log ratio, ln(PTC/FTC) and aggregate diagnostic gap timelines. Results: The results show that the incidence gap between the two cancers widened until 2014 and stabilized thereafter. AG quadrupled from 2.9 per 100,000 population in 1975 (PTC AIR = 3.6 minus FTC AIR = 0.7) to 11.6 in 2014 (PTC AIR = 12.8 minus FTC AIR = 1.2) with no further increase thereafter (AG = 11.6 in 2022 and 2023). Under Approach 1, the natural breakpoints partitioned the timelines into highly diverse behavioral segments. Specifically, the data identified five evolutionary regimes for PTC, three independent regimes for FTC, and four distinct regimes for AG. The breakpoint identified in 1987 coincided with the staging updates introduced that year and marked a clear change in the incidence trends of both histotypes. Between 1987 and 1991, PTC incidence increased, while FTC incidence declined toward its historical minimum. Despite these changes, the aggregate diagnostic gap continued along its existing trend, with no structural break detected. The 2004 WHO third edition corresponded to a systematic upward level shift (β2 = +4.1500) associated with the formal codification of microcarcinomas. Finally, both analytical approaches converged on 2014 as a significant historical turning point in the slowing of incidence growth. This phase is characterized by a significant negative slope change (Δβ = −0.35) consistent with conservative classification updates and subsequent stabilization at a structural plateau. Conclusions: The progressively widening AIR gap between PTC and FTC does not appear to reflect a purely biological phenomenon. Instead, these population-level changes are highly consistent with systematic reporting shifts and diagnostic thresholds introduced in successive international staging and histopathological classifications.
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BibTeX
@article{trovato2026temporal,
title = {{Temporal Associations Between Thyroid Cancer Epidemiological Trends and Classification Revisions}},
author = {Maria Trovato and Balamurugan Pandiyan and Silvia Martina Ferrari and Fausto Famà and Salvatore Benvenga},
journal = {Cancers},
year = {2026},
month = oct,
doi = {10.3390/cancers18213468},
url = {https://www.mdpi.com/2072-6694/18/21/3468},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Temporal Associations Between Thyroid Cancer Epidemiological Trends and Classification Revisions
AU - Maria Trovato
AU - Balamurugan Pandiyan
AU - Silvia Martina Ferrari
AU - Fausto Famà
AU - Salvatore Benvenga
PY - 2026
DA - 2026/10/27
JO - Cancers
DO - 10.3390/cancers18213468
UR - https://www.mdpi.com/2072-6694/18/21/3468
AB - Background/Objectives: This study evaluated potential temporal associations between international histopathological classifications, staging updates, and the long-term divergence observed between papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC) incidence trends. Applying an advanced statistical protocol comprising the recursive Supremum Chow Test, Piecewise Segmented Regression with Regime Switching (PSR-RS), and a non-linear Markov-Switching Intercept and Slope (MSIA) model, we analyzed population-level annual incidence rates (AIR) in the United States from 1975 to 2023. Methods: We implemented a two-pronged approach to identify and validate structural trend changes in incidence trends. Approach 1 tracked endogenous, data-driven incidence shifts, while Approach 2 tested the fixed calendar milestones corresponding to the official publication dates of major classifications. Crucially, this multistage analytical protocol was applied directly to the individual PTC and FTC series, as well as to the scale-independent log ratio, ln(PTC/FTC) and aggregate diagnostic gap timelines. Results: The results show that the incidence gap between the two cancers widened until 2014 and stabilized thereafter. AG quadrupled from 2.9 per 100,000 population in 1975 (PTC AIR = 3.6 minus FTC AIR = 0.7) to 11.6 in 2014 (PTC AIR = 12.8 minus FTC AIR = 1.2) with no further increase thereafter (AG = 11.6 in 2022 and 2023). Under Approach 1, the natural breakpoints partitioned the timelines into highly diverse behavioral segments. Specifically, the data identified five evolutionary regimes for PTC, three independent regimes for FTC, and four distinct regimes for AG. The breakpoint identified in 1987 coincided with the staging updates introduced that year and marked a clear change in the incidence trends of both histotypes. Between 1987 and 1991, PTC incidence increased, while FTC incidence declined toward its historical minimum. Despite these changes, the aggregate diagnostic gap continued along its existing trend, with no structural break detected. The 2004 WHO third edition corresponded to a systematic upward level shift (β2 = +4.1500) associated with the formal codification of microcarcinomas. Finally, both analytical approaches converged on 2014 as a significant historical turning point in the slowing of incidence growth. This phase is characterized by a significant negative slope change (Δβ = −0.35) consistent with conservative classification updates and subsequent stabilization at a structural plateau. Conclusions: The progressively widening AIR gap between PTC and FTC does not appear to reflect a purely biological phenomenon. Instead, these population-level changes are highly consistent with systematic reporting shifts and diagnostic thresholds introduced in successive international staging and histopathological classifications.
SN - 2072-6694
ER -