Global Epidemiological Insights: Temporal Trends and Disparities in Oral Cavity Cancer Mortality in the United States, 1999-2024

Oral cancer constitutes a significant public health burden globally and has long been associated with substantial socioeconomic, racial, and regional disparities worldwide. Population-level mortality surveillance in high-income countries such as the United States can provide crucial epidemiological evidence and methodological references for global cancer control and prevention strategies. However, national-level updated evidence on long-term trends, subgroup heterogeneity, and pre- and post-COVID-19 pandemic trends in oral cancer mortality in the United States remains limited. This study assesses the temporal trends and differences in oral cancer mortality in the United States from 1999 to 2024.

Mortality data were extracted from the CDC WONDER Underlying Cause of Death database. Overall oral cavity cancer was defined using ICD-10 codes C00-C06, while subsite analyses focused on C02-C06. Adults aged 25 years and older were included. Joinpoint regression was used to analyse temporal trends in age-adjusted mortality rates (AAMRs, per 100,000 population) and to estimate annual percent change (APC) and average annual percent change (AAPC), with stratification by sex, region, and subsite. In addition, custom time intervals of 1999-2019 and 2020-2024 were specified to assess trend changes before and during the pandemic period. A supplementary age-stratified analysis comparing adults aged 25 to 44 years and those aged ≥45 years was also performed.

Overall oral cavity cancer mortality exhibited one joinpoint in 2009. Mortality declined significantly from 1999 to 2009 (APC = -1.81%, 95% CI: -2.48% to -1.28%, P < .001), but increased significantly from 2009 to 2024 (APC=1.29%, 95% CI: 0.99% to 1.66%, P < .001), whereas the AAPC for the full study period was not statistically significant (0.04%, 95% CI:-0.11% to 0.19%, P = .624). Mortality rates were consistently higher in males than in females, and pairwise comparison showed that sex-specific trends were neither parallel nor coincident (parallelism P = .012; coincidence P = .001). All 4 U.S. Census regions demonstrated an initial decline followed by a later rebound, although only the Midwest showed a significant net increase over the full study period. Marked heterogeneity was observed across subsites: tongue cancer (C02) was the only subsite with a significantly increased AAPC over the full study period, whereas floor-of-mouth cancer (C04) and palate cancer (C05) showed sustained net declines. Custom interval analyses further demonstrated a declining trend before the pandemic (1999-2019; AAPC=-0.2709%, 95% CI:-0.4281 to -0.1087, P < .001) and an increasing trend during the pandemic period (2020-2024; AAPC=1.2879%, 95% CI: 0.9922 to 1.6558, P < .001). Significant sex-based differences were observed, with additional heterogeneity across regions and subsites. In supplementary age-stratified analyses, no significant joinpoint was identified among adults aged 25-44 years, whereas adults aged ≥45 years showed a significant reversal in mortality trend, suggesting that the overall mortality rebound was driven predominantly by the older age group.

In the United States, oral cavity cancer mortality shifted from a declining trend to a sustained increase around 2009 and accelerated further during 2020-2024, indicating a biphasic rather than a simple linear pattern. Substantial heterogeneity was observed across sex, region, and subsite. Tongue cancer may have been a major contributor to the recent rebound in mortality, while the post-2020 trend reversal underscores the need to further examine the potential effects of diagnostic delay, disparities in healthcare access, and post-pandemic health system recovery on oral cavity cancer outcomes. Supplementary analyses further suggest that this mortality reversal was concentrated mainly in adults aged ≥45 years rather than in younger adults.