Trends in incidence of esophageal squamous cell carcinoma in the United States between 2001–2021: a United States Cancer Statistics database study
Brief Report

Trends in incidence of esophageal squamous cell carcinoma in the United States between 2001–2021: a United States Cancer Statistics database study

Yazan Abboud1, Anila Vasireddy2, Jennifer M. Kolb1, Cadman L. Leggett3, Prasad G. Iyer4, Srinivas Gaddam5, Amrit K. Kamboj5

1Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA; 2Division of Internal Medicine, Pennsylvania Hospital, University of Pennsylvania Health System, Philadelphia, PA, USA; 3Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA; 4Division of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, AZ, USA; 5Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, CA, USA

Correspondence to: Amrit K. Kamboj, MD. Assistant Professor of Medicine, Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA 90048, USA. Email: kambojamrit@gmail.com.

Abstract: While there has been a growing body of literature evaluating the incidence rates and trends of esophageal adenocarcinoma (EAC) in the United States (US), there remains a paucity of data on esophageal squamous cell carcinoma (ESCC). The aim of this study was to assess the national burden of ESCC in the US across different patient populations and subgroups using a nationally representative database. ESCC incidence rates between 2001 and 2021 were collected from the United States Cancer Statistics (USCS) database, which covers approximately 98% of the US population. The rates were age-adjusted to the standard 2000 US population and were categorized by sex, age (young-onset aged <50 years and late-onset aged ³50 years), race/ethnicity, cancer stage at diagnosis, and geographical region in the US. Time-trends were calculated as annual percentage change (APC) and average annual percentage change (AAPC) via Joinpoint regression and the weighted Bayesian Information Criteria method (P<0.05). There were 99,501 patients diagnosed with ESCC between 2001–2021 (65% men, 63% non-Hispanic White, 95% older-onset, 40% from the southern region of the US, and 66% late-stage cancer). Overall ESCC incidence decreased over the study period (AAPC, −2.37%; P<0.001), and this was seen in both men (AAPC, −2.80%; P<0.001) and women (AAPC, −1.67%; P<0.001), and in both young-onset (AAPC, −3.17%; P<0.001) and older-onset ESCC (AAPC, −2.30%; P<0.001). The decrease was noted in all racial/ethnic groups except non-Hispanic American Indian/Alaskan Natives who had a stable trend (AAPC, −0.74%; P=0.34). The decline was also noted in early-stage (AAPC, −2.80%; P<0.001) and late-stage cancers (AAPC, −1.28%; P<0.001), and across all geographical regions (P<0.001). This study provides the most comprehensive analysis of ESCC trends in the US, highlighting a decline in its incidence both overall and across different subgroups over the past two decades. While the reasons behind this decline are not entirely clear, it is possible that the changing epidemiology of known risk factors of ESCC as well as advancements in endoscopic detection and treatment of squamous dysplasia may be contributing factors.

Keywords: Esophageal squamous cell carcinoma (ESCC); United States Cancer Statistics database (USCS database); esophageal cancer; squamous dysplasia

Received: 01 November 2025; Accepted: 19 December 2025; Published online: 30 December 2025.

doi: 10.21037/aoe-2025-1-32

Introduction

Esophageal cancer remains a significant global health burden, with global estimates of 604,100 new cases and 544,100 deaths in 2020 (1). The two main subtypes of esophageal cancer are esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), and their prevalence varies between different countries. While ESCC is the most common histopathological subtype of esophageal cancer globally, EAC is the more common subtype in the United States (US). Consequently, there have been several studies on the epidemiology of EAC in the US evaluating its incidence and disease burden (2,3). An analysis of the Surveillance, Epidemiology, and End Results (SEER) database consisting of 22,562 patients with EAC demonstrated that the incidence of EAC has increased between 1992 and 2019 (2). Furthermore, most recently, a population-based analysis of the United States Cancer Statistics (USCS) database consisting of 12,699 patients with young-onset EAC showed stabilization of overall EAC trends from 2001 to 2021 (3). In contrast, there remains limited data evaluating the epidemiology of ESCC in the US, especially across different demographic groups. This is particularly important given the existing racial and ethnic disparities in ESCC incidence and outcomes in the US (4). Therefore, the aim of the study was to examine incidence trends of ESCC in the US between 2001 and 2021 utilizing a nationally representative database.

Methods

The incidence rates of ESCC between 2001–2021 per 100,000 population were obtained from the USCS database and were age-adjusted to the standard 2000 US population using SEER*Stat software (version 8.4.3, National Cancer Institute) (5). The USCS database encompasses data that is combined from the two major cancer registries in the US: SEER and the National Program of Cancer Registries (NPCR). Each state in the US has a central cancer registry that collects data on patients with cancer and reports to either SEER, NPCR, or both. Data collection and input are done using standardized methodology. The collected cancer data undergoes rigorous review and quality checks through standardized methods to ensure high-quality data prior to its publication. Cancer location was chosen as located in the esophagus using the “Site record ICD-O-3/WHO 2009=8” variable, and the histopathologic diagnosis of ESCC was defined using the International Classification of Diseases for Oncology, Third Edition codes. The incidence rates of ESCC were categorized by different variables, including by sex (men and women), age (young-onset cancer defined by patients age <50 years and older-onset cancer defined by patients aged ≥50 years) (3,6,7), race/ethnicity (non-Hispanic White, non-Hispanic Black, Hispanic, non-Hispanic American Indian/Alaskan Native, and non-Hispanic Asian/Pacific Islander), cancer stage at diagnosis using the stage merged variable (early-stage defined by in-situ and localized cancer, and late-stage defined by regional and distant involvement), and geographical region in the US (Northeast, Midwest, West, and South). The study included only records of patients with known ESCC. Also, only primary tumors and one record per patient were included to avoid any data duplication. Stage-specific analysis included only tumors with a known stage at diagnosis.

Time trends of ESCC incidence rates were reported as annual percentage change (APC) and average annual percentage change (AAPC), which are regression lines that can be segmented that reflect the change of incidence rates over time (8). The trends were estimated utilizing Joinpoint Regression analysis via the Joinpoint Regression Program (version 5.2.0.0, National Cancer Institute). The program also utilizes the weighted Bayesian Information Criteria method with a two-sided P value cutoff at 0.05 for statistical significance (9).

Results

There were 99,501 patients diagnosed with ESCC in the US between 2001 and 2021 and included in the USCS database (Table 1). The majority of patients were men (65%), of non-Hispanic White race/ethnicity (63%), aged ≥50 years (95%), from the southern region of the US (40%), and had a late-stage cancer diagnosis (66%).

Table 1

Patient characteristics and trends related to ESCC in the United States between 2001–2021

   Subgroup Patients with ESCC (N=99,501)† Trends‡
Time period APC (95% CI), % P value AAPC (95% CI), % P value
   Overall 99,501 (100.0) 2001–2012 −2.96* (−3.60 to −2.63) <0.001 −2.37* (−2.55 to −2.19) <0.001
2012–2021 −1.64* (−2.09 to −0.65) 0.01
   Sex
   Males 64,024 (64.4) 2001–2013 −3.28* (−3.88 to −3.00) <0.001 −2.80* (−2.98 to −2.63) <0.001
2013–2021 −2.08* (−2.60 to −0.76) 0.01
   Females 35,477 (35.7) 2001–2004 −0.58 (−3.15 to 3.22) 0.67 −1.67* (−1.95 to −1.39) <0.001
2004–2007 −5.26 (−6.44 to 0.20) 0.05
2007–2021 −1.12* (−2.14 to −0.56) 0.02
Age groups
   Young onset (aged <50 years) 5,202 (5.2) 2001–2014 −4.39* (−10.22 to −0.76) 0.04 −3.17* (−4.22 to −2.38) <0.001
2014–2021 −0.87 (−4.06 to 10.27) 0.77
   Older onset (aged ≥50 years) 94,299 (94.8) 2001–2012 −2.84* (−3.67 to −2.51) <0.001 −2.30* (−2.49 to −2.12) <0.001
2012–2021 −1.64* (−2.08 to −0.34) 0.03
Race/ethnicity
   Non-Hispanic White 62,377 (62.7) 2001–2012 −2.36* (−3.24 to −1.98) <0.001 −1.68* (−1.90 to −1.48) <0.001
2012–2021 −0.84 (−1.38 to 0.66) 0.11
   Non-Hispanic Black 25,255 (25.4) 2001–2021 −4.81* (−5.05 to −4.61) <0.001 −4.81* (−5.05 to −4.61) <0.001
   Hispanic 6,428 (6.5) 2001–2021 −3.12* (−3.68 to −2.50) <0.001 −3.12* (−3.68 to −2.50) <0.001
   Non-Hispanic American Indian/Alaskan Native 635 (0.6) 2001–2021 −0.74 (−2.00 to 0.71) 0.34 −0.74 (−2.00 to 0.71) 0.34
   Non-Hispanic Asian/Pacific Islander 4,504 (4.5) 2001–2021 −1.55* (−2.08 to −0.90) <0.001 −1.55* (−2.08 to −0.90) <0.001
Stage at diagnosis§
   Early-stage 19,836 (19.9) 2001–2014 −5.22* (−6.07 to −4.59) <0.001 −2.80* (−3.25 to −2.41) <0.001
2014–2021 −1.85* (0.08 to 4.76) 0.04
   Late-stage 65,502 (65.8) 2001–2005 0.66 (−0.87 to 4.68) 0.37 −1.28* (−1.51 to −0.99) <0.001
2005–2021 −1.77* (−2.11 to −1.56) <0.001
Geographical region
   Northeast 20,931 (21.0) 2001–2008 −3.41* (−6.20 to −2.61) <0.001 −2.63* (−2.89 to −2.34) <0.001
2008–2021 −2.20* (−2.61 to −0.19) 0.04
   Midwest 21,185 (21.3) 2001–2007 −3.30* (−6.84 to −2.11) <0.001 −2.00* (−2.33 to −1.64) <0.001
2007–2021 −1.44 (−1.81 to 0.04) 0.05
   West 17,812 (17.9) 2001–2016 −2.61* (−4.14 to −2.21) 0.01 −2.00* (−2.42 to −1.65) <0.001
2016–2021 −0.14 (−1.93 to 4.41) 0.94
   South 39,573 (39.8) 2001–2014 −3.07* (−4.05 to −2.78) 0.002 −2.58* (−2.82 to −2.37) <0.001
2014–2021 −1.67 (−2.43 to 0.75) 0.10

Data are presented as number (%). †, data are presented as count numbers followed by percentages of the count numbers from the total cases of ESCC in the database; ‡, time-trends were computed using Joinpoint Regression Program (v5.2.0.0, NCI) with 3 maximum joinpoints allowed (4-line segments); §, data on the stage of diagnosis was not available for 14% of the study population and thus were not included in the stage-specific analysis; *, implies statistical significance (the two-sided P value cutoff was <0.05). Only patients with known variable data were included in the variable-specific subgroup and analysis. AAPC, average annual percentage change; APC, annual percentage change; CI, confidence interval; ESCC, esophageal squamous cell carcinoma; NCI, National Cancer Institute.

Overall, incidence rates of ESCC decreased between 2001 and 2021 [AAPC, −2.37%; 95% confidence interval (CI): −2.55% to −2.19%; P<0.001] (Table 1, Figure 1). This decline in incidence was noted in both men (AAPC, −2.80%; 95% CI: −2.98% to −2.63%; P<0.001) and women (AAPC, −1.67%; 95% CI: −1.95% to −1.39%; P<0.001). For age-specific trends, the declining trend was also seen in both young-onset (AAPC, −3.17%; 95% CI: −4.22% to −2.38%; P<0.001) and older-onset cancer (AAPC, −2.30%; 95% CI: −2.49% to −2.12%; P<0.001). When categorized by race/ethnic groups, all populations experienced a similar decrease in ESCC incidence except non-Hispanic American Indian/Alaskan Natives who had a stable trend (AAPC, −0.74%; 95% CI: −2.00% to 0.71%; P=0.34). The most rapid decrease was seen in non-Hispanic Blacks (AAPC, −4.81%; 95% CI: −5.05% to −4.61%; P<0.001), followed by Hispanics (AAPC, −3.12%; 95% CI: −3.68% to −2.50%; P<0.001), non-Hispanic Whites (AAPC, −1.68%; 95% CI: −1.90% to −1.48%; P<0.001), and lastly non-Hispanic Asian/Pacific Islanders (AAPC, −1.55%; 95% CI: −2.08% to −0.90%; P<0.001). For stage-specific trends, data were available for 86% of the sample size. A decrease was also noted in both early-stage (AAPC, −2.80%; 95% CI: −3.25% to −2.41%; P<0.001) and late-stage cancers (AAPC, −1.28%; 95% CI: −1.51% to −0.99%; P<0.001). When evaluating trends by geographical regions, incidence rates of ESCC were declining in all regions, most notably in the Northeast (AAPC, −2.63%; 95% CI: −2.89% to −2.34%; P<0.001), followed by the South (AAPC, −2.58%; 95% CI: −2.82% to −2.37%; P<0.001), Midwest (AAPC, −2.00%; 95% CI: −2.33% to −1.64%; P<0.001), and West (AAPC, −2.00%; 95% CI: −2.42% to −1.65%; P<0.001). Further details regarding the number and timing of joinpoints can be found in Table 1.

Figure 1 Time trends in incidence rates of esophageal squamous cell carcinoma in the United States from 2001–2021 as follows: (A) overall, and subcategorized by (B) sex, (C) age at diagnosis, and (D) stage at diagnosis.

Discussion

Our study reports the most comprehensive analysis of ESCC in the US, evaluating data from the USCS database, which covers approximately 98% of the population. We provide a national assessment of the burden of ESCC in the US and highlight epidemiologic trends of its incidence both overall and among different demographic groups. There was an overall decline in the incidence of ESCC over the past two decades, and this was also seen in different demographic subgroups, in both early- and late-stage cancer, and across different geographical areas in the US.

Consistent with our findings, a population-based analysis using the SEER 12 database consisting of 15,227 patients with ESCC also demonstrated that incidence rates of ESCC declined between 1992 and 2019 (AAPC, −2.85%) and this decrease in ESCC incidence was noted in different patient subgroups (10). While our study shows similar findings, a key distinction is that our study utilized the USCS database that covers nearly 98% of the US population, as compared to SEER 12 which covers approximately 12% of the population. When evaluating the trends by sex, prior studies demonstrated that while men tend to have higher incidence rates of ESCC than women, both groups have seen a decline in the incidence of ESCC over the past few decades (10,11). These findings are also consistent with our results which highlight that men have higher incidence rates of ESCC and have experienced a greater decline in its incidence as compared to women.

In this study, non-Hispanic Whites accounted for 63% of ESCC cases followed by non-Hispanic Blacks (25%), Hispanics (7%), and non-Hispanic Asians/Pacific Islanders (5%), and all these groups had a decline in ESCC incidence during the study timeframe. Similarly, an analysis of the SEER database showed that the incidence of ESCC has declined in most age-specific subgroups across different racial/ethnic populations in the US between 2000 and 2018 (12). Investigating racial and ethnic disparities in the occurrence of ESCC is informative given the variation in outcomes between different patient subgroups. For instance, a retrospective study consisting of 23,768 patients with ESCC utilizing the SEER database demonstrated that Black patients have worse 5-year survival rates compared to White patients (4). We also showed that the only racial/ethnic group that showed a stable, non-decreasing, trend was non-Hispanic American Indians/Alaskan Natives. Prior studies have shown that non-Hispanic American Indians/Alaskan Natives are less likely to have a healthcare provider (13), and they have the lowest rates of colorectal cancer screening in the US (14). It is possible that the stable (and not declining trend) in this group may be due to disparities in access to care or persistent exposure to risk factors (discussed below) of ESCC in this population. We found decreasing rates of ESCC incidence across various regions of the US as well as a declining trend in ESCC incidence in both early- and late-stage disease, more notably in early-stage disease, and these results also align with prior published data from the SEER database (12).

The reasons behind the steady decline in ESCC incidence over the past two decades are not entirely clear, although there exist a few different hypotheses. It is possible that the decreasing trend in ESCC incidence may be in some part due to increasing public health efforts focused on reducing rates of tobacco smoking, which is a well-established risk factor for ESCC (15,16). A nationwide survey of 1.77 million respondents demonstrated a significant decline in the rates of tobacco use in the US from a national average of 22.8% between 1992–2001 to 9.4% in 2022 (17). The decrease in the rates of alcohol consumption, another known risk factor for ESCC, across various demographics may also be contributing to the declining trend in ESCC (18). Furthermore, given that low body mass index (BMI) is a well-established risk factor for ESCC (19), the increasing rates of obesity (a risk factor for EAC) in the US over the past several decades may have influenced rates of ESCC (20). Moreover, nutritional deficiencies are another risk factor for ESCC, and these have generally declined over the past few decades (21). In addition, with increasing utilization of endoscopies along with novel advancements in imaging modalities and endoscopic techniques, early identification and management of precursor lesions such as esophageal squamous dysplasia may be increasingly feasible (22). In addition to a high-quality white light endoscopic examination, the use of chromoendoscopy with Lugol’s iodine, may help to enhance the detection of squamous dysplasia (23-25). Data is growing on the utility of endoscopic eradication therapy such as with endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD), as well as endoscopic ablation including radiofrequency ablation and cryotherapy for treatment of esophageal squamous dysplasia, given their significant role in providing adequate histologic assessment and effective treatment (26-33). However, advancements in endoscopic technology alone do not entirely explain the decline in ESCC as one would also expect an increase in the diagnosis of early-stage ESCC with the improvement in detection modalities, as compared to a decline across all stages.

This study has several strengths and limitations. The use of the USCS database allows us to capture nearly all cases of ESCC in the US and comprehensively evaluate trends in incidence across different patient populations and geographical regions. In addition, we utilized well-established statistical tools such as joinpoint regression analysis via the weighted Bayesian Information Criteria method which have been used in other epidemiologic analyses of large databases (9). Limitations of the study are inherent to most national database studies, such as the possibility of miscoding cancer, duplication of records, and the retrospective nature of the data (34). These limitations have been noted in the SEER database in the past, and given that SEER is a significant component of the USCS database, those limitations also apply to USCS. However, the USCS database utilizes several processes after data collection to ensure high-quality and standardized data reporting (35). Another limitation is the lack of data granularity in the current database hindering the identification of risk factors associated with ESCC. Therefore, we could not evaluate the trends of any risk factors associated with ESCC. The lack of data on tumor stage at diagnosis in around 14% of the patients somewhat limits the stage-specific trends. Lastly, the ecological nature of the study, the changes in the staging system over the years, and the differences in reporting race/ethnicity between different states are other limitations to consider.

Conclusions

In conclusion, this study provides a comprehensive analysis of ESCC incidence rates and trends across the US population over the past two decades. We demonstrate that the incidence rates of ESCC have significantly decreased in the US both overall and across various patient-specific and tumor-specific subgroups, and in all the geographical regions in the US. While the reasons behind this decline in ESCC incidence are not entirely clear, possible contributors include the changing epidemiology of known ESCC risk factors as well as advancements in endoscopic identification and treatment of esophageal squamous dysplasia. Further research is needed to evaluate the epidemiology of squamous dysplasia in the US and to compare the change of ESCC incidence as well as outcomes between different subgroups.

Acknowledgments

The findings from this study were presented at the American College of Gastroenterology Annual Scientific Meeting & Postgraduate Course on October 27th, 2025, in Phoenix, AZ.

Footnote

Peer Review File: Available at https://aoe.amegroups.com/article/view/10.21037/aoe-2025-1-32/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://aoe.amegroups.com/article/view/10.21037/aoe-2025-1-32/coif). A.K.K. serves as an unpaid editorial board member of Annals of Esophagus from October 2025 to December 2027. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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doi: 10.21037/aoe-2025-1-32
Cite this article as: Abboud Y, Vasireddy A, Kolb JM, Leggett CL, Iyer PG, Gaddam S, Kamboj AK. Trends in incidence of esophageal squamous cell carcinoma in the United States between 2001–2021: a United States Cancer Statistics database study. Ann Esophagus 2025;8:28.

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