Differences in Survival between Black and White Patients with Head and Neck Squamous Cell Carcinoma: Comparison of Data from the DOD Central Cancer Registry and SEER

Head and neck squamous cell carcinoma (HNSCC) accounts for over 90% of head and neck cancers (1, 2). HNSCC arises from the mucosal lining of the aerodigestive tract involving multiple sites, including oral cavity, pharynx, larynx, nasal cavity, and other head and neck sites. For cancer of oral cavity and pharynx alone, in 2022, it was estimated that there were 54,000 patients diagnosed with the diseases and 11,230 deaths in the United States (3). Although the incidence rate of HNSCC was much higher in White population than Black population largely due to the increasing incidence of oropharyngeal cancer in White population during the past 20 years (2, 4, 5), Black patients had a higher mortality rate of the disease than their White counterpart (3, 6, 7). While there may be multiple factors related to the racial disparity, unequal access to health care may be a significant contributor in the U.S. general population (8–11). Barriers to health care access among racial minorities could lead to delayed diagnosis, advanced tumor stage at diagnosis, suboptimal treatment, and poor survival (9, 12–16).

The Department of Defense's (DOD) Military Health System (MHS) provides health care to beneficiaries with various racial background. The beneficiaries include active-duty military members, activated National Guard members, retirees (persons who retired from active-duty service), and their dependents (17). In 2021, there were approximately 9.6 million MHS beneficiaries. MHS beneficiaries receive health care free of charge or with minimal out-of-pocket cost depending on type of beneficiaries and benefit options (18). Therefore, there are no/reduced financial barriers to health care in this system, and racial differences in health care access are reduced compared with the U.S. general population. Our previous studies in the MHS found similar survival outcomes between Black patients and White patients with various cancers, such as cancers of colon (19), prostate (20), lung (21), kidney (22), and bladder (23). However, there have been no studies on racial differences in HNSCC survival within the MHS.

HNSCC is a heterogenous disease that involves multiple head and neck subsites. Oropharyngeal cancer is a type of HNSCC, which is highly associated with human papillomavirus (HPV) infection. Research has found that patients with HPV-positive oropharyngeal cancer had better survival than those of HPV-negative patients (24, 25). Among HNSCC, Black patients had lower rates of HPV positivity than White patients (2, 4). This disparity in HPV positivity between races have led to the extensive discussion on the low HPV positivity in Black patients an alternative explanation to their worse survival than White patients (26–30). Therefore, a study on HNSCC considering this aspect to the disease is significant.

In this study, we investigated whether Black and White patients with HNSCC differed in survival in the universal MHS, using data from the DOD's Central Cancer Registry (CCR). For comparison, we conducted the similar analyses using data from the NCI's Surveillance, Epidemiology and End Results (SEER) program as a representation of the U.S. general population (31). We hypothesized that Black patients and White patients with HNSCC had similar survival in CCR, while Black patients had worse survival than White patients in SEER. We further performed analysis for oropharyngeal (surrogate of the likelihood of HPV infection–related) and non-oropharyngeal sites, separately.

We used two data sources for this study: The DOD CCR and the NCI SEER program. The CCR was the DOD's cancer registry, which was described previously (32). Briefly, the CCR reported DOD beneficiaries with cancer diagnosed or treated at Military Treatment Facilities. The CCR registry collected data on demographic information, cancer diagnosis, tumor characteristics, cancer treatments, follow-up, and vital status. The CCR data collection followed the guidelines established by the North American Association of Central Cancer Registries. Patients were followed for vital status through inpatient or outpatient records, contacts with physicians and patients’ family members, verification via death certificates, the Defense Enrollment Eligibility Reporting System, the National Death Index, and other available sources.

The data from U.S. general population were obtained from the SEER program (RRID:SCR_003293). SEER is a national cancer registry program managed by NCI. SEER collects population-based cancer data in the areas served by the SEER cancer registries. SEER data include demographics, cancer diagnosis and characteristics, first course of treatment, follow-up, vital status, and other information. All SEER cancer registries follow the Commission on Cancer of the American College of Surgeons standards on follow-up and vital status. In this study, we used data from the SEER-18 registries (Atlanta, Connecticut, Detroit, Hawaii, Iowa, New Mexico, San Francisco-Oakland, Seattle-Puget Sound, Utah, Los Angeles, San Jose-Monterey, Rural Georgia, the Alaska Native, Greater California, Greater Georgia, Kentucky, Louisiana, and New Jersey), which represents 27.8% of the U.S. general population.

The study subjects were non-Hispanic Black and non-Hispanic White patients microscopically diagnosed with HNSCC between January 1, 1998 and December 31, 2014 and ages 18 years or older at the time of diagnosis. This diagnosis time frame was chosen based on the availability of the CCR data at the time of the study. The same diagnosis time frame was applied to identify patients from SEER. HNSCC was defined with the cancer site codes and squamous cell carcinoma histology (8050-8089) according to the International Classification of Diseases for Oncology, third edition (ICD-O-3; ref. 33). Patients with multiple primary cancers were excluded to minimize possible effects of multiple cancers on survival.

The study outcome was all-cause death. Cancer-specific death was not used because information on cause of death was not complete in the CCR data. Patients were followed up to death, date of last contact or December 31, 2015, the last date of the data. Patients who were alive at the end date of the data were censored. The race variable had two categories: non-Hispanic Black and non-Hispanic White. Other demographic variables included age at diagnosis, sex (men and women), year of diagnosis, marital status (married, single or never married, divorced, or separated, widowed, and unknown), and active-duty status (yes, no, and unknown, CCR patients only). Tumor variables included tumor stage (I, II, III, IV, unknown), tumor grade (well differentiated, moderately differentiated, poorly differentiated, undifferentiated, differentiation unknown) and tumor site (oral cavity, oral pharynx, pharynx other than oropharynx, larynx, other sites). Tumor stage and grade were defined and grouped according to the American Joint Committee on Cancer (AJCC)’s 6th edition criteria (34). Tumor sites were classified using the ICD-O-3 cancer site codes (33). Treatment variables included receipt of surgery (yes, no, and unknown), receipt of chemotherapy (yes, no, and unknown), and receipt of radiotherapy (yes, no, and unknown). Site-specific cancer-directed surgery codes were used to define cancer-directed surgery and classified as “Yes”, “No”, or “Unknown” following SEER guidelines. Data on chemotherapy and radiotherapy were not available in the SEER public-use database due to the issues of biases and completeness of the SEER data on these treatments (35).

This study was based on the non-identifiable CCR data approved by the Institutional Review Board of the Uniformed Services University (Bethesda, MD). The SEER deidentified data are provided by the NCI for public use.

The distributions of demographic variables, tumor characteristics, and treatment variables by race were compared for the CCR and SEER patient populations, respectively, using the χ² test. In regard to tumor stage, as SEER did not have the AJCC 6th edition or earlier edition stage data for patients with head and neck cancer diagnosed 1998 to 2003, the comparison was conducted only for the period of 2004 to 2014.

Kaplan–Meier survival curves were constructed and compared for Black and White patients for each cohort. Cox proportional hazards models were used to estimate HRs and their 95% confidence intervals (95% CI) for Black patients compared with White patients for CCR and SEER cohort, respectively, in a univariable model (model A) and multivariable models. In fitting, the multivariable models, we obtained the HRs and 95% CIs by sequentially adjusting for demographic variables (model B), tumor and treatment variables (model C), and military-specific variables (model D). As military-specific variables only applied to the CCR cohort, model D was only fitted for CCR patients. Finally, we performed stratified analysis by tumor site (oropharyngeal vs. non-oropharyngeal sites). Stratified analysis was performed on the basis of the final models adjusting for the complete set of covariates for each cohort, namely, model D for CCR and model C for SEER. The proportional hazards assumption was met for all the Cox models.

All statistical analyses were conducted using SAS software version 9.4 (SAS Institute, Inc.). All reported P values are two sided, with the significance level set at P < 0.05.

CCR data are not available for public use. Request access to DOD Cancer Registry data for research purposes should be directed to The Joint Pathology Center.

The comparisons of demographics, tumor characteristics, and treatment receipt between Black and White patients were shown in Table 1. There were 2,107 non-Hispanic White patients and 249 non-Hispanic Black patients, respectively, in the CCR cohort. The corresponding numbers were 80,525 and 12,027 in the SEER cohort.

Table 1 showed that in the CCR cohort, there were no substantial differences in the distributions of age, sex, tumor grade, and radiation treatment between Black and White patients. However, compared with White patients, Black patients had a higher percentage of being diagnosed in more recent periods, a lower percentage of being married, and a higher possibility of having unknown active-duty status than White patients. There were also differences in tumor site by race with White patients having higher percentages of oral cavity and oropharyngeal cancers and Black patients having higher percentages of laryngeal and pharyngeal cancers other than oropharyngeal cancer. Black patients were also more likely to have stage IV tumor than White patients during both the 2004–2014 and the 1998–2003 periods. The likelihood of receiving surgery was lower for Black patients. Black patients were also slightly more likely to have received chemotherapy than White patients. The median follow-up times for Black and White patients were 26 and 32 months, respectively.

Also shown in Table 1, in the SEER cohort, compared with White patients, Black patients were younger and had lower percentage of being married. Similar to the results from CCR, White patients were more likely to have oral cavity and oropharynx cancers, while larynx and pharynx cancers other than oropharynx were more common in Black patients. Black patients were also more likely to have advanced stage tumor, less likely to have well-differentiated tumor and less likely to receive surgical treatment. The median follow-up times were 20 and 37 months for Black and White patients, respectively.

Figure 1 presented the Kaplan–Meier survival curves for Black and White patients in the CCR cohort, and Fig. 2 presented the curves for them in the SEER cohort. There were no survival differences Black and White patients in the CCR cohort, while Black patients in the SEER cohort exhibited worse survival than White patients.

Table 2 showed the HRs of the models sequentially adjusted for covariates of demographics, tumor characteristics and treatments, and military-specific variables (CCR cohort only). There was no racial difference in survival between CCR White patients and Black patients in the univariable model (model A; HR = 1.13, 95% CI = 0.89–1.43). In multivariable models sequentially adjusting for demographics, tumor characteristics and treatments, military-specific variables, White patients and Black patients in the CCR cohort still exhibited similar survival. The HRs (95% CI) of models B and C were 1.20 (0.94–1.53) and 1.07 (0.83–1.37). With the addition of active-duty status, chemotherapy, and radiotherapy (covariates specific to the CCR cohort), the HR was 1.04 (0.81–1.33; model D). In contrast, Black patients in the SEER cohort consistently showed poorer survival than White patients in all models. The HRs (95% CI) from models A, B, C were 1.67 (1.63–1.71), 1.64 (1.60–1.68), and 1.47 (1.43–1.51), respectively. Notably, the differences in HRs between the two cohorts were significant, as shown that the CIs of HRs did not overlap between them. Table 3 showed the HRs of race and the adjusting variables in the fully adjusted model for both patient cohorts (model D for the CCR cohort and model C for the SEER cohort).

Table 4 showed the stratified analysis by tumor site (oropharynx vs. non-oropharynx sites). For the oropharyngeal site, Black patients and White patients in CCR had similar survival (HR = 1.06, 95% CI = 0.64–1.76). In contrast, the survival was significantly worse for Black patients than White patients in the SEER cohort (HR = 1.79, 95% = 1.69–1.91). Similar results were obtained for non-oropharyngeal sites. The HR for the CCR cohort was 0.95 (95% CI = 0.71–1.27), while the HR for the SEER cohort was 1.41 (95% CI = 1.37–1.44). Furthermore, while there were no racial differences for patients with oropharyngeal cancer or non-oropharyngeal cancers in the CCR cohort, the racial differences were significantly more evident for oropharyngeal cancer (HR = 1.79, 95% CI = 1.69–1.91) than non-oropharyngeal cancer for patients in the SEER cohort (HR = 1.41, 95% CI = 1.37–1.44).

In this study, we found no racial differences in survival among patients with HNSCC in the MHS, a health care system where medical care is free or with minimum out-of-pocket cost. In contrast, Black patients had significantly worse survival than White patients in the SEER population. Similar results were obtained when the analysis was stratified by oropharynx versus non-oropharynx sites. Our results support the benefit of equal access to care in reducing HNSCC racial disparity.

In the U.S. general population, barriers to health care access has been associated with delayed diagnosis, advanced tumor stage, suboptimal treatment, and therefore poor prognosis of cancer (36–38). Racial minorities have less access to health care system than the majority due to higher likelihood of having no health insurance, lower socioeconomic status, and other barriers (38–40). The racial disparity of HNSCC in the U.S. general population was well reported in literature (6, 7, 11, 13, 41–43), and the worse survival of Black patients was attributed to late tumor stage at diagnosis (44, 45), lower likelihood receiving treatment (9), delayed treatment (12), poor quality-of-care received (13), and higher refusal rates of suggested treatments (9). In addition, macro-level factors related to structural racism such as racial neighborhood segregation and unequal distribution of resources and hazards may also contribute to the racial disparities in cancer outcomes in the U.S. general population (46–48).

Being different from patients from the U.S. general population, beneficiaries of the MHS have universal access to health care regardless of socioeconomic status. Beneficiaries either receive health care free of charge or minimum out-of-pocket cost depending on their eligibility and benefit type (18, 49). Our previous studies showed that racial disparities in cancer outcomes were not observed among MHS beneficiaries (19–23). This study on HNSCC provides further evidence on no racial differences within the MHS.

Our results corroborated with a few previous studies conducted in the Veteran Health Administration (VHA) system, a health system that provides relatively equal access to health care to veterans. In a recent study, Voora and colleagues found that Black veterans with larynx cancer had similar overall survival and cancer-specific survival as White veterans, while both survival measures were significantly worse for Black patients than White patients from the SEER population (41). The authors attributed the findings to VHA's improved care access with medical care provided to veterans at minimum or no cost. Another study on laryngeal cancer also reported comparable outcomes between Black patients and White patients among veterans treated at a VHA medical center (50).

Although barrier to health care access have been established as a main contributing factor to HNSCC racial disparity as a whole, its role has been challenged in oropharyngeal cancer disparity. As the HPV-positive oropharyngeal cancer is associated with better prognosis (24, 25), and among patients with HNSCC, Black patients exhibit a lower prevalence of HPV positivity (2, 4). The low HPV positivity in Black patients was proposed as an alternative explanation to their worse survival than White patients for oropharyngeal cancer (26–30). In a study among non-Hispanic White patients and African Americans receiving similar multidisciplinary care at a large cancer hospital, Chen and colleagues (2009) reported similar survival for non-Hispanic White patients and African Americans with all HNSCC sites combined overall; however, the survival was significantly worse for African Americans than their White counterparts for oropharyngeal cancer (51). Given that the non-Hispanic White patients and African Americans were matched by key prognostic factors, and all patients in the study, regardless of race, received similar care in the same cancer hospital, the authors concluded that the survival disparity of oropharyngeal cancer was more likely driven by biology-based disparity (i.e., HPV) rather than health care access or treatment-related factors. Zandberg and colleagues (2016) also observed that the worse survival of Black patients persisted only for oropharyngeal cancer, while there was no racial difference for tumor sites other than oropharynx in a long-term follow-up study of patients with HNSCC receiving similar treatments in a single cancer hospital (52). In contrast, we did not observe racial difference in survival for patients with oropharyngeal cancer in the CCR cohort with universal health care access. Our findings suggest that when barriers to health care are minimized or reduced, survival is similar between Black patients and White patients even for oropharyngeal cancer. The different results between our study and the studies of Chen and colleagues (2009) or Zandberg and colleagues (2016) may not be fully understood due to the lack of HPV data in our study and their studies. Nevertheless, recent studies with HPV data showed the importance of health care access to oropharyngeal cancer disparity, despite HPV status (53), suggesting that racial difference in HPV status may not be adequate to explain the racial disparity of oropharyngeal cancer survival in the U.S. general population (42).

It was noteworthy that we found that within the SEER cohort, the racial disparity was more prominent for oropharyngeal cancer than non-oropharyngeal cancer. The very poor survival of Black patients with oropharyngeal cancer in the SEER cohort may be attributed to effects of not only inadequate care access but also low HPV positivity.

Our study has the strength of using data from both an equal access health care system (where medical care is free or with minimum out-of-pocket cost) and the U.S. general population, thus is in a unique position to compare and contrast the survival outcomes of different races in the two systems simultaneously in one study. The DOD's cancer registry and the SEER registries followed the similar data collection standards, making the data largely comparable for a single study using both resources. However, we also recognized the limitations of the current study. First, there are limitations due to the features of the cancer registry data. For example, data are not available to address the role of other potential factors, such as comorbid conditions, socioeconomic status, lifestyles, and health care behaviors, on the survival disparity. Because we were unable to use cancer-specific death as the study outcome due to the incompleteness of data for the CCR cohort, we do not exclude the possibility of the effects of comorbidities, which are related to social economic status, lifestyles, and health care behaviors, on overall survival, the outcome of our study. Second, chemotherapy and radiotherapy were not adjusted for the SEER cohort due to the lack of the data. However, as shown in the results, additionally adjusting for chemotherapy and radiotherapy did not change the results substantially for the CCR cohort, suggesting that their effects on the results might be limited given that tumor stage and other factors, which are related to treatments, were already adjusted in the models, although the residual effects of treatment still existed. Third, while oropharyngeal cancer was analyzed separately as a surrogate of the likelihood of HPV-related tumors, not all oropharyngeal cancers are related to HPV infection. Lack of HPV data limited the capability to assess its impacts on the observed racial disparity. Fourth, the statistical power of our study might be limited for some subgroup analyses due to relatively small numbers of Black patients in the CCR cohort. Fifth, some MHS beneficiaries might also be included in the SEER. However, the proportion of these individuals should be very low in the large SEER data. Furthermore, the inclusion of these individuals in SEER could have only diluted the true differences in results between the two populations. The true differences between the two would be larger. Finally, the catchment areas were different between CCR and SEER populations.

In conclusion, our study suggests that unequal access to health care may play an important role in survival disparity among patients with HNSCC and that improved access to health care could reduce the racial disparity in the U.S. general population.

K. Zhu reports grants from Uniformed Services University during the conduct of the study. No disclosures were reported by the other authors.

The contents of this publication are the sole responsibility of the author(s) and do not necessarily reflect the views, opinions, or policies of Uniformed Services University of the Health Sciences, The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., the DOD or the Departments of the Army, Navy, or Air Force. Mention of trade names, commercial products, or organizations does not imply endorsement by the U.S. Government.

J. Lin: Conceptualization, formal analysis, supervision, investigation, methodology, writing–original draft, writing–review and editing. M.I. Orestes: Conceptualization, investigation, methodology, writing–review and editing. C.D. Shriver: Conceptualization, resources, supervision, funding acquisition, investigation, methodology, writing–review and editing. K. Zhu: Conceptualization, resources, supervision, investigation, methodology, writing–review and editing.

The authors thank The Joint Pathology Center for providing the DOD CCR data and the NCI for the use of the SEER data. This project was supported by Murtha Cancer Center Research Program via Uniformed Services University of the Health Sciences (funding recipient: C.D. Shriver), under the auspices of the Henry. M. Jackson Foundation for the Advancement of Military Medicine.