Abstract
Introduction
Recent studies assessing the effect of marriage on outcomes showed that marriage was associated with better survival, and the protective effect of marriage might result from that married people were associated with earlier stage and more likely to receive recommended or aggressive treatment, which was known as “spousal surveillance.”1-6 In addition, married patients were considered to have more emotional and financial support, which helps them to prolong their overall survival.7-9 However, analysis of marital subgroup, which might reveal the potential mechanism generating the influence of marital status on prognosis, was not further analyzed.
Oral tongue squamous cell carcinoma (OTSCC) is one of the most common cancers of the oral cavity and is considered to occur frequently after 40-years-old.10,11 Understanding the interaction between marital status and gender, race, and age is important for developing tailored interventions aimed at improving socio-emotional support for patients.
Therefore, the objective of this study is to assess the clinical correlates between marital status and survival and whether the association varied by gender, race and age for OTSCC using the Surveillance, Epidemiology and End Results (SEER) database.
Materials and Methods
Cohort Population
We obtained data from the current SEER database, which consists of 18 population-based cancer registries. This database collects and publishes cancer prevalence and survival data covering approximately 28% of the total population in the United States. SEER*Stat Version 8.3.4 (http://www.seer.cancer.gov/seerstat) from the National Cancer Institute was used to identify eligible patients in this study. Because the SEER database began collecting information on the presence or absence of metastases at the time of diagnosis in 2010, we included patients diagnosed with microscopically confirmed OTSCC between January 1, 2010 and December 31, 2014. We selected patients with only 1 primary malignancy in their lifetime. We excluded patients mainly because of lack of pathology type of tumor, unknown racial information, unstaged tumors or “blanks” metastatic site. A total of 5282 OTSCC patients were included.
Statistical Analysis
Descriptive statistics were used to examine the baseline characteristics of the patients. Logistic regression models evaluated the interaction and covariates on early and late stage OTSCC diagnosis. The primary study outcomes were overall survival (OS) and cancer-specific survival (CSS). OS was defined as time to the date of death due to any cause or the date of last follow-up. CSS was defined as time from initial treatment to death due to cancer. Kaplan–Meier survival curves were compared using the log-rank test. Hazard analysis was conducted using the Cox proportional hazards model. SPSS software, version 22.0 (SPSS, Chicago, IL, USA) was used for additional data processing. P value of <.05 was considered statistically significant for all tests.
Results
Clinical Characteristics of All Patients
Among the 5282 patients, the median age was 62 years old (range: 18-102 years old). More than half of patients (3098/58.7%) were males. Among the cohort of the patients, 2971(56.2%), 1242 (23.5%), and 1069 (20.2%) patients were married/partnered, divorced/separated/widowed (DSW), and never married, respectively. According to the seventh edition of UICC/AJCC Staging System (The seer database is only updated to seventh edition of UICC/AJCC Staging System when the manuscript is completed), 3180 (60.2%) and 2102 (39.8%) were stage I-II and stage III-IV, respectively. The rate of being married was higher among Asian or Caucasian, and this rate decreased with higher tumor stage. African American patients, as well as patients younger than 50 years, showed the highest rate of being single. Moreover, married/partnered patients received more surgeries. The clinicopathological features stratified by marital status at diagnosis are listed in Table 1.
Demographic Characteristics of OTSCC Patients Who Were Stratified by Marital Status.
Abbreviation: NOS, not otherwise specified.
Survival
The overall mean follow-up of all patients in the cohort was 17.0 months (range, 0-59 months). In the univariate analysis, age, gender, marital status, grade, T category, N category, distant metastases, and surgery therapies to the primary tumor were significantly associated with OS and CSS (P < .001). Kaplan–Meier analysis indicates that the married/partnered subgroup showed better OS and CSS than the unmarried groups and the DSW patients showed worse prognosis for both genders (P < .001; Figure 1).
Kaplan–Meier analysis of OS and CSS in males and females OTSCC patients. (A) OS in males OTSCC patients (log rank P < .001). (B) OS in females OTSCC patients (log rank P < 0.001). (C) CSS in males OTSCC patients (log rank P < .001). (D) CSS in females OTSCC patients (log rank P < .001).
As previous studies had shown, age, marital status, grade, T category, N category, distant metastases, and surgery therapies to the primary tumor were all independent prognostic factors in the multivariable analysis. While marriage was associated with better survival for both married male and female, we found a differential in OS based on gender, with females benefiting more than males (male P = .038; female P = .009, respectively). Patients who were DSW (male HR = 1.275, 95% CI: 1.085-1.499; female HR = 1.313, 95% CI: 1.083-1.593) and never married (male HR = 1.164, 95% CI: 0.983-1.378; female HR = 1.224, 95% CI: 0.958-1.565) had increased hazard of OS compared with married/partnered patients (male P = .038; female P = .009) (Table 2).
Multivariable Analysis of Overall Survival Stratified by Gender.
P values were calculated using an adjusted Cox proportional-hazards model.
Abbreviations: CI, confidence interval; HR, hazard ratio.
Effects of Marital Status Stratified by Subgroups
To rule out the effects of these variables and further validate the effect of marital status on OS and CSS, we conducted the subgroup analysis based on these variables (Table 3). Remarkably, the protective effect of marriage was consistent in Caucasian, whereas no significant difference was observed in Asian/African American patients. Better CSS of married/partnered patients was found only in patients aged 50 years or older who harbored non-metastatic disease and received surgery (P < .001).
The Effect of Marital Status on Overall Survival and Cancer-Specific Survival Based on Different Subgroup Variables.
P values were calculated using an adjusted Cox proportional-hazards model.
Abbreviations: CI, confidence interval; HR, hazard ratio.
Discussion
We confirmed what previous studies had shown that marital status impacted on treatment outcome of OTSCC patients in this study. Compared to other peers, the worse prognosis of DSW patients might be resulted from negative emotions and worse economic situation due to their unfavorable marital status. We further found that married/partnered females may benefit more than males. In general, males are significantly more likely to seek and utilize social support networks and affiliate with other support systems, and other non-spousal networks such as friends and other family members, especially under stress, than females. Thus, with or without a spouse, males may derive social support from other people in their lives, such as other relatives and friends. 12 To the contrary, females tend to rely heavily on spouses for social support and without additional forms of support, unmarried females are behind the eightball and maybe unable to cope with cancer disease, which would lead to delay in cancer diagnosis and treatment, leading to poorer survival outcomes. The differential protective effect of marriage based on gender among OTSCC patients is a novel finding, which is important for care planning and needs further exploration of the underlying specific mechanism behind this observation.
We then explored the effect of marital status on prognosis by different subgroups, such as age, race, stage, grade, and the surgery situation of patients. Difference of protective effect of marriage was found among variable subgroups, and the CSS benefit of being married over being DSW or single vanished in Asian/African American patients. Previous work has suggested that the effect of marriage on health may differ between African American and Caucasian married men. 13 African American men have reported lower marital quality than Caucasian men, which may adversely affect their health by increasing negative health-related behaviors and promoting stress-related immune system suppression. 14 Some literature has suggested that compared with Caucasian, marriage provides very little health-related protective effects for African Americans. 13 Social support is one mechanism that is associated with producing the protective effects of marriage.15,16 It is posited that social support produces the health benefits associated with marriage by reducing the occurrence of negative health-related behaviors and increasing the occurrence of positive health-related behaviors.15,16 However, previous work has reported African American couples are less likely to report receiving adequate social support from their spouse. 17
In further analysis, we found that the CSS benefit mostly occurred in patients aged 50 years or older who harbored non-metastatic disease and received surgery. The rate of being DSW was highest among patients aged 50 years or older and due to the data limitations of the DSW patients, the CSS benefit mostly occurred in patients aged 50 years or older. When considering patients affected by more aggressive disease, marital status was not significantly associated with higher risk of dying from OTSCC.
To the best of our knowledge, this is the first SEER analysis assessing impact of age, race and gender on the association between marital status and outcomes in OTSCC. Several limitations should be noted in this study. First, the SEER database does not include change of marital status after cancer diagnosis. Second, the lack of data on additional predictors of OS such as performance status, comorbidities, tobacco smoking, alcohol consumption, betel nut and mieng (a fermented ea-leaf) chewing, prevented us to adjust our analyses for these important factors. Finally, also due to the data limitations of the SEER database, positive surgical margins at final pathology were not able to be analyzed between marital status and CSS in this study.
Conclusion
Our results showed that while there are survival benefits for married/partnered patients with OTSCC, married females may benefit more than males. Age, race, and gender could affect the correlation between marital status and survival.
Footnotes
Availability of Data and Materials
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Consent for Publication
Not applicable.
Declaration of Conflicting Interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The study was funded by the Clinical research on health industry of Shanghai Health Commission (Grant numbers: 20214Y0025). The study was funded by the Clinical research of Shanghai Pudong District Health Commission (grant numbers: PW2022A-41).
Ethical Approval and Informed Consent
All procedures performed in studies involving human participants were in accordance with the ethical standards of Fudan University Shanghai Cancer Center Ethics committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The experimental protocols were also approved by Fudan University Shanghai Cancer Center Ethics committee. Written informed consent was obtained from all individual participants included in the study.
