Effects of Marital Status on Hypopharynx Squamous Cell Carcinoma Survival Stratified by Demographic and Pathological Factors: A Retrospective Study

Abstract

Objectives: 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 explore the correlation between marital status and hypopharynx squamous cell carcinoma (SCC) and whether the association varied by age, race, and gender. Methods: We examined the clinicopathological variables using chi-squared tests and we evaluated the association between survival and different variables using the methods of Kaplan-Meier. Univariate and multivariate analyses were performed to determine the effects of each variable on survival. Results: A total of 1686 patients were analyzed. The rate of being married was lower among African American, and this rate decreased with higher tumor stage. While both married male and female survivors benefit from their marital status, subgroups analysis shows a differential in overall survival (OS) based on gender, with males benefiting more than females. Patients who were divorced/separated [male hazard ratio (HR) = 1.214, 95% confidence interval (CI): 0.985-1.495; female HR = 1. 159, 95% CI: 0.691-1.945], never married (male HR = 1.476, 95% CI: 1.234-1.765; female HR = 1.422, 95% CI: 0.901-2.245), and widowed (male HR = 1.795, 95% CI: 1.390-2.317; female HR = 1.663, 95% CI: 1.081-2.559) had increased hazard of OS compared with married/partnered patients. The effect of marital status was significantly associated with treatment outcome only in Caucasian patients who harbored well/moderately differentiated and nonmetastatic disease (P < .001). Conclusion: While there are survival benefits for married patients with hypopharynx SCC, married/partnered males may benefit more than females. Age, race, and gender could affect the correlation between marital status and survival.

Keywords

hypopharynx squamous cell carcinoma marital status gender age race prognosis

Introduction

It is a common understanding that social support, especially spousal support, plays an important role in improving cancer outcomes.^1-6 In addition, many researches in recent years have demonstrated that marital status could independently affect survival in several cancer types.^7-9 However, further analysis of marital subgroups was neglected, which might reveal the potential mechanism generating the influence of marital status on prognosis.

Hypopharynx squamous cell carcinoma (SCC) is one of the most frequent head and neck cancers (HNSCC), and is considered to occur frequently after 40 years of age.^10,11 About 2500 to 3000 cases of hypopharyngeal cancer (HC) are diagnosed annually in the United States, with a 5 year overall survival (OS) of only 30% to 33%.^12-14 Multiple primary SCC of the head and neck is increasing in frequency, especially in the hypopharynx and esophagus.^15-19 According to the Surveillance Epidemiology and End Results (SEER) database, the percentage of cases diagnosed in a localized stage decreased from 23.0% to 9.3% during 1974 to 1999; disease with distant-stage decreased from 25.7% to 18.6%.^12-14 Compared with the dismal 5 year OS of one-third for HC, localized disease has a survival rate of 56.0%.^12-14 Human papilloma virus (HPV)-associated head and neck carcinoma is quite heterogeneous and most of the tumors arise in the oral cavity, oropharynx, hypopharynx, and larynx.^20-25 In addition to HPV exposure, tobacco and alcohol are very strongly associated with the development of HC.^26-28 The efficacy of the current HPV vaccines, Cervarix and Gardasil, in preventing HPV-related HNSCC is at present unknown. Any reduction in tobacco or alcohol intake would be an effective strategy to mitigate HC risk, as well as the risk of few other neoplasms.²⁹

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 explore the correlation between marital status and hypopharynx SCC and whether the association varied by age, race, and gender using the SEER database.

Materials and Methods

Patient and Public Involvement

This research was done without patient and public involvement. Patients were not invited to comment on the study design. Patients were not invited to contribute to the writing or editing of this document for readability or accuracy.

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 hypopharynx SCC between January 1, 2010, and December 31, 2014. We selected patients with only one primary malignancy in their lifetime. We excluded patients for whom the aforementioned data were missing. A total of 1686 hypopharynx SCC patients were included.

Statistical Analysis

Descriptive statistics were performed to investigate patients’ baseline characteristics and clinical characteristics were compared between different categories of marital status using the chi-squared test. The primary study outcomes were OS (time to the date of death due to any cause or the date of last follow-up) and cancer-specific survival (CSS: time from initial treatment to death due to cancer). Kaplan-Meier curves and the log-rank tests were used to evaluate the OS and CSS rates among different categories of marital status. Multivariate Cox proportional analyses were used to assess the influence of marital status on OS and CSS. A 2-sided P value of <.05 was considered as statistically significant. All statistical analyses were performed using SPSS Software, Version 22.0 (SPSS).

Results

Clinical Characteristics of all Patients

The median age was 64 years (range: 31-95 years) and more than half of the patients (1381/1686, 81.9%) were males. A total of 797 (47.3%), 293 (17.4%), 415 (24.6%), and 181 (10.7%) patients were married/partnered, divorced/separated, never married, and widowed, respectively. Married/partnered patients received more surgeries. The rate of being married was higher among Asian or Caucasian, and this rate decreased with higher tumor stage. Black patients, as well as patients younger than 50 years, showed the highest rate of being single (Table 1).

Table 1.

Demographic Characteristics of Hypopharynx SCC Patients Who Were Stratified by Marital Status.

Features	n	%	Married/partnered (n)	Divorced/separated (n)	Never married (n)	Widowed (n)	P
Gender							.000
Male	1381	81.9	679	246	349	107
Female	305	18.1	118	47	66	74
Age							.000
<50	107	6.3	33	18	52	4
50-69	1020	60.5	465	210	296	49
≥70	559	33.2	299	65	67	128
Race							.000
Caucasian	1301	77.2	649	223	283	146
Asian	111	6.6	69	15	19	8
African American	274	16.3	79	55	113	27
T classification							.000
T1	189	11.2	100	33	43	13
T2	586	34.8	289	93	126	78
T3	436	25.9	211	71	103	51
T4a	326	19.3	139	56	107	24
T4b	149	8.8	58	40	36	15
N classification							.000
N0	577	34.2	293	82	120	82
N1	297	17.6	142	56	68	31
N2a	73	4.3	27	18	24	4
N2b	403	23.9	193	65	112	33
N2c	262	15.5	117	55	67	23
N3	74	4.4	25	17	24	8
Grade							.286
1	82	4.9	34	13	24	11
2	861	51.1	399	142	217	103
3	743	44.1	364	138	174	67
Surgery therapy							.014
Yes	423	25.1	227	66	96	34
No	1263	74.9	570	227	319	147
Tumor location							.608
Pyriform sinus	836	49.6	403	150	194	89
Postcricoid region	59	3.5	25	10	15	9
Aryepiglottic fold, hypopharyngeal	133	7.9	65	16	41	11
Posterior wall of hypopharynx	127	7.5	60	21	28	18
Overlapping lesion of hypopharynx	55	3.3	25	14	12	4
Hypopharynx, NOS	476	28.2	219	82	125	50

Abbreviations: NOS, not otherwise specified; SCC, squamous cell carcinoma.

Survival

Median follow-up was 13.0 months (range: 0-59 months). Univariate analysis showed that age, tumor location, marital status, grade, T category, N category, distant metastases, and surgery therapies to the primary tumor were significantly associated with OS and CSS (P < .01). Married subgroup showed significantly better OS and CSS than the unmarried groups (P < .05), while there was no significant difference of OS and CSS between the never married and the widowed groups (Figure 1).

Figure 1.

Kaplan-Meier analysis of OS (A) and CSS (B) for hypopharynx SCC stratified by marital status. OS, overall survival; CSS, cancer-specific survival; SCC, squamous cell carcinoma.

Age, tumor location, marital status, grade, T category, N category, distant metastases, and surgery therapies to the primary tumor were selected in the multivariate model, which were independent prognostic factors in the multivariable analysis (Table 2). Compared to married/partnered patients, the hazard ratios (HRs) for divorced/separated, never married, and widowed patients were 1.164 [95% confidence interval (CI): 0.952-1.422], 1.452 (95% CI: 1.216-1.733), and 1.461 (95% CI: 1.173-1.820), respectively. The same results were found in CSS.

Table 2.

Multivariable Logistic Regression for OS and CSS in the SEER Cohort.

Prognostic factor	OS				CSS
Prognostic factor	P value	HR	Lower 95% CI	Higher 95% CI	P value	HR	Lower 95% CI	Higher 95% CI
Age	.000				.000
<50		1 (reference)				1 (reference)
50-69		1.289	0.945	1.757		1.208	0.845	1.727
≥70		2.178	1.571	3.020		1.948	1.312	2.892
Marital status	.000				.000
Married/partnered		1 (reference)				1 (reference)
Divorced/separated		1.164	0.952	1.422		1.115	0.857	1.451
Never married		1.452	1.216	1.733		1.567	1.241	1.977
Widowed		1.461	1.173	1.820		1.679	1.240	2.273
Race	.000				.003
Caucasian		1 (reference)				1 (reference)
Asian		1.136	0.855	1.508		0.975	0.664	1.431
African American		1.435	1.202	1.713		1.412	1.121	1.780
T classification	.000				.000
T1		1 (reference)				1 (reference)
T2		1.646	1.210	2.238		2.099	1.274	3.460
T3		2.281	1.672	3.112		2.924	1.774	4.819
T4a		3.114	2.270	4.271		4.235	2.556	7.016
T4b		3.017	2.120	4.293		4.039	2.356	6.924
N classification	.007				.000
N0		1 (reference)				1 (reference)
N1		1.057	0.857	1.303		1.143	0.832	1.569
N2a		1.126	0.779	1.629		1.357	0.830	2.217
N2b		1.113	0.919	1.348		1.327	1.011	1.741
N2c		1.194	0.966	1.476		1.660	1.246	2.211
N3		1.745	1.269	2.400		2.378	1.590	3.558
Tumor location	.027				.062
Pyriform sinus		1 (reference)				1 (reference)
Postcricoid region		1.279	0.867	1.887		1.323	0.747	2.343
Aryepiglottic fold, hypopharyngeal		0.933	0.698	1.247		0.769	0.508	1.165
Posterior wall of hypopharynx		1.378	1.068	1.777		1.493	1.059	2.105
Overlapping lesion of hypopharynx		1.054	0.699	1.590		1.233	0.743	2.046
Hypopharynx, NOS		1.230	1.048	1.443		1.250	1.009	1.549
Surgery therapy	.000	1.392	1.175	1.650	.002	1.507	1.171	1.940
Distant metastases	.000				.000
No		1 (reference)				1 (reference)
Single		2.371	1.808	3.108		2.428	1.727	3.413
Multiple		3.442	2.002	5.916		3.527	1.951	6.375

P values were calculated using an adjusted Cox proportional-hazards model.

Abbreviations: CI, confidence interval; CSS, cancer-specific survival; HR, hazard ratio; NOS, not otherwise specified; OS, overall survival; SEER, Surveillance Epidemiology and End Results.

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). While marriage was associated with better survival for both married male and female, subgroups analysis shows a differential in OS based on gender, with males benefiting more than females. Patients who were divorced/separated (male HR = 1.214, 95% CI: 0.985-1.495; female HR = 1. 159, 95% CI: 0.691-1.945), never married (male HR = 1.476, 95% CI: 1.234-1.765; female HR = 1.422, 95% CI: 0.901-2.245), and widowed (male HR = 1.795, 95% CI: 1.390-2.317; female HR = 1.663, 95% CI: 1.081-2.559) had increased hazard of OS compared with married/partnered patients. Remarkably, the protective effect of marriage was consistent in all age groups. Better OS of the married patients was found only in Caucasian patients who harbored well/moderately differentiated and nonmetastatic disease (P < .001). The proportion of postcricoid region, aryepiglottic fold, and overlapping lesion of hypopharynx was obviously lower, in which the protective effect of being married did not occur.

Table 3.

The Effect of Marital Status on Overall Survival Based on Different Subgroup Variables.

Prognostic factor	P value	Divorced/separated vs married			Single vs married			Widowed vs married
Prognostic factor	P value	HR	Lower 95% CI	Higher 95% CI	HR	Lower 95% CI	Higher 95% CI	HR	Lower 95% CI	Higher 95% CI
Age
<50	.021	1.612	0.623	4.173	2.333	1.148	4.740	2.085	0.460	9.450
50-69	.000	1.186	0.927	1.517	1.647	1.333	2.035	1.198	0.763	1.881
≥70	.001	1.612	1.145	2.269	1.326	0.940	1.871	1.533	1.180	1.993
Race
Caucasian	.000	1.198	0.954	1.503	1.466	1.199	1.792	1.664	1.304	2.124
Asian	.802	0.709	0.296	1.694	1.079	0.531	2.191	1.206	0.426	3.410
African American	.064	1.157	0.751	1.785	1.181	0.818	1.704	1.818	1.095	3.019
Gender
Male	.000	1.214	0.985	1.495	1.476	1.234	1.765	1.795	1.390	2.317
Female	.015	1.159	0.691	1.945	1.422	0.901	2.245	1.663	1.081	2.559
Grade
1	.000	1.953	0.666	5.729	2.283	0.998	5.224	6.389	2.663	15.331
2	.000	1.140	0.860	1.511	1.555	1.232	1.963	1.835	1.386	2.429
3	.053	1.215	0.922	1.600	1.318	1.025	1.693	1.185	0.815	1.723
Distant metastases
No	.000	1.208	0.985	1.481	1.478	1.240	1.761	1.744	1.400	2.174
Single	.276	1.573	0.776	3.188	1.150	0.634	2.087	2.020	0.772	5.283
Multiple	.647	0.632	0.157	2.548	1.494	0.421	5.307	-	-	-
Tumor location
Pyriform sinus	.000	1.256	0.952	1.658	1.590	1.237	2.043	1.943	1.430	2.639
Postcricoid region	.940	1.079	0.352	3.305	0.929	0.374	2.308	1.196	0.336	4.253
Aryepiglottic fold, hypopharyngeal	.119	1.708	0.690	4.229	1.967	1.087	3.560	1.083	0.373	3.145
Posterior wall of hypopharynx	.038	1.000	0.502	1.991	1.360	0.746	2.480	2.005	1.066	3.773
Overlapping lesion of hypopharynx	.691	1.250	0.455	3.438	1.123	0.410	3.077	0.587	0.130	2.659
Hypopharynx, NOS	.022	1.093	0.774	1.543	1.318	0.987	1.761	1.438	0.974	2.123

P values were calculated using an adjusted Cox proportional-hazards model.

Abbreviations: CI, confidence interval; HR, hazard ratio; NOS, not otherwise specified.

Discussion

In this study, we confirmed what previous studies had shown, that is, marital status affected OS of hypopharynx SCC patients. Social support can also lead to the pursuit of immediate and aggressive treatment options. Even if there is a general consensus that hypopharynx SCC is predominant in males,^30,31 we further found that married/partnered males may benefit more than females, which relates to spousal influence on adoption of healthy behaviors, as well as support to quit harmful risk factors associated with worse survival outcomes.³² Takagi et al³³ found that there was a spillover effect of the wife’s nonsmoking behavior only among men. Women tend to have a greater influence on their spouse’s health than men because women exert more effort to control their partners’ health habits.^26,32 Generally speaking, the support received by male patients to adopt healthier lifestyles and have a positive outlook may explain their greater survival benefit from being married. The differential protective effect of marriage based on gender among hypopharynx SCC patients is a novel finding, which is important for care planning and needs further studies to reveal the potential mechanism generating the influence of marital status on prognosis. While not explored in this study, another mechanism that might explain the survival benefit of being married could be that unlike those not married, married HNC survivors are able to rely more on their spouses for everyday tasks, such as transportation, cleaning, and shopping.³⁴ Extant literature (about non-head and neck) as well as anecdotal evidence support the idea that being married improves oral intake and hydration especially among married men.³⁵ Another quality of life issue that might be affected by marital status is seeking transportation to treatment facilities. It could be that married patients are more able to rely on their spouses to help with transportation. A previous study on sarcoma survivors alluded to this and this idea also needs to be further tested among head and neck cancer (HNC) survivors.³⁶

We then explored the effect of marital status on prognosis by different subgroups, such as age, race, grade, and tumor location. Difference in protective effect of marriage was observed among variable subgroups, and the OS benefit of being married vanished in Asian/African American patients. Previous work has suggested that the effect of marriage on survival may differ between African American and Caucasian married men.³⁷ 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.³⁸ Some literature has suggested that marriage provides very little health-related protective effects for African Americans when compared with those for Caucasian men.³⁷

In further analysis, we found that the OS benefit mostly occurred in patients who harbored well/moderately differentiated and nonmetastatic disease. When considering patients affected by more aggressive disease, marital status was not significantly associated with higher risk of dying from hypopharynx SCC.

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, and alcohol consumption prevented us to adjust our analyses for these important factors. Third, the study uses data up to 2014, which may not reflect more recent trends in cancer diagnosis and treatment. In addition, the study’s findings may be specific to the population covered by the SEER database and may not be generalizable to other populations. Finally, also due to the data limitations of the SEER database, positive surgical margins at final pathology were not analyzed between marital status and survival in this study.

Conclusion

As far as we know, this is the first study to determine that the effect of marital status on prognosis varies by the demographic and pathological factors in hypopharynx SCC. Our results demonstrated that while there are survival benefits for married patients with hypopharynx SCC, married/partnered males may benefit more than females, which affected by the age, race, and gender. Further studies should be conducted to clarify the specific influence and mechanism of these factors.

Footnotes

Data Availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The study was funded by the Shanghai Municipal Health Commission (Grant Number: 20214Y0025) and the Shanghai Pudong New Area Heath Commission (Grant Number: 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.

ORCID iD

Chaosu Hu

References

Osazuwa-Peters

Boakye

Chen

Tobo

Varvares

. Association between head and neck squamous cell carcinoma survival, smoking at diagnosis, and marital status. JAMA Otolaryngol Head Neck Surg. 2018;144(1):43-50.

Schaefer

Wilson

Goldenberg

Mackley

Koch

Hollenbeak

. Effect of marriage on outcomes for elderly patients with head and neck cancer. Head Neck. 2015;37(5):735-742.

Inverso

Mahal

Aizer

Donoff

Chau

Haddad

. Marital status and head and neck cancer outcomes. Cancer. 2015;121(8):1273-1278.

Aizer

Chen

McCarthy

, et al. Marital status and survival in patients with cancer. J Clin Oncol. 2013;31(31):3869-3876.

Goodwin

Hunt

Key

Samet

. The effect of marital status on stage, treatment, and survival of cancer patients. JAMA. 1987;258(21):3125-3130.

Howren

Christensen

Karnell

LH KL

Van Liew

Funk

. Influence of pretreatment social support on health-related quality of life in head and neck cancer survivors: results from a prospective study. Head Neck. 2013;35(6):779-787.

Osazuwa-Peters

Christopher

Cass

, et al. What’s love got to do with it? Marital status and survival of head and neck cancer. Eur J Cancer Care (Engl). 2019;28(4):e13022.

Liao

Lee

. The influence of marital status on survival for patients aged 65 years and younger with oral cavity cancer. Auris Nasus Larynx. 2018;45(6):1227-1232.

Chen

Liu

, et al. Socioeconomic factors and survival in patients with non-metastatic head and neck squamous cell carcinoma. Cancer Sci. 2017;108(6):1253-1262.

10.

Shield

Ferlay

Jemal

, et al. The global incidence of lip, oral cavity, and pharyngeal cancers by subsite in 2012. CA Cancer J Clin. 2017;67(1):51-64.

11.

Bradley

. Epidemiology of hypopharyngeal cancer. Adv Otorhinolaryngol. 2019;83:1-14.

12.

Carvalho

Nishimoto

Califano

Kowalski

. Trends in incidence and prognosis for head and neck cancer in the United States: a site-specific analysis of the SEER database. Int J Cancer. 2005;114(5):806-816.

13.

. Prevalence and prognostic impact of synchronous distant metastases in patients with hypopharynx squamous cell carcinomas: a SEER-based study. J Cancer. 2019;10(3):620-626.

14.

. Clinical manifestations of hypopharynx squamous cell carcinoma and treatment outcomes according to age at diagnosis. Int J Clin Pract. 2021;75(5):e14059.

15.

Zhang

Wang

Zhang

. Accuracy of artificial intelligence-assisted detection of esophageal cancer and neoplasms on endoscopic images: a systematic review and meta-analysis. J Dig Dis. 2021;22(6):318-328.

16.

Bang

Lee

Baik

. Computer-aided diagnosis of esophageal cancer and neoplasms in endoscopic images: a systematic review and meta-analysis of diagnostic test accuracy. Gastrointest Endosc. 2021;93(5):1006-1015.e13.

17.

Tsai

Mukundan

Chung

, et al. Hyperspectral imaging combined with artificial intelligence in the early detection of esophageal cancer. Cancers (Basel). 2021;13(18):4593.

18.

Wang

Syu

Chen

, et al. Endoscopic images by a single-shot multibox detector for the identification of early cancerous lesions in the esophagus: a pilot study. Cancers (Basel). 2021;13(2):321.

19.

Yang

Shao

, et al. Real-time artificial intelligence for endoscopic diagnosis of early esophageal squamous cell cancer (with video). Dig Endosc. 2021;33(7):1075-1084.

20.

Zaravinos

. An updated overview of HPV-associated head and neck carcinomas. Oncotarget. 2014;5(12):3956-3969.

21.

Vokes

Agrawal

Seiwert

. HPV-associated head and neck cancer. J Natl Cancer Inst. 2015;107(12):djv344.

22.

Rades

Seibold

Gebhard

Noack

Schild

Thorns

. Prognostic factors (including HPV status) for irradiation of locally advanced squamous cell carcinoma of the head and neck (SCCHN). Strahlenther Onkol. 2011;187(10):626-632.

23.

Lenze

Farquhar

Sheth

, et al. Prognostic impact of socioeconomic status compared to overall stage for HPV-negative head and neck squamous cell carcinoma. Oral Oncol. 2021;119:105377.

24.

Sacks

Law

Zhu

, et al. Unique patterns of distant metastases in HPV-positive head and neck cancer. Oncology. 2020;98(3):179-185.

25.

Di Credico

Polesel

Dal Maso

, et al. Alcohol drinking and head and neck cancer risk: the joint effect of intensity and duration. Br J Cancer. 2020;123(9):1456-1463.

26.

Reczek

Pudrovska

Carr

Thomeer

Umberson

. Marital histories and heavy alcohol use among older adults. J Health Soc Behav. 2016;57(1):77-96.

27.

Popescu

Bertesteanu

Mirea

Grigore

Lonescu

Popescu

. The epidemiology of hypopharynx and cervical esophagus cancer. J Med Life. 2010;3(4):396-401.

28.

Wilsnack

Kristjanson

Vogeltanz-Holm

Gmel

. Gender and alcohol consumption: patterns from the multinational GENACIS project. Addiction. 2009;104(9):1487-1500.

29.

Wood

Kaptoge

Butterworth

, et al. Risk thresholds for alcohol consumption: combined analysis of individual-participant data for 599 912 current drinkers in 83 prospective studies. Lancet. 2018;391(10129):1513-1523.

30.

Visini

Giger

Shelan

Elicin

Anschuetz

. Predicting factors for oncological and functional outcome in hypopharyngeal cancer. Laryngoscope. 2021;131(5):E1543-E1549.

31.

Kleist

Bankau

Lorenz

Jäger

Poetsch

. Different risk factors in basaloid and common squamous head and neck cancer. Laryngoscope. 2004;114(6):1063-1068.

32.

Umberson

. Gender, marital status and the social control of health behavior. Soc Sci Med. 1992;34(8):907-917.

33.

Takagi

Kondo

Takada

Hashimoto

. Differences in spousal influence on smoking cessation by gender and education among Japanese couples. BMC Public Health. 2014;14:1184.

34.

Precious

Haran

Lowe

Rogers

. Head and neck cancer patients’ perspective of carer burden. Br J Oral Maxillofac Surg. 2012;50(3):202-207.

35.

Conklin

Forouhi

Surtees

Khaw

Wareham

Monsivais

. Social relationships and healthful dietary behaviour: evidence from over-50s in the EPIC cohort, UK. Soc Sci Med. 2014;100(100):167-175.

36.

Alamanda

Song

Holt

. Effect of marital status on treatment and survival of extremity soft tissue sarcoma. Ann Oncol. 2014;25(3):725-729.

37.

Harris

Lee

Deleone

. Marriage and health in the transition to adulthood: evidence for African Americans in Add Health. J Fam Issues. 2010;31(8):1106-1143.

38.

Robles

Kiecolt-Glaser

. The physiology of marriage: pathways to health. Physiol Behav. 2003;79(3):409-416.