Factors Associated with Head and Neck Cancer Postoperative Radiotherapy Delays: A Systematic Review and Meta-analysis.

OBJECTIVE: Initiating postoperative radiotherapy (PORT) within 6 weeks of surgery for head and neck squamous cell carcinoma (HNSCC) is included in the National Comprehensive Cancer Network Clincal Practice Guidelines and is a Commission on Cancer quality metric. Factors associated with delays in starting PORT have not been systematically described nor synthesized. DATA SOURCES: PubMed, Scopus, and CINAHL. REVIEW METHODS: We included studies describing demographic characteristics, clinical factors, or social determinants of health associated with PORT delay (>6 weeks) in patients with HNSCC treated in the United States after 2003. Meta-analysis of odds ratios (ORs) was performed on nonoverlapping datasets. RESULTS: Of 716 unique abstracts reviewed, 21 studies were included in the systematic review and 15 in the meta-analysis. Study sample size ranged from 19 to 60,776 patients. In the meta-analysis, factors associated with PORT delay included black race (OR, 1.46, 95% confidence interval [CI]: 1.28-1.67), Hispanic ethnicity (OR, 1.37, 95% CI, 1.17-1.60), Medicaid or no health insurance (OR, 2.01, 95% CI, 1.90-2.13), lower income (OR, 1.38, 95% CI, 1.20-1.59), postoperative admission >7 days (OR, 2.92, 95% CI, 2.31-3.67), and 30-day hospital readmission (OR, 1.37, 95% CI, 1.29-1.47). CONCLUSION: Patients at greatest risk for a delay in initiating guideline-adherent PORT include those who are from minoritized communities, of lower socioeconomic status, and experience postoperative challenges. These findings provide the foundational evidence needed to deliver targeted interventions to enhance equity and quality in HNSCC care delivery.

Trends and factors associated with receipt of human papillomavirus (HPV) vaccine in private, public, and alternative settings in the United States.

BACKGROUND: One of the goals of the President's Cancer Panel was to maximize access to human papillomavirus (HPV) vaccination through expansion of alternative settings for receiving the vaccine, such as in public health settings, schools, and pharmacies. METHODS: In a cross-sectional analysis, we utilized the National Immunization Survey-Teen data from 2014 to 2020 (n = 74,645) to describe trends and factors associated with HPV vaccine uptake in private, public, and alternative settings. We calculated annual percent change (APC) between 2014 and 2020, estimating rate of HPV vaccine uptake across settings. Using multinomial logistic regression, we estimated the odds of receipt of HPV vaccine in public health settings and other alternative settings compared to private healthcare settings, adjusting for sociodemographic covariates. RESULTS: We found a 5 % annual increase in the use of private facilities between 2014-2018 (APC = 5.3; 95 % CI 3.4, 7.1), and almost 7 % between 2018-2020 (APC = 6.7; 95 % CI 1.4, 12.3). Adjusted multinomial logistic regression analyses found that odds of receiving vaccinations at a public facility vs. a private facility increased almost two times for adolescents living below poverty (aOR = 1.82, 95 % CI: 1.60, 2.08) compared to above poverty. Additionally, adolescents without physician recommendations had lower odds of receiving vaccines at public versus private facilities (aOR = 1.75, 95 % CI: 1.44, 2.12). Finally, odds of receiving HPV vaccines at public facilities vs. private facilities decreased by 33 % for White adolescents (aOR = 0.67, 95 % CI: 0.57, 0.78) versus Black adolescents. CONCLUSIONS: Sociodemographic factors such as race, and socioeconomic factors such as poverty level, and receipt of physician HPV recommendations are associated with receiving the vaccine at private settings vs. public health facilities and alternative settings. This information is important in strengthening alternative settings for HPV vaccine uptake to increase access to the vaccine among disadvantaged individuals.

"Let him die. He caused it": A qualitative study on cancer stigma in Tanzania.

Cancer stigma presents a critical barrier to care seeking, contributing to delayed presentation and poor cancer outcomes worldwide. The burden of cancer in Tanzania is on the rise, with cancer being the third-leading cause of death in the country. Despite rising incidence and poor outcomes of cancer, cancer-related stigma interventions have received low prioritization. There is a need for sound research that focuses on understanding attitudes driving stigma, its impact on care-seeking and treatment adherence, and intervention models to reduce stigma. We used a cross-sectional qualitative study design. We administered three open-ended qualitative questions to 140 adults newly diagnosed with cancer in Moshi, Tanzania. The questions explored common attitudes toward people with cancer, the perceived impact of cancer-related stigma on care engagement, and ideas for reducing cancer stigma. Patients were recruited during routine appointments at the Cancer Center at Kilimanjaro Christian Medical Center. Data were analyzed using a team-based, applied thematic approach and NVivo 12 software. All participants described stigma as a significant challenge for treatment and receiving support from their social networks. Perceptions of financial burden, misconceptions about cancer, such as the belief that it is contagious, and fear of death, were common attitudes driving cancer stigma. Most participants feared that symptoms would prevent them from being able to work and that the cost of cancer care would drive away loved ones. Stigma was not a ubiquitous response, as some participants reported increased care and social support from family members after a cancer diagnosis. Experiences of stigma contributed to feelings of shame, fear of burdening the family, reduced resources to access treatment, and disengagement from care. Common substitutes to medical therapies included religious interventions and traditional medicine, perceived as less expensive and less stigmatizing. Many participants felt they would benefit from improved financial support, professional counseling, and education for families and communities to reduce stigmatizing attitudes and enhance social support. There is a need for intervention studies focused on improving cancer literacy, community advocacy to reduce cancer stigma, and increasing emotional and practical support for people with cancer and their families. There is also a clear need for policy efforts to make cancer care more affordable and accessible to reduce the financial burden on patients and families.

Neighborhood-Level Disadvantage and Delayed Adjuvant Therapy in Head and Neck Cancer.

Importance: For patients with head and neck squamous cell carcinoma (HNSCC), initiation of postoperative radiation therapy (PORT) within 6 weeks of surgery is recommended by the National Comprehensive Cancer Network Guidelines and the Commission on Cancer. Although individual-level measures of socioeconomic status are associated with receipt of timely, guideline-adherent PORT, the role of neighborhood-level disadvantage has not been examined. Objective: To characterize the association of neighborhood-level disadvantage with delays in receiving PORT. Design, Setting, and Participants: This retrospective cohort study included 681 adult patients with HNSCC undergoing curative-intent surgery and PORT from 2018 to 2020 at 4 US academic medical centers. The data were analyzed between June 21, 2023, and March 5, 2024. Main Outcome Measures and Measures: The primary outcome was delay in initiating guideline-adherent PORT (ie, >6 weeks after surgery). Time-to-PORT (TTP) was a secondary outcome. Census block-level Area Deprivation Index (ADI) scores were calculated and reported as national percentiles (0-100); higher scores indicate greater deprivation. The association of ADI scores with PORT delay was assessed using multivariable logistic regression adjusted for demographic, clinical, and institutional characteristics. PORT initiation across ADI score population quartiles was evaluated with cumulative incidence plots and Cox models. Results: Among 681 patients with HNSCC undergoing surgery and PORT (mean [SD] age, 61.5 [11.2] years; 487 [71.5%] men, 194 [29.5%] women) the PORT delay rate was 60.8% (414/681) and median (IQR) TTP was 46 (40-56) days. The median (IQR) ADI score was 62.0 (44.0-83.0). Each 25-point increase in ADI score was associated with a corresponding 32% increase in the adjusted odds ratio (aOR) of PORT delay (aOR, 1.32; 95% CI, 1.07-1.63) on multivariable regression adjusted for institution, age, race and ethnicity, insurance, comorbidity, cancer subsite, stage, postoperative complications, care fragmentation, travel distance, and rurality. Increasing ADI score population quartiles were associated with increasing TTP (hazard ratio of PORT initiation, 0.71; 95% CI, 0.53-0.96; 0.59; 95% CI, 0.44-0.77; and 0.54; 95% CI, 0.41-0.72; for ADI quartiles 2, 3, and 4 vs ADI quartile 1, respectively). Conclusions and Relevance: Increasing neighborhood-level disadvantage was independently associated with a greater likelihood of PORT delay and longer TTP in a dose-dependent manner. These findings indicate a critical need for the development of multilevel strategies to improve the equitable delivery of timely, guideline-adherent PORT.

Racial and ethnic disparities in human papillomavirus (HPV) vaccine uptake among United States adults, aged 27-45 years.

In 2018, the Food and Drug Administration expanded the age of eligibility for the human papillomavirus (HPV) vaccine to 27 to 45 years. However, it is unclear if there are racial/ethnic disparities in HPV vaccine uptake for this age-group following this expanded recommendation. We aimed to identify any disparities in HPV vaccine in 27 to 45 year-olds based on sociodemographic factors. We analyzed nationally representative, cross-sectional data from the 2019 National Health Interview Survey (n = 9440). Logistic regression models estimated the odds of vaccine uptake (receipt of ≥1 vaccine dose) based on sociodemographic factors. Participants were mostly Non-Hispanic Whites (60.7%) and females (50.9%). In adjusted models, females had over three times greater odds of vaccine uptake compared to males (aOR = 3.58; 95% CI 3.03, 4.23). Also, compared to Non-Hispanic Whites, Non-Hispanic Blacks were 36% more likely (aOR = 1.36; 95% CI 1.09, 1.70), and Hispanics were 27% less likely (aOR = 0.73; 95% CI 0.58, 0.92) to receive the vaccine. Additionally, individuals without a usual place of care had lower odds of vaccine uptake (aOR = 0.72; 95% CI 0.57, 0.93), as were those with lower educational levels (aORhigh school = 0.62; 95% CI 0.50, 0.78; aORsome college = 0.83; 95% CI 0.70, 0.98). There are disparities in HPV vaccine uptake among 27 to 45 year-olds, and adult Hispanics have lower odds of receiving the vaccine. Given the vaccine's importance in cancer prevention, it is critical that these disparities are addressed and mitigated.

Association between number of Adverse Childhood Experiences and depression among older adults is moderated by race.

OBJECTIVE: This study aimed to assess the association between number of Adverse Childhood Experiences (ACE) and history of depression among older adults and to explore the interaction by race. METHODS: This study was a cross-sectional analysis of the 2020 Behavioral Risk Factor Surveillance System (BRFSS) data among 60,122 older respondents (≥ 60 years old). The ACE score (zero, one, two-three, ≥four) included questions assessing exposure to eight types of ACEs before age 18. The outcome was the respondent's self-report depression diagnosed (yes/no). Multivariable logistic regression models examined the association between ACEs and depression stratified by race. Each model adjusted for age, smoking status, income, education, marital status, and body mass index. RESULTS: In this sample of older adults, 47%, 23%, 19% and 10% reported having experienced zero, one, two-three, and four or more types of ACEs, respectively. Depression was reported by 16% of survey respondents. There was a significant interaction between ACE score and race and depression (p = 0.038). Respondents who experienced ≥4 ACEs had higher likelihood of reporting depression for all race/ethnicity groups: non-Hispanic Whites (aOR = 3.83; 95% CI: 3.07, 4.79), non-Hispanic Blacks (aOR = 3.39, 95% CI: 1.71, 6.71), or Hispanics (aOR = 12.61; 95% CI: 4.75, 33.43). This translated to a large effect size for non-Hispanic Whites and Hispanics although the magnitude was bigger for Hispanics. CONCLUSION: The association between number of ACEs and depression was strongest for older adults who identify as Hispanic, but weaker and less consistent for adults who identify as White and Black.

The impact of individual-level income predicted from the BRFSS on the association between insurance status and overall survival among adults with cancer from the SEER program.

INTRODUCTION: Among patients with cancer in the United States, Medicaid insurance is associated with worse outcomes than private insurance and with similar outcomes as being uninsured. However, prior studies have not addressed the impact of individual-level socioeconomic status, which determines Medicaid eligibility, on the associations of Medicaid status and cancer outcomes. Our objective was to determine whether differences in cancer outcomes by insurance status persist after accounting for individual-level income. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was queried for 18-64 year-old individuals with cancer from 2014-2016. Individual-level income was imputed using a model trained on Behavioral Risk Factors Surveillance Survey participants including covariates also present in SEER. The association of 1-year overall survival and insurance status was estimated with and without adjustment for estimated individual-level income and other covariates. RESULTS: A total of 416,784 cases in SEER were analyzed. The 1-yr OS for patients with private insurance, Medicaid insurance, and no insurance was 88.7%, 76.1%, and 73.7%, respectively. After adjusting for all covariates except individual-level income, 1-year OS differences were worse with Medicaid (-6.0%, 95% CI = -6.3 to -5.6) and no insurance (-6.7%, 95% CI = -7.3 to -6.0) versus private insurance. After also adjusting for estimated individual-level income, the survival difference for Medicaid patients was similar to privately insured (-0.4%, 95% CI = -1.9 to 1.1) and better than uninsured individuals (2.1%, 95% CI = 0.7 to 3.4). CONCLUSIONS: Income, rather than Medicaid status, may drive poor cancer outcomes in the low-income and Medicaid-insured population. Medicaid insurance coverage may improve cancer outcomes for low-income individuals.

Head and Neck Cancer Incidence in the United States Before and During the COVID-19 Pandemic.

Importance: Research about population-level changes in the incidence and stage of head and neck cancer (HNC) associated with the COVID-19 pandemic is sparse. Objective: To examine the change in localized vs advanced HNC incidence rates before and during the first year of the pandemic. Design, Setting, and Participants: In this cross-sectional study of patients in the US diagnosed with HNC from 2017 to 2020, the estimated number with cancer of the oral cavity and pharynx (floor of mouth; gum and other mouth; lip; oropharynx and tonsil; and tongue) and larynx were identified from the SEER cancer registry. Subgroup analyses were stratified by race and ethnicity, age, and sex. Data were analyzed after the latest update in April 2023. Exposure: The COVID-19 pandemic in 2020. Main Outcomes and Measures: The primary outcomes were the annual incidence rates per 100 000 people for localized HNC (includes both localized and regional stages) and advanced HNC (distant stage) and weighted average annual percentage change from 2019 to 2020. Secondary outcomes included annual percentage change for 2017 to 2018 and 2018 to 2019, which provided context for comparison. Results: An estimated 21 664 patients (15 341 [71%] male; 10 726 [50%] ≥65 years) were diagnosed with oral cavity and pharynx cancer in 2019 in the US, compared with 20 390 (4355 [70%] male; 10 393 [51%] ≥65 years) in 2020. Overall, the HNC incidence rate per 100 000 people declined from 11.6 cases in 2019 to 10.8 in 2020. The incidence rate of localized cancer declined to 8.8 cases (-7.9% [95% CI, -7.5 to -8.2]) from 2019 to 2020. The localized cancer incidence during the first year of the pandemic decreased the most among male patients (-9.3% [95% CI, -9.2 to -9.5]), Hispanic patients (-12.9% [95% CI, -12.9 to -13.0]), and individuals with larynx cancer (-14.3% [95% CI, -13.6 to -15.0]). No change in the overall incidence rate was found for advanced HNC. Conclusions and Relevance: In this cross-sectional study, the incidence of localized HNC declined during the first year of the pandemic. A subsequent increase in advanced-stage diagnoses may be observed in later years.

Culturally-informed adaptation and psychometric properties of the Cataldo Cancer Stigma Scale in Northern Tanzania.

BACKGROUND: Cancer-related stigma impacts patients' emotional health, care engagement, and cancer outcomes, but few measures of cancer stigma exist. We culturally adapted and assessed psychometric properties of the Cataldo Cancer Stigma Scale (CCSS) in Tanzania. METHODS: We administered the CCSS short version (21 items), plus 12 locally-derived items, to 146 adult cancer patients. We conducted exploratory factor analysis, examined internal consistency/reliability, and assessed convergent validity with relevant measures. RESULTS: We identified a 17-item cancer stigma scale with strong psychometric properties and four subscales: enacted stigma, shame and blame, internalized stigma, and disclosure concerns. Stigma was rare except for disclosure concerns. Stigma was positively associated with depression and anxiety and negatively associated with social support, quality of life, and illness acceptance. CONCLUSIONS: The scale provides valid, culturally-informed measurement of cancer stigma in Tanzania. Future studies should assess associations with care engagement, which will inform interventions to reduce stigma and improve outcomes.

Malnutrition and Adverse Outcomes After Surgery for Head and Neck Cancer.

Importance: Patients with head and neck cancer (HNC) have an increased risk of malnutrition, partly due to disease location and treatment sequelae. Although malnutrition is associated with adverse outcomes, there is little data on the extent of outcomes and the sociodemographic factors associated with malnutrition in patients with HNC. Objectives: To investigate the association of race, ethnicity, and payer type with perioperative malnutrition in patients undergoing HNC surgery and how malnutrition affects clinical outcomes. Design, Setting, and Participants: This retrospective cohort study used data from the Premier Healthcare Database to assess adult patients who had undergone HNC surgery from January 2008 to June 2020 at 482 hospitals across the US. Diagnosis and procedure codes were used to identify a subset of patients with perioperative malnutrition. Patient characteristics, payer types, and hospital outcomes were then compared to find associations among race, ethnicity, payer type, malnutrition, and clinical outcomes using multivariable logistic regression models. Analyses were performed from August 2022 to January 2023. Exposures: Race, ethnicity, and payer type for primary outcome, and perioperative malnutrition status, race, ethnicity, and payer type for secondary outcomes. Main Outcomes and Measures: Perioperative malnutrition status. Secondary outcomes were discharge to home after surgery, hospital length of stay (LOS), total cost, and postoperative pulmonary complications (PPCs). Results: The study population comprised 13 895 adult patients who had undergone HNC surgery during the study period; they had a mean (SD) age of 63.4 (12.1) years; 9425 male (67.8%) patients; 968 Black (7.0%), 10 698 White (77.0%), and 2229 (16.0%) individuals of other races; and 887 Hispanic (6.4%) and 13 008 non-Hispanic (93.6%) individuals. Among the total sample, there were 3136 patients (22.6%) diagnosed with perioperative malnutrition. Compared with White patients and patients with private health insurance, the odds of malnutrition were higher for non-Hispanic Black patients (adjusted odds ratio [aOR], 1.31; 95% CI, 1.11-1.56), Medicaid-insured patients (aOR, 1.68; 95% CI, 1.46-1.95), and Medicare-insured patients (aOR, 1.24; 95% CI, 1.10-1.73). Black patients and patients insured by Medicaid had increased LOS, costs, and PPCs, and lower rates of discharge to home. Malnutrition was independently associated with increased LOS (ß, 5.20 additional days; 95% CI, 4.83-5.64), higher costs (ß, $15 722 more cost; 95% CI, $14 301-$17 143), increased odds of PPCs (aOR, 2.04; 95% CI, 1.83-2.23), and lower odds of discharge to home (aOR, 0.34; 95% CI, 0.31-0.38). No independent association between malnutrition and mortality was observed. Conclusions and Relevance: This retrospective cohort study found that 1 in 5 patients undergoing HNC surgery were malnourished. Malnourishment disproportionately affected Black patients and patients with Medicaid, and contributed to longer hospital stays, higher costs, and more postoperative complications.

An Exploration of Black Men's Attitudes and Experiences Communicating with Dentists about Oral and Pharyngeal Cancer.

BACKGROUND: Poor oral and pharyngeal cancer (OPC) survival among Black men is partially due to their limited knowledge about OPCs, which is exacerbated by dentists' limited training and discomfort in discussing OPC risk factors. The purpose of this study was to assess the attitudes and experiences that Black men have communicating with dentists about OPCs. METHODS: To qualitatively assess these attitudes and experiences, a focus group guide and recruitment strategy were developed using a community engagement approach. Data were analyzed using grounded theory. RESULTS: Twenty-three self-identified Black men participated in three focus groups through the Zoom platform (mean age of 46.1 years). Four main themes emerged, which identified that participants: (1) had little knowledge of OPCs; (2) felt that addressing OPC risk among Black men was not a priority for dentists; (3) stressed the importance of dentists acknowledging the complexity of how race and gender affects Black men's healthcare experiences; and (4) expressed a benefit to receiving information from multiple social networks. CONCLUSION: The focus groups provided context for how dentists might engage with Black men in discussions about OPC prevention and treatment.

State Public Assistance Spending and Survival Among Adults With Cancer.

Importance: Social determinants of health contribute to disparities in cancer outcomes. State public assistance spending, including Medicaid and cash assistance programs for socioeconomically disadvantaged individuals, may improve access to care; address barriers, such as food and housing insecurity; and lead to improved cancer outcomes for marginalized populations. Objective: To determine whether state-level public assistance spending is associated with overall survival (OS) among individuals with cancer, overall and by race and ethnicity. Design, Setting, and Participants: This cohort study included US adults aged at least 18 years with a new cancer diagnosis from 2007 to 2013, with follow-up through 2019. Data were obtained from the Surveillance, Epidemiology, and End Results program. Data were analyzed from November 18, 2021, to July 6, 2023. Exposure: Differential state-level public assistance spending. Main Outcome and Measure: The main outcome was 6-year OS. Analyses were adjusted for age, race, ethnicity, sex, metropolitan residence, county-level income, state fixed effects, state-level percentages of residents living in poverty and aged 65 years or older, cancer type, and cancer stage. Results: A total 2 035 977 individuals with cancer were identified and included in analysis, with 1 005 702 individuals (49.4%) aged 65 years or older and 1 026 309 (50.4%) male. By tertile of public assistance spending, 6-year OS was 55.9% for the lowest tertile, 55.9% for the middle tertile, and 56.6% for the highest tertile. In adjusted analyses, public assistance spending at the state-level was significantly associated with higher 6-year OS (0.09% [95% CI, 0.04%-0.13%] per $100 per capita; P < .001), particularly for non-Hispanic Black individuals (0.29% [95% CI, 0.07%-0.52%] per $100 per capita; P = .01) and non-Hispanic White individuals (0.12% [95% CI, 0.08%-0.16%] per $100 per capita; P < .001). In sensitivity analyses examining the roles of Medicaid spending and Medicaid expansion including additional years of data, non-Medicaid spending was associated with higher 3-year OS among non-Hispanic Black individuals (0.49% [95% CI, 0.26%-0.72%] per $100 per capita when accounting for Medicaid spending; 0.17% [95% CI, 0.02%-0.31%] per $100 per capita Medicaid expansion effects). Conclusions and Relevance: This cohort study found that state public assistance expenditures, including cash assistance programs and Medicaid, were associated with improved survival for individuals with cancer. State investment in public assistance programs may represent an important avenue to improve cancer outcomes through addressing social determinants of health and should be a topic of further investigation.

Differences in Receipt of Immunotherapy Treatment Among Patients With Head and Neck Cancer.

Importance: The US Food and Drug Administration approved immune checkpoint inhibitors (immunotherapy) for select cases of head and neck squamous cell carcinoma (HNSCC) in 2016. However, it is unclear whether there are clinical or sociodemographic differences among patients receiving immunotherapy as part of their care. Given the known disparities in head and neck cancer care, we hypothesized that there are differences in receipt of immunotherapy among patients with HNSCC based on clinical and nonclinical characteristics. Objective: To characterize clinical and nonclinical factors associated with receipt of immunotherapy among older patients with HNSCC. Design, Setting, and Participants: This retrospective cohort study included patients 65 years or older diagnosed with HNSCC (n = 4860) in a community oncology care setting. Electronic health records from Navigating Cancer were assessed from January 1, 2017, to April 30, 2022. Main Outcomes and Measures: Multivariable logistic regression was used to characterize clinical (tumor stage [localized vs advanced] and anatomical subsite [oropharyngeal vs nonoropharyngeal]) and nonclinical (age, smoking history, race and ethnicity, sex, and marital status) factors associated with receipt of immunotherapy. Results: In the study cohort of 4860 patients, 3593 (73.9%) were men; 4230 (87.0%) were White and 630 (13.0%) were of other races. A total of 552 patients (11.4%) had received immunotherapy. After adjusting for covariates, in the final model, White patients with HNSCC had 80% increased odds of receiving immunotherapy (adjusted odds ratio [AOR], 1.80 [95% CI, 1.30-2.48]) compared with patients of other races. There were no statistically significant differences in the odds of receiving immunotherapy based on age, sex, or smoking history. Patients with nonoropharyngeal disease were significantly more likely to receive immunotherapy than those with oropharyngeal cancer (AOR, 1.29 [95% CI, 1.05-1.59]), as were those with advanced compared with local disease (AOR, 2.39 [95% CI, 1.71-3.34]). Conclusions and Relevance: The findings of this cohort study suggest that among older patients with HNSCC, White patients may be more likely to receive immunotherapy as part of their care. Equitable access to immunotherapy and other treatment options will reduce cancer-related health disparities and improve survival of patients with HNSCC.

Deconstructing Olfactory Epithelium Developmental Pathways in Olfactory Neuroblastoma.

Olfactory neuroblastoma is a rare tumor arising from the olfactory cleft region of the nasal cavity. Because of the low incidence of this tumor, as well as an absence of established cell lines and murine models, understanding the mechanisms driving olfactory neuroblastoma pathobiology has been challenging. Here, we sought to apply advances from research on the human olfactory epithelial neurogenic niche, along with new biocomputational approaches, to better understand the cellular and molecular factors in low- and high-grade olfactory neuroblastoma and how specific transcriptomic markers may predict prognosis. We analyzed a total of 19 olfactory neuroblastoma samples with available bulk RNA-sequencing and survival data, along with 10 samples from normal olfactory epithelium. A bulk RNA-sequencing deconvolution model identified a significant increase in globose basal cell (GBC) and CD8 T-cell identities in high-grade tumors (GBC from ∼0% to 8%, CD8 T cell from 0.7% to 2.2%), and significant decreases in mature neuronal, Bowman's gland, and olfactory ensheathing programs, in high-grade tumors (mature neuronal from 3.7% to ∼0%, Bowman's gland from 18.6% to 10.5%, olfactory ensheathing from 3.4% to 1.1%). Trajectory analysis identified potential regulatory pathways in proliferative olfactory neuroblastoma cells, including PRC2, which was validated by immunofluorescence staining. Survival analysis guided by gene expression in bulk RNA-sequencing data identified favorable prognostic markers such as SOX9, S100B, and PLP1 expression. Significance: Our analyses provide a basis for additional research on olfactory neuroblastoma management, as well as identification of potential new prognostic markers.

Changes in cancer mortality after Medicaid expansion and the role of stage at diagnosis.

BACKGROUND: Medicaid expansion is associated with improved survival following cancer diagnosis. However, little research has assessed how changes in cancer stage may mediate improved cancer mortality or how expansion may have decreased population-level cancer mortality rates. METHODS: Nationwide state-level cancer data from 2001 to 2019 for individuals ages 20-64 years were obtained from the combined Surveillance, Epidemiology, and End Results National Program of Cancer Registries (incidence) and the National Center for Health Statistics (mortality) databases. We estimated changes in distant stage cancer incidence and cancer mortality rates from pre- to post-2014 in expansion vs nonexpansion states using generalized estimating equations with robust standard errors. Mediation analyses were used to assess whether distant stage cancer incidence mediated changes in cancer mortality. RESULTS: There were 17 370 state-level observations. For all cancers combined, there were Medicaid expansion-associated decreases in distant stage cancer incidence (adjusted odds ratio = 0.967, 95% confidence interval = 0.943 to 0.992; P = .01) and cancer mortality (adjusted odds ratio = 0.965, 95% confidence interval = 0.936 to 0.995; P = .022). This translates to 2591 averted distant stage cancer diagnoses and 1616 averted cancer deaths in the Medicaid expansion states. Distant stage cancer incidence mediated 58.4% of expansion-associated changes in cancer mortality overall (P = .008). By cancer site subgroups, there were expansion-associated decreases in breast, cervix, and liver cancer mortality. CONCLUSIONS: Medicaid expansion was associated with decreased distant stage cancer incidence and cancer mortality. Approximately 60% of the expansion-associated changes in cancer mortality overall were mediated by distant stage diagnoses.