Poor oral health affects survival in head and neck cancer

Introduction Poor oral health has emerged as a risk factor for squamous cell carcinoma of the head and neck (HNSCC) but its impact on survival has not been examined. We sought to estimate the impact of oral health indicators on survival in a population-based HNSCC cohort. Materials and methods Cases (n = 1381) and age-, sex- and race-matched controls (n = 1396) were participants in the Carolina Head and Neck Cancer Epidemiologic Study (CHANCE). Vital status was determined via linkage with the National Death Index. Survival was considered at 5 years post-diagnosis or study-enrollment for controls. Oral health was assessed using self-reported indicators including frequency of routine dental exams and tooth brushing. We used Kaplan-Meyer analyses and Cox regression to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI). Results Routine dental visits during the preceding 10 years were associated with decreased mortality risk (>10 visits: HR = 0.6, 95% CI = 0.4–0.8) after adjusting for confounders. This effect was most pronounced for oral cavity cancer—(e.g., >10 visits: HR = 0.4, 95% CI = 0.2–0.9). Dental visits were also positively associated with survival among controls. No other routine health screening (e.g., eye exams) was associated with survival. Conclusion We found significant associations between markers of oral health and survival among both HNSCC cases and controls. This association was most pronounced for sites closer to the dentition. Oral health may have a direct effect on tumor biology due to the associated immune or inflammatory response. It may also represent a proxy for wellness or unmeasured social determinants of health

Academic Affiliation and Surgical Volume Predict Survival in Head and Neck Cancer Patients Receiving Surgery

Objective: To determine whether the academic affiliation or surgical volume affects the overall survival (OS) of human papillomavirus (HPV)–negative head and neck squamous cell carcinoma (HNSCC) patients receiving surgery. Methods: A retrospective study of 39 North Carolina Medical Centers was conducted. Treatment centers were classified as academic hospitals, community cancer centers, or community hospitals and were divided into thirds by volume. The primary outcome was 5-year OS. Hazard ratios (HR) were determined using Cox proportional hazard models, adjusting for demographics, tumor site, stage, insurance status, tobacco use, alcohol use, stage, chemotherapy, and radiation therapy. Patients were also stratified by stage (early stage and advanced stage). Results: Patients treated at community cancer centers had significantly better 5-year OS (HR 0.68, 95% confidence interval [CI] = 0.48–0.98), and patients treated at academic hospitals trended toward better 5-year OS (HR 0.72, 95% CI = 0.50–1.04) compared to patients treated at community hospitals. The effect for academic affiliation on survival was more pronounced for patients with advanced stage cancer at diagnosis (HR 0.60, 95% CI = 0.37–0.95). There were no significant survival differences among early stage patients by treatment center type. Top-third (HR = 0.64, 95% CI = 0.42–0.96) centers by surgical volume had significantly better 5-year OS, and middle-third (HR = 0.71, 95% CI = 0.51–1.03) centers by volume trended toward better 5-year OS when compared to the bottom-third centers by volume. Conclusion: Patients treated at academic hospitals, community cancer centers, and hospitals in the top third by case volume have favorable survival for HPV-negative HNSCC. The effect for academic hospitals is most pronounced among advanced stage patients. Level of Evidence: 4 Laryngoscope, 131:E479–E488, 2021

Long-Time Behavior of Macroscopic Quantum Systems: Commentary Accompanying the English Translation of John von Neumann's 1929 Article on the Quantum Ergodic Theorem

The renewed interest in the foundations of quantum statistical mechanics in recent years has led us to study John von Neumann's 1929 article on the quantum ergodic theorem. We have found this almost forgotten article, which until now has been available only in German, to be a treasure chest, and to be much misunderstood. In it, von Neumann studied the long-time behavior of macroscopic quantum systems. While one of the two theorems announced in his title, the one he calls the "quantum H-theorem", is actually a much weaker statement than Boltzmann's classical H-theorem, the other theorem, which he calls the "quantum ergodic theorem", is a beautiful and very non-trivial result. It expresses a fact we call "normal typicality" and can be summarized as follows: For a "typical" finite family of commuting macroscopic observables, every initial wave function $\psi_0$ from a micro-canonical energy shell so evolves that for most times $t$ in the long run, the joint probability distribution of these observables obtained from $\psi_t$ is close to their micro-canonical distribution.Comment: 34 pages LaTeX, no figures; v2: minor improvements and additions. The English translation of von Neumann's article is available as arXiv:1003.213

Travel time to provider is associated with advanced stage at diagnosis among low income head and neck squamous cell carcinoma patients in North Carolina

Objective: There is considerable variation in the travel required for a patient with head and neck squamous cell carcinoma (HNSCC) to receive a diagnosis. The impact of this travel on the late diagnosis of cancer remains unexamined, even though presenting stage is the strongest predictor of mortality. Our aim is to determine whether travel time affects HNSCC stage at diagnosis independently of other risk factors, and whether this association is affected by socioeconomic status. Materials and methods: Cases were obtained from the CHANCE database, a population-based case-control study in North Carolina (n = 808). The mean age was 59.6 and 72% were male. Stage at diagnosis was categorized as early (T1-T2) or advanced (T3-T4) T stage and the presence or absence of nodal metastasis. Multivariate logistic regression models were used to estimate odds ratios for stage-at-diagnosis based on travel time, after adjustment for variables including demographics, income, insurance status, alcohol, and tobacco use. Results: The adjusted odds ratio (OR) of advanced T-stage at diagnosis was 1.97 for each hour driven (95% CI 1.36–2.87). There was no association with nodal metastases. There was a significant interaction between travel time and income (p = 0.026) with a pattern of higher ORs for increased distance among lower income ($20,000) patients. Discussion: Travel time was an independent contributor to advanced T stage at diagnosis among low income patients. This suggests travel burden may be a barrier to early diagnosis of HNSCC for impoverished patients

Socioeconomic Status Drives Racial Disparities in HPV-negative Head and Neck Cancer Outcomes

Objectives/Hypothesis: To determine drivers of the racial disparity in stage at diagnosis and overall survival (OS) between black and white patients with HPV-negative head and neck squamous cell carcinoma (HNSCC). Study Design: Retrospective cohort study. Methods: Data were examined from of a population-based HNSCC study in North Carolina. Multivariable logistic regression and Cox proportional hazards models were used to assess racial disparities in stage at diagnosis and OS with sequential adjustment sets. Results: A total of 340 black patients and 864 white patients diagnosed with HPV-negative HNSCC were included. In the unadjusted model, black patients had increased odds of advanced T stage at diagnosis (OR 2.0; 95% CI [1.5–2.5]) and worse OS (HR 1.3, 95% CI 1.1–1.6) compared to white patients. After adjusting for age, sex, tumor site, tobacco use, and alcohol use, the racial disparity persisted for advanced T-stage at diagnosis (OR 1.7; 95% CI [1.3–2.3]) and showed a non-significant trend for worse OS (HR 1.1, 95% CI 0.9–1.3). After adding SES to the adjustment set, the association between race and stage at diagnosis was lost (OR: 1.0; 95% CI [0.8–1.5]). Further, black patients had slightly favorable OS compared to white patients (HR 0.8, 95% CI [0.6–1.0]; P =.024). Conclusions: SES has an important contribution to the racial disparity in stage at diagnosis and OS for HPV-negative HNSCC. Low SES can serve as a target for interventions aimed at mitigating the racial disparities in head and neck cancer. Level of Evidence: 4 Laryngoscope, 131:1301–1309, 2021

Evaluation of pathologic staging using number of nodes in p16-negative head and neck cancer

Objectives: The 8th edition AJCC staging guidelines for head and neck squamous cell carcinoma (HNSCC) recently introduced pathologic staging criteria for nodal disease among p16-positive patients. In this study we evaluate pathologic staging in p16-negative HNSCC. Materials and Methods: We compared pathologic staging to the 7th and 8th edition AJCC staging systems using a statewide population-based cohort. All M0 p16-negative surgical patients were included. The outcome was five-year overall survival. Results: Of 304 patients identified, 113 were N0, 157 had 1–4 positive nodes, and 34 had ≥4 nodes. Survival was 71% (95% CI 61–78%) with no nodes, 48% (36%−60%) for 1–4 nodes, and 24% (11 – 39%) for > 4 nodes. When compared to the AJCC systems, the pathologic staging yielded a larger total survival gradient, more montonic survival, better consistency across primary sites, and a slightly lower Bayesian information criterion (1510 vs 1538). After adjusting for disease characteristics, demographics, and tobacco use, hazard ratios for survival were similar using pathologic and AJCC criteria. Conclusion: In this cohort, pathological staging was more prognostic than AJCC staging. This is the first study to evaluate pathologic staging in p16-negative cancer; if these findings are verified, a universal nodal staging system could be introduced

Prognostic impact of socioeconomic status compared to overall stage for HPV-negative head and neck squamous cell carcinoma

Objective: To estimate the relative prognostic ability of socioeconomic status (SES) compared to overall stage for HPV-negative head and neck squamous cell carcinoma (HNSCC) Materials and methods: Data were obtained from the Carolina Head and Neck Cancer Epidemiology Study (CHANCE). An empirical 4-category SES classification system was created. Cox proportional hazards models, survival gradients, Bayesian information criterion (BIC), and Harrell's C index were used to estimate the prognostic ability of SES compared to stage on overall survival (OS). Results: The sample consisted of 1229 patients with HPV-negative HNSCC. Patients with low SES had significantly increased risk of mortality at 5 years compared to patients with high SES (HR 3.11, 95% CI 2.07–4.67; p < 0.001), and the magnitude of effect was similar to overall stage (HR 3.01, 95% CI 2.35–3.86; p < 0.001 for stage IV versus I). Compared to overall stage, the SES classification system had a larger total survival gradient (35.8% vs. 29.1%), similar model fit (BIC statistic of 7412 and 7388, respectively), and similar model discriminatory ability (Harrell's C index of 0.61 and 0.64, respectively). The association between low SES and OS persisted after adjusting for age, sex, race, alcohol, smoking, overall stage, tumor site, and treatment in a multivariable model (HR 2.96, 95% CI 1.92–4.56; p < 0.001). Conclusion: SES may have a similar prognostic ability to overall stage for patients with HPV-negative HNSCC. Future research is warranted to validate these findings and identify evidence-based interventions for addressing barriers to care for patients with HNSCC

Socioeconomic status, access to care, risk factor patterns, and stage at diagnosis for head and neck cancer among black and white patients

Background: Little is known about how factors combine to influence progression of squamous cell carcinoma of the head and neck (HNSCC). We aimed to evaluate multidimensional influences of factors associated with HNSCC stage by race. Methods: Using retrospective data, patients with similar socioeconomic status (SES), access to care (travel time/distance), and behavioral risk factors (tobacco/alcohol use and dental care) were grouped by latent class analysis. Relative frequency differences (RFD) were calculated to evaluate latent classes by stage, race, and p16 status. Results: We identified three latent classes. Advanced T-stage was higher for black (RFD = +20.2%; 95% CI: −4.6 to 44.9) than white patients (RFD = +10.7%; 95% CI: 2.1–19.3) in the low-SES/high-access/high-behavioral risk class and higher for both black (RFD = +29.6%; 95% CI: 4.7–54.5) and white patients (RFD = +23.9%; 95% CI: 15.2–32.6) in the low-SES/low-access/high-behavioral risk class. Conclusion: Results suggest that SES, access to care, and behavioral risk factors combine to underly the association with advanced T-stage. Additionally, differences by race warrant further investigation

UNMASC: Tumor-only variant calling with unmatched normal controls

Despite years of progress, mutation detection in cancer samples continues to require significant manual review as a final step. Expert review is particularly challenging in cases where tumors are sequenced without matched normal control DNA. Attempts have been made to call somatic point mutations without a matched normal sample by removing well-known germline variants, utilizing unmatched normal controls, and constructing decision rules to classify sequencing errors and private germline variants. With budgetary constraints related to computational and sequencing costs, finding the appropriate number of controls is a crucial step to identifying somatic variants. Our approach utilizes public databases for canonical somatic variants as well as germline variants and leverages information gathered about nearby positions in the normal controls. Drawing from our cohort of targeted capture panel sequencing of tumor and normal samples with varying tumortypes and demographics, these served as a benchmark for our tumor-only variant calling pipeline to observe the relationship between our ability to correctly classify variants against a number of unmatched normals. With our benchmarked samples, approximately ten normal controls were needed to maintain 94% sensitivity, 99% specificity and 76% positive predictive value, far outperforming comparable methods. Our approach, called UNMASC, also serves as a supplement to traditional tumor with matched normal variant calling workflows and can potentially extend to other concerns arising from analyzing next generation sequencing data

Changes in photosynthetic capacity, carboxylation efficiency, and CO 2 compensation point associated with midday stomatal closure and midday depression of net CO 2 exchange of leaves of Quercus suber

The carbon-dioxide response of photosynthesis of leaves of Quercus suber , a sclerophyllous species of the European Mediterranean region, was studied as a function of time of day at the end of the summer dry season in the natural habitat. To examine the response experimentally, a “standard” time course for temperature and humidity, which resembled natural conditions, was imposed on the leaves, and the CO 2 pressure external to the leaves on subsequent days was varied. The particular temperature and humidity conditions chosen were those which elicited a strong stomatal closure at midday and the simultaneous depression of net CO 2 uptake. Midday depression of CO 2 uptake is the result of i) a decrease in CO 2 -saturated photosynthetic capacity after light saturation is reached in the early morning, ii) a decrease in the initial slope of the CO 2 response curve (carboxylation efficiency), and iii) a substantial increase in the CO 2 compensation point caused by an increase in leaf temperature and a decrease in humidity. As a consequence of the changes in photosynthesis, the internal leaf CO 2 pressure remained essentially constant despite stomatal closure. The effects on capacity, slope, and compensation point were reversed by lowering the temperature and increasing the humidity in the afternoon. Constant internal CO 2 may aid in minimizing photoinhibition during stomatal closure at midday. The results are discussed in terms of possible temperature, humidity, and hormonal effects on photosynthesis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47468/1/425_2004_Article_BF00397440.pd