Oral health and human papillomavirus-associated head and neck squamous cell carcinoma.

BACKGROUND: Indicators of poor oral health, including smoking, have been associated with increased risk of head and neck squamous cell carcinoma, especially oropharyngeal squamous cell carcinoma (OPSCC), yet few studies have examined whether this association is modified by human papillomavirus (HPV) status. METHODS: Data from interviews and tumor HPV status from a large population-based case-control study, the Carolina Head and Neck Cancer Study (CHANCE), were used to estimate the association between oral health indicators and smoking among 102 HPV-positive patients and 145 HPV-negative patients with OPSCC and 1396 controls. HPV status was determined by p16INK4a (p16) immunohistochemistry. Unconditional, multinomial logistic regression was used to estimate odds ratios (ORs) for all oral health indictors adjusting for important covariates. RESULTS: Routine dental examinations were associated with a decreased risk of both HPV-negative OPSCC (OR, 0.52; 95% confidence interval [CI], 0.35-0.76) and HPV-positive OPSCC (OR, 0.55; 95% CI, 0.36-.86). Tooth mobility (a proxy for periodontal disease) increased the risk of HPV-negative disease (OR, 1.70; 95% CI, 1.18-2.43) slightly more than the risk for HPV-positive disease (OR, 1.45; 95% CI, 0.95-2.20). Ten or more pack-years of cigarette smoking were strongly associated with an increased risk of HPV-negative OPSCC (OR, 4.26; 95% CI, 2.85-6.37) and were associated less with an increased risk of HPV-positive OPSCC (OR, 1.62; 95% CI, 1.10-2.38). CONCLUSIONS: Although HPV-positive and HPV-negative HNSCC differ significantly with respect to etiology and tumorigenesis, the current findings suggest a similar pattern of association between poor oral health, frequency of dental examinations, and both HPV-positive and HPV-negative OPSCC. Future research is required to elucidate interactions between poor oral health, tobacco use, and HPV in the development of OPSCC. Cancer 2017;71-80. © 2016 American Cancer Society.

Exploring the genetic basis of chronic periodontitis: a genome-wide association study.

Chronic periodontitis (CP) is a common oral disease that confers substantial systemic inflammatory and microbial burden and is a major cause of tooth loss. Here, we present the results of a genome-wide association study of CP that was carried out in a cohort of 4504 European Americans (EA) participating in the Atherosclerosis Risk in Communities (ARIC) Study (mean age-62 years, moderate CP-43% and severe CP-17%). We detected no genome-wide significant association signals for CP; however, we found suggestive evidence of association (P < 5 × 10(-6)) for six loci, including NIN, NPY, WNT5A for severe CP and NCR2, EMR1, 10p15 for moderate CP. Three of these loci had concordant effect size and direction in an independent sample of 656 adult EA participants of the Health, Aging, and Body Composition (Health ABC) Study. Meta-analysis pooled estimates were severe CP (n = 958 versus health: n = 1909)-NPY, rs2521634 [G]: odds ratio [OR = 1.49 (95% confidence interval (CI = 1.28-1.73, P = 3.5 × 10(-7)))]; moderate CP (n = 2293)-NCR2, rs7762544 [G]: OR = 1.40 (95% CI = 1.24-1.59, P = 7.5 × 10(-8)), EMR1, rs3826782 [A]: OR = 2.01 (95% CI = 1.52-2.65, P = 8.2 × 10(-7)). Canonical pathway analysis indicated significant enrichment of nervous system signaling, cellular immune response and cytokine signaling pathways. A significant interaction of NUAK1 (rs11112872, interaction P = 2.9 × 10(-9)) with smoking in ARIC was not replicated in Health ABC, although estimates of heritable variance in severe CP explained by all single nucleotide polymorphisms increased from 18 to 52% with the inclusion of a genome-wide interaction term with smoking. These genome-wide association results provide information on multiple candidate regions and pathways for interrogation in future genetic studies of CP.

Adult height and head and neck cancer: a pooled analysis within the INHANCE Consortium.

Several epidemiological studies have shown a positive association between adult height and cancer incidence. The only study conducted among women on mouth and pharynx cancer risk, however, reported an inverse association. This study aims to investigate the association between height and the risk of head and neck cancer (HNC) within a large international consortium of HNC. We analyzed pooled individual-level data from 24 case-control studies participating in the International Head and Neck Cancer Epidemiology Consortium. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated separately for men and women for associations between height and HNC risk. Educational level, tobacco smoking, and alcohol consumption were included in all regression models. Stratified analyses by HNC subsites were performed. This project included 17,666 cases and 28,198 controls. We found an inverse association between height and HNC (adjusted OR per 10 cm height = 0.91, 95% CI 0.86-0.95 for men; adjusted OR = 0.86, 95% CI 0.79-0.93 for women). In men, the estimated OR did vary by educational level, smoking status, geographic area, and control source. No differences by subsites were detected. Adult height is inversely associated with HNC risk. As height can be considered a marker of childhood illness and low energy intake, the inverse association is consistent with prior studies showing that HNC occur more frequently among deprived individuals. Further studies designed to elucidate the mechanism of such association would be warranted.

Poor Dental Health as a Risk Factor for Alveolar Ridge Malignancies.

OBJECTIVE: To determine the association between poor dental health and risk of oral cavity squamous cell cancer (OCSCC) at individual tumor subsites. STUDY DESIGN: Case-control and cross-sectional METHODS: A case-control study was performed using a population-based cohort in North Carolina (Carolina Head and Neck Cancer Epidemiology Study [CHANCE]). A secondary cross-sectional analysis was performed with an institutional cohort (WashU/Siteman). Cases were adults with primary OCSCC and an identifiable tumor subsite. In the CHANCE cohort, controls were adults without head and neck cancer. In the Washington University/Siteman cohort, patients with tongue cancer served as the comparator group. We used number of missing teeth (categorized 0-6, 7-24, 25-28) as a surrogate for poor dental health, which was self-reported in CHANCE and measured on a pretreatment computed tomography scan in the WashU/Siteman study. Adjusted odds ratios (aORs) for missing teeth were estimated for each tumor subsite using binomial logistic regression models. RESULTS: Near complete tooth loss (25-28 teeth) was associated with a 3.5-fold increased risk of alveolar ridge malignancy (aOR: 3.51; 95% confidence interval [CI]: 1.14-11.01, P = .03) in the CHANCE study. This association was confirmed in our cross-sectional analysis (WashU/Siteman study) where missing 25-28 teeth was associated with an increased risk of alveolar ridge compared to tongue cancer (aOR: 4.60; 95% CI: 1.97-11.10, P = .001). CONCLUSIONS: This study suggests an association between poor dental health and risk of alveolar ridge cancer independent of smoking, alcohol use, age, race, and sex. Future prospective and translational studies are needed to confirm this association and elucidate the mechanism of dental disease in alveolar ridge malignancies.

Poor oral health influences head and neck cancer patient survival: an International Head and Neck Cancer Epidemiology Consortium pooled analysis.

BACKGROUND: Poor oral health has been identified as a prognostic factor potentially affecting the survival of patients with head and neck squamous cell carcinoma. However, evidence to date supporting this association has emanated from studies based on single cohorts with small-to-modest sample sizes. METHODS: Pooled analysis of 2449 head and neck squamous cell carcinoma participants from 4 studies of the International Head and Neck Cancer Epidemiology Consortium included data on periodontal disease, tooth brushing frequency, mouthwash use, numbers of natural teeth, and dental visits over the 10 years prior to diagnosis. Multivariable generalized linear regression models were used and adjusted for age, sex, race, geographic region, tumor site, tumor-node-metastasis stage, treatment modality, education, and smoking to estimate risk ratios (RR) of associations between measures of oral health and overall survival. RESULTS: Remaining natural teeth (10-19 teeth: RR = 0.81, 95% confidence interval [CI] = 0.69 to 0.95; ≥20 teeth: RR = 0.88, 95% CI = 0.78 to 0.99) and frequent dental visits (>5 visits: RR = 0.77, 95% CI = 0.66 to 0.91) were associated with better overall survival. The inverse association with natural teeth was most pronounced among patients with hypopharyngeal and/or laryngeal, and not otherwise specified head and neck squamous cell carcinoma. The association with dental visits was most pronounced among patients with oropharyngeal head and neck squamous cell carcinoma. Patient-reported gingival bleeding, tooth brushing, and report of ever use of mouthwash were not associated with overall survival. CONCLUSIONS: Good oral health as defined by maintenance of the natural dentition and frequent dental visits appears to be associated with improved overall survival among head and neck squamous cell carcinoma patients.

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.

Oral health and risk for head and neck squamous cell carcinoma: the Carolina Head and Neck Cancer Study.

OBJECTIVE: Recent reports have linked oral health and periodontal disease indicators with increased risk of squamous cell carcinoma of head and neck (SCCHN). Thus far, evidence has been inconclusive; our objective was to study the association between oral health and SCCHN risk in the context of a large population-based study. METHODS: A population-based case-control study of incident SCCHN, the Carolina Head and Neck Cancer Study was carried out in 2002-2006 in 46 counties in North Carolina. Controls (n = 1,361) were frequency matched with cases (n = 1,289) on age, race, and gender. Oral health was assessed using interview data on tooth loss and mobility, mouthwash use, and frequency of dental visits. RESULTS: Subjects were 26-80 years old (median age = 61). The distribution of tooth loss among controls was 0-5 teeth = 60%; 5-14 = 15%; and 16-28 = 25%. After controlling for covariates, tooth loss did not yield any notable association with SCCHN (16-28 vs. 0-5 lost teeth: OR: 1.21, 95% CI: 0.94, 1.56). Self-reported history of tooth mobility was moderately associated with increased SCCHN risk (OR: 1.33, 95% CI: 1.07, 1.65); however, the association did not persist among never smokers. Routine dental visits were associated with 30% risk reduction (OR: 0.68, 95% CI: 0.53, 0.87). CONCLUSIONS: These data provide support for a possible modest association of periodontal disease, as measured by self-reported tooth loss indicators, but not tooth loss per se, with SCCHN risk.

Preliminary examination of polymorphisms of GSTM1, GSTT1, and GSTZ1 in relation to semen quality.

BACKGROUND: Environmental, lifestyle, and occupational exposures on semen quality have been investigated in epidemiological studies with inconsistent results. Genetic factors involved in toxicant activation and detoxification have been examined in relation to the risk of outcomes such as cancer, cardiovascular, and neurologic disorders. However, the effect of common genetic variants in the metabolism of toxicants on semen quality parameters has rarely been evaluated. In this analysis, we evaluated functional SNPs of three genes of the glutathione-S-transferase (GSTM1, GSTT1, GSTZ1) enzyme family. METHODS: Participants were 228 presumed fertile men recruited as part of a community-based study. Semen outcome data from this study included total sperm count and concentration, sperm morphology, and sperm DNA integrity and chromatin maturity. DNA was obtained from 162 men from a mouth-rinse sample and genotyped for the presence of GSTT1-1 and GSTM1-1 null genotypes and the GSTZ1 SNPs at positions 94 (rs3177427) and 124 (rs3177429). We used multivariable linear regression to assess the relationship between each genotype and sperm outcomes. RESULTS: Overall, our results did not reveal a consistent pattern between GSTM1 and GSTZ genotypes and increased occurrence of adverse sperm outcomes. However, the GSTT1 non-null genotype yielded the coefficients with the largest magnitude for sperm count and sperm concentration (beta=-0.528, 95% CI -1.238 to 0.199 and beta=-0.353, 95% CI -0.708 to 0.001, respectively), suggesting that it might be adverse. CONCLUSIONS: These results indicate that common polymorphisms in GST genes do not negatively impact sperm parameters in healthy men with good semen quality. Contrary to expectations, the GSTT1 non-null genotype was associated with reduced sperm concentration and count in semen. Further study with a larger study size and inclusion of gene-exposure interactions is warranted.

Access to preventive care services and stage at diagnosis in head and neck cancer.

BACKGROUND: Decreased access to preventive care services has been proposed as a mechanism for the association between low socioeconomic status (SES) and advanced stage at diagnosis in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: Retrospective analysis of patients diagnosed with HNSCC in North Carolina between 2002 and 2006. RESULTS: A total of 1108 patients with HNSCC were included in the study. In the multivariable analysis, use of annual routine dental services (OR 0.7, 95% CI 0.5-0.9) and colonoscopy in the past 10 years (OR 0.7, 95% CI 0.5-0.9) were associated with lower odds of advanced T stage at diagnosis. Having no insurance (OR 1.8, 95% CI 1.1-2.9), an income <$20 000 (OR 1.6 95% CI 1.03-2.6), and >10 pack-years tobacco use (OR 1.5, 95% CI 1.04-2.2) were associated with advanced T stage at diagnosis. CONCLUSION: Use of preventive care services and SES independently predict stage at diagnosis in HNSCC.

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 5years 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 10years 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.