A risk prediction model for head and neck cancers incorporating lifestyle factors, HPV serology and genetic markers.

Head and neck cancer is often diagnosed late and prognosis for most head and neck cancer patients remains poor. To aid early detection, we developed a risk prediction model based on demographic and lifestyle risk factors, human papillomavirus (HPV) serological markers and genetic markers. A total of 10 126 head and neck cancer cases and 5254 controls from five North American and European studies were included. HPV serostatus was determined by antibodies for HPV16 early oncoproteins (E6, E7) and regulatory early proteins (E1, E2, E4). The data were split into a training set (70%) for model development and a hold-out testing set (30%) for model performance evaluation, including discriminative ability and calibration. The risk models including demographic, lifestyle risk factors and polygenic risk score showed a reasonable predictive accuracy for head and neck cancer overall. A risk model that also included HPV serology showed substantially improved predictive accuracy for oropharyngeal cancer (AUC = 0.94, 95% CI = 0.92-0.95 in men and AUC = 0.92, 95% CI = 0.88-0.95 in women). The 5-year absolute risk estimates showed distinct trajectories by risk factor profiles. Based on the UK Biobank cohort, the risks of developing oropharyngeal cancer among 60 years old and HPV16 seropositive in the next 5 years ranged from 5.8% to 14.9% with an average of 8.1% for men, 1.3% to 4.4% with an average of 2.2% for women. Absolute risk was generally higher among individuals with heavy smoking, heavy drinking, HPV seropositivity and those with higher polygenic risk score. These risk models may be helpful for identifying people at high risk of developing head and neck cancer.

Use of antihistamine medications during early pregnancy and selected birth defects: The National Birth Defects Prevention Study, 1997-2011.

BACKGROUND: It is estimated that approximately 10-15% of pregnant women report antihistamine use during pregnancy. Although antihistamines are generally considered safe during pregnancy, results from published studies are inconsistent. METHODS: Using a case-control study design we analyzed 41,148 pregnancies (30,091 cases and 11,057 controls) from the National Birth Defects Prevention Study (1997-2011). Logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals for 64 birth defect groupings in relation to early pregnancy exposure to 14 distinct antihistamines. Models were adjusted for maternal age, race, parity, education level, prenatal care, folic acid use, smoking and alcohol use, and study site. RESULTS: Approximately 13% of cases and controls were exposed to an antihistamine during early pregnancy. Analyses were restricted to those defects where more than five cases were exposed to the antihistamine of interest, generating 340 analyses which yielded 20 (5.9%) significant positive associations (adjusted ORs ranging from 1.21 to 4.34). CONCLUSIONS: Only a few of our findings were consistent with previous studies. There is a lack of strong evidence to conclude that birth defects are associated with exposure to antihistamines during early pregnancy.

A Bayesian Sensitivity Analysis to Partition Body Mass Index Into Components of Body Composition: An Application to Head and Neck Cancer Survival.

Previous studies have suggested a "J-shaped" relationship between body mass index (BMI, calculated as weight (kg)/height (m)2) and survival among head and neck cancer (HNC) patients. However, BMI is a vague measure of body composition. To provide greater resolution, we used Bayesian sensitivity analysis, informed by external data, to model the relationship between predicted fat mass index (FMI, adipose tissue (kg)/height (m)2), lean mass index (LMI, lean tissue (kg)/height (m)2), and survival. We estimated posterior median hazard ratios and 95% credible intervals for the BMI-mortality relationship in a Bayesian framework using data from 1,180 adults in North Carolina with HNC diagnosed between 2002 and 2006. Risk factors were assessed by interview shortly after diagnosis and vital status through 2013 via the National Death Index. The relationship between BMI and all-cause mortality was convex, with a nadir at 28.6, with greater risk observed throughout the normal weight range. The sensitivity analysis indicated that this was consistent with opposing increases in risk with FMI (per unit increase, hazard ratio = 1.04 (1.00, 1.08)) and decreases with LMI (per unit increase, hazard ratio = 0.90 (0.85, 0.95)). Patterns were similar for HNC-specific mortality but associations were stronger. Measures of body composition, rather than BMI, should be considered in relation to mortality risk.

Geographic heterogeneity in the prevalence of human papillomavirus in head and neck cancer.

Human papillomavirus (HPV) causes oropharyngeal squamous cell carcinoma (OPSCC), although strongly divergent results have been reported regarding the prevalence of HPV16 in different countries, whether this represents important differences in etiology remains unclear. Applying rigorous protocols for sample processing, we centrally evaluated 1,420 head and neck tumors (533 oropharynx, 395 oral cavity and 482 larynx) from studies conducted in the US, Europe and Brazil for mucosal HPV DNA and p16INK4a expression to evaluate regional heterogeneity in the proportion of HPV16-associated OPSCC and other head and neck cancer, and to assess covariates associated with the risk of HPV16-positive OPSCC. While majority of OPSCC in the US (60%) were HPV16-positive, this proportion was 31% in Europe and only 4% in Brazil (p < 0.01). Similar differences were observed for other head and neck tumors, ranging from 7% in the US and 5% in Europe, to 0% in South America. The odds of HPV16-positive OPSCC declined with increasing pack years of smoking (OR: 0.75; 95% CI: 0.64-0.87) and drink years of alcohol use (OR: 0.64; 95% CI: 0.54-0.76). These results suggest that while the contribution of HPV16 is substantial for the oropharynx, it remains limited for oral cavity and laryngeal cancers.

Effect of HPV on head and neck cancer patient survival, by region and tumor site: A comparison of 1362 cases across three continents.

OBJECTIVES: To explore whether HPV-related biomarkers predict oropharyngeal squamous cell cancer (OPSCC) survival similarly across different global regions, and to explore their prognostic utility among non-oropharyngeal (non-OP) head and neck cancers. METHODS: Data from 1362 head and neck SCC (HNSCC) diagnosed 2002-2011 was used from epidemiologic studies in: Brazil (GENCAPO study, n=388), U.S. (CHANCE study, n=472), and Europe (ARCAGE study, n=502). Tumors were centrally tested for p16INK4a and HPV16 DNA (by PCR). Risk of mortality was examined using Cox proportional hazard models. RESULTS: There were 517 OPSCC and 845 non-OP HNSCC. Cases were primarily male (81%), ever smokers (91%), with median age of 58yearsandmedian follow-up of 3.1years (IQR=1.4-5.9). Among OPSCC, the risk of mortality was significantly lower among 184 HPV-related (i.e., p16+/HPV16+) compared to 333 HPV-unrelated (p16- and/or HPV16-) cases (HR=0.25, 95%CI=0.18-0.34). Mortality was reduced among HPV-related OPSCC cases from the U.S., Europe, and Brazil (each p⩽0.01) and after adjustment, remained significantly reduced (aHR=0.34, 95%CI=0.24-0.49). Among non-OP HNSCC, neither p16 (aHR=0.83, 95%CI=0.60-1.14), HPV16 DNA (aHR=1.20, 95%CI=0.89-1.63), or p16+/HPV16+ (aHR=0.59, 95%CI=0.32-1.08) was a significantly predictor of mortality. When interaction was tested, the effect of HPV16/p16 was significantly different in OPSCC than non-OP HNSCC (p-interaction=0.02). CONCLUSION: HPV-related OPSCCs had similar survival benefits across these three regions. Prognostic utility of HPV among non-OP HNSCC is limited so tumor HPV/p16 testing should not be routinely done among non-OP HNSCC.

Factors that impact health-related quality of life over time for individuals with head and neck cancer.

OBJECTIVES/HYPOTHESIS: To identify sociodemographic, behavioral, and clinical factors associated with health-related quality of life (HRQOL) for head and neck cancer (HNC) patients over time. STUDY DESIGN: A population-based longitudinal cohort study. METHODS: Newly diagnosed HNC patients (N = 587) were administered the Functional Assessment of Cancer Therapy-Head and Neck questionnaire at baseline (median 3 months postdiagnosis) and two follow-up assessments (median 22 and 42 months). Linear mixed-effect models were used with backward variable selection to identify factors associated with HRQOL over time (P < .05). Adjusted means reported at 2 years postdiagnosis. RESULTS: African Americans reported better Functional Well-Being than whites (mean of 20.01 vs. 18.53) and fewer HNC symptoms over time. Older patients (75+ years) reported better HRQOL than younger patients (< 50 years). Current tobacco use compared to no tobacco use had worse Physical (20.20 vs. 21.50), Emotional (17.55 vs. 19.06), Social (21.28 vs. 22.88), and Functional (17.32 vs. 19.29) Well-Being and more HNC symptoms (21.50 vs. 23.71). Radiation therapy was associated with worse Physical and Functional Well-Being and more head and neck symptoms over time, but HRQOL was similar to those who were not irradiated by 2 to 4 years postdiagnosis. CONCLUSION: This study identified key factors for individuals at risk for poorer HRQOL that may help clinicians and caregivers find solutions to address these decrements. Smoking cessation programs can be encouraged for survivors who use tobacco. Psychological and social support and medications may help for dealing with emotional distress and dealing with the physical symptoms from treatment. LEVEL OF EVIDENCE: 4. Laryngoscope, 126:2718-2725, 2016.