Summary Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. Here, we describe the genomic landscape of 496 PTCs. We observed a low frequency of somatic alterations (relative to other carcinomas) and extended the set of known PTC driver alterations to include EIF1AX, PPM1D and CHEK2 and diverse gene fusions. These discoveries reduced the fraction of PTC cases with unknown oncogenic driver from 25% to 3.5%. Combined analyses of genomic variants, gene expression, and methylation demonstrated that different driver groups lead to different pathologies with distinct signaling and differentiation characteristics. Similarly, we identified distinct molecular subgroups of BRAF-mutant tumors and multidimensional analyses highlighted a potential involvement of oncomiRs in less-differentiated subgroups. Our results propose a reclassification of thyroid cancers into molecular subtypes that better reflect their underlying signaling and differentiation properties, which has the potential to improve their pathological classification and better inform the management of the disease.

BACKGROUND: Studies have reported an increasing incidence of thyroid cancer since 1980. One possible explanation for this trend is increased detection through more widespread and aggressive use of ultrasound and image‐guided biopsy. Increases resulting from increased detection are most likely to involve small primary tumors rather than larger tumors, which often present as palpable thyroid masses. The objective of the current study was to investigate the trends in increasing incidence of differentiated (papillary and follicular) thyroid cancer by size, age, race, and sex. METHODS: Cases of differentiated thyroid cancer (1988‐2005) were analyzed using the National Cancer Institute's Surveillance Epidemiology and End Results (SEER) dataset. Trends in incidence rates of papillary and follicular cancer, race, age, sex, primary tumor size (<1.0 cm, 1.0‐2.9 cm, 3.0‐3.9 cm, and >4 cm), and SEER stage (localized, regional, distant) were analyzed using joinpoint regression and reported as the annual percentage change (APC). RESULTS: Incidence rates increased for all sizes of tumors. Among men and women of all ages, the highest rate of increase was for primary tumors <1.0 cm among men (1997‐2005: APC, 9.9) and women (1988‐2005: APC, 8.6). Trends were similar between whites and blacks. Significant increases also were observed for tumors ≥4 cm among men (1988‐2005: APC, 3.7) and women (1988‐2005: APC, 5.70) and for distant SEER stage disease among men (APC, 3.7) and women (APC, 2.3). CONCLUSIONS: The incidence rates of differentiated thyroid cancers of all sizes increased between 1988 and 2005 in both men and women. The increased incidence across all tumor sizes suggested that increased diagnostic scrutiny is not the sole explanation. Other explanations, including environmental influences and molecular pathways, should be investigated. Cancer 2009. © 2009 American Cancer Society.

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To determine the factors predictive of improved survival among patients with advanced laryngeal cancer.Design: National hospital-based cancer registry.Patients: Patients treated with total laryngectomy (TL), radiation therapy alone (RT), or combined chemotherapy and radiation therapy (chemo-RT).Results: Of the 10 590 patients meeting the initial inclusion criteria, 7019 had appropriate nonmissing values in all study variables and were included in the analysis. Overall, TL was significantly associated with increased likelihood of survival compared with RT or chemo-RT (PϽ.001). Among patients with stage III cancer, TL and chemo-RT had similar impacts on survival (each showed increased survival compared with RT), whereas TL was associated with significantly greater survival than chemo-RT or RT among patients with stage IV disease (PϽ.001). Overall survival was also decreased among men, black patients (compared with white patients), and patients with Medicare or Medicaid or those who were uninsured (compared with those with private insurance).Conclusions: Among patients with the most advanced disease (stage IV), TL was associated with increased survival compared with chemo-RT or RT, whereas both TL and chemo-RT improved survival over RT among patients with stage III cancer. Insurance type and black race also showed significant associations with survival, which may reflect barriers in access to care (PϽ.001).

Objective (1) Describe current epidemiology of thyroid cancer in the United States; (2) evaluate hypothesized causes of the increased incidence of thyroid cancer; and (3) suggest next steps in research and clinical action. Methods Analysis of data from Surveillance, Epidemiology and End Results System and the National Center for Vital Statistics. Literature review of published English-language articles through December 31, 2013. Results The incidence of thyroid cancer has tripled over the past 30 years, whereas mortality is stable. The increase is mainly comprised of smaller tumors. These facts together suggest the major reason for the increased incidence is detection of subclinical, nonlethal disease. This has likely occurred through: health care system access, incidental detection on imaging, more frequent biopsy, greater volumes of and extent of surgery, and changes in pathology practices. Because larger-size tumors have increased in incidence also, it is possible that there is a concomitant true rise in thyroid cancer incidence. The only clearly identifiable contributor is radiation exposure, which has likely resulted in a few additional cases annually. The contribution of the following causes to the increasing incidence is unclear: iodine excess or insufficiency, diabetes and obesity, and molecular disruptions. The following mechanisms do not currently have strong evidence to support a link with the development of thyroid cancer: estrogen, dietary nitrate, and autoimmune thyroid disease. Conclusion Research should focus on illuminating which thyroid cancers need treatment. Patients should be advised of the benefits as well as harms that can occur with treatment of incidentally identified, small, asymptomatic thyroid cancers.

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BACKGROUND: Paranasal sinus squamous cell carcinomas (PNSSCC) account for 3% of all head and neck malignancies. There has been little information on the trends in incidence and survival, and no randomized trials have been conducted to guide therapy. METHODS: Patients with PNSSCC reported to the Surveillance, Epidemiology, and End Results (SEER) Program from 1973 through 2009 were categorized by sex, age, year of diagnosis, primary site, stage, and treatment. The incidence and survival were then compared across different demographic and disease-related categories by calculating rate ratios (RRs) and mortality hazard ratios along with the corresponding 95% confidence intervals (CIs). RESULTS: In total, 2553 patients with PNSSCC were identified. While incidence of PNSSCC showed a gradual decline, survival remained largely unchanged.

Among patients with early-stage laryngeal cancer, we observed an increasing proportion of primary surgical therapy during this study period. Among patients with advanced-stage cancer, we observed an increasing proportion of CRT. Not only were clinical factors associated with type of treatment, but select sociodemographic elements were also associated with treatment. Further investigation as to the decision-making process of patients with different sociodemographic backgrounds will assist in mitigating the differences in survival for this group of patients.