Patterns of Cancer Incidence, Mortality, and Prevalence Across Five Continents: Defining Priorities to Reduce Cancer Disparities in Different Geographic Regions of the World.

Efforts to reduce global cancer disparities begin with an understanding of geographic patterns in cancer incidence, mortality, and prevalence. Using the GLOBOCAN (2002) and Cancer Incidence in Five Continents databases, we describe overall cancer incidence, mortality, and prevalence, age-adjusted temporal trends, and age-specific incidence patterns in selected geographic regions of the world. For the eight most common malignancies-cancers of lung, breast, colon and rectum, stomach, prostate, liver, cervix, and esophagus-the most important risk factors, cancer prevention and control measures are briefly reviewed.In 2002, an estimated 11 million new cancer cases and 7 million cancer deaths were reported worldwide; nearly 25 million persons were living with cancer. Among the eight most common cancers, global disparities in cancer incidence, mortality, and prevalence are evident, likely due to complex interactions of nonmodifiable (ie, genetic susceptibility and aging) and modifiable risk factors (ie, tobacco, infectious agents, diet, and physical activity). Indeed, when risk factors among populations are intertwined with differences in individual behaviors, cultural beliefs and practices, socioeconomic conditions, and health care systems, global cancer disparities are inevitable. For the eight most common cancers, priorities for reducing cancer disparities are discussed.

Human Papillomavirus and Rising Oropharyngeal Cancer Incidence in the United States.

PURPOSE: Recent increases in incidence and survival of oropharyngeal cancers in the United States have been attributed to human papillomavirus (HPV) infection, but empirical evidence is lacking. PATIENTS AND METHODS: HPV status was determined for all 271 oropharyngeal cancers (1984-2004) collected by the three population-based cancer registries in the Surveillance, Epidemiology, and End Results (SEER) Residual Tissue Repositories Program by using polymerase chain reaction and genotyping (Inno-LiPA), HPV16 viral load, and HPV16 mRNA expression. Trends in HPV prevalence across four calendar periods were estimated by using logistic regression. Observed HPV prevalence was reweighted to all oropharyngeal cancers within the cancer registries to account for nonrandom selection and to calculate incidence trends. Survival of HPV-positive and HPV-negative patients was compared by using Kaplan-Meier and multivariable Cox regression analyses. RESULTS: HPV prevalence in oropharyngeal cancers significantly increased over calendar time regardless of HPV detection assay (P trend < .05). For example, HPV prevalence by Inno-LiPA increased from 16.3% during 1984 to 1989 to 71.7% during 2000 to 2004. Median survival was significantly longer for HPV-positive than for HPV-negative patients (131 v 20 months; log-rank P < .001; adjusted hazard ratio, 0.31; 95% CI, 0.21 to 0.46). Survival significantly increased across calendar periods for HPV-positive (P = .003) but not for HPV-negative patients (P = .18). Population-level incidence of HPV-positive oropharyngeal cancers increased by 225% (95% CI, 208% to 242%) from 1988 to 2004 (from 0.8 per 100,000 to 2.6 per 100,000), and incidence for HPV-negative cancers declined by 50% (95% CI, 47% to 53%; from 2.0 per 100,000 to 1.0 per 100,000). If recent incidence trends continue, the annual number of HPV-positive oropharyngeal cancers is expected to surpass the annual number of cervical cancers by the year 2020. CONCLUSION: Increases in the population-level incidence and survival of oropharyngeal cancers in the United States since 1984 are caused by HPV infection.

Bimodal age distribution at diagnosis in breast cancer persists across molecular and genomic classifications.

PURPOSE: Female breast cancer demonstrates bimodal age frequency distribution patterns at diagnosis, interpretable as two main etiologic subtypes or groupings of tumors with shared risk factors. While RNA-based methods including PAM50 have identified well-established clinical subtypes, age distribution patterns at diagnosis as a proxy for etiologic subtype are not established for molecular and genomic tumor classifications. METHODS: We evaluated smoothed age frequency distributions at diagnosis for Carolina Breast Cancer Study cases within immunohistochemistry-based and RNA-based expression categories. Akaike information criterion (AIC) values compared the fit of single density versus two-component mixture models. Two-component mixture models estimated the proportion of early-onset and late-onset categories by immunohistochemistry-based ER (n = 2860), and by RNA-based ESR1 and PAM50 subtype (n = 1965). PAM50 findings were validated using pooled publicly available data (n = 8103). RESULTS: Breast cancers were best characterized by bimodal age distribution at diagnosis with incidence peaks near 45 and 65 years, regardless of molecular characteristics. However, proportional composition of early-onset and late-onset age distributions varied by molecular and genomic characteristics. Higher ER-protein and ESR1-RNA categories showed a greater proportion of late age-at-onset. Similarly, PAM50 subtypes showed a shifting age-at-onset distribution, with most pronounced early-onset and late-onset peaks found in Basal-like and Luminal A, respectively. CONCLUSIONS: Bimodal age distribution at diagnosis was detected in the Carolina Breast Cancer Study, similar to national cancer registry data. Our data support two fundamental age-defined etiologic breast cancer subtypes that persist across molecular and genomic characteristics. Better criteria to distinguish etiologic subtypes could improve understanding of breast cancer etiology and contribute to prevention efforts.

Divergent breast cancer incidence trends by hormone receptor status in the state of Sarawak, Malaysia.

Recent studies from high-risk countries such as the US, Denmark and Ireland have shown rising incidence rates of hormone receptor (HR)-positive and falling rates of HR-negative breast cancers (BC). However, it remains unclear whether a similar pattern occurs in low-risk countries. Detailed clinical and risk factor data were collected from 2,977 female invasive BC patients (≥20 years) in Sarawak General Hospital, Malaysia, representing 93% of the population. The population-at-risk was obtained from the Department of Statistics Malaysia. Secular trends in age-standardized incidence rates were assessed using estimated average annual percent changes. Associations between established BC risk factors and tumor subtypes defined by HR or joint human epidermal growth factor receptor 2 (HR/HER2) status were examined by case-case comparisons using logistic regression. From 2006 to 2015, incidence rates increased for HR-positive cancers by 4.46%/year (95% CI = 2.19-6.78) and decreased for HR-negative cancers by 2.29%/year (95% CI = -4.31 to -0.24). When further stratified by HER2, the most contrasting difference in linear trends was observed between HR+/HER2- and HR-/HER2- subtypes. After controlling for potential confounders, cases with excess body weight (ORoverweight vs. normal = 0.82; 95% CI = 0.69-0.98; ORobese vs. normal = 0.62; 95% CI = 0.48-0.80), later age at first birth (OR≥26 years vs. <23 years = 0.82; 95% CI = 0.66-1.02), nulliparity (ORnulliparous vs. <23 years = 0.74; 95% CI = 0.59-0.94) and never-breastfeeding (ORnever vs. ever = 0.73; 95% CI = 0.55-0.97) were less frequent among HR-negative cases than among HR-positive cases. Diverging incidence trends by HR expression were similar in Sarawak and Western countries, possibly reflecting changes in the prevalence of risk factors with opposing effects by tumor subtypes in low- and high-risk populations.

Evaluation of miscanthus productivity and water use efficiency in southeastern United States.

Second generation biofuels, such as perennial grasses, have potential to provide biofuel feedstock while growing on degraded land with minimal inputs. Perennial grasses have been reported to sequester large amounts of soil organic carbon (SOC) in the Midwestern United States (USA). However, there has been little work on biofuel and carbon sequestration potential of perennial grasses in the Southeastern US. Biofuel productivity for dryland Miscanthus × gigantus and irrigated maize in Georgia, USA were quantified using eddy covariance observations of evapotranspiration (ET) and net ecosystem exchange (NEE) of carbon. Miscanthus biomass yield was 15.54 Mg ha-1 in 2015 and 11.80 Mg ha-1 in 2016, while maize produced 30.20 Mg ha-1 of biomass in 2016. Carbon budgets indicated that both miscanthus and maize fields lost carbon over the experiment. The miscanthus field lost 5 Mg C ha-1 in both 2015 and 2016 while the maize field lost 1.37 Mg C ha-1 for the single year of study. Eddy covariance measurement indicated that for 2016 the miscanthus crop evapotranspired 598 mm and harvest water use efficiencies ranged from 6.95 to 13.84 kg C ha-1 mm-1. Maize evapotranspired 659 mm with a harvest water use efficiency of 19.12 kg C ha-1 mm-1. While biomass yields and gross primary production were relatively high, high ecosystem respiration rates resulted in a loss of ecosystem carbon. Relatively low biomass production, low water use efficiency and high respiration for Miscanthus × gigantus in this experiment suggest that this strain of miscanthus may not be well-suited for dryland production under the environmental conditions found in South Georgia USA.

Molecular Classification of Epithelial Ovarian Cancer Based on Methylation Profiling: Evidence for Survival Heterogeneity.

PURPOSE: Ovarian cancer is a heterogeneous disease that can be divided into multiple subtypes with variable etiology, pathogenesis, and prognosis. We analyzed DNA methylation profiling data to identify biologic subgroups of ovarian cancer and study their relationship with histologic subtypes, copy number variation, RNA expression data, and outcomes. EXPERIMENTAL DESIGN: A total of 162 paraffin-embedded ovarian epithelial tumor tissues, including the five major epithelial ovarian tumor subtypes (high- and low-grade serous, endometrioid, mucinous, and clear cell) and tumors of low malignant potential were selected from two different sources: The Polish Ovarian Cancer study, and the Surveillance, Epidemiology, and End Results Residual Tissue Repository (SEER RTR). Analyses were restricted to Caucasian women. Methylation profiling was conducted using the Illumina 450K methylation array. For 45 tumors array copy number data were available. NanoString gene expression data for 39 genes were available for 61 high-grade serous carcinomas (HGSC). RESULTS: Consensus nonnegative matrix factorization clustering of the 1,000 most variable CpG sites showed four major clusters among all epithelial ovarian cancers. We observed statistically significant differences in survival (log-rank test, P = 9.1 × 10-7) and genomic instability across these clusters. Within HGSC, clustering showed three subgroups with survival differences (log-rank test, P = 0.002). Comparing models with and without methylation subgroups in addition to previously identified gene expression subtypes suggested that the methylation subgroups added significant survival information (P = 0.007). CONCLUSIONS: DNA methylation profiling of ovarian cancer identified novel molecular subgroups that had significant survival difference and provided insights into the molecular underpinnings of ovarian cancer.See related commentary by Ishak et al., p. 5729.

Black-White Breast Cancer Incidence Trends: Effects of Ethnicity.

Recent reports of converging black and white breast cancer incidence rates have gained much attention, potentially foreshadowing a worsening of the black-white breast cancer mortality disparity. However, these incidence rates also reflect the sum of non-Hispanics and Hispanics that may mask important ethnicity-specific trends. We therefore assessed race- and ethnicity-specific breast cancer trends using the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) 13 Registries Database (1992-2014). Age-period-cohort models projected rates for 2015-2030. Results confirmed merging of age-standardized incidence rates for blacks and whites circa 2012, but not for non-Hispanic black (NHB) and non-Hispanic white (NHW) women. Incidence rates were highest for NHW women (n = 382 290), followed by NHB women (n = 51 074), and then Hispanic white women (n = 48 651). The sample size for Hispanic blacks was too small for analysis (n = 693). Notably, future incidence rates are expected to slowly increase (2015 through 2030) among NHW women (0.24% per year, 95% confidence interval [CI] = 0.17 to 0.32) and slowly decrease for NHB women (-0.14% per year, 95% CI = -0.15 to -0.13). A putative worsening of the black-white mortality disparity, therefore, seems unlikely. Ethnicity matters when assessing race-specific breast cancer incidence rates.

Breast cancer in Portugal: Temporal trends and age-specific incidence by geographic regions.

BACKGROUND: Female breast cancer incidence rates have been increasing in Portugal for years. We, therefore, conducted the first nationwide breast cancer study to assess regional differences. METHODS: Cases were obtained from population-based cancer registries covering the country's Mainland (South, North, Centre), as well as the two Autonomous Regions (Azores and Madeira), for the time-period 1998 through 2011. Analyses were restricted to ages 30-84 years and stratified by region. We used the age-period-cohort (APC) framework to complement standard descriptive techniques and to forecast future trends. Estimable APC parameters included net drift, longitudinal age-specific incidence rate curves, and fitted age-specific incidence rate ratios. RESULTS: There were 71 545 breast cancer cases diagnosed in Portugal at ages 30-84 years from 1998 to 2011. The South presented the highest age-standardized rate (155.8/100 000), while the North presented the fastest rate of increase (3.6%/year). Age-specific statistical interactions were observed between regions. Younger women in the North revealed a decreased risk of developing breast cancer compared to women from the same age group in the South and Centre, while that risk was reversed in older women (p < 0.05). We estimate that from 2014 onwards, the North might rank first among all regions. CONCLUSION: The variant patterns observed could be due to a combination of different screening practices and/or exposure to risk factors across regions. Disease heterogeneity among younger and older women may also explain part of the differences in age-specific rates. These results justify continued monitoring of breast cancer incidence by region.

The Changing Face of Noncardia Gastric Cancer Incidence Among US Non-Hispanic Whites.

Background: The initial step for noncardia gastric carcinogenesis is atrophic gastritis, driven by either Helicobacter pylori infection or autoimmunity. In recent decades, the prevalence rates of these two major causes declined and increased, respectively, with changes in Western lifestyles. We therefore assessed gastric cancer incidence trends for US race/ethnic groups, 1995-2013. Methods: Age-standardized rates (ASRs) from 45 North American Association of Central Cancer Tumor Registries were summarized by estimated annual percentage change (EAPC) and 95% confidence intervals (CIs). Age period cohort models supplemented standard descriptive techniques and projected future trends. Results: There were 137 447 noncardia cancers in 4.4 billion person-years of observation. Among non-Hispanic whites, the ASR was 2.2 per 100 000 person-years, with an EAPC of -2.3% (95% CI = -2.0% to -2.6%). Notwithstanding this overall decline, EAPCs rose 1.3% (95% CI = 0.6% to 2.1%) for persons younger than age 50 years and fell -2.6% (95% CI = -2.4% to -2.9%) for older individuals. These converging trends manifested a birth cohort effect more pronounced among women than men, with incidence among women born in 1983 twofold (95% CI = 1.1-fold to 3.6-fold) greater than those born in 1951. Age interaction was also statistically significant among Hispanic whites, with slightly increasing vs decreasing EAPCs for younger and older individuals, respectively. Incidence declined regardless of age for other races. Current trends foreshadow expected reversals in both falling incidence and male predominance among non-Hispanic whites. Conclusions: Dysbiosis of the gastric microbiome associated with modern living conditions may be increasing risk of autoimmune gastritis and consequent noncardia cancer. The changing face by age and sex of gastric cancer warrants analytical studies to identify potential causal mechanisms.

Past, Current, and Future Incidence Rates and Burden of Metastatic Prostate Cancer in the United States.

BACKGROUND: Metastatic prostate cancer (PCA) remains a highly lethal malignancy in the USA. As prostate-specific antigen testing declines nationally, detailed assessment of current age- and race-specific incidence trends and quantitative forecasts are needed. OBJECTIVE: To evaluate the current trends of metastatic PCA by age and race, and forecast the number of new cases (annual burden) and future trends. DESIGN, SETTING, AND PARTICIPANTS: We derived incidence data for men aged ≥45 yr who were diagnosed with metastatic PCA from the population-based Surveillance, Epidemiology, and End Results registries. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We examined the current trends of metastatic PCA from 2004 to 2014, and forecast the annual burden and incidence rates by age and race for 2015-2025, using age-period-cohort models and population projections. We also examined alternative forecasts (2012-2025) using trends prior to the revised screening guidelines issued in 2012. RESULTS AND LIMITATIONS: Metastatic PCA, steadily declining from 2004 to 2007 by 1.45%/yr, began to increase by 0.58%/yr after 2008, which accelerated to 2.74%/yr following the 2012 United States Preventive Services Task Force recommendations-a pattern that was magnified among men aged ≤69 yr and white men. Forecasts project the incidence to increase by 1.03%/yr through 2025, with men aged 45-54 yr (2.29%/yr) and 55-69 yr (1.53%/yr) increasing more rapidly. Meanwhile, the annual burden is expected to increase 42% by 2025. Our forecasts estimated an additional 15 891 metastatic cases from 2015 to 2025 compared with alternative forecasts using trends prior to 2012. CONCLUSIONS: The recent uptick in metastatic PCA rates has resulted in forecasts that project increasing rates through 2025, particularly among men aged ≤69 yr. Moreover, racial disparities are expected to persist and the annual burden will increase considerably. The impact of the prior and current PCA screening recommendations on metastatic PCA rates requires continued examination. PATIENT SUMMARY: In this report, we assessed how the incidence of metastatic prostate cancer has changed over recent years, and forecast future incidence trends and the number of new cases expected each year. We found that the incidence of metastatic prostate cancer has been increasing more rapidly since 2012, resulting in a rise in both future incidence and the number of new cases by 2025. Future incidence rates and the number of new cases were reduced in alternative forecasts using data prior to the 2012 United States Preventive Services Task Force (USPSTF) recommendations against prostate-specific antigen (PSA) testing for prostate cancer. There is a need for additional research that examines whether national declines in PSA testing contributed to increases in rates of metastatic disease. The incidence of metastatic disease in black men is still expected to occur at considerably higher rates compared with that in white men.

Divergent oestrogen receptor-specific breast cancer trends in Ireland (2004-2013): Amassing data from independent Western populations provide etiologic clues.

The aetiology and clinical behaviour of breast cancers vary by oestrogen receptor (ER) expression, HER2 expression and over time. Data from the United States and Denmark show rising incidence rates for ER+ and falling incidence rates for ER- breast cancers. Given that Ireland is a somewhat similar Western population but with distinctive risk exposures (especially for lactation), we analysed breast cancer trends by ER status; and for the first time, by the joint expression of ER±/HER2±. We assessed invasive breast cancers (n = 24,845; 2004-2013) within the population-based National Cancer Registry of Ireland. The population at risk was obtained from the Irish Central Statistics Office (n = 10,401,986). After accounting for missing ER and HER2 data, we assessed receptor-specific secular trends in age-standardised incidence rates (ASRs) with the estimated annual percentage change (EAPC) and corresponding 95% confidence intervals (95% CI). Age-period-cohort models were also fitted to further characterise trends accounting for age, calendar-period and birth-cohort interactions. ASRs increased for ER+ (EAPC: 2.2% per year [95% CI: 0.97, 3.45%/year]) and decreased for ER- cancers (EAPC: -3.43% per year [95% CI: -5.05, -1.78%/year]), as well as for specific age groups at diagnosis (<30-49, 50-64 and ≥65 years). ER+/HER2- cancers rose, ER+/HER2+ cancers were statistically flat and ER-/HER± cancers declined. Secular trends for ER± cancers in Ireland were like those previously observed. Stratification by HER2± expression did not substantively alter ER± trends. The divergence of ER± incidence rates among independent Western populations likely reflects calendar-period and/or risk factor changes with differential effects for ER+ and ER- breast cancers.

Chemical Analysis of Fermentable Sugars and Secondary Products in 23 Sweet Sorghum Cultivars.

Sorghum (Sorghum bicolor (L.) Moench) is a heat- and drought-tolerant crop that has promise to supplement corn (Zea mays L.) for biofuel production from fermentable sugars (for sweet cultivars) and lignocellulosic biomass. Quantitative relationships are lacking to predict the accumulation of primary (stem sugars) and secondary (organic acids, phenolics, and inorganic species) products that could either expand (as the value-added product) or limit (as the fermentation inhibitor) the market value of a cultivar. Five male (Atlas, Chinese, Dale, Isidomba, N98) and three female (N109B, N110B, and N111B) inbred lines and their hybrids (23 cultivars total) were planted on a Tifton loamy sand in April, May, and June of 2015 in a triplicate split-plot design and were harvested at the hard-dough maturity stage. Stalk juices were analyzed for sugar (glucose, fructose, and sucrose) and organic acid (citrate, oxalate, and cis- and trans-aconitic acid) concentrations, Brix, pH, electric conductivity (EC), total organic carbon (TOC), and total nitrogen (TN), and by fluorescence excitation emission spectrophotometry with parallel factor analysis (EEM/PARAFAC). Later plantings consistently (p < 0.05) (1) increased sucrose, total sugar, and trans-aconitic acid concentrations, Brix, and TOC and (2) decreased EC. Sucrose, total sugar, pH, EC, and Brix showed significant cultivar × planting date interactions. Observed linear relationships (Pearson's) could be used to deploy simple and inexpensive electrode (EC) and fluorescence-based field methods to predict the primary products from secondary products, and vise versa.

Colorectal Cancer Incidence Patterns in the United States, 1974-2013.

Background: Colorectal cancer (CRC) incidence in the United States is declining rapidly overall but, curiously, is increasing among young adults. Age-specific and birth cohort patterns can provide etiologic clues, but have not been recently examined. Methods: CRC incidence trends in Surveillance, Epidemiology, and End Results areas from 1974 to 2013 (n = 490 305) were analyzed by five-year age group and birth cohort using incidence rate ratios (IRRs) and age-period-cohort modeling. Results: After decreasing in the previous decade, colon cancer incidence rates increased by 1.0% to 2.4% annually since the mid-1980s in adults age 20 to 39 years and by 0.5% to 1.3% since the mid-1990s in adults age 40 to 54 years; rectal cancer incidence rates have been increasing longer and faster (eg, 3.2% annually from 1974-2013 in adults age 20-29 years). In adults age 55 years and older, incidence rates generally declined since the mid-1980s for colon cancer and since 1974 for rectal cancer. From 1989-1990 to 2012-2013, rectal cancer incidence rates in adults age 50 to 54 years went from half those in adults age 55 to 59 to equivalent (24.7 vs 24.5 per 100 000 persons: IRR = 1.01, 95% confidence interval [CI] = 0.92 to 1.10), and the proportion of rectal cancer diagnosed in adults younger than age 55 years doubled from 14.6% (95% CI = 14.0% to 15.2%) to 29.2% (95% CI = 28.5% to 29.9%). Age-specific relative risk by birth cohort declined from circa 1890 until 1950, but continuously increased through 1990. Consequently, compared with adults born circa 1950, those born circa 1990 have double the risk of colon cancer (IRR = 2.40, 95% CI = 1.11 to 5.19) and quadruple the risk of rectal cancer (IRR = 4.32, 95% CI = 2.19 to 8.51). Conclusions: Age-specific CRC risk has escalated back to the level of those born circa 1890 for contemporary birth cohorts, underscoring the need for increased awareness among clinicians and the general public, as well as etiologic research to elucidate causes for the trend. Further, as nearly one-third of rectal cancer patients are younger than age 55 years, screening initiation before age 50 years should be considered.

Metformin use and survival after non-small cell lung cancer: A cohort study in the US Military health system.

Research suggests that metformin may be associated with improved survival in cancer patients with type II diabetes. This study assessed whether metformin use after non-small cell lung cancer (NSCLC) diagnosis is associated with overall survival among type II diabetic patients with NSCLC in the U.S. military health system (MHS). The study included 636 diabetic patients with histologically confirmed NSCLC diagnosed between 2002 and 2007, identified from the linked database from the Department of Defense's Central Cancer Registry (CCR) and the Military Health System Data Repository (MDR). Time-dependent multivariate Cox proportional hazards models were used to assess the association between metformin use and overall survival during follow-up. Among the 636 patients, 411 died during the follow-up. The median follow-up time was 14.6 months. Increased post-diagnosis cumulative use (per 1 year of use) conferred a significant reduction in mortality (adjusted hazard ratio (HR) = 0.76; 95% CI = 0.65-0.88). Further analysis by duration of use revealed that compared to non-users, the lowest risk reduction occurred among patients with the longest duration of use (i.e. use for more than 2 years) (HR = 0.19; 95% CI = 0.09-0.40). Finally, the reduced mortality was particularly observed only among patients who also used metformin before lung cancer diagnosis and among patients at early stage of diagnosis. Prolonged duration of metformin use in the study population was associated with improved survival, especially among early stage patients. Future research with a larger number of patients is warranted.

Rising incidence of oral tongue cancer among white men and women in the United States, 1973-2012.

BACKGROUND: Despite significant reductions in tobacco use in the US, oral tongue cancer incidence has reportedly increased in recent years, particularly in young white women. We conducted age-period-cohort analyses to identify birth cohorts that have experienced increased oral tongue cancer incidence, and compared these with trends for oropharyngeal cancer, a cancer caused by human papillomavirus (HPV) that has also recently increased. METHODS: We utilized cancer incidence data (1973-2012) from 18 registries maintained by the NCI SEER Program. Incidence trends were evaluated using log-linear joinpoint regression and age-period-cohort modeling was utilized to simultaneously evaluate effects of age, calendar year, and birth year on incidence trends. RESULTS: Incidence of oral tongue cancer increased significantly among white women during 1973-2012 (0.6% annual increase, p<0.001) and white men during 2008-2012 (5.1% annual increase, p=0.004). The increase was most apparent among younger white individuals (<50years; annual increase of 0.7% for men [p=0.02] and 1.7% for women [p<0.001] during 1973-2012). Furthermore, the magnitude of the increase during 1973-2012 was similar between young white men and women (2.3 vs. 1.8 cases per million, respectively). Incidence trends for oropharyngeal cancer were similar to trends for oral tongue cancer and similar birth cohorts (born after the 1940s) experienced rising incidence of these cancers (p-value: white men=0.12, white women=0.42), although the magnitude of increase was greater for oropharyngeal cancer. CONCLUSIONS: The incidence of oral tongue and oropharyngeal cancer has significantly increased among young white men and women within the same birth cohorts in the US.