Philip S. Rosenberg

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.

PURPOSE: Human papillomavirus (HPV) has been identified as the cause of the increasing oropharyngeal cancer (OPC) incidence in some countries. To investigate whether this represents a global phenomenon, we evaluated incidence trends for OPCs and oral cavity cancers (OCCs) in 23 countries across four continents. METHODS: We used data from the Cancer Incidence in Five Continents database Volumes VI to IX (years 1983 to 2002). Using age-period-cohort modeling, incidence trends for OPCs were compared with those of OCCs and lung cancers to delineate the potential role of HPV vis-à-vis smoking on incidence trends. Analyses were country specific and sex specific. RESULTS: OPC incidence significantly increased during 1983 to 2002 predominantly in economically developed countries. Among men, OPC incidence significantly increased in the United States, Australia, Canada, Japan, and Slovakia, despite nonsignificant or significantly decreasing incidence of OCCs. In contrast, among women, in all countries with increasing OPC incidence (Denmark, Estonia, France, the Netherlands, Poland, Slovakia, Switzerland, and United Kingdom), there was a concomitant increase in incidence of OCCs. Although increasing OPC incidence among men was accompanied by decreasing lung cancer incidence, increasing incidence among women was generally accompanied by increasing lung cancer incidence. The magnitude of increase in OPC incidence among men was significantly higher at younger ages (< 60 years) than older ages in the United States, Australia, Canada, Slovakia, Denmark, and United Kingdom. CONCLUSION: OPC incidence significantly increased during 1983 to 2002 predominantly in developed countries and at younger ages. These results underscore a potential role for HPV infection on increasing OPC incidence, particularly among men.

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.

BACKGROUND: Age-period-cohort (APC) analysis can inform registry-based studies of cancer incidence and mortality, but concerns about statistical identifiability and interpretability, as well as the learning curves of statistical software packages, have limited its uptake. METHODS: We implemented a panel of easy-to-interpret estimable APC functions and corresponding Wald tests in R code that can be accessed through a user-friendly Web tool. RESULTS: Input data for the Web tool consist of age-specific numbers of events and person-years over time, in the form of a rate matrix of paired columns. Output functions include model-based estimators of cross-sectional and longitudinal age-specific rates, period and cohort rate ratios that incorporate the overall annual percentage change (net drift), and estimators of the age-specific annual percentage change (local drifts). The Web tool includes built-in examples for teaching and demonstration. User data can be input from a Microsoft Excel worksheet or by uploading a comma-separated-value file. Model outputs can be saved in a variety of formats, including R and Excel. CONCLUSIONS: APC methodology can now be carried out through a freely available user-friendly Web tool. The tool can be accessed at http://analysistools.nci.nih.gov/apc/. IMPACT: The Web tool can help cancer surveillance researchers make important discoveries about emerging cancer trends and patterns.

BACKGROUND: Cancer trends in young adults, often under 50 years, reflect recent changes in carcinogenic exposures, which could foreshadow the future overall disease burden. Previous studies reported an increase in early onset colorectal cancer, which could partly reflect the obesity epidemic. We examined age-specific contemporary incidence trends in the USA for 30 common cancers, including 12 obesity-related cancers. METHODS: We obtained incidence data for invasive cancers among people aged 25-84 years diagnosed from Jan 1, 1995, to Dec 31, 2014, for 25 population-based state registries in the USA. All patients in the registry were included in the analyses. We considered the 20 most common cancer types and 12 obesity-related cancers (30 cancer types in total). We used age-period-cohort modelling to estimate average annual percentage change in incidence rates by 5-year age group (25-29 years to 80-84 years in 5-year increments) and incidence rate ratios (IRR) by birth cohort (10-year overlapping birth cohorts from 1910-19 to 1980-89 in 5-year increments). No exclusion criteria were applied after including all invasive cancer cases based on age group and diagnosis year. FINDINGS: From 1995 to 2014 there were 14 672 409 incident cases for 30 types of cancer. Incidence significantly increased for six of 12 obesity-related cancers (multiple myeloma, colorectal, uterine corpus, gallbladder, kidney, and pancreatic cancer) in young adults (25-49 years) with steeper rises in successively younger generations. Annual increases ranged from 1·44% (95% CI -0·60 to 3·53) for multiple myeloma to 6·23% (5·32-7·14) for kidney cancer at age 25-29 years, and ranged from 0·37% (0·03-0·72) for uterine corpus cancer to 2·95% (2·74-3·16) for kidney cancer at age 45-49 years. Compared with people born around 1950, IRRs for those born around 1985 ranged from 1·59 (95% CI 1·14-2·21) for multiple myeloma to 4·91 (4·27-5·65) for kidney cancer. Conversely, incidence in young adults increased in successively younger generations for only two cancers (gastric non-cardia cancer and leukaemia), and decreased for eight of the 18 additional cancers, including smoking and HIV infection-associated cancers. INTERPRETATION: The risk of developing an obesity-related cancer seems to be increasing in a stepwise manner in successively younger birth cohorts in the USA. Further studies are needed to elucidate exposures responsible for these emerging trends, including excess bodyweight and other risk factors. FUNDING: Intramural Research Department of the American Cancer Society and the Intramural Research Program of the National Cancer Institute.