BACKGROUND: Cancer is a leading cause of death by disease among children and adolescents in the United States. This study updates cancer incidence rates and trends using the most recent and comprehensive US cancer registry data available. METHODS: We used data from US Cancer Statistics to evaluate counts, age-adjusted incidence rates, and trends among children and adolescents aged <20 years diagnosed with malignant tumors during 2003-2019. We calculated average annual percent change and annual percent change (APC) using joinpoint regression. Rates and trends were stratified by demographic and geographic characteristics and by cancer type. RESULTS: With 248,749 cases reported during 2003-2019, the overall cancer incidence rate was 178.3 per 1 million; incidence rates were highest for leukemia (46.6), central nervous system (CNS) neoplasms (30.8), and lymphoma (27.3). Rates were highest for males, children aged 0-4 years, Non-Hispanic White children and adolescents, those in the Northeast census region, top 25% of counties by economic status, and metropolitan counties with population ≥1 million. While the overall incidence rate of pediatric cancer increased 0.5% per year on average during 2003-2019, the rate increased during 2003-2016 (APC = 1.1%) and then decreased during 2016-2019 (APC = -2.1%). During 2003-2019, rates of leukemia, lymphoma, hepatic tumors, bone tumors, and thyroid carcinomas increased, while melanoma rates decreased. CNS neoplasms rates increased until 2017 and then decreased. Other cancer types remained stable. CONCLUSIONS: Incidence of pediatric cancer increased overall, although increases were limited to certain cancer types. These findings may guide future public health and research priorities.

BACKGROUND: Since 2012, the Lower Anogenital Squamous Terminology (LAST) Project recommended a 2-tiered nomenclature, low-grade and high-grade squamous intraepithelial lesion (LSIL and HSIL), to replace the 3-tiered cervical intraepithelial neoplasia (CIN) system for HPV-associated lesions. Prior to 2019, preinvasive cervical lesions classified as CIN3, severe dysplasia, carcinoma in situ (CIS), and adenocarcinoma in situ (AIS) were considered reportable to the Louisiana Tumor Registry for a CIN3 project funded by the Centers for Disease Control and Prevention (CDC); but lesions classified exclusively as high-grade/HSIL based on the 2-tiered system were not considered reportable. Due to the terminology changes, we wanted to know whether pre-2019 reportable criteria need to be modified to capture all reportable precancerous cervical cases diagnosed in 2019 forward. OBJECTIVES: To evaluate the utilization of LAST 2-tiered classification, low-grade and high-grade squamous intraepithelial lesion, and p16 immunohistochemistry (IHC) testing on cervical biopsy/surgical specimens, assess the search criteria needed to identify high-grade lesions for the CDC-funded CIN3 project, and assess the impact of underreporting cervical lesions caused by terminology changes. METHODS: An equal number of abnormal/precancerous and normal cervical findings from biopsy pathology reports received in 2015 were randomly selected by an artificial intelligence (AI) search engine developed by Artificial Intelligence in Medicine Inc (AIM) using pre2019 search criteria. Selected pathology reports were reflagged for the reportability by AIM audit software based on 2019 search criteria and manually reviewed for the use of reportable terms including CIN3, severe dysplasia, CIS, AIS, highgrade/HSIL terminology, and CIN2 or CIN2-3 with positive p16 IHC testing. Cohen's kappa statistic was used to assess the agreement between AIM auto-coding and manual review. Positive predictive values (PPV) and sensitivity tests were computed to evaluate the reportable terms. RESULTS: Six out of 9 surveyed laboratories used 2-tiered terminology on cervical biopsy pathology reports and 7 performed p16 IHC tests. Of 1,974 randomly selected reports from 5 laboratories, 987 were flagged as precancer by AI using pre-2019 search criteria. After adding the high-grade/HSIL term into pre-2019 search criteria, precancerous reports increased by 29%. After manual review, 41.6% of these cases were reportable precancerous cervical cases with a PPV of 0.65 (95% CI, 0.62-0.67) and 13.6% had p16 IHC performed. CONCLUSIONS: Both the 2-tiered and 3-tiered nomenclature are needed to ensure complete identification of all reportable high-grade cervical lesions.

Invasive Salmonella infection is a common cause of acute febrile illness (AFI) among children in sub-Saharan Africa; however, diagnosing Salmonella bacteremia is challenging in settings without blood culture. The Uganda AFI surveillance system includes blood culture-based surveillance for etiologies of bloodstream infection (BSIs) in hospitalized febrile children in Uganda. We analyzed demographic, clinical, blood culture, and antimicrobial resistance data from hospitalized children at six sentinel AFI sites from July 2016 to January 2019. A total of 47,261 children were hospitalized. Median age was 2 years (interquartile range, 1-4) and 26,695 (57%) were male. Of 7,203 blood cultures, 242 (3%) yielded bacterial pathogens including Salmonella (N = 67, 28%), Staphylococcus aureus (N = 40, 17%), Escherichia spp. (N = 25, 10%), Enterococcus spp. (N = 18, 7%), and Klebsiella pneumoniae (N = 17, 7%). Children with BSIs had longer median length of hospitalization (5 days versus 4 days), and a higher case-fatality ratio (13% versus 2%) than children without BSI (all P < 0.001). Children with Salmonella BSIs did not differ significantly in length of hospitalization or mortality from children with BSI resulting from other organisms. Serotype and antimicrobial susceptibility results were available for 49 Salmonella isolates, including 35 (71%) non-typhoidal serotypes and 14 Salmonella serotype Typhi (Typhi). Among Typhi isolates, 10 (71%) were multi-drug resistant and 13 (93%) had decreased ciprofloxacin susceptibility. Salmonella strains, particularly non-typhoidal serotypes and drug-resistant Typhi, were the most common cause of BSI. These data can inform regional Salmonella surveillance in East Africa and guide empiric therapy and prevention in Uganda.

BACKGROUND: To date, the human papillomavirus (HPV) vaccine impact on invasive cervical cancers in the United States has not been documented due, in part, to the time needed for cancer to develop, and to recent changes to cervical cancer screening guidelines and recommendations which complicate data interpretation. METHODS: We examined incidence rates of cervical squamous cell carcinoma (SCC) and adenocarcinoma (AC)among women aged 15-29 years diagnosed during 1999-2017 using population-based cancer registry data covering 97.8% of the US population. Trends were stratified by age and histology. The annual percent change in cervical cancer incidence per year was calculated using Joinpoint regression. RESULTS: During 1999-2017, SCC rates decreased 7.9% per year among women aged 15-20 years, 5.5% among women aged 21-24 years, and 2.3% among women aged 25-29 years. The declines in SCC rates were largest among women aged 15-20 years from 2011 to 2017, with a decrease of 22.5% per year. Overall, AC rates decreased 4.1% per year among women aged 15-20 years, 3.6% per year among women aged 21-24 years, and 1.6% per year among women 25-29 years. AC rates declined the most among women aged 15-20 years during 2005 to 2017, decreasing 11.2% per year. CONCLUSIONS: Since HPV vaccine introduction, both SCC and AC incidence rates declined among women aged 15-20 years, a group not typically screened for cervical cancer, suggesting HPV vaccine impact. IMPACT: Timely vaccination and improved screening and follow-up among recommended age groups could result in further reductions in invasive cervical cancer.

Cancer-related mortality in the US-Affiliated Pacific Island (USAPI) jurisdictions is unknown. This is the first ever reporting of cancer-related mortality in the USAPI using cancer registry data. The individual USAPI jurisdictions collected incident cancer data and submitted it to the Pacific Regional Central Cancer Registry (PRCCR). All cases reported to PRCCR (n = 3,118) with vital status of dead (n = 1,323) during 2008-2013 were examined. Cause of death was coded based on clinical information provided in the cancer registry. Incidencebased mortality (IBM) rates were calculated using SEER*Stat software and age adjusted to the US standard population. Total cancer IBM rates among males were highest in Palau (151.5 per 100,000), Republic of the Marshall Islands (RMI, 142.0), and Guam (133.2); rates were lowest in American Samoa (21.7), the Commonwealth of the Northern Mariana Islands (CNMI, 22.7), and the Federated States of Micronesia (FSM, 28.9). Total cancer IBM rates among females were highest in RMI (120.3 per 100,000), Palau (107.7), and Guam (72.2); rates were lowest in CNMI (19.0), FSM (23.2), and American Samoa (42.8). The median time from cancer diagnosis to death was 8-28 days in the Freely Associated States and 102-128 days in the Flag Territories. IBM rates were higher among individuals in USAPI jurisdictions than among Asian/ Pacific Islanders in Hawai'i for many cancers preventable through vaccination, smoking cessation, overweight and obesity prevention, and cancer screening. Geographic remoteness, underreporting, delay in reporting, and challenges with accurate death registration and certification led to lower IBM rates for some jurisdictions. These mortality data can help prioritize evidence-based interventions to reduce cancer-related deaths through risk factor reduction, early detection, and improved quality of life after a cancer diagnosis through palliative care.

India's cervical cancer screening was launched in 2016 and we evaluated baseline facility readiness using nationally representative data from the 2012-13 District Level Household and Facility Survey on 4 tiers of the public health care system - 18,367 sub-health centres (SHC's), 8540 primary health centres (PHC's), 4810 community health centres and 1540 district/sub-divisional hospitals. To evaluate facility readiness we used the Improving Data for Decision Making in Global Cervical Cancer Programmes toolkit on six domains - potential staffing, infrastructure, equipment and supplies, infection prevention, medicines and laboratory testing, and data management. Composite scores were created by summing responses within domains, standardizing scores across domains at each facility level, and averaging across districts/states. Overall, readiness scores were low for cervical cancer screening. At SHC's, the lowest scores were observed in 'infrastructure' (0.55) and 'infection prevention' (0.44), while PHC's had low 'potential staffing' scores (0.50) due to limited manpower to diagnose and treat (cryotherapy) potential cases. Scores were higher for tiers conducting diagnostic work-up and treatment/referral. The highest scores were in 'potential staffing' except for PHC's, while the lowest scores were in 'infection & prevention' and 'medicines and laboratory'. Goa and Maharashtra were consistently top 5 ranking states for readiness. Substantial heterogeneity in facility readiness for cervical cancer screening spans states and tiers of India's public healthcare system. Infrastructure and staffing are large barriers to screening at PHCs, which are crucial for referral of high-risk patients. Our results suggest focus areas in cervical cancer screening at the district level for policy makers.

Background: Zika virus (ZIKV) infection has been associated with severe thrombocytopenia. We describe the incidence, clinical manifestations, and outcomes of patients with ZIKV infection and thrombocytopenia. Methods: We reviewed medical records of patients with ZIKV infection and thrombocytopenia (platelet count <100 x10(9) cells/L) in Puerto Rico during 2016. Severe thrombocytopenia was defined by platelet count <20 x10(9)/L or a platelet count <50 x10(9)/L and treatment for immune thrombocytopenia (ITP). Results: Of 37 878 patients with ZIKV infection, 47 (0.1%) had thrombocytopenia in the absence of an alternative etiology (1.4 cases/100 000 population), including 12 with severe thrombocytopenia. Most patients with thrombocytopenia were adult (77%) and male (53%). Platelet nadir occurred a median (range) of 6 (1-16) and 5 (0-34) days after symptom onset for patients with severe and nonsevere thrombocytopenia, respectively. Among patients with severe thrombocytopenia, all had bleeding, 33% were admitted to the intensive care unit, and 8% died; 50% were treated for ITP. Among 5 patients with severe thrombocytopenia who received intravenous immunoglobulin, the median platelet count increase (range) was 112 (65-202) x10(9)/L. In contrast, among 4 patients who received platelet transfusion, the median increase in platelet count (range) was 8.5 (-6 to 52) x10(9)/L. Conclusions: Patients with severe thrombocytopenia and ZIKV infection experienced prominent acute morbidity. Consistent with recommended management, administration of ITP treatments to such patients may be more efficacious than platelet transfusion in resolving thrombocytopenia. Severe thrombocytopenia should be considered a rare outcome of ZIKV infection.

Cervical cancer is the second leading cause of new cancer cases and cancer-related deaths among women in India, with an estimated 96,922 new cases and 60,078 deaths each year.* Despite the availability of effective low-cost screening options in India, limited access to screening and treatment services, diagnosis at a later stage, and low investment in health care infrastructure all contribute to the high number of deaths (1). In 2016 the Ministry of Health and Family Welfare of India recommended cervical cancer screening using visual inspection with acetic acid every 5 years for women aged 30-65 years (per World Health Organization [WHO] guidelines) (2,3). To establish a baseline for cervical cancer screening coverage, survey data were analyzed to estimate the percentage of women aged 30-49 years who had ever been screened for cervical cancer (defined as ever having had a cervix examination). Cervical cancer screening was estimated using data from the Fourth National Family Health Survey(dagger) (NFHS-4), a nationally representative survey conducted at the district level during 2015-2016, which included 699,686 Indian women aged 15-49 years. Lifetime cervical cancer screening prevalence was low (29.8%) and varied by geographic region, ranging from 10.0% in the Northeast Region to 45.2% in the Western Region. Prevalence of screening was higher among women with higher levels of education and household wealth, those who had ever been married, and urban residents. This screening prevalence can be used as a baseline indicator for cervical cancer screening in India in accordance with the WHO Noncommunicable Diseases Global Monitoring Framework during state-based programmatic rollout and program evaluation (4).

Human papillomavirus (HPV) is a known cause of cervical cancer, as well as some oropharyngeal, vulvar, vaginal, penile, and anal cancers. To assess trends, characterized by average annual percent change (AAPC), in HPV-associated cancer incidence during 1999-2015, CDC analyzed data from cancer registries covering 97.8% of the U.S. POPULATION: A total of 30,115 new cases of HPV-associated cancers were reported in 1999 and 43,371 in 2015. During 1999-2015, cervical cancer rates decreased 1.6% per year; vaginal squamous cell carcinoma (SCC) rates decreased 0.6% per year; oropharyngeal SCC rates increased among both men (2.7%) and women (0.8%); anal SCC rates also increased among both men (2.1%) and women (2.9%); vulvar SCC rates increased (1.3%); and penile SCC rates remained stable. In 2015 oropharyngeal SCC (15,479 cases among men and 3,438 among women) was the most common HPV-associated cancer. Continued surveillance through high-quality cancer registries is important to monitor cancer incidence and trends in these potentially preventable cancers.

Cancer is one of the leading causes of morbidity and mortality worldwide. In 2012, there were > 14 million new cancer cases and > 8 million cancer deaths, with 70% of these deaths occurring in low- and middle-income countries (LMICs). Part of the success of cancer prevention and control efforts requires the development and strengthening of the public health workforce, particularly in LMICs where the cancer burden is the greatest. The US Centers for Disease Control and Prevention (CDC) supports workforce capacity development globally through Field Epidemiology Training Programs (FETPs) established in ministries of health in > 70 countries. To enhance training in cancer prevention and control in FETPs, the CDC has developed an open-access curriculum in applied cancer epidemiology and supports FETP trainees who conduct cancer-related planned projects. The curriculum contains modules on cancer registration, screening, and comprehensive cancer control that are particularly relevant to current cancer control efforts in many LMICs. Pilot testing of the curriculum showed an increase in trainees' cancer knowledge and covered content trainees found to be relevant to their field epidemiology training and projects and future work in cancer prevention and control. Since 2013, the CDC has supported 13 trainees with cancer-related projects; two have published articles, two have presented their results at international conferences, and others are writing manuscripts on their project outcomes. Through the development of an open-access applied cancer epidemiology curriculum and by supporting cancer-related projects for FETP trainees, the CDC provided technical assistance for LMICs to build capacity for cancer prevention and control efforts.

Approximately 15,000 persons aged <20 years receive a cancer diagnosis each year in the United States (1). National surveillance data could provide understanding of geographic variation in occurrence of new cases to guide public health planning and investigation (2,3). Past research on pediatric cancer incidence described differences by U.S. Census region but did not provide state-level estimates (4). To adequately describe geographic variation in cancer incidence among persons aged <20 years in the United States, CDC analyzed data from United States Cancer Statistics (USCS) during 2003-2014 and identified 171,432 cases of pediatric cancer during this period (incidence = 173.7 cases per 1 million persons). The cancer types with the highest incidence rates were leukemias (45.7), brain tumors (30.9), and lymphomas (26.2). By U.S. Census region, pediatric cancer incidence was highest in the Northeast (188.0) and lowest in the South (168.0), whereas by state (including the District of Columbia [DC]), rates were highest in New Hampshire, DC, and New Jersey. Among non-Hispanic whites (whites) and non-Hispanic blacks (blacks), pediatric cancer incidence was highest in the Northeast, and the highest rates among Hispanics were in the South. The highest rates of leukemia were in the West, and the highest rates of lymphoma and brain tumors were in the Northeast. State-based differences in pediatric cancer incidence could guide interventions related to accessing care (e.g., in states with large distances to pediatric oncology centers), clinical trial enrollment, and state or regional studies designed to further explore variations in cancer incidence.

Acute lymphoblastic leukemia (ALL) is the most prevalent cancer among children and adolescents in the United States, representing 20% of all cancers diagnosed in persons aged <20 years, or >3,000 new cases each year (1). Past studies reported increasing trends of ALL overall and among Hispanics, but these represented ≤28% of the U.S. population and did not provide state-based estimates (1-3). To describe U.S. ALL incidence rates and trends among persons aged <20 years during 2001-2014, CDC analyzed rigorous data (based on established publication criteria) from the United States Cancer Statistics data set, which includes incidence data on approximately 15,000 new cases per year of all types of invasive cancer among children and adolescents aged <20 years (4). The data set represented 98% of the U.S. population during the study period. Overall incidence of pediatric ALL during 2001-2014 was 34.0 cases per 1 million persons and among all racial/ethnic groups was highest among Hispanics (42.9 per 1 million). Both overall and among Hispanics, pediatric ALL incidence increased during 2001-2008 and remained stable during 2008-2014. ALL incidence was higher in the West than in any other U.S. Census region. State-specific data indicated that the highest rates of pediatric ALL incidence were in California, New Mexico, and Vermont. These demographic and geographic ALL incidence data might better inform public health interventions targeting the following areas: exposures to recognized risk factors for leukemia; ALL treatment, including clinical trial enrollment; survivorship care planning; and studies designed to understand the factors affecting changes in pediatric cancer incidence.