Antibodies against HPV16 early proteins have been shown to be promising biomarkers for the identification of HPV-driven oropharyngeal cancer (HPV-OPC) among OPC cases in multiple studies. A systematic literature search was performed to identify original research articles comparing HPV early antigen serology with established reference methods to determine molecular HPV tumor status. Random-effects models were used to calculate summary estimates for sensitivity and specificity of HPV16 E2, E6 and E7 serology for HPV-OPC. Subgroup analyses were performed to explore heterogeneity across studies and describe variables associated with test performance. We identified n = 23 studies meeting all eligibility criteria and included these in the meta-analysis. E6 serology showed the best performance with pooled sensitivity and specificity estimates of 83.1% (95% confidence interval (CI) 72.5–90.2%) and 94.6% (95% CI 89.0–97.4%), respectively, while E2 and E7 serological assays were highly specific (E2: 92.5% (95% CI 79.1–97.6%); E7: 88.5% (95% CI 77.9–94.4%)) but moderately sensitive (E2: 67.8% (95% CI 58.9–75.6%); E7: 67.0% (95% CI 63.2–70.6%)). Subgroup analyses revealed increased pooled sensitivity for bacterially (89.9% (95% CI 84.5–93.6%)) vs. in vitro expressed E6 antigen (55.3% (95% CI 41.0–68.7%)), while both showed high specificity (95.2% (95% CI 93.0–96.7%) and 91.1% (95% CI 46.6–99.2%), respectively). Pooled specificity estimates for HPV16 E2, E6 and E7 serology were significantly lower in studies utilizing HPV DNA PCR as the only molecular reference method compared to those using a combination of any two reference methods (HPV DNA, RNA, in situ hybridization (ISH), p16 immunohistochemistry (IHC)), or histopathological reference methods (ISH or p16 IHC) as stand-alone marker. In conclusion, HPV16 E6 seropositivity is a highly sensitive and specific biomarker for HPV-OPC. However, its performance differs between serological assays and depends on molecular reference methods.

Leukemia is the most common type of cancer among children and adolescents worldwide. The aim of this umbrella review was (1) to provide a synthesis of the environmental risk factors for the onset of childhood acute lymphoblastic leukemia (ALL) by exposure window, (2) evaluate their strength of evidence and magnitude of risk, and as an example (3) estimate the prevalence in the German population, which determines the relevance at the population level. Relevant systematic reviews and pooled analyses were identified and retrieved through PubMed, Web of Science databases and lists of references. Only two risk factors (low doses of ionizing radiation in early childhood and general pesticide exposure during maternal preconception/pregnancy) were convincingly associated with childhood ALL. Other risk factors including extremely low frequency electromagnetic field (ELF-MF), living in proximity to nuclear facilities, petroleum, benzene, solvent, and domestic paint exposure during early childhood, all showed some level of evidence of association. Maternal consumption of coffee (high consumption/>2 cups/day) and cola (high consumption) during pregnancy, paternal smoking during the pregnancy of the index child, maternal intake of fertility treatment, high birth weight (≥4000 g) and caesarean delivery were also found to have some level of evidence of association. Maternal folic acid and vitamins intake, breastfeeding (≥6 months) and day-care attendance, were inversely associated with childhood ALL with some evidence. The results of this umbrella review should be interpreted with caution; as the evidence stems almost exclusively from case-control studies, where selection and recall bias are potential concerns, and whether the empirically observed association reflect causal relationships remains an open question. Hence, improved exposure assessment methods including accurate and reliable measurement, probing questions and better interview techniques are required to establish causative risk factors of childhood leukemia, which is needed for the ultimate goal of primary prevention.

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Highlights RF-EMF was classified by IARC as possibly carcinogenic to humans (2B) in May 2011 A systematic review of all subject-relevant epidemiological studies is now needed. A detailed protocol ensures the review's transparency, utility and credibility. Original study validity will be evaluated with a customized OHAT risk of bias tool. Internal coherence and external plausibility will inform conclusions.

The growing population of long‐term childhood cancer survivors is at increased risk for severe, therapy‐related late effects and premature mortality. The cardiac and vascular late sequelae in long‐term survivors of childhood cancer (CVSS) study is a cohort of patients from Germany diagnosed with a neoplasia prior to 15 years of age in the time period 1980 to 1990. Late mortality was evaluated in a total of 4505 individuals who survived 5 years or more after the initial diagnosis (5‐year survivors). Survivors with a second primary tumor were excluded. Standardized mortality ratios (SMRs) were calculated. By December 2014, 400 patients had died. Available cause of death information from 188 individuals was used to estimate cause‐specific mortality for all deceased persons. Compared to the population of (former) West Germany, we observed an excess overall mortality risk (SMR = 9.53, 95% confidence interval [CI] = 8.62‐10.51). After correcting for missing cause of death information, an increased cancer mortality (SMR = 43.50, 95% CI = 25.79‐73.50) in the 5‐year survivors was detected. Cardiac death was ascertained in 14 individuals, resulting in an SMR of 10.85 (95% CI = 2.80‐32.02) after correcting for missing values. In conclusion, childhood cancer survivors diagnosed in Germany in 1980 to 1990 have a higher mortality risk overall and an elevated risk of dying from cancer and cardiac causes in particular. The results are consistent with those of international cohort studies. However, the reported results are based on few cases and individuals with secondary cancers were excluded.