What's new?

Most cervical cancers result from human papillomavirus (HPV) infection and therefore are preventable through screening and vaccination. Nonetheless, efforts toward HPV-attributable cancer prevention frequently are undermined by limited access to necessary resources. The present study estimates that worldwide as many as 4.5% of new cancer cases, including cancers of the cervix, anogenital tract and head and neck, are associated with HPV infection. Cervical cancer alone accounts for 83% of those cases, most of which affect women in less-developed countries. The findings emphasize the importance of HPV screening and vaccination and the need for less-costly vaccines.

What's new?

What's the public health impact of cancer screening over the long term? Not much data has been collected to quantitatively answer that. To find out, these authors collected data on breast cancer mortality in the Netherlands over a period of 20 years after the introduction of a national screening program. They observed a 30% decrease in breast cancer mortality among women age 55–74 after screening commenced. Similarly, in older women, age 75–79, mortality decreased by 34%.

What's new?

The association between specific genetic factors and pancreatic-cancer survival has been unclear. In this analysis of a large, genome-wide association study (GWAS) of pancreatic-cancer patients, the authors found that a particular SNP variant was associated with a significant decrease in survival. Next, they found that a tumor-suppressor gene near this SNP had reduced expression compared to normal controls. These findings may help identify novel therapeutic targets for pancreatic cancer.

What's new?

While smoking is a well-established risk factor for pancreatic cancer, the effect of smokeless tobacco is less well understood. Smokeless tobacco like snus yields lower exposure to tobacco carcinogens compared with smoking, because it does not undergo combustion, but delivers an equivalent dose of nicotine. Using pooled individual data from the Swedish Collaboration on Health Effects of Snus Use, here the authors show that Swedish snus use does not appear to be implicated in the development of pancreatic cancer in men. Tobacco smoke constituents other than nicotine or its metabolites may account for the relationship between smoking and pancreatic cancer.

What's new?

High-quality population-based cancer data are unavailable for much of Africa. To help fill that gap, the authors of this study calculated cancer incidence rates for Blantyre, Malawi, using data from the Malawi Cancer Registry. From 2008 to 2010, cancer burden in the area was characterized primarily by young age at diagnosis and by high incidence of HIV-associated cancers, particularly Kaposi sarcoma in men. Cervical cancer was the most common malignancy in women, while esophageal cancer rates were among the highest in the world. The data suggest that histopathology services in the area have improved, with nearly half of all diagnosed cancers verified microscopically.

What's new?

Testing for human papillomavirus (HPV) is gaining traction for cervical-cancer screening. However, most HPV infections are transient. Additional screening tests are thus needed, to identify women with precancerous or cancerous lesions who need further testing and treatment. Certain tumor-suppressor genes in cervical cancer cells have been found to have altered methylation. In this study, the authors used pyrosequencing and next-generation bisulfite sequencing to identify and validate several new DNA-methylation markers, which may lead to better screening tests.

What's new?

Aflatoxin B₁ (AFB₁), a potent carcinogen produced by fungi, is the most abundant aflatoxin found in contaminated food. Here, the authors examined its association with liver cirrhosis risk. Using an ELISA to measure AFB₁-albumin adducts in the blood, they found that AFB₁ exposure increases the risk of developing cirrhosis and liver cancer, and may also accelerate the progression of chronic hepatitis B virus infection to both conditions. They conclude that AFB₁ may not only contribute to hepatocarcinogenesis directly, but also indirectly by rendering liver cells more vulnerable by promoting cirrhosis.

What's new?

How do different genetic variants of Rho GTPases affect cutaneous melanoma survival? To find out, these authors looked at data from two different genome-wide association studies of cutaneous melanoma cases. They found SNPs in four genes that were independently predictive of survival. Including the number of unfavorable genotypes carried by a patient at these loci improved the prediction accuracy of the CM survival model. These results suggest a biological function for Rho GTPases and related regulator genes in the progression of cutaneous melanoma.

What's new?

The mechanisms underlying prostate cancer disparities among racial groups remain largely unknown. Here, the authors assessed the role of stemness-related genetic variants in racial differences in prostate cancer risk by re-analyzing published datasets from four genome-wide association studies of African descendants and non-Hispanic whites. They found that SNPs in TP63, ALDH1A1, WNT1, MET and EGFR were significantly associated with prostate cancer risk and showed differences between the racial groups. Bioinformatics analyses revealed RNA splicing-regulatory SNPs in EGFR, MET and ALDH1A1 as possible novel biomarkers that may provide new insights into the molecular mechanisms underlying racial disparities in prostate cancer risk.

What's new?

Although breast cancer incidence is low in Palestine compared to Europe or North America, most Palestinian breast cancer patients have a family history of breast or ovarian cancer or were diagnosed at a young age. Among familial and young onset patients, 13% carry a germ-line pathogenic mutation in one of eleven breast cancer genes. Most mutations were in BRCA1 or BRCA2, but the single most frequent mutation was TP53 p.R181C, which predisposes specifically to breast cancer.

What's new?

Can diet influence the persistence of HPV infection? Certain B vitamins, for instance, can promote viral integration, while other nutrients hinder it. This is the first study to investigate whether diet contributes to persistent oncogenic HPV-infection in men. Looking at a Brazilian cohort of men age 18–70, these authors tested the men for HPV over a period of 4 years. At each meeting, they gave them a questionnaire, asking about their diet. Persistent nononcogenic HPV infection was associated with B12 consumption, they found, but they could link none of the nutrients to persistent oncogenic HPV infection.

What's new?

This study has for the first time demonstrated that loss of H2Bub1 is associated with enhanced malignancy and poor differentiaton of lung adenocarcinoma. The study has further uncovered these potential molecules and signaling pathways underlying loss of H2Bub1 in lung adenocarcinoma. The study has indicated that loss of H2Bub1 plays an oncogenic role in lung adenocarcinoma via modulating multiple cancer signaling pathways, and represents a prognostic biomarker and therapeutic target for lung adenocarcinoma.

What's new?

Mutations on the tumor suppressor gene VHL are observed in most RCC cases. We previously identified a small molecule, STF-62247 tha tis capable to kill VHL-inactivated tumor cells. Here they used SILAC proteomics, IPA, and bioinformatics to show that STF-62247 may arrest protein synthesis in VHL-negative cells, while sparing normal cells. This approach also identified novel signaling pathways that could provide new, personalized therapeutic targets for ccRCC.

What's new?

The mechanisms by which hyperglycemia and other diabetes-related factors promote tumourigenesis are not fully understood, and while glucose metabolites and glycolytic precursors are implicated, their involvement remains largely undefined. In this investigation of hyperglycemia and glucose metabolism in esophageal squamous cell cancer cells, abrogated insulin signalling was found to work in combination with hyperglycemia to redirect glucose usage from glycolytic catabolism to anabolism of HA, an extracellular matrix polysaccharide synthesized from precursors in the first stages of glycolysis. Augmented HA facilitated the development of a malignant phenotype and tumour progression. Its synthesis was blocked by the inhibitor 4-methylumbelliferone.

What's new?

Molecules that block the activation of certain receptors in the spinal cord produce profound pain-relieving effects. The N-methyl-d-aspartate (NMDA) and group I metabotropic glutamate receptors (mGlu1/5) are especially important in this regard. The present study shows that co-inhibition of NMDA and mGlu1/5 receptors by levo-corydalmine (l-CDL), a compound from the plant Corydalis yanhusuo, attenuates bone cancer pain in rats following tumor cell implantation. Pain relief was associated with decreased p-PKCγ and p-ERK1/2 phosphorylation in the spinal cord. The findings warrant further investigation of NMDA and mGlu1/5 receptor co-inhibition in the spinal cord for the relief of bone cancer pain.

What's new?

Osteosarcoma (OS) is characterized by highly complex karyotypes with structural and numerical chromosomal alterations. The observed OS-specific characteristics in localization and frequencies of chromosomal breakages implicate a specific set of responsible driver genes or specific mechanism of fragility induction. Here, a comprehensive assessment of somatic copy number alterations (SCNAs) was performed in 160 OS samples. Breakage analysis revealed OS specific unstable regions in which well-known OS tumor suppressor genes, including TP53, RB1, WWOX, DLG2 and LSAMP are located. A complex breakage pattern–chromothripsis–was suggested as a widespread phenomenon in OS and found to be predictive of patient clinical outcome.

What's new?

Visual examination of cervical tissue obtained by biopsy provides information on morphological changes associated with human papillomavirus (HPV) infection and transformation to precancerous cervical intraepithelial neoplasia 2/3 (CIN2/3). The accuracy of CIN2/3 diagnosis by visual interpretation, however, could be improved through the use of complementary objective tests. This study describes two such tests: quantitative p16 mRNA analysis and digital analysis of immunohistochemical p16-protein staining. CIN2/3 diagnostic accuracy benefitted especially from the addition of p16-mRNA testing. Both new approaches could prove useful in locations lacking trained pathologists and could help avoid overtreatment in HPV-positive women, many of whom recover spontaneously.

What's New?

Folic acid is celebrated for its health benefits, particularly its ability to prevent certain birth defects. But its relationship with adult cancers is complex, with supplementation potentially increasing cancer risk in populations lacking folic acid-fortified foods. In this study of Chinese patients diagnosed with hypertension but lacking history of stroke or myocardial infarction and having relatively low folic acid intake, supplementation with 0.8 mg/d folic acid had no impact on cancer risk. Analyses of folate levels and MTHFR C677T genotypes uncovered beneficial effects for enalapril-folic acid treatment in patients with the MTHFR 677 TT variant, naturally associated with low serum folate levels.

What's new?

Kaposiform hemangioendothelioma (KHE) is an aggressive disease with high morbidity and mortality. Responses to standard therapies have been variable and unpredictable. In this study, the authors found that the drug sirolimus (rapamycin) provides a safe and effective treatment option for patients with progressive KHE. They caution, however, that the regimen should be tailored to individual patients. In cases complicated by Kasabach-Merritt phenomenon (KMP), a life-threatening coagulopathy, the short-term addition of prednisolone is also recommended.