What's new?

Cervical cancer incidence, human papillomavirus (HPV) vaccination coverage, and screening performance vary widely across Europe. This report addresses for the first time the issue of how Europe should respond to the ambitious call from the World Health Organization to reduce the incidence of cervical cancer to less than 4/100,000/year. To meet this target, all European countries should put in place programs to reach 90% and 70% of HPV vaccination and screening coverage, respectively, and manage 90% of screen-positive women by 2030. Despite the temporary interruptions of prevention activities caused by COVID-19, the pandemic should not deviate stakeholders from this ambition.

What's new?

Inherited cancer-predisposing genetic variants vary in identity and frequency across populations, potentially impacting genetic testing for risk assessment and treatment. This study examined the spectrum and prevalence of pathogenic variants specifically among Turkish breast and colorectal cancer patients. A total of 25 cancer susceptibility genes were analyzed. Overall, pathogenic variants were mostly non-recurrent or recurrent at low frequencies in the study population. The most notable exception, occurring at greater frequency, was deletion of exons 17-18 in BRCA1, a potential founder variant that originated in northeastern Turkey. The findings could inform region-specific strategies for genetic screening in cancer prevention.

What's new?

Clinical trials on first-line systemic therapy in metastatic colorectal cancer (mCRC) patients suggest a marked improvement in median overall survival (mOS). However, uncertainty exists in how the survival reported in trials relates to the real-life mCRC population. This is the first population-based study providing multiple scenarios for patient survival. The results show that real-life mCRC patients receiving systemic therapy have a shorter mOS compared to trial patients, likely reflecting patient selection in clinical trials. Clinicians should consider presenting multiple scenarios for survival based on real-life data instead of point estimates from clinical trials when informing patients about their life expectancy.

What's new?

Some studies have suggested that serum lipids may correlate with endometrial cancer (EC) risk, but results have been inconsistent. In our study, the authors used genetic markers to predict LDL and HDL cholesterol levels and analyze EC risk. They found that when lower LDL or higher HDL levels were predicted, EC risk was increased. These results support a role for LDL and HDL cholesterol in the development of EC, and lipid levels may represent a risk factor for EC. Further studies are required to assess the biological and clinical significance of these associations.

What's new?

Human papillomavirus (HPV)-based screening and vaccination are key strategies for early detection and prevention of cervical intraepithelial neoplasia grade 3 and cancer (CIN3+). Here the authors estimated the lifetime screen-detected CIN3+ risk expected under different HPV vaccination scenarios using a novel statistical, data-driven approach that deals with multiple-type HPV infections. The model estimated that the lifetime CIN3+ risks under five-yearly primary HPV screening will become very low in vaccinated women, in particular when protection is life-long and provided beyond genotypes 16 and 18. These CIN3+ risks are important when defining new extended screening intervals for vaccinated cohorts.

What's new?

Esophageal squamous cell carcinoma (ESCC) poses a particularly considerable threat to the Chinese population and is usually characterized by poor prognosis. Here, the authors developed a prediction model of ESCC with good discriminative ability based on eight potential epidemiological risk factors—age, sex, upper gastrointestinal cancer family history, smoking status, retrosternal, back, or neck pain, salted food consumption, fresh fruit consumption, and peptic ulcer or esophagitis disease history. The prediction model could be used as a low-cost pre-screening tool for mass ESCC screening in China by identifying a limited group of high-risk individuals who may be considered for endoscopic screening.

What's new?

In sub-Saharan Africa, most women with breast cancer are diagnosed long after symptoms first arise. Here, the authors studied the diagnostic journey for breast cancer among the African Breast Cancer-Disparities in Outcome cohort. This is the largest study to quantify the length of the diagnostic journey across various settings in sub-Saharan Africa. Time to final diagnosis decreased substantially when a woman recognized her symptoms as cancer. Most delays, they found, were due to extended time between first examination and final diagnosis. Promotion of breast cancer awareness among both women and healthcare providers could help reduce these delays.

What's new?

Telomere length is a promising biomarker for cancer risk, with longer- and shorter-than-expected telomeres variously linked to increased risk of malignancy. Among Asian populations, however, relationships between telomere length, cancer incidence, and cancer mortality remain understudied. Here, investigation of more than 26 500 Chinese adults with greater than 12 years of health follow-up shows that longer telomere length is associated with significantly elevated risk of total and cancer-specific incidence and mortality and with reduced risk of all-cause and non-cancer-related mortality. The data highlight the relevance of longer telomere length in the development and outcome of specific cancer types and non-cancerous diseases.

What's new?

There is mounting evidence that cancer patients have a greater likelihood of having coronavirus disease 2019 (COVID-19), but consistency is still lacking. This study provides the first estimate after correction for publication bias of cancer prevalence in patients with COVID-19 based on a comprehensive literature search and analysis. The results show that patients with cancer and cancer survivors are at an elevated risk of developing COVID-19 and are also 2- to 3-fold more likely of suffering severe events and death. These findings have implications for public health, calling for the establishment of appropriate measures to manage cancer patients with COVID-19.

What's new?

While granulocyte colony-stimulating factors (G-CSFs) are increasingly used alongside chemotherapy for breast cancer, G-CSF support has been linked to elevated risk of hematologic malignancies. Here, investigation of hematologic malignancies in women who received chemotherapy and G-CSF for primary invasive breast cancer reveals a significant positive association between G-CSF support and acute lymphoblastic leukemia/lymphocytic lymphoma (ALL/LL). No significant association was detected for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS), though risk of ALL/LL, AML, and MDS increased with increasing number of G-CSF doses. The findings call for further investigation into associations between G-CSFs and secondary hematologic malignancies in cancer patients.

What's new?

Platinum-based chemotherapy is not standard of care for unselected or genetically-selected patients with metastatic castration-resistant prostate cancer (mCRPC). However, several studies have shown that platinum-based chemotherapy may still have a role in postponing progression in selected patient groups. This new study investigating DNA damage repair gene alterations and response to platinum-based chemotherapy provides evidence that deep and durable responses are primarily associated with patients harbouring BRCA2 inactivation. Based on these data and the limited available literature, platinum-based chemotherapy followed by PARP inhibition is potentially emerging as the optimal treatment sequence in pre-selected mCRPC patients.

What's new?

In HPV screening for cervical cancer, cytology has been used to triage those women who are hrHPV-positive. However, cytology is subjective, and skilled cytologists are often in short supply. A molecular test using specific biomarkers might offer better results. In this large European study, the authors found that a new standardized test for the methylation biomarker combination FAM19A4/miR124-2 did indeed yield results that were equal to or better than triage by cytology, in determining which hrHPV-positive women should be referred for colposcopy.

What's new?

Breast cancer is the leading cause of death among European women. Although screening for breast cancer is available in all European countries, not all eligible women aged 50-69 get screened. Here, the authors calculated how many deaths could be prevented if screening coverage reached 100%, considering both organized and opportunistic screening. Already, screening prevents 21 680 deaths per year, and if all countries reached full examination coverage, an additional 12 434 deaths per year could be prevented across Europe.

What's new?

Chimeric antigen receptor T (CART) cells targeting CD19 have shown promising results in chronic lymphocytic leukemia (CLL). However, naïve-like T cells play an important role in CART expansion and long-term persistence in vivo, and these cells are sparse in CLL patients. Here, the authors show that BTK/ITK inhibition with Ibrutinib during CART cell generation may improve CLL patient-derived CART cell products and enhance CART cell function. Supplementing CART cell production with ibrutinib increases CART cell yields and enriches CART cells with less-differentiated phenotypes and lower expression of exhaustion markers, representing a potential avenue to improve the clinical outcome of patients.

What's new?

The National Comprehensive Cancer Network (NCCN) is an alliance of 30 cancer centers in the USA, which creates clinical practice guidelines regarded to be the standard in oncology. In 2010, only 6% of the guidelines were found to be based on high levels of evidence. Here, the authors evaluated the 2019 guidelines, and found that again, less than 10% of the 2019 guidelines were based on high levels of evidence. Yet the NCCN guidelines are perceived as evidence-based rather than authority-based. This finding underscores the need for research to expand the evidence upon which clinical guidelines can be based.

What's new?

JQ-1, a small-molecule BRD4 inhibitor, blocks PD-1/PD-L1 signaling by decreasing PD-L1 expression on tumor cells and increases the activity of antitumor cytotoxic T cells. However, the toxicity of JQ-1 limits its clinical applications. Here, the authors coupled JQ-1 with a TLR7 agonist to study whether concurrent activation of innate immune cells could enhance JQ-1's efficacy. The novel immunogenic BRD4 inhibitor effectively activated innate immune cells, blocked PD-1/PD-L1 signaling, and abrogated immune toxicity, leading to enhanced antitumor effects in a mouse melanoma model. The work provides new insights for the development of anti-melanoma drugs that concurrently target innate and adaptive immunity.

What's new?

Infection with cutaneous human papillomavirus (HPV) or human polyomavirus (HPyV), may influence risk of keratinocyte carcinoma, but it's not known what role ultraviolet radiation (UVR) plays. Here, the authors undertook the first epidemiological study to probe the association between these viral infections and UVR exposure. They used a spectrophotometer to quantitatively measure UVR exposure, and they tested for biomarkers of 24 different HPV types and 4 types of HPyV. People with the highest levels of UVR exposure were the most likely to test positive for beta-HPV, in blood tests, in eyebrow hairs and in skin swabs.

What's new?

The molecular features of gynecologic clear cell carcinomas remain largely unknown and no targeted therapy is available. Here, the authors identified ALK aberrations in 94% (91/97) of gynecologic clear cell carcinoma cases, including 5 cases with ALK rearrangement and 77 cases with ALK copy number gain. A novel BABAM2-ALK fusion in one of the rearrangement cases was confirmed by next-generation sequencing. Altogether, the findings suggest that ALK aberrations may represent functional and clinically-actionable alterations. ALK fusion, which is targetable in other cancers, may be a pathogenetic mechanism in a small number of gynecologic clear cell carcinomas.

What's new?

Androgen receptor (AR) signaling is the dominant driver of AR-dependent castration-resistant prostate cancer (CRPC) development and progression, even with continuous androgen deprivation therapy. The mechanisms causing the reactivation of AR signaling in CRPC remain unclear. Here, the authors demonstrate that the adaptor protein GRB10 sustains AR activity in CRPC. Data from high-throughput proteomics analysis indicate that the reported tumor suppressor PP2A is a mediator of AR modulation by GRB10. GRB10 interacts with PP2A and promotes its degradation, thereby protecting phosphorylated AR from dephosphorylation and sustaining active AR signaling. Inhibiting GRB10 therapeutically could potentially improve CRPC management.

What's new?

The mixture of epithelial and stromal components in pancreatic ductal adenocarcinoma may confound sequencing-based studies of tumor gene expression and new approaches have been sought to segregate the two components. This study shows that the stratified examination of biochemical expression in the stroma and epithelial components of pancreatic ductal adenocarcinoma has the potential to identify prognostic information inaccessible by whole tumour assessment. The authors identified proteins that can be easily assessed and input into a predictive model which can be used to prognosticate individual patients. The findings may offer a new approach for pancreatic ductal adenocarcinoma research and clinical practice.

What's new?

Primary cervical cancer screening with DNA testing for human papillomavirus (HPV) is limited by its lower specificity relative to conventional cytology, thus requiring more efficient triage strategies to avoid excess colposcopy and overtreatment of cervical lesions. This study compared the clinical performance of dual-stained cytology and HPV genotyping among women referred to colposcopy for abnormal cervical cancer screening results. The data provide further evidence that the combined biomarker p16/Ki-67, indicative of transforming HPV infections, has a higher specificity for high-grade cervical lesions than cytology and HPV genotyping. Dual-stained cytology could support the triaging management of patients with positive high-risk HPV.

What's new?

Genetic mutations do not always alter just a single protein. In some cases, they can affect the transcription of an entire pathway. In this study, the authors correlated somatic mutations and gene expression in cancer. They developed a platform that enables correlations to be analyzed in two directions: first, to identify changes in gene expression that are related to a specific mutation, and second, to identify mutations that alter the expression of selected genes. An online portal should enable this type of analysis for any new agent, to help researchers identify potential biomarkers and therapeutic targets.