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The pursuit of highly sensitive and specific cancer diagnostics based on cell-free (cf) nucleic acids isolated from minimally invasive liquid biopsies has been an area of intense research and commercial effort for at least two decades. Most of these tests detect cancer-specific mutations or epigenetic modifications on circulating DNA derived from tumor cells (ctDNA). Although recent FDA approvals of both single and multi-analyte liquid biopsy companion diagnostic assays are proof of the tremendous progress made in this domain, using ctDNA for the diagnosis of early-stage (stage I/II) cancers remains challenging due to several factors, such as low mutational allele frequency in circulation, overlapping profiles in genomic alterations among diverse cancers, and clonal hematopoiesis. This review discusses these analytical challenges, interim solutions, and the opportunity to complement ctDNA diagnostics with microbiome-aware analyses that may mitigate several existing ctDNA assay limitations.

Cancer screening can play an important role in early detection, improving treatment outcomes and reducing morbidity and mortality. Breast and cervical cancers belong to the most common gynaecological cancers group. Countries provide different screening programmes on its eligible population basis centred on different health care policies. This scientific study aims to assess and understand the health inequalities in the member countries of the European Board & College of Obstetrics and Gynaecology (EBCOG) as regards screening programmes of gynaecological cancer, with a special focus on breast and cervical cancers' screening strategies. A descriptive questionnaire-based study was conducted, addressed to EBCOG member countries. Ninety-one percent of the countries have an organized national or regional screening programme for cervical cancer. Of these, 45% of countries use both cytology and testing for Human Papilloma Virus (HPV) as screening test, 31% use cytology exclusively and 17% only perform HPV testing. Considerable differences were found regarding the interval of screening test: there are countries performing HPV detection triennially, while others perform only conventional cytology every 5 years. Sixty-nine percent of countries included in this study begin screening for cervical cancer in women aged 25 to 29 years, four of them using HPV detection as the screening test. Six countries begin cervical cancer screening before the age of 25. As regards vaccination against HPV, almost all countries have implemented national HPV vaccination programme, except in Poland and Turkey. The 9-valent HPV vaccine is the most frequently offered (77% of countries) and the majority vaccination programmes include both girls and boys. As regards breast cancer screening, all thirty-two countries have an implemented screening programme. All countries perform mammography as the screening test, 62.5% of them begin in women aged 50 to 54, with a 2-yearly interval in the majority. In five countries, screening programmes are performed biennially, starting between 45 and 49 years old. Seven countries start in women aged 41 to 44. There are discrepancies around gynaecological cancer screenings provision among EBCOG member countries. It is important to establish European recommendations about screening for gynaecological cancers, in order to standardize the access to equitable better health care in gynaecological cancers within Europe. [ABSTRACT FROM AUTHOR]

Abstract Background Little is known about the association between the COVID‐19 pandemic and early survival among newly diagnosed cancer patients. Methods This retrospective population‐based cohort study used linked administrative datasets from Ontario, Canada. Adults (≥18 years) who received a cancer diagnosis between March 15 and December 31, 2020, were included in a pandemic cohort, while those diagnosed during the same dates in 2018/2019 were included in a pre‐pandemic cohort. All patients were followed for one full year after the date of diagnosis. Cox proportional hazards regression models were used to assess survival in relation to the pandemic, patient characteristics at diagnosis, and the modality of first cancer treatment as a time‐varying covariate. Interaction terms were explored to measure the pandemic association with survival for each cancer type. Results Among 179,746 patients, 53,387 (29.7%) were in the pandemic cohort and 37,741 (21.0%) died over the first post‐diagnosis year. No association between the pandemic and survival was found when adjusting for patient characteristics at diagnosis (HR 0.99 [95% CI 0.96–1.01]), while marginally better survival was found for the pandemic cohort when the modality of treatment was additionally considered (HR 0.97 [95% CI 0.95–0.99]). When examining each cancer type, only a new melanoma diagnosis was associated with a worse survival in the pandemic cohort (HR 1.25 [95% CI 1.05–1.49]). Conclusions Among patients able to receive a cancer diagnosis during the pandemic, one‐year overall survival was not different than those diagnosed in the previous 2 years. This study highlights the complex nature of the COVID‐19 pandemic impact on cancer care.

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and one of the leading causes of cancer-related death worldwide. Despite the improvements in surveillance and treatment, the prognosis of HCC remains poor. Extracellular vesicles (EVs) are a heterogeneous group of phospholipid bilayer-enclosed particles circulating in the bloodstream and mediating intercellular communication. Emerging studies have shown that EVs play a crucial role in regulating the proliferation, immune escape, and metastasis of HCC. In addition, because EVs are present in the circulation at relatively early stages of disease, they are getting attention as an attractive biomarker for HCC detection. Over the past decade, dedicated efforts have been made to isolate EVs more efficiently and make them useful tools in different clinical settings. In this review article, we provide an overview of the EVs isolation methods and highlight the role of EVs as mediators in the pathogenesis and progression of HCC. Lastly, we summarize the potential applications of EVs in early-stage HCC detection.

To overcome early cancer detection challenges, diagnostic tools enabling more sensitive, rapid, and noninvasive detection are necessary. An attractive cancer target for diagnostic blood tests is human Ecto-NOX disulfide–thiol exchanger 2 (ENOX2), expressed in most human cancer types and regularly shed into blood sera. Here, we developed an electrochemical DNA-based (E-DNA) biosensor that rapidly detects physiologically relevant levels of ENOX2. To identify ENOX2-binding aptamers that could potentially be used in a biosensor, recombinantly expressed ENOX2 was used as a binding target in an oligonucleotide library pull-down that generated a highly enriched ENOX2-binding aptamer. This candidate aptamer sensitively bound ENOX2 via gel mobility shift assays. To enable this aptamer to function in an ENOX2 E-DNA biosensor, the aptamer sequence was modified to adopt two conformations, one capable of ENOX2 binding, and one with disrupted ENOX2 binding. Upon ENOX2 introduction, a conformational shift to the ENOX2 binding state resulted in changed dynamics of a redox reporter molecule, which generated a rapid, significant, and target-specific electrical current readout change. ENOX2 biosensor sensitivity was at or below the diagnostic range. The ENOX2 E-DNA biosensor design presented here may enable the development of more sensitive, rapid, diagnostic tools for early cancer detection. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) remains one of the most common and deadly malignancies despite advancements in screening, diagnostic capabilities, and treatment. The ability to detect and remove precancerous and cancerous lesions via screening has altered the epidemiology of the disease, decreasing incidence, mortality, and late-stage disease presentation. The fecal immunochemical test (FIT) is a screening test that aims to detect human hemoglobin in the stool. FIT is the most common CRC screening modality worldwide and second most common in the United States. Its use in screening programs has been shown to increase screening uptake and improve CRC outcomes. However, FIT-based screening programs vary widely in quality and effectiveness. In health systems with high-quality FIT screening programs, only superior FIT formats are used, providers order FIT appropriately, annual patient participation is high, and diagnostic follow-up after an abnormal result is achieved in a timely manner. Proper utilization of FIT involves multiple steps beyond provider recommendation of the test. In this commentary, we aim to highlight ongoing challenges in FIT screening and suggest interventions to maximize FIT effectiveness. Through active engagement of patients and providers, health systems can use FIT to help optimize CRC screening rates and improve CRC outcomes.

Circulating tumor DNA holds substantial promise as an early detection biomarker, particularly for cancers that do not have currently accepted screening methodologies, such as ovarian, pancreatic, and gastric cancers. Many features intrinsic to ctDNA analysis may be leveraged to enhance its use as an early cancer detection biomarker: including ctDNA fragment lengths, DNA copy number variations, and associated patient phenotypic information. Furthermore, ctDNA testing may be synergistically used with other multi-omic biomarkers to enhance early detection. For instance, assays may incorporate early detection proteins (i.e., CA-125), epigenetic markers, circulating tumor RNA, nucleosomes, exosomes, and associated immune markers. Many companies are currently competing to develop a marketable early cancer detection test that leverages ctDNA. Although some hurdles (like early stage disease assay accuracy, high implementation costs, confounding from clonal hematopoiesis, and lack of clinical utility studies) need to be addressed before integration into healthcare, ctDNA assays hold substantial potential as an early cancer screening test.

We present an image sensor incorporating angle-selective gratings for resolution enhancement in contact imaging applications. Optical structures designed in the CMOS metal layers above each photodiode form the angle-selective gratings that limit the sensor angle of view to ±18 °, rejecting background light and deblurring the image. The imager is based on a high-gain capacitive transimpedance amplifier pixel using a custom 11fF MOM capacitor, achieving [Formula: see text] sensitivity. The pixel includes a leakage current minimization circuit to remove signal-dependent reset switch leakage and the corresponding dark current is [Formula: see text]. The resulting 4.7 mm by 2.25 mm sensor (80 by 36 pixels) is designed specifically for intraoperative cancer imaging in order to solve the pervasive challenge of identifying microscopic residual cancer foci in vivo, where they can be removed. We demonstrate imaging and detection of foci containing less than 200 cancer cells labeled with fluorescent biomarkers in 50 ms with signal-to-noise ratios greater than 15 dB and the detection of microscopic residual tumor in mice models. The absence of large optical elements enables extreme miniaturization, allowing manipulation within a small, morphologically complex, tumor cavity.

Cancer remains the most lethal disease in today's scientific and technological age, claiming the lives of thousands of people every day. In many cases, cancer can be cured with our present technology interventions when it is detected at an early stage. State-of-the-art diagnostic devices are one of the viable strategies to combat cancer. Among various methods, optical and photoelectrochemical biosensors are the most popular for detecting cancer. This review article has focused on different optical analysis techniques and photoelectrochemical techniques for the early diagnosis of cancer via the detection of several cancer biomarkers. Optical analysis techniques involve the use of light properties such as resonance, interference, luminescence, scattering, etc. To detect analytes with high sensitivity and specificity making the techniques desirable over the traditional techniques. The photoelectrochemical technique which uses light-activating photoresponsive materials has also gained popularity lately due to its low cost, high sensitivity, and specificity. These techniques can be used to identify specific biomarkers that are associated with cancer, enabling early detection and diagnosis. Furthermore, the role of nanomaterials in designing the biosensor was taken into consideration for this study. Nanomaterials-based biosensors can detect very low concentrations of biomarkers, which is crucial for early cancer diagnosis. Additionally, the performance limitations of optical and photoelectrochemical nanobiosensors have been analyzed. Given the huge number of articles published in recent years, studies published only in the last five years have been reviewed.

Cancer, a local disease at an early stage, systemically evolves as it progresses by triggering alterations in surrounding microenvironment, disturbing immune surveillance and further disseminating its molecular contents into circulation. This pathogenic characteristic of cancer makes the use of biofluids such as blood/serum/plasma, urine, tear and cerebrospinal fluids credible surrogates harboring tumor tissue-derived molecular alterations for the detection of cancer. Most importantly, a number of recent reports have credentialed the clinical validity of saliva for the detection of systemic diseases including cancers. In this review, we discussed the validity of saliva as credible biofluid and clinical sample type for the detection of cancers. We have presented the molecular constituents of saliva that could mirror the systemic status of our body and recent findings of salivaomics associated with cancers. Recently, liquid biopsy to detect cancer-derived circulating tumor DNA has emerged as a credible cancer-detection tool with potential benefits in screening, diagnosis and also risk management of cancers. We have further presented the clinical validity of saliva for liquid biopsy of cancers and a new technology platform based on electrochemical detection of cancer-derived ctDNA in saliva with superior sensitivity and point-of-care potential. The clinical utilities of saliva for the detection of cancers have been evidenced, but biological underpinning on the existence of molecular signatures of cancer-origin in saliva, such as via exosomal distribution, should be addressed in detail.

A liquid biopsy is a minimally invasive or non-invasive method to analyze a range of tumor material in blood or other body fluids, including circulating tumor cells (CTCs), cell-free DNA (cfDNA), messenger RNA (mRNA), microRNA (miRNA), and exosomes, which is a very promising technology. Among these cancer biomarkers, plasma cfDNA is the most widely used in clinical practice. Compared with a tissue biopsy of traditional cancer diagnosis, in assessing tumor heterogeneity, a liquid biopsy is more reliable because all tumor sites release cfDNA into the blood. Therefore, a cfDNA liquid biopsy is less invasive and comprehensive. Moreover, the development of next-generation sequencing technology makes cfDNA sequencing more sensitive than a tissue biopsy, with higher clinical applicability and wider application. In this publication, we aim to review the latest perspectives of cfDNA liquid biopsy clinical significance and application in cancer diagnosis, treatment, and prognosis. We introduce the sequencing techniques and challenges of cfDNA detection, analysis, and clinical applications, and discuss future research directions.