The World Health Organization set a 2030 target of 70% cervical cancer screening coverage for women aged 35-45 years. Coverage stood at 37% in China in 2015.

Introduction Colon and rectal cancer are usually grouped together as they share similar features. They are the third most common cancer in the world and the second most common cancer in the Kingdom of Saudi Arabia (KSA). Awareness and preventive screening programs play a vital role in early diagnosis and improving the survival rate of such patients. This study aimed to assess the awareness and knowledge of colorectal cancer (CRC) among the adult population in the Qassim region of Saudi Arabia. Methods This is a cross-sectional study conducted among the adult population living in the Qassim region of Saudi Arabia. A self-administered questionnaire was disseminated among the adult population using WhatsApp and Twitter. The questionnaire contained demographic data and questions to assess the awareness, knowledge, and attitude regarding CRC risk factors and complications and the importance of screening. Results A total of 431 respondents were involved. The most common symptoms of colon cancer were abdominal pain and change in bowel habits. Risk factors associated with colon cancer were inflammatory bowel disease and fatty food. Colonoscopy was the most dominant choice for the detection of colon cancer. Conclusion The awareness of the adult population toward CRC was deficient. Better awareness can be predicted among individuals with better education. Addressing the gaps in awareness is vital to alleviate fears and misconceptions surrounding this disease.

Cancer immunotherapy with immune-checkpoint blockade has improved the outcomes of patients with various malignancies, yet a majority do not benefit or develop resistance. To address this unmet need, efforts across the field are targeting additional coinhibitory receptors, costimulatory proteins, and intracellular mediators that could prevent or bypass anti-PD1 resistance mechanisms. The CD28 costimulatory pathway is necessary for antigen-specific T cell activation, though prior CD28 agonists did not translate successfully to clinic due to toxicity. Casitas B lymphoma-b (Cbl-b) is a downstream, master regulator of both CD28 and CTLA-4 signaling. This E3 ubiquitin ligase regulates both innate and adaptive immune cells, ultimately promoting an immunosuppressive tumor microenvironment (TME) in the absence of CD28 costimulation. Recent advances in pharmaceutical screening and computational biology have enabled the development of novel platforms to target this once 'undruggable' protein. These platforms include DNA encoded library screening, allosteric drug targeting, small-interfering RNA inhibition, CRISPR genome editing, and adoptive cell therapy. Both genetic knock-out models and Cbl-b inhibitors have been shown to reverse immunosuppression in the TME, stimulate cytotoxic T cell activity, and promote tumor regression, findings augmented with PD1 blockade in experimental models. In translating Cbl-b inhibitors to clinic, we propose specific gene expression profiles that may identify patient populations most likely to benefit. Overall, novel Cbl-b inhibitors provide antigen-specific immune stimulation and are a promising therapeutic tool in the field of immuno-oncology.

Since October 2021 in Germany all people with a statutory health insurance aged 35 and older have the right to be tested once for hepatitis B and C in a general preventative examination, regardless of specific risk-factors. This is a milestone on the way of eliminating these infections and also a great contribution to cancer prevention.In the USA the Centers of Disease Control and Prevention in April 2020 recommended a one-time screening for all adults aged 18 and older in addition to testing people with known risk-factors, because a significant part of the affected population cannot be identified with risk-based screening. Corresponding CDC-Recommendations for HBV are currently elaborated. According to available Data this screening strategy combined with a vaccination for HBV is necessary in Germany too to reach the agreed elimination goals till the year of 2030. Furthermore, an offer of such a testing for all adults can be regarded as ethically imperative to prevent as many life-threatening consequences or deaths as possible by effective therapies.

Recent guidelines from the American Cancer Society stress HPV vaccination series initiation at the youngest opportunity, i.e., age 9 years. There are limited data on the association between initiating HPV vaccination at ages 9-10 years and up-to-date (UTD) status. In this study, we compare nationally representative UTD HPV vaccination rates between adolescents who initiated the series younger (ages 9-10 years) vs. older (≥ age 11 years). Five years of pooled data (2016-2020) from National Immunization Survey-Teen were used to estimate the UTD HPV vaccination prevalence among younger vs. older initiating 13-17-year-olds. Adjusted logistic regression models estimated prevalence ratios (aPRs), differences (aDs), and difference in differences (aDDs) in prevalence of being UTD to assess the overall association of age at initiation with being UTD and differences in sociodemographic predictors of being UTD among younger vs. older initiators. UTD prevalence for younger initiators was 93% compared with 72% among older initiators (aPR: 1.27,95%CI: 1.24,1.31). Among older initiators, UTD prevalence was significantly different by sex, insurance status, and current age; no such differences were observed among younger initiators. Results indicate that younger initiation is associated with a 27% higher UTD prevalence, highlighting the importance of promoting younger initiation, particularly among those with health-care barriers.

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder affecting ciliary structure and function. PCD exhibiting dynein regulatory complex subunit 1 (DRC1) exon 1-4 deletion has been reported in several Japanese PCD patients; however, no large scale studies have been performed. Here, we aimed to determine the prevalence and founder effect of this variant in the Korean population. Using an in-house copy number variation tool, we screened for DRC1 exon 1-4 deletion in 20 patients with PCD and exome data of 1435 patients in the Seoul National University Hospital repository. In cases of suspected DRC1 deletion, confirmatory gap-PCR was performed. In a PCD cohort, three of 20 (15%) patients were positive for DRC1 exon 1-4 deletion (NM_145038.5(DRC1): c.1-3952_540 + 1331del27748-bp) while pathogenic variants were found in CCDC39 (N = 1), DNAAF6 (N = 1), DNAH9 (N = 1). In the 1,435-sample exome data, seven patients (0.49%) were confirmed to have DRC1 exon 1-4 deletion. A chimeric sequence including the junction was searched from the 1000 Genomes Project data repository. One Japanese patient (0.96%) was found to have the same DRC1 exon 1-4 deletion, which was absent in other populations. This study demonstrated that the DRC1 exon 1-4 deletion is a founder mutation based on haplotype analysis. In summary, the prevalence of PCD based on DRC1 exon 1-4 deletion is particularly high in Korean and Japanese populations, which is attributed to the founder effect. Genetic testing for DRC1 exon 1-4 deletion should be considered as an initial screening tool for Korean and Japanese patients with PCD.

Various biomarkers targeting cell-free DNA (cfDNA) and circulating proteins have been tested for pan-cancer detection. Oncofetal chondroitin sulfate (ofCS), which distinctively modifies proteoglycans (PGs) of most cancer cells and binds specifically to the recombinant Plasmodium falciparum VAR2CSA proteins (rVAR2), is explored for its potential as a plasma biomarker in pan-cancer detection. To quantitate the plasma ofCS/ofCSPGs, we optimized an ELISA using different capture/detection pairs (rVAR2/anti-CD44, -SDC1, and -CSPG4) in a case-control study with six cancer types. We show that the plasma levels of ofCS/ofCSPGs are significantly higher in cancer patients (P values, 1.2 × 10-2 to 4.4 × 10-10). Validation studies are performed with two independent cohorts covering 11 malignant tumors. The individuals in the top decile of ofCS-CD44 have more than 27-fold cancer risk (OR = 27.8, 95%CI = 18.8-41.4, P = 2.72 × 10-62) compared with the lowest 20%. Moreover, the elevated plasma ofCS-CD44 could be detected at the early stage of pan-cancer with strong dose-dependent odds risk prediction.

Antimicrobial resistance (AMR) is a growing global public health concern and is becoming a significant challenge in the management of patients with cancer. Due to the immunosuppressive nature of cancer treatment, infection is a common complication and the necessary high usage of antibiotics increases the risk of AMR. Failure to adequately prevent and treat infection in patients with cancer as a result of AMR can increase the morbidity and mortality of the disease. The objective of this scoping review is to understand the relationship between AMR and cancer in order to develop effective antimicrobial stewardship in this patient population and minimise the detrimental effects of AMR on cancer outcomes.

Pancreatic cancer surveillance can improve outcomes in high-risk individuals. However, little is known about its applicability and findings in routine clinical practice. Our aim was to evaluate findings on screening tests in high-risk individuals in a clinical practice setting and to analyze factors associated with the presence of relevant pancreatic lesions. We developed a prospective observational study of pancreatic cancer high risk patients that meet criteria of surveillance from the International Cancer of the Pancreas Screening Consortium. The demographic variables, other risk factors and imaging findings are collected. Patients with significant findings are compared to those without noteworthy findings. Of 70 high-risk individuals, 25 fitted the criteria for pancreatic cancer surveillance. The most frequent condition was hereditary breast and ovarian cancer syndrome (60%). We identified eleven abnormal imaging findings (44%) and three of them (12%) were relevant: two intraductal papillary mucinous neoplasms and one localized pancreatic neoplasm. BRCA2 mutation was more frequent in patients with significant lesions (66.7% vs 30%, p=0.376) but smoking and diabetes were not associated with relevant findings (0 vs 18 %, p=0.578 and 0 vs 4.5%, p=0.880 respectively). Screening test could detect early-stage or resectable lesions in a significant in a significant percentage of the selected high-risk population. The most relevant findings were in patients belonging to hereditary breast and ovarian cancer syndrome.

Persistent high-risk human papillomavirus (HPV) infection is the pivotal cause of cervical carcinogenesis. HPV types distribution varies greatly by region, and its long-term changes of prevalence remain to be fully characterized in China. Here, the largest population of 198,111 consecutive women who underwent routine cervical screening were investigated from 2015 to 2021 in Guangzhou, south China. The results showed that the overall HPV prevalence was 21.66% (42,911/198,111), and the annual prevalence increased significantly from 2015 to 2021 (p < 0.001). HPV52, 16, 58, CP8304, 51, 53, 39, and 68 were the most prevalent HPV types. The relative HPV-positive rate correlated positively with the progression of cervical intraepithelial neoplasia (p < 0.001); HPV16 was the predominant carcinogenic type, followed by HPV52 and HPV18. HPV infections were significantly age-specific, and 26.51% (11,375/42,911) of cases were caused by multiple HPV types. In addition, HPV infections typically cleared over a median time of 16 (interquartile range 9-31) months, and the clearance of HPV16 was significantly faster than that of other types (p < 0.001). These findings may serve as a guide for local governments to evaluate HPV vaccination and cervical cancer prevention strategies in south China.

In 2017, cervical cancer screening in the Netherlands switched from cytology to human papillomavirus (HPV) testing using the validated PCR-based cobas 4800. Women could order and subsequently received a free self-sampling kit (Evalyn Brush) at their home address instead of clinician sampling. In the laboratory, the shipped brush was placed into 20 mL of PreservCyt fluid, before testing. In the first 2 years of the new program, only 7% of screening tests were performed on a self-sample. Those who chose self-sampling versus clinician sampling were more likely to have never been screened previously and differed also with respect to sociodemographic factors. Subsequent more active promotion and increasing the ease to obtain kits increased the proportion opting for self-sampling (16% in 2020). HPV positivity and detection rate of precancer (CIN3+) were lower in the self-sampling compared with the clinician-sampling group (adjusted ORs of 0.65 and 0.86, respectively). Although population differences may partially explain these results, self-samples may have been too dilute, thereby reducing the analytic and clinical sensitivity. The Dutch findings demonstrate the importance of optimizing outreach, specimen handling and testing protocols for self-samples to effectively screen the target population and reach in particular the women at highest risk for cervical cancer. See related article by Aitken et al., p. 183.

The incidence of colorectal cancer diagnosed before age 50, often referred to as early-onset colorectal cancer, has been increasing, whereas the overall colorectal cancer incidence has declined. Elucidating the drivers for the rising burden of early-onset colorectal cancer is a priority in cancer epidemiology and prevention. In this issue of Cancer Epidemiology, Biomarkers & Prevention, Chen and colleagues demonstrated that ecologic studies are a helpful method to reveal emerging risk factors at the population level and concluded that alcohol use might be a potential contributor to the rising incidence of early-onset colorectal cancer. Moving forward, because of the observed birth cohort effect in early-onset colorectal cancer, where younger generations have a steeper increase, hypothesis-driven investigations on emerging risk factors in recent generations, especially during early life, are warranted. Ultimately, the identified risk factors could be integrated with well-established microsimulation models of colorectal cancer, powerful tools that can simultaneously capture population-level secular changes in risk factors, relative risk estimates for each risk factor, and the natural history of colorectal cancer. This would allow us to quantitatively estimate the explained and unexplained portion of the rising incidence of early-onset colorectal cancer by calendar period and birth cohorts, and to help identify priorities in etiologic research, prevention, and early detection. See related article by Chen et al., p. 217.

Persons living with HIV (PLWH) are at high risk of developing anal high-grade squamous intraepithelial lesions (HSIL). We aimed to develop a prediction model for anal HSIL based on individual characteristics of PLWH.

Introduction Human papillomaviruses (HPV) are known to be the main culprit of cervical cancer. It is the fourth most common cancer among women worldwide. In recent years, it has begun to spread more widely in Saudi Arabia. Saudi Arabia's Ministry of Health recently added HPV vaccination for women to the list of recommended vaccinations. Aim This study aimed to assess Saudi females' knowledge regarding HPV infection, screening, and the available tools for prevention in Qassim, Saudi Arabia. Subject and methods This is a descriptive cross-sectional study conducted among women living in the Qassim region of Saudi Arabia. A self-administered pre-structured questionnaire was distributed among the targeted women using an online platform. The questionnaire includes socio-demographic characteristics (i.e. age, education, occupation, etc.) knowledge questionnaire and a questionnaire about the attitude toward HPV protection. The minimum required sample size was 385. This means 385 or more measurements/surveys are needed to have a confidence level of 95% that the real value is within ±5% of the measured/surveyed value. All females aged 18 years and above who are living in the Qassim region of Saudi Arabia were included in our study. Males are excluded from this study. All data analyses were performed using Statistical Product and Service Solutions (SPSS) (IBM SPSS Statistics for Windows, Version 26.0, Armonk, NY). Results Of the 387 women involved, 52.2% were aged between 18 and 25 years old. The prevalence of women who have heard of HPV was 49.1%. Fifty-four percent were willing to accept HPV vaccination if offered. The overall mean knowledge score was 3.56 (SD 2.51) out of 11 points. Poor knowledge levels constituted most of the women (71.1%), 24.5% had moderate knowledge and only 4.4% were considered good. Increased awareness was more prevalent in younger women, more educated, those who underwent Pap smear, and those who were willing to accept HPV vaccination. Conclusion The awareness of women toward HPV infection was deficient. Younger women who had a better education and who are willing to receive HPV vaccination were more likely to demonstrate better awareness levels toward HPV infection as compared to the rest of the women. More research is needed to establish the level of awareness among women in our region.

DNA methyltransferases (DNMTs) catalyze methylation at the C5 position of cytosine with S-adenosyl-L-methionine. Methylation regulates gene expression, serving a variety of physiological and pathophysiological roles. The chemical mechanisms regulating DNMT enzymatic activity, however, are not fully elucidated. Here, we show that protein S-nitrosylation of a cysteine residue in DNMT3B attenuates DNMT3B enzymatic activity and consequent aberrant upregulation of gene expression. These genes include Cyclin D2 (Ccnd2), which is required for neoplastic cell proliferation in some tumor types. In cell-based and in vivo cancer models, only DNMT3B enzymatic activity, and not DNMT1 or DNMT3A, affects Ccnd2 expression. Using structure-based virtual screening, we discovered chemical compounds that specifically inhibit S-nitrosylation without directly affecting DNMT3B enzymatic activity. The lead compound, designated DBIC, inhibits S-nitrosylation of DNMT3B at low concentrations (IC50 ≤ 100 nM). Treatment with DBIC prevents nitric oxide (NO)-induced conversion of human colonic adenoma to adenocarcinoma in vitro. Additionally, in vivo treatment with DBIC strongly attenuates tumor development in a mouse model of carcinogenesis triggered by inflammation-induced generation of NO. Our results demonstrate that de novo DNA methylation mediated by DNMT3B is regulated by NO, and DBIC protects against tumor formation by preventing aberrant S-nitrosylation of DNMT3B.

Pulmonary complications constitute a major cause of morbidity and mortality in the post-allogenic hematopoietic stem cell transplant (alloHSCT) period. While Chest X-ray (CXR) is customarily used for screening, we have utilized chest computed tomography (CT). To characterize the prevalence of abnormalities and explore their impact on alloHSCT eligibility and outcomes post-transplant, we conducted a retrospective analysis utilizing real-world data collected at our center for adult patients who were evaluated for alloHSCT from January 2013 through December 2020 and identified 511 eligible patients. The most common primary disease was acute myeloid leukemia in 49% of patients, followed by myelodysplastic syndrome in 23%, lymphoma in 11%, and acute lymphocytic leukemia in 10%. Abnormal screening chest CT was found in 199 patients (39%). The most frequent detected abnormality was pulmonary nodule in 78 patients (35%), followed by consolidation in 42 (19%), ground-glass opacification in 33 (15%), bronchitis and bronchiolitis in 25 (11%), pleural effusions in 14 (6%), and new primary cancer in 7 (2%). CXR detected abnormalities in only about half of the patients (48%) with an abnormal chest CT. Among 199 patients with abnormal chest CT, 98 patients (49%) underwent further assessment and/or intervention before transplant. The most common work up was pulmonary consultation in 32%, infectious diseases consultation in 24%. Lung biopsy was obtained in 20% and antimicrobial therapy was initiated after confirming an infection diagnosis in 20% of patients. Patients with abnormal chest CT demonstrated worse overall survival (P= 0.032), non-relapse mortality (P=0.015), and pulmonary related death (P < 0.001) compared to those who had normal chest CT. Our study suggests that pre-transplant screening chest CT is beneficial in uncovering invasive infections and underlying malignancies and allows appropriate interventions before alloHSCT to prevent potentially serious post-transplant complications without causing a delay in alloHSCT. Nevertheless, abnormal CT findings prior to transplant may be associated with overall worse prognosis.

This qualitative study examined fatalistic beliefs and cancer causal attributions among people without cancer. Participants were 30 Israeli women and men aged 51-70 from diverse sociocultural backgrounds who participated in four focus groups. Three main themes emerged, referring to the variability in fatalistic beliefs of cancer occurrence and cancer outcome, the duality in attributing causality to divine providence and mere luck or chance, and the connection between distinct fatalistic beliefs and health behaviors. Data analysis enabled an expansion of the understanding of cancer fatalism as a multidimensional structure, whereby interactions between causality attribution and different fatalistic beliefs are related to prevention and screening behaviors.

Australia's cervical screening program transitioned from cytology to HPV-testing with genotyping for HPV16/18 in Dec'2017. We investigated whether program data could be used to monitor HPV vaccination program impact (commenced 2007) on HPV16/18 prevalence and compared estimates with pre-vaccination benchmark prevalence. Pre-vaccination samples (2005-2008) (n = 1933; WHINURS), from 25 to 64-year-old women had been previously analysed with Linear Array (LA). Post-vaccination samples (2014) (n = 2989; Compass pilot), from 25 to 64-year-old women, were analysed by cobas 4800 (cobas), and by LA for historical comparability. Age standardised pre-vaccination HPV16/18 prevalence was 4.85% (95%CI:3.81-5.89) by LA; post-vaccination estimates were 1.67% (95%CI:1.21-2.13%) by LA, 1.49% (95%CI:1.05-1.93%) by cobas, and 1.63% (95%CI:1.17-2.08%) for cobas and LA testing of non-16/18 cobas positives (cobas/LA). Age-standardised pre-vaccination oncogenic HPV prevalence was 15.70% (95%CI:13.79-17.60%) by LA; post-vaccination estimates were 9.06% (95%CI:8.02-10.09%) by LA, 8.47% (95%CI:7.47-9.47%) by cobas and cobas/LA. Standardised rate ratios between post-vs. pre-vaccination rates were significantly different for HPV16/18, non-16/18 HPV and oncogenic HPV: 0.34 (95%CI:0.23-0.50), 0.68 (95%CI:0.55-0.84) and 0.58 (95%CI:0.48-0.69), respectively. Additional strategies (LA for all cobas positives; combined cobas and LA results on all samples) had similar results. If a single method is applied consistently, it will provide important data on relative changes in HPV prevalence following vaccination.