The Mulher Study: cervical cancer screening with primary HPV testing in Mozambique

Objective To evaluate cervical cancer screening with primary human papillomavirus (HPV) testing in Mozambique, a country with one of the highest burdens of cervical cancer globally. Methods Women aged 30­49 years were prospectively enrolled and offered primary HPV testing using either self- collected or provider- collected specimens. Patients who tested positive for HPV underwent visual assessment for treatment using visual inspection with acetic acid to determine eligibility for thermal ablation. If ineligible, they were referred for excision with a loop electrosurgical excision procedure, for cold knife conization, or for cervical biopsy if malignancy was suspected. Results Between January 2020 and January 2023, 9014 patients underwent cervical cancer screening. Median age was 37 years (range 30­49) and 4122 women (45.7%) were patients living with HIV. Most (n=8792, 97.5%) chose self- collection. The HPV positivity rate was 31.1% overall and 39.5% among patients living with HIV. Of the 2805 HPV- positive patients, 2588 (92.3%) returned for all steps of their diagnostic work- up and treatment, including ablation (n=2383, 92.1%), loop electrosurgical excision procedure (n=169, 6.5%), and cold knife conization (n=5, 0.2%). Thirty- one patients (1.2%) were diagnosed with cancer and referred to gynecologic oncology. Conclusion It is feasible to perform cervical cancer screening with primary HPV testing and follow- up in low- resource settings. Participants preferred self- collection, and the majority of screen- positive patients completed all steps of their diagnostic work- up and treatment. Our findings provide important information for further implementation and scale- up of cervical cancer screening and treatment services as part of the WHO global strategy for the elimination of cervical cancer.

Early detection of multiple endocrine neoplasia type 1: A case report.

BACKGROUND: Multiple endocrine neoplasias (MENs) are a group of hereditary diseases involving multiple endocrine glands, and their prevalence is low. MEN type 1 (MEN1) has diverse clinical manifestations, mainly involving the parathyroid glands, gastrointestinal tract, pancreas and pituitary gland, making it easy to miss the clinical diagnosis. CASE SUMMARY: We present the case of a patient in whom MEN1 was detected early. A middle-aged male with recurrent abdominal pain and diarrhea was admitted to the hospital. Blood tests at admission revealed hypercalcemia and hypophosphatemia, and emission computed tomography of the parathyroid glands revealed a hyperfunctioning parathyroid lesion. Gastroscopy findings suggested a duodenal bulge and ulceration. Ultrasound endoscopy revealed a hypoechoic lesion in the duodenal bulb. Further blood tests revealed elevated levels of serum gastrin. Surgery was performed, and pathological analysis of the surgical specimens revealed a parathyroid adenoma after parathyroidectomy and a neuroendocrine tumor after duodenal bulbectomy. The time from onset to the definitive diagnosis of MEN1 was only approximately 1 year. CONCLUSION: For patients who present with gastrointestinal symptoms accompanied by hypercalcemia and hypophosphatemia, clinicians need to be alert to the possibility of MEN1.

Non-participation of asymptomatic candidates in screening protocols reduces early diagnosis and worsens prognosis of colorectal cancer.

The Agatsuma et al's study shows that despite the evidence of the benefits of an early colorectal cancer (CRC) diagnosis, through screening in asymptomatic subjects, up to 50% of candidates reject this option and many of those affected are diagnosed later, in advanced stages. The efficacy of screening programs has been well-established for several years, which reduces the risk of CRC morbidity and mortality, without taking into account the test used for screening, or other tools. Nevertheless, a significant proportion of patients remain unscreened, so understanding the factors involved, as well as the barriers of the population to adherence is the first step to possibly modify the participation rate. These barriers could include a full range of social and political aspects, especially the type of financial provision of each health service. In Japan, health services are universal, and this advantageous situation makes it easier for citizens to access to these services, contributing to the detection of various diseases, including CRC. Interestingly, the symptomatic CRC group had a lower early-stage diagnosis rate than the patients detected during follow-up for other comorbidities, and symptomatic and cancer screening groups showed similar early-stage diagnosis.

Factors Affecting Colorectal Cancer Screening in Primary Care Physician Practices in Ukraine.

PURPOSE: This study aims to identify the factors influencing colorectal cancer (CRC) screening practices, along with the barriers and facilitators from the perspective of primary care physicians (PCPs) in Ukraine. Considering health care system challenges, including those posed by the ongoing war, this research seeks to inform improvements in CRC screening and outcomes in Ukraine and other low- and middle-income countries (LMICs). METHODS: A survey was designed and distributed electronically to Ukrainian PCPs, focusing on CRC screening practices, beliefs, and barriers. The survey incorporated questions adapted from established cancer screening surveys and frameworks. Complete responses were collected from 740 PCPs. Sample statistics were computed, and population-level perceptions and associations with CRC screening practices were estimated by standardizing responses to national PCP demographics. RESULTS: The majority of respondents were women (91%) and specialized in family medicine (84%). Respondents believed in the effectiveness of colonoscopy for reducing CRC mortality (80%), with 75% of PCPs referring patients for this screening modality. Major barriers identified include inadequate training of PCPs in screening and lack of resources. Respondents reported high utilization of fecal occult blood test and colonoscopy for screening when these tests were said to be available in their practices. Self-reported familiarity with CRC screening guidelines and participation in educational workshops were positively associated with screening referrals. CONCLUSION: The study highlights the role of access to CRC screening tests and awareness of screening guidelines in enhancing CRC screening practices among Ukrainian PCPs. Addressing training and resource barriers, alongside public health interventions targeting patient-related barriers, is essential. These findings offer valuable insights for LMICs facing similar challenges, emphasizing the need for tailored strategies to improve cancer screening in these health care settings.

HPV Extended Genotyping to Triage Abnormal Cervical Cancer Screens-Balancing the Harms and Benefits of an Additional Triage Test before Direct Colposcopy Referral.

The Netherlands' cervical cancer screening program transitioned to primary human papillomavirus (HPV) screening in 2017. After the introduction of HPV-based screening, the country saw increases in colposcopy referral rates and detections of low-grade lesions. In July 2022, genotyping was introduced, and those with borderline or mild dyskaryotic (BMD) cytologic abnormalities were only referred to colposcopy if positive for HPV type 16 or 18, and repeat screening otherwise. In this article, various strategies using extended genotyping (HPV16/18/31/33/45/52/58) as a triage test after an abnormal screen were explored using data from HPV-positive participants with normal or BMD cytology in the Population-Based Screening Study Amsterdam (POBASCAM) trial. The authors assessed positive and negative predictive values and colposcopy referral rates for each strategy using extended genotyping to triage women to either direct referral to colposcopy or repeat screening. Direct referral did not meet positive and negative predictive value thresholds for efficiency for any strategies. However, the authors note that direct referral may nonetheless be useful among those with BMD due to minimal increases in colposcopy referrals and concerns of loss to follow-up at repeat screening. These findings demonstrate the potential utility of extended genotyping as a triage test in primary HPV screening programs. The results should be considered alongside the fact that referral to repeat screening may result in loss of engagement of women who need treatment to prevent invasive cancer. See related article by Kroon et al., p. 1037.

Trends in colorectal cancer surgical resection rates during the screening era: a retrospective study in Italy.

BACKGROUND: Faecal immunochemical test (FIT)-based screening is effective in reducing colorectal cancer (CRC) incidence, but its sensitivity for proximal lesions remains low. OBJECTIVES: We compared age-adjusted CRC surgical resection rates across anatomic sites (proximal colon, distal colon, rectum), age groups and sex over 20 years in a large Italian population. We particularly focused on changes in trends following FIT-screening implementation in the target population (50-69 years). DESIGN: This retrospective study analysed data from the Veneto Region's administrative Hospital Discharge Dataset, involving over 54 000 patients aged 40-89 (43.4% female) who underwent CRC surgery between 2002 and 2021. RESULTS: Overall, surgery rates increased until 2007 (annual percentage changes: 2.5% in males, 2.9% in females) and then declined (-4.2% in males, -3.4% in females). This decline was steeper for distal and rectal cancers compared with proximal cancer, suggesting a shift towards more right-sided CRC surgery.In males, the prescreening increase in proximal surgery was reversed after screening implementation (slope change: -6%) while the prescreening decline accelerated for distal (-4%) and rectal (-3%) surgeries. In females, stable prescreening trends shifted downward for all sites (-5% for proximal, -8% for distal and -7% for rectal surgery). However, the change in trends between prescreening and postscreening periods was not different across anatomic sites for either sex (all slope change differences in pairwise comparisons were not statistically significant). CONCLUSION: The shift towards proximal surgery may not be entirely due to the FIT's low sensitivity but may reflect an underlying upward trend in proximal cancers independent of screening.

Efficacy of Magnifying Endoscopy with Narrow-Band Imaging in the Diagnosis of Early Gastric Cancer and Gastric Intraepithelial Neoplasia.

Early diagnosis of gastric cancer can improve the prognosis of patients, especially for those with early gastric cancer (EGC), but only 15% of patients, or less, are diagnosed with EGC and precancerous lesions. Magnifying endoscopy with narrow-band imaging (ME-NBI) can improve diagnostic accuracy. We assess the efficacy of ME-NBI in diagnosing ECG and precancerous lesions, especially some characteristics under NBI+ME. This was a retrospective analysis of 131 patients with EGC or gastric intraepithelial neoplasia (IN) who had undergone endoscopic submucosal dissection and were pathologically diagnosed with EGC or IN according to 2019 WHO criteria for gastrointestinal tract tumors. We studied the characteristics of lesions under ME-NBI ,compared the diagnostic efficacy of ME-NBI and white light endoscopy (WLI) plus biopsy, and investigated the effect of Helicobacter pylori infection on microvascular and microsurface pattern. The diagnostic accuracy of ME-NBI for EGC, high-grade IN (HGIN), and low-grade IN (LGIN) was 76.06%, 77.96%, and 77.06%, respectively. The accuracy of WLI plus biopsy in diagnosing the above lesions was 69.7%, 57.5%, and 60.53%, respectively. The rate of gyrus-like tubular pattern was highest in LGIN (60.46%), whereas the highest rate of papillary pattern was 57.14% in HGIN and villous tubular pattern was 52% in EGC. Demarcation lines have better sensitivity for differentiating EGC from IN (92.06%). The ME-NBI has higher diagnostic accuracy for EGC than WLI plus biopsy. Demarcation lines and villous and papillary-like microsurface patterns are more specific as EGC and HGIN characteristics. The cerebral gyrus-like microsurface pattern is more specific for LGIN.

Skin cancer detection through attention guided dual autoencoder approach with extreme learning machine.

Skin cancer is a lethal disease, and its early detection plays a pivotal role in preventing its spread to other body organs and tissues. Artificial Intelligence (AI)-based automated methods can play a significant role in its early detection. This study presents an AI-based novel approach, termed 'DualAutoELM' for the effective identification of various types of skin cancers. The proposed method leverages a network of autoencoders, comprising two distinct autoencoders: the spatial autoencoder and the FFT (Fast Fourier Transform)-autoencoder. The spatial-autoencoder specializes in learning spatial features within input lesion images whereas the FFT-autoencoder learns to capture textural and distinguishing frequency patterns within transformed input skin lesion images through the reconstruction process. The use of attention modules at various levels within the encoder part of these autoencoders significantly improves their discriminative feature learning capabilities. An Extreme Learning Machine (ELM) with a single layer of feedforward is trained to classify skin malignancies using the characteristics that were recovered from the bottleneck layers of these autoencoders. The 'HAM10000' and 'ISIC-2017' are two publicly available datasets used to thoroughly assess the suggested approach. The experimental findings demonstrate the accuracy and robustness of the proposed technique, with AUC, precision, and accuracy values for the 'HAM10000' dataset being 0.98, 97.68% and 97.66%, and for the 'ISIC-2017' dataset being 0.95, 86.75% and 86.68%, respectively. This study highlights the possibility of the suggested approach for accurate detection of skin cancer.

Challenges regarding the implementation of cervical cancer screening guidelines in Limpopo province, South Africa.

BACKGROUND:  The World Health Organization's (WHO) call to eliminate cervical cancer is essential in improving structures and processes at primary healthcare facilities by galvanising change in providing cervical cancer screening services. AIM:  The main objective of this study was to explore challenges affecting the implementation of cervical cancer screening guidelines in selected districts in Limpopo Province. SETTING:  The study was carried out at primary health care services (PHCs) in Vhembe and Mopani districts, Limpopo province. METHODS:  Qualitative non-experimental research design of an exploratory, descriptive and contextual nature of a qualitative paradigm to understand cervical cancer screening programme challenges from healthcare professionals' perspectives. The study population comprised two males and 16 female professional registered nurses working in Limpopo province's PHC services. The sample size was 18 professional nurses. A face-to-face interview guided by unstructured questionnaires was undertaken to elicit information regarding the implementation of cervical cancer screening services. Captured data were analysed using Tesch's open-coding method. RESULTS:  The study revealed that the cervical cancer guidelines were not effectively implemented as there were contradictions and gaps when applying the guidelines about the management of HIV and AIDS, age restrictions and gestation. Furthermore, structural factors contributed to the inadequacy rate and failure to reach the set targets. CONCLUSION:  Primary health care is an essential health care and human right; therefore, the government should ensure that guidelines and policies are supported financially and that professional nurses are capacitated for the efficient implementation of services.Contribution: Addressing the inequalities in the implementation of social policies for the prevention of cervical cancer prevention and improving the nurses' knowledge and practice behaviour regarding cervical cancer prevention are imperative.

CER818: A Highly Specific and Sensitive HPV L1 High-Risk Serological Lateral Flow Rapid Test for Early Detection of Cervical Cancer and Its Precursor Lesions.

Objective: The objective of the study is to validate a new human papillomavirus (HPV) L1 high-risk specific serological assay in a case-control study. Methods: Serum samples of 138 patients (cervical intraepithelial neoplasia (CIN) 1, 2, and 3 and cervical cancer), 21 vaccinees, and 246 female controls were tested for the presence of HPV L1 high-risk specific antibodies. Results: HPV L1 high-risk antibodies were detected in 100% of the CIN1 and 2, 86.6% of the CIN3 and 82.4% of the cervical cancer cases, 100% of the vaccinees, and 3.9% of the female controls. Area under the curve (AUC) was calculated with 0.91 for controls versus CIN2+, 0.923 for controls versus CIN1+, and 0.968 for controls versus CIN1/2. Conclusion: The HPV L1 high-risk specific serological lateral flow rapid test shows promising data in the field of early detection of HPV high-risk induced cervical cancer and its precursor lesions. This easy-to-use, robust, and affordable approach could offer a chance to reach women in low- or middle-income countries (LMICs) that could not be reached by HPV molecular testing-based cervical cancer screening programs.

Screening Low-Risk Individuals for Lung Cancer: The Need May Be Present, but the Evidence of Benefit Is Not.

Worldwide, lung cancer is the most common killer among cancers, advanced disease has worse outcomes, earlier stage detection leads to better outcomes, and high-quality screening has a favorable net benefit. With the mortality reduction recognized from annual low-radiation dose computed tomography by screening those at high risk, there has been consideration that this benefit could translate to those who have never smoked. There have been several large-scale, single-arm, observational trials in Asia in persons with light to no smoking histories, with or without a family history of lung cancer, which have revealed high or higher lung cancer detection rates than previously reported in high-risk persons who currently or formerly smoked. The Early Detection Program for Lung Cancer in Taiwan, of nearly 50,000 persons, revealed that the cancer detection rate for those screened with low-radiation dose computed tomography was more than twofold higher in light- or never-smokers with a family history of lung cancer compared with high-risk persons with more than 30 or more pack-years exposure and meeting U.S. Preventative Services Task Force criteria for screening. In addition, more than 90% of the cancers detected in those with a family history were in early stage. On the basis of those findings, the researchers concluded that screening first-degree relatives of those with a family history of lung cancer, irrespective of smoking history, would lead to a decrease in lung cancer mortality. We believe that the findings in this cohort and others like it represent substantial overdiagnosis and that the harms associated with screening a population that has a low likelihood of developing lethal cancers have not been thoroughly considered. Here, we provide our perspective and consider the potential benefits and harms of screening populations outside those currently eligible using the U.S. Preventative Services Task Force criteria.

Cervical Human Papillomavirus Testing: Current and Future Impact on Patient Care.

Cervical cancer is the fourth most common malignancy in women worldwide. The identification of human papillomavirus (HPV) as the main etiologic cause of cervical cancer has led to the development and adaptation of HPV molecular diagnostics as a cervical cancer screening and prevention tool. This article highlights six Food and Drug Administration-approved HPV molecular platforms, each with unique advantages and disadvantages. In addition, HPV vaccination and the emergence of HPV self-collection as an alternative testing strategy are discussed.

Detection rate of colorectal cancer by routine colonoscopy is comparable in patients aged 45-49 and 50-54 years.

OBJECTIVES: Colorectal carcinoma remains one of the most common malignancies worldwide. Colonoscopy screening is most effective for early detection and tumour prevention and is currently recommended in Europe for adults aged over 50 years. However, given that an increasing proportion of patients are diagnosed before the age of 50, we set out to determine the detection rate of colorectal carcinoma in patients younger than 50 years and to determine the best threshold for starting colonoscopy screening. METHODS: Single-centre, retrospective cohort study of all colonoscopies performed, regardless of indication, in our department at a tertiary Swiss university hospital in patients aged ≥18 and <60 years between 2016 and 2021. Colorectal cancer detection rate was calculated per 5-year age group and analysed separately by sex. RESULTS: The current analysis included 2846 colonoscopies performed for any indication. Colorectal carcinoma was found in 5/366 (1.4%) patients aged 45-49 years (3/210 or 1.4% of males and 2/156 or 1.3% of females) and in 9/819 (1.1%) patients aged 50-54 years (5/495 or 1.0% of males and 4/324 or 1.2% of females). Adenomas with high-grade dysplasia were found in 5/366 (1.4%) patients aged 45-49 years and in 11/819 (1.3%) aged 50-54 years; by sex, in 4/210 or 1.9% of males and 1/156 or 0.6% of females aged 45-49 years, and in 6/495 or 1.2% of males and 5/324 or 1.5% of females aged 50-54 years. Detection of adenoma with low-grade dysplasia increased from 14.6% (21/144) at age <30 years to 41% (150/366) at 45-49 years and 43.5% (356/819) at 50-54 years. A similar increasing trend was also seen if we analysed these groups by sex. CONCLUSIONS: The detection rate of colorectal carcinoma, but also adenomas, in our patients aged 45-49 years was similar to that in patients aged over 50, in both sexes. Thus our data are in line with the assumption that lowering the screening age to 45 years might be reasonable from a medical point of view for achieving a reduction in disease-specific mortality by improved screening strategies.

Integrative plasma and fecal metabolomics identify functional metabolites in adenoma-colorectal cancer progression and as early diagnostic biomarkers.

Changes in plasma and fecal metabolomes in colorectal cancer (CRC) progression (normal-adenoma-CRC) remain unclear. Here, plasma and fecal samples were collected from four independent cohorts of 1,251 individuals (422 CRC, 399 colorectal adenoma [CRA], and 430 normal controls [NC]). By metabolomic profiling, signature plasma and fecal metabolites with consistent shift across NC, CRA, and CRC are identified, including CRC-enriched oleic acid and CRC-depleted allocholic acid. Oleic acid exhibits pro-tumorigenic effects in CRC cells, patient-derived organoids, and two murine CRC models, whereas allocholic acid has opposing effects. By integrative analysis, we found that oleic acid or allocholic acid directly binds to α-enolase or farnesoid X receptor-1 in CRC cells, respectively, to modulate cancer-associated pathways. Clinically, we establish a panel of 17 plasma metabolites that accurately diagnoses CRC in a discovery and three validation cohorts (AUC = 0.848-0.987). Overall, we characterize metabolite signatures, mechanistic significance, and diagnostic potential of plasma and fecal metabolomes in CRC.

Barriers and proposed solutions to at-home colorectal cancer screening tests in medically underserved health centers across three US regions to inform a randomized trial.

INTRODUCTION: At-home colorectal cancer (CRC) screening is an effective way to reduce CRC mortality, but screening rates in medically underserved groups are low. To plan the implementation of a pragmatic randomized trial comparing two population-based outreach approaches, we conducted qualitative research on current processes and barriers to at-home CRC screening in 10 community health centers (CHCs) that serve medically underserved groups, four each in Massachusetts and California, and two tribal facilities in South Dakota. METHODS: We conducted 53 semi-structured interviews with clinical and administrative staff at the participating CHCs. Participants were asked about CRC screening processes, categorized into eight domains: patient identification, outreach, risk assessment, fecal immunochemical test (FIT) workflows, FIT-DNA (i.e., Cologuard) workflows, referral for a follow-up colonoscopy, patient navigation, and educational materials. Transcripts were analyzed using a Rapid Qualitative Analysis approach. A matrix was used to organize and summarize the data into four sub-themes: current process, barriers, facilitators, and solutions to adapt materials for the intervention. RESULTS: Each site's process for stool-based CRC screening varied slightly. Interviewees identified the importance of offering educational materials in English and Spanish, using text messages to remind patients to return kits, adapting materials to address health literacy needs so patients can access instructions in writing, pictures, or video, creating mailed workflows integrated with a tracking system, and offering patient navigation to colonoscopy for patients with an abnormal result. CONCLUSION: Proposed solutions across the three regions will inform a multilevel intervention in a pragmatic trial to increase CRC screening uptake in CHCs.

Randomized experimental population-based study to evaluate the acceptance and completion of and preferences for cervical cancer screening.

Cervical cancer has high incidence and mortality rates, especially in less-developed countries. Prevention methods are well established, but there are still barriers preventing some Brazilian women from undergoing a Pap sample. The objective of the study was to evaluate the acceptance, preferences and completion of four screening methods. This has an experimental design (community trial). A total of 164 participants who had never had a Pap sample or had not had one for more than three years were included. The city's urban area was stratified by census tracts and divided according to income and education levels. Women belonging to the lower-income strata were considered in the study. Random blocks were numbered into five intervention groups (Group 1- Pap sample at the hospital; Group 2- Pap sample in the mobile unit; Group 3- urine self-collection; Group 4- vaginal self-collection; Group 5- woman's choice). Only 164 women met all of the eligibility criteria (15.3%). Most of them accepted the assigned method (92%), but only 84% of the women completed the collection step. The acceptance rates were as follows: Group 1 (100%), Group 2 (64.5%), Group 3 (100%) and Group 4 (91.4%). In Group 5, the women's preferences were distributed as follows: examination performed at the hospital, 13 women (33.3%); examination performed at the mobile unit, 11 women (28.2%); urine self-collection, 11 women (28.2%); and vaginal self-collection, 4 women (10.3%). This study suggests that methods that allow cervical sampling collected near the women's domicile might improve the acceptance and completion of preventive tests. This finding is relevant for the development of new cervical cancer screening strategies.

Are we ready for human papillomavirus testing? Assessment of patient knowledge of and preferences for cervical cancer screening in Ontario.

OBJECTIVE: To determine patient knowledge and preferences about primary human papillomavirus (HPV) testing. DESIGN: Cross-sectional survey. SETTING: Two family practice clinics (urban and suburban) and the social media platforms of 2 hospitals in the greater Toronto area between January and February 2023. PARTICIPANTS: A total of 413 Ontario residents aged 25 to 69 years, with a cervix, who qualified for Papanicolaou (Pap) screening and could communicate in English. METHODS: Electronic survey containing questions about knowledge of, and preferences for, cervical cancer screening, including types of screening and screening intervals, and about education related to HPV and screening intervals. MAIN FINDINGS: Of 441 potential participants, 426 were eligible and consented to participate in the study; ultimately 413 provided completed or partially completed surveys (96.9% response rate). Of those who completed a recent Pap test, 57.8% (208 of 360) knew of HPV testing. Initially, 27.8% thought HPV testing was better than Pap testing for cervical cancer screening. After learning HPV tests exist and have self-sampling options, most participants preferred HPV testing (self-sampling 46.3%, provider sampling 34.1%). Annual cervical cancer screening was preferred by 50.1% of participants despite knowing that, for most people, Pap tests should be conducted every 3 years (74.8%). After learning about HPV testing, participants were more likely to prefer 5-year screening intervals (43.8%); however, those in the family practice group were still more likely to prefer 3-year intervals compared with those in the social media group (P<.01). CONCLUSION: Participants in this study identified a preference for HPV testing and self-sampling options. Concerns were raised about extended screening intervals and the safety of self-collected samples that need to be addressed in public health education initiatives during rollout of new screening programs.