Cancer Screening Tests Research Articles

Advantages and Limitations of Ultrasound as a Screening Test for Ovarian Cancer.

Ovarian cancer (OC) is the seventh most common malignancy diagnosed among women, the eighth leading cause of cancer mortality globally, and the most common cause of death among all gynecological cancers. Even though recent advances in technology have allowed for more accurate radiological and laboratory diagnostic tests, approximately 60% of OC cases are diagnosed at an advanced stage. Given the high mortality rate of advanced stages of OC, early diagnosis remains the main prognostic factor. Our aim is to focus on the sonographic challenges in ovarian cancer screening and to highlight the importance of sonographic evaluation, the crucial role of the operator΄s experience, possible limitations in visibility, emphasizing the importance and the necessity of quality assurance protocols that health workers have to follow and finally increasing the positive predictive value. We also analyzed how ultrasound can be combined with biomarkers (ex. CA-125) so as to increase the sensitivity of early-stage OC detection or, in addition to the gold standard examination, the CT (Computed tomography) scan in OC follow-up. Improvements in the performance and consistency of ultrasound screening could reduce the need for repeated examinations and, mainly, ensure diagnostic accuracy. Finally, we refer to new very promising techniques such as liquid biopsies. Future attempts in order to improve screening should focus on the identification of features that are unique to OC and that are present in early-stage tumors.

Electronic Health Record Prompt to Improve Lung Cancer Screening in Primary Care

Lung cancer is the leading cause of cancer death in the U.S. Combusted tobacco use, the primary risk factor, accounts for 90% of all lung cancers. Early detection of lung cancer improves survival, yet lung cancer screening rates are much lower than those of other cancer screening tests. Electronic health record (EHR) systems are an underutilized tool that could improve screening rates. This study was conducted in the Rutgers Robert Wood Johnson Medical Group, a university-affiliated network in New Brunswick, NJ. Two novel EHR workflow prompts were implemented on July 1, 2018. These prompts included fields to determine tobacco use and lung cancer screening eligibility and facilitated low-dose computed tomography ordering for eligible patients. The prompts were designed to improve tobacco use data entry, allowing for better lung cancer screening eligibility identification. Data were analyzed in 2022 retrospectively for the period July 1, 2017 to June 30, 2019. The analyses represented 48,704 total patient visits. The adjusted odds of patient record completeness to determine eligibility for low-dose computed tomography (AOR=1.19, 95% CI=1.15, 1.23), eligibility for low-dose computed tomography (AOR=1.59, 95% CI=1.38, 1.82), and whether low-dose computed tomography was ordered (AOR=1.04, 95% CI=1.01, 1.07) all significantly increased after the electronic medical record prompts were implemented. These findings show the utility and benefit of EHR prompts in primary care settings to increase identification for lung cancer screening eligibility as well as increased low-dose computed tomography ordering.

Utilization of PAX1 methylation test for cervical cancer screening of non-HPV16/18 high-risk HPV infection in women.

Aim: To evaluate the clinical performance of PAX1 methylation (PAX1m) and cytology for patients with non-HPV16/18 high-risk HPV (hrHPV) infection. Methods: Cervical exfoliated cells from 387 outpatients with non-HPV16/18 hrHPV - positive were collected for cytology and PAX1m assays. Results: The PAX1m level increased with the severity of cytology and histopathology. For cervical intraepithelial neoplasia (CIN)CIN2+/CIN3+, the areas under the curve were both 0.87. The specificity and positive predictive value (PPV) of PAX1m were greater than abnormal cytology (CIN2+specificity: 75.5vs 24.8%; PPV: 38.8vs 18.7%; CIN3+specificity: 69.3vs 22.7%; PPV: 14.0vs 6.7%). Conclusion: PAX1m increased specificity and PPV for CIN2+/CIN3+ compared with cytology for women with non-HPV16/18hrHPV (+).

Differential impact of test performance characteristics on burden-to-benefit tradeoffs for blood-based colorectal cancer screening: A microsimulation analysis.

To inform the development and evaluation of new blood-based colorectal cancer (CRC) screening tests satisfying minimum United States (US) coverage criteria, we estimated the impact of the different test performance characteristics on long-term testing benefits and burdens. A novel CRC-Microsimulation of Adenoma Progression and Screening (CRC-MAPS) model was developed, validated, then used to assess different screening tests for CRC. We compared multiple, hypothetical blood-based CRC screening tests satisfying minimum coverage criteria of 74% CRC sensitivity and 90% specificity, to measure how changes in a test's CRC sensitivity, specificity, and adenoma sensitivity (sizes 1-5 mm, 6-9 mm, ≥10 mm) affect total number of colonoscopies (COL), CRC incidence reduction (IR), CRC mortality reduction (MR), and burden-to-benefit ratios (incremental COLs per percentage-point increase in IR or MR). A blood test meeting minimum US coverage criteria for performance characteristics resulted in 1576 lifetime COLs per 1000 individuals, 46.7% IR and 59.2% MR compared to no screening. Tests with increased CRC sensitivity of 99% ( + 25%) vs. increased ≥10 mm adenoma sensitivity of 13.6% ( + 3.6%) both yielded the same MR, 62.7%. Test benefits improved the most with increases in all-size adenoma sensitivity, then size-specific adenoma sensitivities, then specificity and CRC sensitivity, while increases in specificity or ≥10 mm adenoma sensitivity resulted in the most favorable burden-to-benefit tradeoffs (ratios <11.5). Burden-to-benefit ratios for blood-based CRC screening tests differ by performance characteristic, with the most favorable tradeoffs resulting from improvements in specificity and ≥10 mm adenoma sensitivity.

Abstract 81: The Introduction of a High Risk HPV DNA Test for the Cervical Cancer Screening Among Mongolian Women

Abstract Purpose: A global strategy developed by the World Health Organization aims to reduce cervical cancer burden by screening 70% of women with high performance tests at least twice during their lifetime. While Mongolia has implemented a PAP test-based cervical cancer screening program over the past few decades, cervical cancer remains the leading cause of death in the country. Therefore, it is necessary to introduce high-risk HPV DNA detection tests in cervical cancer screening program. Methods: Cervical screening was conducted in 6 districts of the UB and in 4 regional provinces between March 01 and July 01, 2019. A high risk HPV DNA test was conducted on all women using the careHPV test, and then all positive samples were double-tested using the PAP test. All positive women were followed by HPV genotyping test and colposcopy with direct biopsy or endocervical curettage as necessary. Results: A total of 2725 women were screened for HPV DNA, with 8.5%(239) of these detecting high risk HPV DNA, and 61% (138) of positive results having a negative result for intraepithelial neoplasia as determined by PAP tests. It was determined that 10% of samples contained atypical squamous cells of undetermined significance, 4% contained atypical squamous cells of unknown significance, and cannot exclude high grade, 17% of the samples contained low grade squamous intraepithelial lesions, and 10% contained high grade squamous intraepithelial lesions. A colposcopy examination was performed on 181 women who were high-risk HPV DNA positive. An abnormal colonoscopy result was observed in 18% of the women, for which biopsies were taken. A total of 31% of them were confirmed with CIN I, 31% with CIN II, 9% with CIN III, 11% with CIS, and 6% with SCC. Additionally, 105 high-risk HPV DNA-positive samples were genotyped for HPV. There were 25.7% of individuals who were found to have HPV genotype 16, 4.7% who were found to have HPV genotype 18, and 69.6% who were found to have other high-risk genotypes. Conclusion: By incorporating high-risk HPV DNA tests into cervical cancer screening program, its coverage and effectiveness could be increased. Citation Format: Enkhjargal Bayarsaikan. The Introduction of a High Risk HPV DNA Test for the Cervical Cancer Screening Among Mongolian Women [abstract]. In: Proceedings of the 11th Annual Symposium on Global Cancer Research; Closing the Research-to-Implementation Gap; 2023 Apr 4-6. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(6_Suppl):Abstract nr 81.

Primary care provider perceptions of patient participation in a multi-cancer early detection trial.

e13607 Background: Randomized clinical trials of multi-cancer early detection (MCED) tests are being planned, and primary care providers (PCPs) are likely to encounter patients who are considering participation. Little information has been reported about provider support for patient participation in such trials. Methods: We surveyed PCPs from 4 practices in a large health system to learn about their views on patient participation in a hypothetical MCED test trial. The PCPs received a link to view a patient-oriented infographic that described a trial in which participants would undergo serial blood draws for MCED testing and would be randomly assigned either to standard care or to receive MCED test results and follow-up, as needed. After viewing the infographic, respondents were asked to complete a brief survey that included statements related to factors that would affect their receptivity to patient participation in the trial, using a 5-point Likert type response scale that ranged from 1 = Strongly Disagree to 5 = Strongly Agree. The survey also included a single item that asked respondents if they would support patient participation in the trial and provided an opportunity to report the main reason for their answer. Finally, the survey contained a background characteristics section. We computed frequency distributions of survey responses. Results: Twenty-seven of 37 (73%) invited primary care providers completed the survey. About half of the respondents were women and two thirds were white; 81% were physicians while 19% were nurse practitioners, 54% were in practice for less than 20 years, all were board certified, and 74% had a hospital affiliation. Receptivity scores regarding a future MCED trial were high, with a mean of 3.8 and standard deviation of 0.6. Overall, 25 providers (93%) reported that they would support patient participation in an MCED test trial. The most commonly reported reasons for supporting patient participation were the belief that early cancer detection is important and the belief that research to develop new cancer screening tests is needed. The most commonly cited reasons for not supporting participation were concern about managing patients diagnosed with cancer in the trial and worry that trial participants would require too many practice resources. Conclusions: The overwhelming majority of respondents supported patient participation in an MCED test trial, but many were concerned about trial impact on their capacity to meet patient needs. Further research is needed in a larger study to validate these results and learn more about factors likely to influence PCP support for patient participation in MCED test trials and actual participation.

AI blood signature in common blood tests for detection of gastric cancer in a cohort of 190,000 individuals.

1500 Background: Gastric cancer is the fourth leading cause of cancer death worldwide. Lack of symptoms in the early stage of disease leads to delayed presentation and low overall survival rate. Early detection is key, but there is not yet an established test for non-invasive gastric cancer screening. Routine blood test panels, including complete blood count, liver function, renal function and clotting profiles, could be potentially useful in reflecting bodily processes related to cancer. Current literature and territory-wide statistical data analyses from Hong Kong have shown these subtle changes and differences in measured levels of subcomponents between individuals with and without gastric cancer, that are not recognized clinically, form recognizable patterns distinct to gastric cancer. In this study, we hypothesized that gastric cancer signatures could be identified in routine blood data. Deep learning AI algorithms are used to identify the gastric cancer signature. Results from testing and validation of the identified routine blood signature using a Big Clinical Data cohort are reported. Methods: This is a territory-wide healthcare database study using data from Hong Kong Hospital Authority data collaboration laboratory. All patients prescribed with medications for dyspepsia and with all blood tests components (CBC, LFT, RFT, clotting function) available in the period between 2004-2015 inclusive were included. In the period, data from 2004 to 09 and 2011 to 14 were used as training cohort and the rest were used as testing cohort. A blood gastric cancer signature was generated using deep learning AI algorithms, and applied to predict gastric cancer in Big Data population. Results: 193,117 patients were included in the captioned period, in whom 4,790 patients were diagnosed to have gastric cancer. 151,449 (3,815 pts with gastric cancer and 147,634 pts disease free) patients were included In training cohort. In the testing cohort in 2010 and 2015 (975 pts with gastric cancer and 40,693 pts disease-free), the tumor signature yielded a sensitivity of 0.79, specificity of 0.99, positive predictive value of 0.95 and a negative predictive value of 0.99. Conclusions: The hypothesis of the presence of a distinctive gastric cancer signature from parameters in routine blood test data is tested and validated in a large population cohort with dyspepsia. The signature has high accuracy and high sensitivity with low false positive and false negative rates. Multicenter prospective testing is being conducted in cohort indicated for OGD in Hong Kong.[Table: see text]

Start so young? Defense of the primary HPV test as a screening test for cervical cancer in women aged 25 and over in Brazil.

e17531 Background: Cervical cancer (CC) is the most frequent type of cancer on woman at reproductive age and on the puerperal pregnancy cycle in Brazil. It is a disease that can be prevented with the resources already available at Brazil’s public healthcare system.The most important risk factor for developing cervical cancer is infection with human papillomavirus (HPV). With the covid 19 pandemic, there was an advance in the possibility of carrying out an HPV test by PCR by through the government initiative "uterus is life" and we was asked what age should start the HPV test in the proposed screening organized. Methods: Descriptive, observational, cross sectional study Carried two cancer centers( using an adapted form, between 2020 2021 Sociodemographic data, cancer characteristics. Descriptive statistics were used to analyze the data and evaluation of secondary data from the ministry of health (DATASUS) This study was approved by the institution’s ethics committee. Recife, Brazil. Results: From 2021 -2022, 240 patients with CC mean age 50,48y (SD ± 13.8; range 24-87), 15, 8 % &lt; 35 y, age of first sexual intercourse: mean age 16,7 (SD ± 3.2, range 11- 30) and 79,6 % &lt; 18y. age of first pregnancy mean 18 (SD ± 6.54; range 12- 36) 77,4 % &lt; 18 y.In the year 2019 of the number of patients undergoing treatment in the Brazilian public system (SUS), by age group, 14.076 patients &lt;35 y (58%). $821,000 was spent in 2019 on anticancer chemotherapy for CC in women &lt; 35 y. Conclusions: With a view to establishing an organized screening policy using the HPV test, considering the window of opportunity to diagnose the non-invasive cervical cancer stage, the onset of sexual activity and the age of first pregnancy among patients with invasive cervical cancer and the representativeness of patients with &lt; 35 years undergoing treatment for advanced CC. The "Utero é Vida" initiative recommended starting the screening of the HPV test from the age of 25 y, in addition to intensifying vaccination coverage against HPV.

Estimated life-years gained and resultant cost savings from follow-up colonoscopy after a positive multi-target stool DNA (mt-sDNA) test for colorectal cancer screening in commercially insured and Medicare populations.

6642 Background: Although follow up colonoscopy (COL) after a positive stool-based colorectal cancer (CRC) screening test is necessary to complete the CRC screening process, follow-up COL rates remain suboptimal, especially among underserved populations. As of January 2023, federal policies require commercial insurers and Medicare to eliminate out of pocket costs for follow-up COL. To estimate the implications of this policy change, we compared the clinical and fiscal outcomes for a simulated cohort receiving a follow-up COL after a non-invasive CRC test ($0 cost sharing), compared to the same cohort not completing follow-up COL (status quo). Methods: Using the validated CRC-AIM model, we simulated a cohort of 6 million average-risk individuals who received mt-sDNA (commercial patients at age 45 and Medicare patients at age 65) and further analyzed only the population with positive mt-sDNA. Life-years gained, CRC incidence, CRC-related mortality and total costs of care (inclusive of CRC screening and treatment) were calculated for a cohort that underwent follow-up COL and compared these outcomes to that same cohort that did not complete follow-up COL. The cost of follow-up COL was assumed to be $1,576 for Medicare and $3,086 for commercially insured patients ($0 out of pocket costs for all). Results: Patients undergoing follow-up COL after a positive mt-sDNA experienced more life-years (83 per 1,000 commercially insured patients and 80 per 1,000 Medicare beneficiaries) compared to those who did not undergo follow-up COL. The follow-up COL resulted in reductions in CRC incidence and CRC mortality by 14% and 16% for commercial and 19% and 23% for Medicare beneficiaries, respectively. Compared to those patients with a mt-sDNA positive test result and did not complete follow-up COL, the total cost per patient for those receiving follow-up COL was $3,339 less for commercially insured ($15,690 – no follow up vs. $12,351 – follow up) and $4,382 less for Medicare beneficiaries ($19,337 – no follow up vs. $14,955 – follow up). Total spending for patients receiving follow-up COL was cost-saving when compared to no follow-up as long as the COL costs were less than $6,269 for commercial plans and $5,753 for Medicare. Conclusions: Completing a follow-up COL after a positive mt-sDNA screening saves lives, enhances equity, and lowers total expenditures. Thus, health care stakeholders should invest in efforts to identify and reduce barriers that ultimately lead to an increase uptake of this potentially lifesaving and cost-reducing intervention.

HTA62 Efficacy and Safety of Digital Tomosynthesis As a Screening Test for Breast Cancer

To evaluate safety and effectiveness of digital breast tomosynthesis including M2D(DBT-M2D) compared to digital mammography(MD) in breast cancer(BC) screening.

Cancer risk factors and screening tests in the Pantanal population, a rural area in Brazil.

e18526 Background: Cancer is a severe public health problem in Brazil, and prevention and screening measures are uneven throughout the country, despite universal guidelines of the NCI/Sistema Único de Saúde (SUS). The non-governmental and multidisciplinary expedition “Alma Pantaneira” is one of the few health programs in the Pantanal region, state of Mato Grosso do Sul, inland Brazil, with a rural population of 45,000 inhabitants. The expedition takes place regularly for over ten years on a pre-established route. Methods: This is a observational study involving data collection through questionnaires from the Alma Pantaneira Expedition, previously submitted and approved by the Local Ethics Committee. The questionnaire was distributed to six physicians who volunteered to apply. Patients of both sexes and over 18 years old were included. The study sample was defined by convenience, including all patients treated by the program in the period established between 11/18/21 to 11/30/21. Results: The collection involved 156 patients, with a mean age of 41.25 ± 13.95 years of which 63.5% were men and 36.5% were women. We observed that among the study population, 70.5% declared themselves brown, 10.9% black, and 15.4% white. More than half of the population, 25.6%, and 32.1%, were classified as overweight and having grade 1 obesity, respectively. The most prevalent comorbidity was systemic arterial hypertension (SAH) at 23.7%, followed by diabetes mellitus (DM) at 3.2%. When we analyze other risk factors, 38.5% of the population are active smokers, 3.2% are former smokers, and 51.3% are frequent alcohol consumers. When it comes to population screening for cancer, 65.9% of women over 25 years of age underwent the Papanicolaou Test in the last two years; 42.9% of men over 45 years old had performed a PSA test, and only 5.8% of the population underwent a colonoscopy over 45 years of age. Regarding the family history of cancer, it was identified that 12.3% of the population had a first- and second-degree relative with a positive history of cancer; 7.7% of the population had a first- or second-degree relative with a history of breast cancer before age 50, and 5.1% with a history of bowel cancer before age 50. In addition, 4.5% of the population had three or more first- or second-degree relatives with a history of cancer before age 50. Conclusions: The present study generated epidemiological data hitherto unavailable in the Pantanal region, inland Brazil, on the prevalence of the main risk factors for the development of malignant neoplasms, as well as secondary prevention measures. Population screening for cancer is below the target set by the WHO for the most prevalent types of cancer. Risk factors such as smoking, alcohol consumption, and being overweight are above the average for the Brazilian population. The need to adopt public policies in the study population and increase access to prevention, screening, diagnosis and early cancer treatment is urgent.

Patient-provider communication factors associated with mt-sDNA screening for colorectal cancer.

e22514 Background: Several colorectal cancer (CRC) screening tests, shown to reduce CRC incidence and mortality, are recommended for average-risk adults aged 45-75 years. CRC screening is underutilized in the US with access to facility-based options, such as colonoscopy, representing a barrier to screening. Stool-based tests are guideline-endorsed and offer patients a convenient and more accessible CRC screening option that can be completed at home. Provider recommendation is consistently identified as the primary factor driving patient adherence. Understanding how aspects of patient-provider communication influence CRC screening can inform interventions to improve adherence. We developed a survey, informed by behavioral theory, to identify communication factors associated with completion of mt-sDNA screening. Methods: Adults aged 45-75 years, with a US postal address, who received a valid order for mt-sDNA and whose kit was shipped between 5/21-9/21 were eligible for sampling. The survey was administered by RTI International between 3/22-6/22. Participants could complete electronic or paper surveys. We fit a multivariable logistic regression to identify patient-provider communication factors associated with mt-sDNA test completion. Results: 2,973 respondents completed the survey (response rate = 21.7%). The majority (77.3%) completed the mt-sDNA test and said they would be ‘very likely’ (76.8%) to complete Cologuard in the future. The proportion of respondents who had conversations with their healthcare provider about Cologuard, and the specific content of those conversations, was significantly different between completers and non-completers and between respondents who said they were ‘very likely’ to complete Cologuard in the future compared to respondents who were not. Results from a binary logistic regression suggested that discussions with a healthcare provider related to step-by-step instructions for completing Cologuard (OR = 1.62) and needing to have a colonoscopy follow-up (OR = 1.93), as well as feeling included ‘a great deal’ in the decision-process with respondents’ healthcare provider (compared to ‘somewhat’ or ‘not at all’) increase the odds of kit completion. Additionally, healthcare provider discussions relating to test cost (OR = 1.47) and performance (OR = 1.72), as well as feeling included ‘a great deal’ in the decision-process was positively associated with respondents indicating they were ‘very likely’ to use Cologuard in the future. Provider discussions about the cost of a follow-up colonoscopy was negatively associated with a ‘very likely’ future user (OR = 0.52). Conclusions: Healthcare providers play a key role in patient adherence to CRC screening and must be appropriately prepared and resourced to educate and to engage patients in shared decision-making about CRC screening.

Understanding patient acceptance and compliance of a blood-based colorectal cancer screening test.

TPS6654 Background: The Covid-19 pandemic has caused a significant disruption in healthcare utilization. The halt and delay of CRC screening have led to a substantial decline in CRC screening rates. The backlog and the slow resuming of CRC screening will have significant consequences. Although COVID-19 created challenges in CRC screening, it also presents an opportunity for potential innovative approaches that may improve patient compliance and screening rates, such as a blood-based CRC screening test which can be done at the point of care without preparation. Adherence to CRC screening is poor among vulnerable populations even before COVID-19, and these populations disproportionately receive health care in safety-net settings, such as federally qualified health centers (FQHCs). Thus, FQHCs play a significant role in improving CRC-related outcomes and ensuring health equity. This study will examine patient compliance with CRC screening by offering another option, a blood-based screening test, after failing to complete a stool-based screening test or colonoscopy in six months at three FQHCs. Methods: The study will use a stepped wedge cluster trial design and include an initial period of no exposure. Each FQHC will have a cluster of 10 to 17 primary care clinics. After the initial no-exposure period, two FQHCs will implement a blood-based CRC screening test at their primary care clinics. Another FQHC will follow nine months later. Each FQHC will contribute to exposed and unexposed observations and function as its own control. This study will collect quarterly data to capture the impact, feasibility, and acceptability over time. The primary endpoint will be assessed by calculating the number of participants who, otherwise, will not have participated in the CRC screening. In addition, the effectiveness of the implementation strategies will be assessed since transferring innovations into real-world settings is complex, and practical strategies are critical to accelerating future implementation and assisting decision-making. The study will recruit patients who fail to complete a CRC screening after six months and meet the inclusion criteria: between 45-75 years of age, average risk for CRC, capable of and willing to give informed consent, and willing to provide a blood sample. For eligible patients, a blood-based CRC screening test developed by a CLIA-certified laboratory and made commercially available (Guardant Health, CA) will be offered at no cost. An order will be obtained from the participant’s primary care provider before the blood sample is collected. This study plans to enroll up to 2,400 patients over a 3-year period. Patient compliance is a significant barrier to improving CRC screening, and the key to increasing screening participation is patient acceptance of the screening method. A blood-based screening test may offer an alternative for patients who fail to comply with other CRC screening modalities. Clinical trial information: NCT05536713 .

Abstract 39: Factors Associated With Receiving Results and Attending Colposcopy in Patients With Positive HPV Screens in Mexico City

Abstract Purpose: Unlike in high-income countries, where cervical cancer (CC) screening programs have resulted in a dramatic decrease in incidence and mortality of this nearly fully preventable disease, in low- and middle-income countries, the impact of these programs has been limited. Poor follow-up to abnormal cancer screening tests lessens the benefit of CC screening. We sought to identify multilevel factors at the level of patient, provider, and healthcare system related to receipt of screening results and attendance to colposcopy among patients with positive screening results in a CC screening program in Mexico. Methods: We studied 1,351 patients who were scheduled for colposcopy after testing positive for high-risk human papillomavirus in two screening demonstration studies conducted in Mexico City’s Tlalpan District (2017-2018). Multilevel factors associated with receipt of screening results and with adherence to a colposcopy appointment were identified using multivariable logistic regression. Results: Participants had a median age of 40 years, 58% had less than high school education, and 74% had a Pap screening recently (i.e., in the last 5 years). Fifty-five percent of participants retrieved their screening results at the healthcare facility before being reminded to do so. Greater adherence to obtaining screening test results was associated with providing an email address as contact information (Odds Ratio 1.35 [95% Confidence Interval 1.03-1.77]), attending a facility with family medicine (1.54 [1.07-2.21]), and receiving care from experienced nurses (1.85 [1.30-2.70]). Fifty-seven percent of participants attended their first scheduled colposcopy appointment. Providing a phone number as contact information was linked to improved adherence to colposcopy (1.27 [1.01-1.59]), whereas longer travel time between the healthcare facility and the colposcopy clinic was associated with a decrease in colposcopy adherence (0.68 [0.49-0.94]). Having a Pap recently was positively associated with better compliance with both outcomes (1.36 [0.96-1.94] for receiving results; 1.59 [1.10-2.29] for colposcopy adherence). Conclusion: We identified multilevel factors associated with abnormal test follow-up in patients in Mexico City. Additional research is necessary to design and test components for a multilevel intervention to address these factors and enable successful implementation of the follow-up process for abnormal screens from screening to diagnosis and treatment. Citation Format: Leith León-Maldonado, Raul U. Hernández-Ramírez, Leticia Torres-Ibarra, Donna Spiegelman, Sangini S Sheth, Eduardo Lazcano-Ponce, José Damián Cadena-Fiscal, Jorge Salmerón. Factors Associated With Receiving Results and Attending Colposcopy in Patients With Positive HPV Screens in Mexico City [abstract]. In: Proceedings of the 11th Annual Symposium on Global Cancer Research; Closing the Research-to-Implementation Gap; 2023 Apr 4-6. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(6_Suppl):Abstract nr 39.

Estimated value-based pricing for blood-based colorectal cancer screening test versus multi-target stool DNA test.

e18911 Background: Stool-based colorectal cancer (CRC) screening with the multi-target stool DNA (mt-sDNA) test is a guideline endorsed strategy for average-risk individuals age ≥45 years and provides a reference for value-based pricing (VBP); maximum price at which a willingness-to-pay threshold is reached. Blood-based tests (BT) are an emerging screening option. Using recent reported BT performance data from the ECLIPSE study (Guardant Health, Inc.)1, the potential VBP of BT compared with multi-target stool DNA (mt-sDNA) was analyzed. Methods: Using the validated CRC-AIM model, we simulated a cohort of 2 million average-risk individuals who received screening with BT at 1, 2, or 3-year intervals or triennial mt-sDNA between the ages of 45-75 years. For BT, CRC sensitivity, advanced adenoma sensitivity, and specificity were based on reported clinical trial data (83%, 13%, and 90%, respectively). Adherence assumptions for BT and mt-sDNA screening were modeled at perfect (100%) or real-world mt-sDNA adherence (RWE). Key outcomes were life-years gained (LYG) per 1000 individuals vs no screening, and VBP of BT vs mt-sDNA ($895 vs $508) was assessed at a willingness-to-pay (WTP) threshold of $50,000 per quality-adjusted life-year. Results: The triennial mt-sDNA was more effective and less costly vs BT at all intervals with both perfect and RWE adherence at the current price. Compared with mt-sDNA screening, LYG of screening with BT was lower (320 vs. 241-314) and the VBP should be at most $49 and $11 and no-cost at the 1-, 2-, and 3-year intervals, respectively (Table), when perfect adherence is assumed. With RWE adherence, the LYG with mt-sDNA was 306 compared to 229-284 with BT across all intervals. To be comparable to RWE triennial mt-sDNA screening, the maximum VBP for BT would need to be $13 at the 1-year interval and no cost for 2- and 3-year interval. Conclusions: Compared to annual, biannual, and triennial BT, triennial mt-sDNA was more effective at all intervals and 44% to 102% less costly. The maximum price of BT should not exceed $49 to be considered a cost-effective option compared to mt-sDNA when WTP is 50,000. [Table: see text]

EE278 A Systematic Review of Economic Evaluations of Cervical Cancer Screening Methods

Cervical cancer screening is a public health priority with the potential to improve pre-cancerous lesion detection in high-risk females for disease prevention. The objective of the systematic review was to identify primary and model-based economic evaluations of cervical cancer screening methods, and to provide a contextual summary of valuation outcomes associated with three types of cervical cancer screening tests: Visual Inspection with Acetic Acid, Human Papilloma Virus Deoxyribonucleic Acid, and Papanicolaou Smear.

Test sensitivity in a prospective cancer screening program: A critique of a common proxy measure.

The true sensitivity of a cancer screening test, defined as the frequency with which the test returns a positive result if the cancer is present, is a key indicator of diagnostic performance. Given the challenges of directly assessing test sensitivity in a prospective screening program, proxy measures for true sensitivity are frequently reported. We call one such proxy empirical sensitivity, as it is given by the observed ratio of screen-detected cancers to the sum of screen-detected and interval cancers. In the setting of the canonical three-state Markov model for progression from preclinical onset to clinical diagnosis, we formulate a mathematical relationship for how empirical sensitivity varies with the screening interval and the mean preclinical sojourn time and identify conditions under which empirical sensitivity exceeds or falls short of true sensitivity. In particular, when the inter-screening interval is short relative to the mean sojourn time, empirical sensitivity tends to exceed true sensitivity, unless true sensitivity is high. The Breast Cancer Surveillance Consortium (BCSC) has reported an estimate of 0.87 for the empirical sensitivity of digital mammography. We show that this corresponds to a true sensitivity of 0.82 under a mean sojourn time of 3.6 years estimated based on breast cancer screening trials. However, the BCSC estimate of empirical sensitivity corresponds to even lower true sensitivity under more contemporary, longer estimates of mean sojourn time. Consistently applied nomenclature that distinguishes empirical sensitivity from true sensitivity is needed to ensure that published estimates of sensitivity from prospective screening studies are properly interpreted.

Multi-cancer early detection screening tools: A dream come true or a nightmare in the offing.

e18926 Background: US cancer deaths were at 610,000 in 2022 with 1.9 million new diagnoses of cancer, 86% of which were patients over age fifty. Roughly 150,000 advanced cancers were diagnosed with five current screening techniques. That leaves 1.75 million cancers to be diagnosed symptomatically, largely in advanced stages. The dream is to screen in a minimally invasive fashion for multiple types of cancer at earlier, treatable, life-saving stages. The Galleri test claims to fulfill that dream by identifying more than fifty different cancers, and their location, using a blood test that captures ctDNA linked to aberrant methylation. As their dream approaches reality, with a dozen US hospital systems already offering Galleri, a fiscal and ethical nightmare is likely to ensue. We will demonstrate to providers that Galleri’s analytical validity and clinical utility is marginal at best – largely due to uncertainty surrounding the nature of those fifty malignancies. Methods: Systematic review of literature was performed across multiple databases using the key terms "Cancer Early Detection" AND OR "MCED" AND OR "GALLERI." Grail’s optimistic portrayal of the test’s current efficacy is largely derived from Hubbell and colleagues’ recent work modelling a Galleri-like test that claimed an achievable 24% reduction in cancer mortality (~150,000 lives). Critics contend that their assumptions are too optimistic. The natural histories of most of those fifty cancers are poorly understood, such as tumor latency periods, which means the cancer shift detection to an earlier stage is unknowable. Moreover, we cannot know whether these cancers would have been caught earlier, symptomatically, and successfully treated - which is true of 68% of diagnosed cancers. Etzioni and colleagues concluded that 6% of cancer deaths might be reduced by Galleri, despite that number is still uncertain and optimistic. Galleri cannot take credit for those saved lives. Results: GRAIL proposes population-based screening for 110 million Americans over age fifty annually at a cost of $950 per test. That would add over $100 billion per year to the health costs to discover no cancer in 99% of the persons tested. Roughly $50 billion would be added to Medicare program costs, now at $1 trillion. To save 18,000 Medicare lives would cost $2.8 million per life saved, a significant misallocation of Medicare resources, given many less costly opportunities to save more lives. Finally, individuals with marginal or no health insurance would be informed by Galleri they had an early-stage cancer unaffordable to treat. They represent statistically salvageable lives not actually salvaged, which is a presumptive injustice. This argument holds, despite the company’s pledge to reduce cost by over 40% over four years. Conclusions: In sum, Galleri, as a population-based cancer screening test, is not economically affordable, not ethically equitable, and only marginally medically beneficial.

Identifying small non-coding RNAs as biomarkers for cervical cancer.

e17507 Background: Small non-coding RNAs (sncRNAs) that control post-transcriptional gene expression are attractive candidate molecular targets for cancer screening tests. We evaluated whether sncRNAs expression are markedly different in benign, precancerous, and cancerous cervical tissue. Methods: We examined the expression of six sncRNA species: circular RNAs (circRNAs) microRNAs (miRNAs), piwi-interacting RNA (piRNAs), small nuclear RNA (snRNAs), small nucleolar RNA (snoRNAs), and transfer RNA (tRNA), from archival formalin-fixed paraffin-embedded cervical specimen obtained from 172 women (74 benign, 58 high-grade squamous intraepithelial lesion (HSIL) and 40 invasive cervical cancer). We used DESeq2 to identify differentially expressed sncRNA molecules with adjusted p-value &lt; 0.05 and at least 2-fold up- or down-regulation. Results: Comparing benign to HSIL samples, we foundseveral statistically significant, differentially expressed sncRNAs: 906 circRNAs (*circ_0066810, p=3.76x10-16), 87 miRNAs (*miR-149-5p, p=1.30x10-14), 11 piRNAs (*piR_016945, p=8.32x10-13), 32 snRNAs (*RNU1-17P, p=1.90x10-10), 5 snoRNAs (*SCARNA18, p=1.35x10-5), and 24 tRNA (*tRNA-Glu-TTC-8-1, p=6.45x10-17). Comparing benign to invasive cervical cancer samples, we also foundseveral statistically significant, differentially expressed sncRNAs: 3,192 circRNAs (*circ_0123115, p=7.46x10-50), 325 miRNAs (*miR-7-5p, p=6.72x10-36), 82 piRNAs (*piR-hsa-27513, p=1.44x10-15), 71 snRNAs (*RNU1-20P, p=1.37x10-45), 52 snoRNAs (*SNORD95, p=1.68x10-23), and 68 tRNA (*tRNA-Cys-GCA-9-3, p=1.01x10-21). * Indicates the sncRNA with the smallest p-value, for each specie. Conclusions: Our results identify sncRNAs with potential utility of as diagnostic and prognostic biomarkers, and therapeutic targets for cervical precancer and cancer.

Breast Self-Examination: An Early Familiar Diagnostic Test of Breast Cancer

Background: Among female patients’ breast cancer are a growing threat for over a century. In women, breast cancer is the most common malignancy universally such as 154 of 185 nations. Breast self-examination (BSE) is a simple, very low-cost, non-invasive early detection method used to detect early breast cancer, which involves the woman herself looking at and feeling for any change in their breast as early as possible, which yields a better survival rate. BSE should be done for all women older than 20 years. This study intended to determine knowledge, attitude, and practice (KAP) of breast cancer among medical and non-medical undergraduate students. Material &amp; Methods: A descriptive cross‑sectional study was conducted from October to November 2019 to assess the knowledge, attitude, and practice of BSE. The target population consisted of undergraduate female medical and non‑medical students. A total of 154 (N=154) undergraduate female students participated in this study. Verbal consent was taken before recruiting the study population. Completed data forms were reviewed, edited, and processed for computer data entry. The data analysis was performed using Statistical Package for the Social Sciences (SPSS) Version 25.0. Results: Among the study population (N=154) with an early familiar diagnosis of breast cancer ”breast self-examination, the mean age of them was 20.434±4.38. Of seventy-eight respondents (n=78), breast cancer screening test was heard by around half of the medical students (42, 53.8%) &amp; of seventy-six non-medical respondents (n=76), around three-fifth of them (46, 60.5%) did not hear about breast cancer screening test. There was no significant relationship between them (p=0.394). Forty medical students (40, 51.3% and twenty-five non-medical students (25, 32.9%) had no idea, twenty-four medical students (24, 30.8%) &amp; forty-three (43, 56.6%) non-medical students had monthly BSE done. Conclusion: Initial diagnosis and treatment of breast cancer have a definite survival benefit. So early detection is an issue of necessity to be uplifted. The results of the present study suggested that knowledge regarding breast cancer, its risk factors, sign symptoms, prevention measures, and performance of BSE is insufficient.