Cancer is the leading cause of death worldwide and the second leading cause of death in the United States. In 2022, there will be an estimated 1,918,030 cancer cases diagnosed and approximately 609,360 deaths from cancer in the country ^[1][2][1,2]. Among cancers for which screening tests are currently recommended ^[3][4][5][6][3,4,5,6], the distribution of early stage disease at diagnosis is as follows: female breast cancer (65%), uterine cervix (44%), colorectal (34%), and lung (24%) [1]. The development of new minimally invasive methods for testing biospecimens (e.g., blood, saliva, urine, stool samples) for genomic characteristics may provide additional tools to screen for these and other types of cancer ^[7][8][7,8].

Lokshin et al. [9] explain that such biomarkers can identify changes in the “genetic, epigenetic, proteomic, glycomic, and metabolomic profile of normal tissues”. When performed using biofluids to identify cancer-specific biomarkers, such testing has been referred to as “liquid biopsy” [10]. These tests have the potential to detect one type of cancer or to detect multiple cancer types [10]. When used to detect multiple cancers, the tests are often referred to as “multi-cancer early detection” (MCED) tests [11]. It is hoped that liquid biopsy and MCED tests can help to find early stage, curable cancers for which there are currently recommended screening tests (i.e., breast cancer, cervical cancer, colorectal cancer, and lung cancer) and for which there are no currently recommended screening tests (e.g., ovarian cancer and pancreatic cancer). It is not yet known, however, if the widespread use of such tests will reduce cancer morbidity and mortality ^[12][13][12,13].

2. Genetic TestiDiscussiong in Primary Care

Some studies have identified potential barriers to the incorporation of genetic testing in primary care. Such reports have identified a number of factors, including limited provider knowledge about genetic testing, the logistics of integrating genetic testing into the clinical workflow, the time and effort required to provide genetic testing, provider confidence in managing genetic test results, and health system-level issues ^[14][15][16][25,26,27]. A recently published study ^[17][28], not included in this escopintryg review, suggested that primary care providers may be especially receptive to liquid biopsy and MCED testing for cancer screening for use with patients who are unable to undergo invasive standard of care screening procedures, are concerned about the convenience of screening, and are reticent about undergoing standard of care screening. To date, the United States Food and Drug Administration (FDA) has granted approval for only one blood-based liquid biopsy test (Septin9) as a colorectal cancer screening test for use in concert with recommended screening tests. Importantly, there are no published guidelines on the use of genomic testing for single or multiple cancers in clinical practice. It is important to mention that the FDA has granted a number of genomic tests “breakthrough device” status, a designation that encourages expedited test development and evaluation. Current cancer screening guidelines do not address the use of such testing as part of standard of care screening. There is a pressing need for research on factors that are likely to affect provider uptake of the new genomic methods of cancer screening prior to widespread promotion of their use in the primary care landscape. Findings from ouresearchers' entry review of studies that addressed patient perceptions highlight patient receptivity to liquid biopsy screening and MCED testing. These studies suggest that patients are likely to be receptive to these new approaches to cancer screening, especially if they are easy to do, convenient, and non-invasive; are as effective as currently recommended screening; and are recommended by a provider. These published results also suggest that patients value screening tests that can find more than one type of cancer. These observations are consistent with those reported in a recent study, which reported on survey results for 1700 patients 50 to 80 years of age who were recruited through a recruiter database, online panels, and social media ^[18][29]. Interestingly, that report noted that survey respondents also indicated a preference for MCED tests that were able to identify cancer at specific sites. In practice, it is likely that factors identified in ouresearchers' entry scoping review and in more recent publications, along with other factors, such as costs associated with testing and the nature of diagnostic follow-up, will affect patient uptake of genomic cancer screening tests. Furthermore, it is possible that the uptake of liquid biopsy and MCED testing for cancer screening may vary among patients from different sociodemographic backgrounds. In this regard, rwesearchers found only two studies that reported on opinions about such testingacross diverse patient populations. Importantly, the studies indicated that there were no racial differences in perceptions about liquid biopsy. Given the need to ensure equity in cancer screening, it is important to explore those factors that are likely to affect uptake of testing in primary care with patients from diverse populations more thoroughly. Regarding the introduction of liquid biopsy and MCED cancer screening in clinical practice, Ignatiadis et al. ^[19][30] pointed out that there are substantial challenges to be addressed. These challenges include the need to minimize the number of false positive and false negative test results, and address the emotional and financial effects on patients of receiving test results that indicate the presence of cancer and the subsequent need for diagnostic follow-up to confirm the finding. As noted by Etzioni, Gulati, and Weiss ^[20][31], it is also important to determine the effects of such testing in terms of over-diagnosis, as some cancers that are indolent and not life threatening may be detected. Moreover, there is much to learn about the impact of test use on mortality and survival related to specific cancers. Furthermore, it is important to identify effective strategies to address obstacles to implementation in practice. A collaborative effort involving the public and private sectors, along with health systems, providers, and patients is needed if the promise of genomic test use in cancer screening is to be realized. ResWearchers limited studies included in this entryreview to those related to primary care providers and patients and that focused on cancer screening. ResearchersWe did not include other health care providers, such as specialists who use liquid biopsy tests in the course of treating patients who have been diagnosed with cancer to guide treatment decision making. In addition, researcherswe excluded reports that may have provided insights into perceptions of diagnosed patients regarding the use of such testing modalities. This decision was influenced by the view that perceptions of primary care providers and asymptomatic patients related to the detection of cancer are likely to differ from those of specialists and diagnosed patients who are actively engaged in treatment. Furthermore, rwesearchers excluded studies that may have reported on direct-to-consumer (DTC) genomic testing. ResearchersWe based this decision on the fact that such tools were not developed for the specific purpose of cancer screening, and, to researchers'our knowledge, are not being used in clinical care. It is also important to mention that this entryreview generated little information about factors that might affect the use of liquid biopsy and MCED testing in health systems, among primary care practice settings, and with diverse patient populations. A potential limitation of this report is that rwesearchers focused the review on publications that appeared in the literature from 2000 to 2021. It is possible that other articles on the topic were published earlier than 2000. However, researcherswe found a small number of articles published during the search period and found no relevant articles published between 2000 and 2005. Given the recent emergence of liquid biopsy and MCED testing related to cancer screening, researcherswe believe that the publication of informative articles prior to 2000 is unlikely. Cancer mortality rates could be reduced substantially by increasing the proportion of persons who are diagnosed with and treated for early stage neoplasia. Existing preventive health guidelines encourage screening for and treating early stage breast, cervical, colorectal, and lung cancer. As noted earlier, research is underway to develop and evaluate genomic approaches that can be used to identify persons with early stage cancer. It is hoped that, ultimately, research in this area along with studies on interventions to facilitate uptake in clinical practice will lead to substantial improvement in cancer prevention and control.