Cancer Screening Progress and Non-invasive Screening Opportunities Since Onset of the COVID-19 Pandemic

Abstract

Cancer screening lowers morbidity and mortality from cancer, and is cost-effective. The COVID-19 pandemic upended cancer screening utilization in 2020 with data showing a deficit in screened patients in 2020 and 2021 as compared to 2019, with return to 2019 baseline screening levels by December 2022. The cumulative shortfall in screenings, lasting nearly three years into the pandemic, are predicted by models to generate an incremental population cancer burden in the out years of the models. Recovery of screening rates may vary based on the racial or ethnic population, and time will tell if there is an uneven burden of future cancers that worsen cancer incidence and mortality in those populations, some even after years of gains of reducing disparities for cancer screening. For some cancer screenings, particularly cervical and colorectal cancer, use of at-home non-invasive tests may increase screening participation overall across multiple populations, and may help mitigate some of the screening shortfalls from 2020 to 2022 by elevating numbers of the population screened. For colorectal cancer, new additional comparably sensitive or ease-of-use non-invasive screening tests are being added for utilization.

INTRODUCTON

Preventive screening for common human cancers reduces the incidence, morbidity, and mortality from those malignancies. Cost-effective population-based screening programs have been active for breast, cervical, prostate, colorectal and other cancers for several years through the use of techniques to detect each cancer at early stages (Table 1) (1,2). With screening, the incidence and deaths from these cancers have diminished compared to no screening, and with continued gains in acceptance and uptake in the percentage of eligible asymptomatic persons screened, even more cancers and deaths from cancers can be prevented (1). In particular, colorectal cancer screening can be achieved by programs involving 8 different tests albeit some are now relatively obsolete; importantly colorectal and now HPV-associated cervical cancer can be screened with self-administered at-home tests that do not specifically require the use of in-facility imaging or point-of-care laboratory tests (Table 1) (3,4). These at-home approaches may increase screening utilization overall for these cancers’ prevention.

Table 1.

Incidence and mortality and screening approaches in the U.S. for some common cancers.

Cancer	Incidence (US 2025)	Deaths (US 2025)	Screening Techniques
Breast	319,750	42,680	mammography
Cervical	13,360	4,320	pap smear; HPV testing
Prostate	313,780	35,770	PSA, rectal examination
Colorectal	154,270	52,900	First tier: FIT, colonoscopy; Second tier: CT Colonography, stool DNA tests/FIT; Third tier: capsule colonoscopy; Relatively obsolete: FOBT, barium enema

Data constructed from Siegel et al (1) and Rex et al (2). Outside of Rex et al (2) representing the MultiSociety Task Force on Colorectal Cancer, other professional society recommendations do not specifically tier colorectal cancer screening tests. PSA: prostate specific antigen; CT: computed tomography; FIT: fecal immunochemical test; FOBT: fecal occult blood test; HPV: human papilloma virus

Perturbations of national screening programs are rare, as general growth of the screening programs are achieved by increasing public awareness and provider implementation with patients. Many professional organizations have targets of at least 80% of age-eligible persons being up-to-date on cancer-specific screening; most have not achieved that aspiration but have been incrementally gaining screening utilization over time. For instance for colorectal cancer screening, national screening of eligible persons reached ~69% of those eligible in 2019 with gains year-over-year prior, and disparities in screening rates between Black and White persons in the U.S. had reached an all time low of 3% difference lower for Black persons, the narrowest difference ascertained (5,6). However, data such as these were obtained before the world-wide COVID-19 pandemic that commenced in December 2019 that triggered immediate acute effects on health systems and available cancer screening through the first half of 2020, with likely lingering effects thereafter. Additionally, there is little data on cancer screening rate recovery based on race and ethnicity since the pandemic, where disparities had been substantively diminished for several cancers prior to the pandemic. Here we reviewed availble data to examine the status of cancer screening in the US since the initial stages of the pandemic through into 2024.

As the COVID-19 pandemic took hold in 2020, predictions of incremental future cancers were estimated based on the impact of near cessation of screening that occurred with global transmission of the novel SARS-CoV-2 virus and the near complete shut down of ambulatory clinic sites (7,8). It was estimated that over a 10-year period after a 6-month cessation solely for breast and colorectal cancer screening due to COVID-19 in the U.S. that there would be a cumulative 10,000 excess deaths (~5500 for breast and ~4500 for colorectal) (7), and would be greater numbers for deaths depending on how long the cessation or slow down for screening occurred (8). While mortallity data will take time to accumulate to support or repudiate those estimates, in the interim, the utilization of cancer screening since the COVID-19 pandemic commenced may provide clues to a trajectory, particularly for some cancers like colorectal and cervical cancer in which at-home options are available and being utilized more to mitigate shortfalls in screening generated by the pandemic.

IMMEDIATE EFFECT OF COVID-19 ON CANCER SCREENING

In March 2020, most U.S.-based ambulatory medical clinics shut down or extremely limited any outpatient clinic access to help prevent person-to-person spread of the SARS-CoV-2 virus after a national emergency delaration by the federal government, which had the subsequent effect of nearly eliminating cancer screening. Patient avoidance due to fear and anxiety related to potential transmission of COVID-19 were also at play. Colorectal cancer screening via colonoscopy plummeted 84.5% from January 2020 to April 2020 and mammography for breast cancer screening dropped 89.2% in the same period nationally (9). Additionally, new incident cancer patient encounters for lung, breast, prostate, colorectal, and hematologic cancers and melanomas all plummeted 40% to 80% lower than 2019, meaning that provider diagnosis of patients with these cancers dropped due to patients not coming to health care providers to diagnose those conditions (9). The cancers were likely still occurring as it would not be expected that natural rates would change, but they were not diagnosed in the healthcare setting and subject to tabulation by cancer registries or insurance billing capture. From April 2020 to July 2000, non-invasive mammograms for breast cancer screening had returned to previous baseline levels seen at the end of 2019, whereas the colonoscopy for colorectal cancer screening had recovered to only 85% of pre-pandemic levels (10). This relative increase in breast and colorectal cancer screening occurred despite coinciding with a second surge of COVID-19 in the U.S. in July and August 2020 (11), because there was no further shutdown of ambulatory sites combined with complete use of personal protection equipment for both providers and patients to allow continued screening. During the ambulatory outpatient shutdown nationally in Spring 2020 there were an estimated 285,000 missed breast cancer screenings, an estimated 95,000 missed colorectal cancer screenings, and an estimated 40,000 missed cervical cancer screenings (12).

SCREENING AND CANCER DIAGNOSES IN THE FIRST YEAR POST-COVID-19

Novel mRNA vaccines were released to the general public beginning in December 2020, a year after the discovery of the SARS-COV-2 virus. By January 2021, overall mammogram use for breast cancer screening even exceeded 2019 levels by ~10% (11), likely due to backlogs and ability to increase screening throughput for this screening procedure. On the contrary, by January 2021, overall colonoscopy use for colorectal cancer screening was still 10-15% below 2019 levels (11) despite the backlogs for this screening procedure. Prostate cancer screening through the use of prostate specific antigen (PSA) blood testing was back to 2019 levels by January 2021.

Screening mammogram rates dropped the most for Black patients over any other racial or ethnic group in April 2020, with recovery similar to other racial and ethnic groups by January 2021; diagnostic mammograms for Black patients lagged 5-10% in recovery behind other racial and ethnic groups (11). Similarly, the largest drop for colorectal cancer screening was in Black patients in April 2020; however recovery of screening lagged 5-10% behind other racial and ethnic groups by January 2021, with all racial and ethnic groups not reaching 2019 baseline levels for screening (11). For prostate cancer, Black patients had less of a drop in PSA screening than White and Hispanic patients in April 2020, and all races and ethnicities were similarly recovered in screening rates by January 2021 (11). By January 2021, confirmed diagnoses of breast cancer was above baseline by 10-15% from Asians and Hispanics compared to 2019, and was above baseline by 5% for Whites and Blacks (11). This could be the result of the higher throughput for breast cancer screening. Confirmed diagnoses of colorectal cancer was 18% below the 2019 baseline for Blacks in January 2021, with Whites and Hispanics about 5% below baseline, and Asians 12% above baseline (11). These observations could be a result of not reaching baseline screening rates for colorectal cancer a year into the COVID-19 pandemic. By January 2021, surgical resections for breast, colorectal and prostate cancer were −20%, −45%, and −30%, repectively, below 2019 baseline irrespective of race or ethnicity.

Observed-to-Expected (O/E) ratios for newly-diagnosed cancers were all reduced in April 2020, with a rebound in ratios by December 2020 (13). For instance, female breast cancer had an O/E ratio of 0.4 in April 2020 that rebounded to 1.2 in December 2020; similarly prostate cancer had an O/E ration of 0.4 that rebounded to 1.18 by December 2020. The rebound for colorectal cancer was evident but muted as compared to breast and prostate cancer, with an O/E ratio of 0.4 in April 2020 and rebound to 1.0 in December 2020 (13). O/E ratios for thyroid, lung and pancreatic cancer showed rebound patterns as well (13). In general, O/E ratios for cancers were lower for localized staged versus advanced stage diagnoses (13). By sex, O/E ratios were not different for colorectal, breaset, lung, pancreas or thyroid (13). By race, Asian/Pacific Islanders showed slightly lower O/E ratios for colorectal, breast, lung, prostate and thyroid as compared to Whites, Blacks and American Indian/Alaskan Native groups (13). By age, those aged >65 years had lower O/E ratio (0.75) for lung cancer compared to those aged 40-64 years (0.95) and those <40 years of age (0.95), whereas there was no difference between age groups for colorectal, breast, prostate, thyroid and pancreas cancers (13).

Cancer staging is a key determinant for patient outcome. Examining 2.4 million individuals with newly-diagnosed cancer between 2018 and 2020, the proportion of stage I cancer diagnoses dropped to 30% of all stages in April 2020 and recovered to its baseline of 40% by December 2020 (14). The proportion of stage IV cancers increased from 20% to 27% of all stages in April 2020 and by December 2020 had not quite returned to basesline at 22% (14). The decrease in stage I and increase in stage IV diagnoses was most prominent among Hispanic and Asian/Pacific Islander patients, the uninsured, and those from lower socioeconomic classes (14). Proportions of stage II and III diagnoses were relatively stable at baseline despite the COVID-19 pandemic, with stage III moving from 17% to 19% of all stages and stage II moving from 19% to 17% in April 2020, with return to baseline by December 2020 (14). Patterns were slightly different based on the type of cancer. For breast cancers where stage I is the most common stage, there was a drop from 65% to 59% for stage I in April 2020, with slight increases in stage II, III and IV (~3-4% each) that returned to the 2019 baseline by December 2020. For colorectal cancers, stage IV proportions increased from 44% to 52% in April 2020, with stage I dropping from 25% to 20%, stage III dropping from 20% to 18%, and stage II unchanged at 9% (14). By December 2020, the proportion of stage IV was still elevated at 48% and stage III was 19% and stage II was 8% (14), meaning proportions had not returned to the 2019 baseline by that date. For prostate cancers, the proportions of stage II dropped from 39% to 37%, stage III increased from 22% to 26%, stage I dropped from 21% to 15% ans stage IV increased from 10% to16% (14).

SCREENING AND CANCER DIAGNOSES IN THE SECOND AND THIRD YEAR POST-COVID-19

Overall data for breast, colorectal and cervical cancer screening show a decline in screening volumes during 2021. For breast cancer, a systematic review of 74 studies (covering January 2020 to March 2021) showed that 66% of studies reported reductions in breast cancer diagnosis; there was higher proportion of symptomatic over screen-detected cancers, and there were lower proportions of early stage and higher proportions of advanced stage diagnoses (15). During 2021, as compared to the 2017-2019 average, breast cancer screening volumes overall was down 2.7% (12). Similarly, colorectal cancer screening volumes during 2021 were down 3.4% (12). Cervical cancer screening volumes during 2021 were down 10% (12). These shortfalls for 2021 would be in addition to the shortfalls observed in 2020. For cervical cancer specifically, a population-based study demonstrated less localized staging and more advanced staging for cervical cancer through 2021, with stage I dropping from 32% to 12%, stage II dropping from 37% to 33%, stage III increasing from 17% to 38% and stage IV increasing from 9% to 12% (16). Thus, two years after the discovery of the SARS-CoV-2 virus, screening for breast (via mammography), colorectal (via colonoscopy), and cervical (via Pap smear) cancers had not fully returned to 2019 baselines, meaning 2020 and 2021 cumulative increases in screening shortfalls that could turn into future cancer deaths.

Future cancer deaths as a result of reduced population screening would likely not be observed until the later years of modeling. Indeed, estimates from European modeling predictions from 2020 to 2050 specific for colorectal cancer predict 13,600 additional incidental cases and 7989 additional deaths, assuming screening rates returned to the 2019 baseline, with additional incidence and mortality starting be be recognized beginning in 2025, five years after the initial outpatient ambulatory near cessation of screening (17). Additional colorectal cancer incidence and mortality climb in the models depending on relative screening decrease continuance. Actual data through July 2022 demonstrate the overall number of direct cancer deaths in the U.S. remained steady since 2018 at just under 12,000 deaths per week (18). Additionally, data from EPIC Cosmos comprising 373,574 cancer diagnoses entered from January 1, 2018 through December 31, 2022 showed that cancer screening rates for 2022 returned to the 2018-2019 baseline, along with cancer detection rates returning to baseline (19). Thus overall, it took 3 years to get back to the previous cancer screening baseline in the U.S.

A National Health Interview Survey study comparing cancer screening between 2019 and 2021 demonstrated a 6% drop in breast cancer screening between 2019 and 2021, a 15% drop in cervical cancer screening, a 10% drop in prostate cancer screening, but no change in colorectal cancer screening, using weighted national population estimates of 49M persons screened for breast, 81M persons screened for cervical, 28M persons screened for prostate and 96M persons screened for colorectal cancer (20). The largest decline in screening was amongst Asians. For colorectal cancer, as reported by others there was a drop in colonoscopy utilization (from 14.5M to 13.2M age-eligible persons), but there was a dramatic increase in non-invasive stool testing in 2021 (from 6.2M to 9.8M age eligible persons) countering the drop in colonoscopy usage, with increased non-invasive testing most pronounced among Hispanic and Black persons (Table 2) (20).

Table 2.

U.S. age-eligible adults (in millions) who reported being screened in 2019 and 2021.

Cancer Screened	2019	2021	Non-weighted Percent change	Percent change based on weighted total population for year assessed
Breast	28.8	27.7	−3.8%	−6%
Cervical	35.9	31.5	−12.3%	−15%
Prostate	10.3	9.7	−5.8%	−10%
Colorectal	20.2	21.7	+7.4%	0%
Colorectal - colonsocopy	14.5	13.2	−9.0%	−1.7%
Colorectal – stool testing	6.2	9.8	+58.0%	+3.3%

Data constructed from Star et al (20) and are from weighted national population estimates of persons screened using the 2019 and 2021 National Health Interview Survey. Numbers of adults for colorectal cancer screening tests do not sum up due to other screening modalities, overlap usage of screening modalities, and calculated weighted estimates of the number of persons screened.

NONINVASIVE CANCER SCREENING OPPORTUNITIES POST-COVID-19

The near cessation of screening as a consequence of an unexepcted historic viral pandemic has created opportunities to model and study this perturbation on the occurrence of human cancer, but also opens up and widens avenues towards mitigation of the prediction of excess colorectal cancer mortality. Screening has largely been performed in clinical settings, but the pandemic has necessitated conditions that expand and explore at-home options for specific types of cancer screening, and creates opportunities that may increase overall cancer screening and increase screening participation from marginalized groups. At-home testing is most readily available for colorectal and cervical cancer screening.

Cervical cancer screening has largely been completed by Papanicolaou tests in an ambulatory clinical setting. Cervical cancer screening since COVID-19 commenced is 15% lower in 2021 than in 2019, and had not recovered to the extent that prostate, colorectal and breast cancer screening had (20). Because most cervical cancers are associated with human papilloma virus (HPV) infection, the U.S. Preventive Services Task Force in 2018 added primary HPV-only screening as a recommended screening option for persons between 30 to 65 years of age. The sensitivity of HPV screening is higher than Papanicolaou testing, and samples can be collected by the provider or self-sampled. Mailed HPV self-sampling showed uptake of 26.3% versus 17.4% in controls among 9843 individuals, with older indivuals and those with the longest intervals from their last Papanicolaou tests more likely to use that mailed kit (4). Although there was no differences with uptake between Hispanic and non-Hispanic groups, 42.9% of American Indian/Alaskan Natives, 40.1% of Asian, 39.2% of Black, 24.2% of Native Hawaiian/Pacific Islander, and 47.6% of Whites utilized the mailed test (4). There are opportunities for marketing and improving cervical cancer screening through at-home HPV testing that could mitigate screening gaps, including with the use of navigation.

Colorectal cancer incidence and mortality are highest among American Indians/Alaskan Natives followed by Black persons in the U.S. (1,6,21). Because the COVID-19 pandemic demonstrated similar demographic disparities with SARS-CoV-2 infection and death as with certain cancers (8,22,23), prediction modeling suggested that the recovery of screening for cancers may be worse for underserved groups, with widening of the disparity after many years of gains closing the disparity gap (8,24). In 2019, average-risk population colonoscopy screening utilization for colorectal cancer prevention was at 65% for Whites and 62% for Blacks nationally, the lowest difference observed (25–27). As it takes years for the incidence and mortality to be lowered with equity in screening, not surprisingly there remained higher incidence and mortality rates for Blacks as compared to Whites by 2020 (25–27). Both colonoscopy with navigation and non-invasive fecal immunochemical testing (FIT) with navigation can eliminate both the colorectal incidence and mortality disparity observed for Blacks as shown with studies conducted between 10 and 15 years in length (28,29). Athough in the initial stages of the COVID-19 pandemic all screening tests, including non-invasive at-home tests, were utilized less (30), non-invasive FIT tests as well as DNA stool tests combined with FIT were administered at home more frequently as the pandemic lengthened, and particularly were utilized more among typically disparate populations (20), supporting predictions for this opportunity (30). The largest contribution to colorectal cancer disparities between Black and White patients is the Area Deprivation Index, similar to one’s zip code of residence, with 29% of the relative contribution towards the observed disparity (31,32). Additional persons may be screened with at-home tests due to potential lesser cost, less time for test, and no absence from work compared with colonoscopy screening (8,23). FIT or DNA tests with FIT need to be mailed to a home, and may require navigation to complete the non-invasive test for best results (29). Additionally, the provider must be able to follow-up with the patient on positive tests which require a subsequent colonoscopy (8,33). With national colorectal cancer screening rates not achieving the 80% screened goal, coupled with the expansion of screening-eligible persons down to age 45 years increasing the unscreened pool by 19 million individuals (5,34,35), non-invasive colorectal cancer screening is in a renaissance and affords the opportunity to expand the screened population, reduce patient and provider barriers for screening, and may mitigate reductions in screening with any future viral pandemic. Next generation fecal DNA tests with FIT (36), fecal RNA tests with FIT (37), and cell-free DNA blood-based tests (38) are new to implement to fill the gap that colonoscopy alone cannot fill. The new non-invasive or blood colorectal cancer screening tests are not ideally intended as modalities to replace screening in persons who are actively screened, but more ideally to expand the pool of persons who have never been screened (39).

CONCLUSIONS

The COVID-19 pandemic greatly affected preventive cancer screening in the U.S., with marked perturbation in April 2020 due to near cessation of ambulatory clinic activity and continued shortfalls from the 2019 baseline through 2021. Data for December 2022 suggests that screening utilization has returned to the 2019 baseline, taking 3 years to do so (19), and ongoing data through September 2024 confirm that (Figure 1) (40). Prediction modeling indicated that we will encounter multiple excess cancers as a result of the COVID-19-era cumulative shortfalls in screening that will be most prominently observed in the out years of the model. Recovery from shortfalls are varied based on type of cancer, with the most recovery observed after the second year post-COVID-19 with colorectal cancer screening due to increase in non-invasive testing that can be administered at home. Despite HPV home testing, by the end of the second year post-COVID-19, cervical cancer screening has not recovered in similar fashion to that observed for colorectal cancer screening perhaps due to lack of full awareness and marketing, with a screening gap of 15% from the 2019 baseline. As demonstrated via colonoscopy and non-invasive testing (FIT) for colorectal cancer screening, incident and mortality disparities can be eliminated in a 10 to 15 year time frame (28,29). Those studies utilized navigation to eliminate disparities, and navigated preventive services whether in ambulatory settings or at-home may increase patient compliance for the screening tests. Use of at-home screening is likely to increase screening if the test is acceptable to utilize by most persons, and saves time and travel for the patient. In particular, multi-target stool DNA tests combined with FIT are growing in popularity (41). At-home tests can increase participation for cancer screening from disparate populations.

Figure 1.

Colorectal cancer screenings in the U.S. from January 2020 to September 2024. Data points are presented in quarter years and are rates of screenings per 100,000 persons. Note dramatic declines in April 2020 overall and steady increases in screening in the 45-54 year age group due to changes to screening recommendations to begin screening at age 45 years in 2021, and a decline in screenings for those over 85 years of age. Data obtained from Epic Research (40). CRC: colorectal cancer.