SUSPSTF: The Best Colorectal Cancer Screening Strategy Is the One That Gets Done

In an updated recommendation statement on colorectal cancer (CRC) screening, the U.S. Preventive Services Task Force (USPSTF) emphasized the benefit of screening in individuals ages 50 to 75 without expressing preference for any particular testing method or strategy (JAMA 2016; doi:10.1001/jama.2016.5989). Citing “convincing evidence” that screening for CRC with several different methods accurately detects early-stage disease, USPSTF concluded with “high certainty” that screening in average-risk adults is of “substantial net benefit.”

The recommendation effectively puts stool-based tests like guaiac-based fecal occult blood test (gFOBT), fecal immunochemical test (FIT), and multitargeted DNA stool test (FIT-DNA) on par with direct visualization tests such as colonoscopy and flexible sigmoidoscopy. USPSTF found no head-to-head studies demonstrating that any particular screening strategy is more effective than any other. It also noted that the tests have varying levels of evidence supporting their effectiveness, as well as different strengths and limitations.

Studies evaluating the test characteristics of various screening methods looked at a one-time use of each test, making it “not possible to draw meaningful inferences about the ultimate performance” of the tests as they would actually be used, with repeated screenings over time, according to USPSTF.

FITs, USPSTF noted, have higher sensitivity than gFOBT in detecting CRC. Among FITs cleared by the Food and Drug Administration, the OC FIT-CHEK family of tests have the best test performance, according to USPSTF. In comparison to FIT, FIT-DNA has higher single-test sensitivity for detecting CRC, but lower specificity. The latter means FIT-DNA produces more false-positive results, possibly leading to more follow-up colonoscopies and thereby more adverse events per screening test. Colonoscopy, USPSTF found, is the main source of harms associated with CRC screening.

USPSTF issued a draft of the updated recommendations in October 2015, which used the term “alternative” to describe the testing strategies it found lacked clarity and were “confusing to interpret,” including certain FITs. Based on public comments USPSTF received on the draft document, in the final recommendation it removed both this term and “recommended” to “better communicate the primary message of importance,” that screening for CRC provides “substantial benefit.”

USPSTF emphasized that CRC screening is a “substantially underused preventive health strategy … The best screening strategy is the one that gets done.”

Single HCV Core Antigen Test Could Replace Two-Step Screening Algorithm

A World Health Organization (WHO)-commissioned systematic review and meta-analysis found that five commercially available hepatitis C virus core antigen (HCVcAg) tests are highly sensitive and specific and could replace the current two-step HCV testing algorithm (Ann Intern Med 2016; doi:10.7326/M16-0065). WHO commissioned the study in advance of its forthcoming guidance on HCV screening.

The investigators noted that 130 million to 150 million individuals have chronic HCV infection, nearly three-quarters of whom are from low- and middle-income countries (LMIC). The current two-step HCV diagnostic algorithm involves screening for HCV antibodies (anti-HCV), followed by confirmatory nucleic acid testing (NAT) in the case of positive anti-HCV results.

While this algorithm is cost-effective, it poses challenges in LMIC, where “a significant proportion of patients” who test positive by anti-HCV do not receive NAT or are lost to follow-up, keeping them from crucial early treatment that can stanch and even cure the disease. As such, the two-step anti-HCV/NAT algorithm is a “major bottleneck” in getting HCV-infected patients into care and achieving WHO’s goal of eliminating the disease, according to the authors.

HCVcAg is a potential replacement for NAT, as it can be detected earlier than antibodies and throughout HCV infection.

The investigators considered 44 studies that compared HCVcAg tests with NAT reference standard, including Abbott ARCHITECT ACV Ag, Fujirebio Lumipulse Ortho HCV Ag, Eiken Lumispot HCV Ag, Hunan Jynda Bioengineering Group HCV Ag ELISA, and Ortho HCV Ag Elisa. The authors did not have enough data for a meta-analysis of the Fujirebio Lumipulse Ortho HCV Ag and Eiken Lumispot HCV Ag assays, but they concluded that several HCVcAg assays had sensitivity >90% and specificity >98%.

Even though the best-performing tests are less sensitive than NAT, well-performing HCVcAg tests could replace NAT for HCV detection, according to the authors. They also suggested that point-of-care HCVcAg tests be investigated to increase the number of patients diagnosed and receiving care.