New Low-Cost Molecular HPV Screening Tools Evaluated With Promising Results From New E6 Oncoprotein Test
Development and validation of novel, low-cost, and robust human papillomavirus (HPV) screening strategies are needed to address the disproportionate burden of cervical cancer in resource-limited areas of the world. A clinical trial published in the September issue of Cancer Prevention Research provides some important advances in establishing evidence for population-based screening using emerging lower-cost tests. […]
Development and validation of novel, low-cost, and robust human papillomavirus (HPV) screening strategies are needed to address the disproportionate burden of cervical cancer in resource-limited areas of the world. A clinical trial published in the September issue of Cancer Prevention Research provides some important advances in establishing evidence for population-based screening using emerging lower-cost tests. The study both confirmed the comparability of the lower-cost careHPV (Qiagen) DNA test to a U.S. Food and Drug Administration (FDA)-approved test and demonstrated that a new E6 oncoprotein low-cost test might be useful for screening in high-HPV-prevalence populations. The increased sensitivity of molecular high-risk HPV (HR-HPV) testing provides an advantage over Pap testing, but it is too complex and costly for use in low-resource areas. Lower-cost tests are in development and validation, including careHPV, a signal amplification DNA test for a pool of 14 HR-HPV genotypes, as well as the lateral flow immunoassay OncoE6 (Arbor Vita Corp.) that targets HPV E6 oncoproteins, which are typically overexpressed in the precancerous phenotype. The researchers conducted a large-scale clinical trial of both of these tests as well as evaluation of multiple screening strategies. More than 7,500 women (aged 25 to 65 years) living in rural China self-collected a cervicovaginal specimen, had two cervical specimens collected by a clinician, and underwent visual cervical inspection after acetic acid (VIA). The self- and one clinician-collected specimens underwent HR-HPV DNA testing using careHPV and Qiagen’s FDA-approved Hybrid Capture 2 (HC2). The other clinician-collected specimen was tested for HPV16, 18, and 45 E6 using OncoE6. The researchers found that 30.4 percent of women tested positive by at least one of the screening tests. The sensitivity for cervical intraepithelial neoplasia grade 3 or more severe (CIN3+; 99 cases) was 53.5 percent for OncoE6, 97 percent for both careHPV and HC2 using the clinician-collected specimen, 83.8 percent and 90.9 percent, respectively using the self-collected specimen, and 50.5 percent for VIA. OncoE6 had the greatest positive predictive value (PPV), at 40.8 percent for CIN3+, compared with the other tests, all of which had a PPV of less than 10 percent. “In those areas with insufficient resources to manage large numbers of screen-positive women that would result from using a more sensitive but less specific HR-HPV DNA test, the OncoE6 test might be used for primary screening, thereby achieving a sensitivity similar or superior to VIA, which is already being widely used,” writes senior author Philip Castle, Ph.D., from the Global Cancer Initiative (Chestertown, Md.). “However, because of its much higher specificity compared with VIA, screening with HPV E6 might reduce either the number of referrals to colposcopy . . . or overtreatment.” Several authors report financial ties to the diagnostics industry, including Arbor Vita Corp. Takeaway: HPV E6 oncoprotein detection appears useful for identifying women who have cervical precancer and cancer in low-resource areas.