Issues

The cover image is adapted from Figure 1 in the article “Clinical Utility of Reflex Testing with Cancer Biomarkers to Improve Diagnostic Accuracy of Primary Human Papillomavirus Screening,” by Johnson and colleagues. The original figure shows the distribution of Biomarkers by disease status and HIV status. HPV testing is the cornerstone of cervical cancer screening with outstanding sensitivity but only moderate specificity. The authors evaluated whether reflex testing for cancer biomarkers improves the sensitivity/specificity balance of screening. When used as reflex tests after a positive HPV result, biomarkers discriminated well between women with and without CIN2+. The inclusion of both CDKN2A and MKi67 had the best performance with area under the curve (AUC) of 0.9171 and 0.8734 in women without and with HIV, respectively. While excellent, these performance parameters did not improve on an approach utilizing only HPV testing with more stringent cycle threshold cut-offs and HPV genotype selection which achieved AUC of 0.9059 and 0.8705 in women without and with HIV, respectively. Biomarkers can be used as triage after positive HPV results but do not out-perform an approach utilizing higher viral load cut-offs on selected high-risk genotypes. A screening approach using HPV testing alone can be more easily implemented at the point-of-care. For more information, see the article beginning on page 595.