Human Papillomavirus (HPV) testing has been extensively studied in randomized controlled trials of primary cervical screening. Based on encouraging results concerning its high detection rates and a ...high negative predictive value for high-grade cervical intraepithelial neoplasia (CIN), HPV testing will probably replace cytology in future primary cervical screening. However, HPV testing is associated with more frequent false-positive tests compared to cytology. False-positive tests are defined as positive screening tests which are not subsequently confirmed with high-grade CIN. Several authors have claimed that the frequency of false-positive HPV tests could be reduced if an additional test was used to decide on referral for colposcopy of HPV-positive women. Data from the trials, however, do not support this claim. In fact, when compared to standard cytology screening and triage procedures, HPV testing leads to more screen-positive women being referred for colposcopy without having high-grade CIN, and to more women undergoing repeated testing. The only reasonable solution to the problem of false-positive tests appears to be a revised definition of a positive HPV screening test. However, further studies are needed to determine how this definition could be revised while at the same time keeping the high negative predictive value of HPV testing.
Abstract Aim Based on data from randomised controlled trials (RCT) on primary cervical screening, it has been reported that the problem of more frequent false-positive tests in Human Papillomavirus ...(HPV) DNA screening compared to cytology could be overcome. However, these reports predominantly operated with a narrow definition of a (false-)positive test. The aim of this paper was to illustrate how the narrow definition affected the measured adverse effects of HPV DNA screening compared with cytology screening. Methods In the European RCT data, we measured the impact of the narrow definition of a positive screening test on the published relative positive predictive values (PPV), an indicator of the relative frequency of false-positive screening tests. Results Using the trialists’ definitions of positive screening tests, HPV screening combined with cytology triage had relative PPVs of 0.87 (95% confidence interval (CI): 0.60–1.26) for ⩾CIN3 based on Swedish RCT data, and 0.78 (0.52–1.16) for ⩾CIN2 in the Italian Phase 1 RCT (25–34 years). These PPVs changed to 0.44 (0.30–0.64) and 0.51 (0.33–0.79), respectively, when all positive HPV or cytology screening tests were accounted for. In the Finnish RCT data, HPV screening using the cut-off point of ⩾10 pg/ml had a relative PPV of 0.27 (0.15–0.50) for ⩾CIN3, which changed to 1.84 (0.99–3.41). Conclusion The relative PPV was incorrectly estimated in six out of seven studies. In three of those six studies, the relative PPV changed significantly after inclusion of the previously erroneously excluded false-positive HPV or cytology tests.
