Patient Safety and the Next Generation of HPV DNA TestsThe Authors’ ReplyPostscript

Abstract

The article by Kinney et al1 in the August 2010 issue of the Journal expressed concern about the approval by the US Food and Drug Administration (FDA) of the Cervista HPV HR (high-risk human papillomavirus) test (Third Wave Technologies, Madison, WI; now owned by Hologic, Bedford, MA) and questioned the safety of the device owing to the positivity rate seen in the study population for women 30 years and older with negative cytologic findings (NILM ≥30). The clinical cutoff for the Cervista HPV HR test was set in the same manner as for the only other FDA-approved HR-HPV test, Hybrid Capture 2 (HC2; Qiagen, Gaithersburg, MD), by evaluating clinical sensitivity and specificity in the population with atypical squamous cells of undetermined significance (ASC-US). The rationale for this approach is that the ASC-US population, as a population with equivocal cytologic findings, provides an informative profile of how an HPV test performs in an intended-use population in which disease prevalence is sufficient for characterizing a clinical cutoff and disease end points can be readily assessed. A head-to-head comparison against the HC2 test was performed during review of the Cervista HPV HR device. This evaluation revealed equivalent clinical specificity for cervical intraepithelial neoplasia (CIN) 2 or worse for the 2 tests in the Cervista ASC-US data set, and the Cervista HPV HR test detected 100% of cases of CIN 3 or worse. In determining whether an in vitro diagnostic device is safe and effective, the FDA must consider whether the probable benefits of using the device outweigh the probable risks when the device is used in accordance with its approved labeling. Per current screening guidelines,2 the predominant use of HPV testing in the NILM ≥30 population is to extend cervical cancer screening intervals in HPV– women. In a worst-case scenario in …