Clinical Evaluation of the Cartridge-Based GeneXpert Human Papillomavirus Assay in Women Referred for Colposcopy

Abstract

High-risk human papillomavirus (hrHPV) testing is now being introduced as a potential primary screening test for improved detection of cervical precancer and cancer. Current U.S. Food and Drug Administration-approved tests are batch tests that take several hours to complete. A rapid, non-batch test might permit point-of-care (POC) testing, which can facilitate same-day screen and management strategies. For a non-batch, random-access platform (GeneXpert; Cepheid, Sunnyvale, CA), a prototype hrHPV assay (Xpert) has been developed where testing for 14 hrHPV types can be completed in 1 h. In the first clinical evaluation, Xpert was compared to two validated hrHPV tests, the cobas HPV test (cobas, Roche Molecular Systems) and Hybrid Capture 2 (hc2, Qiagen), and to histologic outcomes using specimens from colposcopy referral populations at 7 clinical sites in the United States (n ‫؍‬ 697). The sensitivity of Xpert for cervical intraepithelial neoplasia grade 2 or more severe diagnoses (CIN2؉) (n ‫؍‬ 141) was equal to that of cobas (90.8% versus 90.8%, P ‫؍‬ 1) and greater than that of hc2 (90.8% versus 81.6%, P ‫؍‬ 0.004). Xpert was more specific than cobas (42.6% versus 39.6%, P ‫؍‬ 0.02) and less specific than hc2 (42.6% versus 47.7%, P < 0.001). Similar results were observed for cervical intraepithelial neoplasia grade 3 or higher (CIN3؉) (n ‫؍‬ 91). HPV16 detection by Xpert identified 41.8% of the CIN2؉ specimens with a positive predictive value (PPV) of 54.6%. By comparison, HPV16 detection by cobas identified 42.6% of the CIN2؉ specimens with a PPV of 55.0%. hrHPV detection by the Xpert demonstrated excellent clinical performance for identifying women with CIN2؉ and CIN3؉ that was comparable to that of currently available clinically validated tests.

Field Evaluation of Xpert HPV Point-of-Care Test for Detection of Human Papillomavirus Infection by Use of Self-Collected Vaginal and Clinician-Collected Cervical Specimens

“…These tests are more sensitive than cytology for the detection of high-grade cervical intraepithelial neoplasia (CIN) and invasive disease and have comparable specificities (1,2), and their potential efficacy for populationbased cervical screening has been conclusively demonstrated in large-scale randomized trials and prospective studies (3)(4)(5). These findings led to recommendations in Europe, the United States, Australia, and other high-income settings for cervical screening programs to incorporate hrHPV DNA testing (2,(5)(6)(7).…”

Performance of a Cartridge-Based Assay for Detection of Clinically Significant Human Papillomavirus (HPV) Infection: Lessons from VALGENT (Validation of HPV Genotyping Tests)

“…Furthermore, storage of VALGENT-2 samples prior to testing may affect assay performance to an extent. However, if storage were to have a deleterious impact on assay detection, lower sensitivity may be anticipated, whereas the sensitivity of the Xpert HPV for CIN2ϩ and CIN3ϩ was high and equivalent to or higher than that described in the prospective series (7,8). In addition, as biopsies were only indicated as a consequence of preceding abnormal cytology, some CIN2ϩ may have been missed, although further longitudinal follow-up of the cohort, which is planned, will address this.…”

“…This said, the data available thus far have been encouraging. Einstein et al (8) assessed the clinical performance of the Xpert HPV on 697 samples obtained from colposcopy referral populations across 7 U.S. sites, with performance compared to the Cobas HPV test and the hc2. The Xpert HPV showed sensitivity for CIN2ϩ comparable to the COBAS HPV test and the hc2, whereas the highest specificity was conferred by the hc2 followed by the Xpert HPV and then the Cobas HPV test, leading the authors to conclude that the Xpert HPV performance was "comparable to that of currently available clinically validated tests.…”

“…It differs from many competitor HPV assays in that the extraction and amplifi-cation processes are contained within an individual cartridge with minimal operator input other than addition of 1 ml of (unmanipulated) original sample (7). The initial reports on performance have been favorable when it is compared to FDA-approved assays in both primary screening contexts and colposcopy settings (7,8). However, further data on performance pertaining to the Meijer criteria are lacking as are data on the performance/concordance of the type-specific aspects of the assay.…”

Performance Evaluation of Cartridge-Type Blood Gas Analyzer: i-Smart 300

“…The users of POC analyzers are often unfamiliar with laboratory instruments and unacquainted with the maintenance and quality control of the instrument. Therefore, cartridge-type instruments are welcomed for most POC instruments, not only blood gas analyzers, but also molecular diagnostic analyzers [3]. If, however, Background: Blood gas analysis plays a crucial role in critical care settings, and immediate and precise analysis improves clinical outcomes through prompt treatment.…”