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

• Published in: Journal of clinical microbiology Vol. 52; no. 6; pp. 2089 - 2095
• Main Authors: Einstein, Mark H., Smith, Katherine M., Davis, Thomas E., Schmeler, Kathleen M., Ferris, Daron G., Savage, Ashlyn H., Gray, Jermaine E., Stoler, Mark H., Wright, Thomas C., Ferenczy, Alex, Castle, Philip E.
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 01.06.2014
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Early Detection of Cancer - methods; Female; Histocytochemistry; Human papillomavirus; Human papillomavirus 16; Humans; Middle Aged; Molecular Diagnostic Techniques - methods; Papillomaviridae - isolation & purification; Papillomavirus Infections - diagnosis; Prospective Studies; Sensitivity and Specificity; United States; Uterine Cervical Neoplasms - diagnosis; Uterine Cervical Neoplasms - virology; Virology; Young Adult; United States
• ISSN: 0095-1137; 1098-660X; 1098-660X
• DOI: 10.1128/JCM.00176-14

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.