Clinical evaluation of the cartridge-based GeneXpert human papillomavirus assay in women referred for colposcopy.
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.
Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, New York, USA meinstei@montefiore.org.
Mark H
MH
Einstein
Oklahoma University Health Sciences Center, Oklahoma City, Oklahoma, USA.
Katherine M
KM
Smith
Indiana University, Indianapolis, Indiana, USA.
Thomas E
TE
Davis
The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Kathleen M
KM
Schmeler
Georgia Regents University, Augusta, Georgia, USA.
Daron G
DG
Ferris
Medical University of South Carolina, Charleston, South Carolina, USA.
Ashlyn H
AH
Savage
University of Mississippi Medical Center, Jackson, Mississippi, USA.
Jermaine E
JE
Gray
University of Virginia, Charlottesville, Virginia, USA.
Mark H
MH
Stoler
Columbia University, New York, New York, USA.
Thomas C
TC
Wright
McGill University and Jewish General Hospital, Montreal, Quebec, Canada.
Alex
A
Ferenczy
Global Cancer Initiative, Chestertown, Maryland, USA.
Philip E
PE
Castle
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D006651:Histocytochemistry; D006801:Humans; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D027383:Papillomaviridae / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000175:diagnosis*; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D014481:United States; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000821:virology; D055815:Young Adult