title: High-risk human papillomavirus (hrHPV) E6/E7 mRNA testing by PreTect HPV-Proofer for detection of cervical high-grade intraepithelial neoplasia and cancer among hrHPV DNA-positive women with normal cytology.
abstract: Our aim was to investigate whether high-risk HPV (hrHPV) mRNA detection by PreTect HPV-Proofer can be used to stratify hrHPV DNA-positive women of different cytology classes for risk of high-grade cervical intraepithelial neoplasia or worse (cervical precancer or cancer, i.e., cervical intraepithelial neoplasia grade 2 or higher [≥ CIN2]). A total of 375 women participating in population-based screening, with a GP5+/6+-PCR hrHPV DNA-positive cervical scrape with normal cytology (n = 202), borderline or mild dyskaryosis (BMD) (n = 88), or moderate dyskaryosis or worse (>BMD) (n = 85), were enrolled. Cervical scrapes were additionally subjected to HPV16/18/31/33/45 E6/E7 mRNA analysis by PreTect HPV-Proofer (mRNA test). Referral and follow-up policies were based on cytology, hrHPV DNA, and mRNA testing. The primary study endpoint was the number of ≥CIN2 detected within 3 years of follow-up. The mRNA positivity increased with the severity of cytological abnormality, ranging from 32% (64/202) in hrHPV DNA-positive women with normal cytology to 47% (41/88) in BMD and 68% (58/85) in >BMD groups (P < 0.01). Women with ≥ CIN2 were more likely to test positive by mRNA test (63%) than women without evidence of ≥ CIN2 (32%; P < 0.01). A positive mRNA test result conferred an increased ≥ CIN2 risk in hrHPV DNA-positive women with normal cytology, i.e., 0.55 (95% confidence interval [95% CI], 0.34 to 0.76) in mRNA-positive versus 0.20 (95% CI, 0.07 to 0.33) in mRNA-negative women. In hrHPV DNA-positive women with BMD or >BMD, the result of the mRNA test did not influence the ≥ CIN2 risk. In conclusion, mRNA testing by PreTect HPV-Proofer might be of value to select hrHPV DNA-positive women with normal cytology in need of immediate referral for colposcopy.
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: D C
authors.initials: DC
authors.lastname: Rijkaart
authors.forename: D A M
authors.initials: DA
authors.lastname: Heideman
authors.forename: V M H
authors.initials: VM
authors.lastname: Coupe
authors.forename: A A T P
authors.initials: AA
authors.lastname: Brink
authors.forename: R H M
authors.initials: RH
authors.lastname: Verheijen
authors.forename: H
authors.initials: H
authors.lastname: Skomedal
authors.forename: F
authors.initials: F
authors.lastname: Karlsen
authors.forename: E
authors.initials: E
authors.lastname: Morland
authors.forename: P J F
authors.initials: PJ
authors.lastname: Snijders
authors.forename: C J L M
authors.initials: CJ
authors.lastname: Meijer
mesh_terms: D000328:Adult; D000368:Aged; D003584:Cytological Techniques / Q000379:methods; D005260:Female; D006801:Humans; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D009856:Oncogene Proteins, Viral / Q000096:biosynthesis* / Q000235:genetics; D030361:Papillomavirus Infections / Q000175:diagnosis* / Q000821:virology; D012333:RNA, Messenger / Q000032:analysis* / Q000235:genetics / Q000302:isolation & purification; D012367:RNA, Viral / Q000032:analysis* / Q000235:genetics / Q000302:isolation & purification; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000821:virology; D014773:Virology / Q000379:methods*
chemical_list: D009856:Oncogene Proteins, Viral; D012333:RNA, Messenger; D012367:RNA, Viral