title: Head-to-Head Comparison of the RNA-Based Aptima Human Papillomavirus (HPV) Assay and the DNA-Based Hybrid Capture 2 HPV Test in a Routine Screening Population of Women Aged 30 to 60 Years in Germany.
abstract: Testing for E6/E7 mRNA in cells infected with high-risk (HR) human papillomavirus (HPV) might improve the specificity of HPV testing for the identification of cervical precancerous lesions. Here we compared the RNA-based Aptima HPV (AHPV) assay (Hologic) and the DNA-based Hybrid Capture 2 (HC2) HPV test (Qiagen) to liquid-based cytology (LBC) for women undergoing routine cervical screening. A total of 10,040 women, 30 to 60 years of age, were invited to participate in the study, 9,451 of whom were included in the analysis. Specimens were tested centrally by LBC, the AHPV test, and the HC2 test, and women who tested positive on any test were referred for colposcopy. Genotyping was performed on all HR-HPV-positive samples. Test characteristics were calculated based on histological review. As a result, we identified 90 women with cervical intraepithelial neoplasia grade 2+ (CIN2+), including 43 women with CIN3+. Sensitivity differences between the AHPV test and the HC2 test in detecting CIN2+ (P = 0.180) or CIN3+ (P = 0.0625) lesions were statistically nonsignificant. Of three CIN3 cases that were missed with the AHPV test, two cases presented lesion-free cones and one had a non-HR HPV67 infection. The specificity (<CIN2) and positive predictive value (CIN2+) of the AHPV test were significantly higher (both P < 0.001) than those of the HC2 test. The overall agreement between the tests was substantial (κ = 0.77). Finally, we present results for several possible triage strategies, based on the primary screening test being either the AHPV test or the HC2 test. In summary, the AHPV assay is both specific and sensitive for the detection of high-grade precancerous lesions and may be used in primary cervical cancer screening for women ≥30 years of age.
authors.affiliation: Division of Experimental Virology, Institute of Medical Virology, University Hospital Tübingen, Tübingen, Germany thomas.iftner@med.uni-tuebingen.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Iftner
authors.affiliation: Department of Gynecology and Obstetrics, University Hospital Tübingen, Tübingen, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Becker
authors.affiliation: Frauenärzte am Staden, Saarbrücken, Germany.
authors.forename: Klaus-Joachim
authors.initials: KJ
authors.lastname: Neis
authors.affiliation: Centre for Cancer Prevention, Queen Mary University of London, London, United Kingdom.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Castanon
authors.affiliation: Division of Experimental Virology, Institute of Medical Virology, University Hospital Tübingen, Tübingen, Germany.
authors.forename: Angelika
authors.initials: A
authors.lastname: Iftner
authors.affiliation: Division of Experimental Virology, Institute of Medical Virology, University Hospital Tübingen, Tübingen, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Holz
authors.affiliation: Department of Pathology and Neuropathology, University Hospital Tübingen, Tübingen, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Staebler
authors.affiliation: Department of Gynecology and Obstetrics, University Hospital Tübingen, Tübingen, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Henes
authors.affiliation: Department of Gynecology and Obstetrics, University Hospital Tübingen, Tübingen, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Rall
authors.affiliation: Division of Experimental Virology, Institute of Medical Virology, University Hospital Tübingen, Tübingen, Germany.
authors.forename: Juliane
authors.initials: J
authors.lastname: Haedicke
authors.affiliation: Department of Pathology and Neuropathology, University Hospital Tübingen, Tübingen, Germany.
authors.forename: Claus Hann
authors.initials: CH
authors.lastname: von Weyhern
authors.affiliation: Department of Gynecology, Obstetrics, and Medical Microbiology, Albert Ludwigs University of Freiburg, Freiburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Clad
authors.affiliation: Department of Gynecology and Obstetrics, University Hospital Tübingen, Tübingen, Germany.
authors.forename: Sara
authors.initials: S
authors.lastname: Brucker
authors.affiliation: Centre for Cancer Prevention, Queen Mary University of London, London, United Kingdom.
authors.forename: Peter
authors.initials: P
authors.lastname: Sasieni
mesh_terms: D000328:Adult; D003584:Cytological Techniques / Q000379:methods; D004279:DNA, Viral / Q000032:analysis*; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D005838:Genotype; D005858:Germany; D006651:Histocytochemistry; D006801:Humans; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D027383:Papillomaviridae / Q000145:classification / Q000235:genetics; D030361:Papillomavirus Infections / Q000175:diagnosis*; D011230:Precancerous Conditions / Q000175:diagnosis*; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000032:analysis; D012367:RNA, Viral / Q000032:analysis*; D012680:Sensitivity and Specificity; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis*
chemical_list: D004279:DNA, Viral; D012333:RNA, Messenger; D012367:RNA, Viral