Roosmarijn Luttmer1, Johannes Berkhof2, Maaike G Dijkstra3, Folkert J van Kemenade4, Peter J F Snijders5, Daniëlle A M Heideman6, Chris J L M Meijer7. 1. VU University Medical Center, Department of Pathology, PO Box 7057, 1007 MB Amsterdam, The Netherlands. Electronic address: r.luttmer@vumc.nl. 2. VU University Medical Center, Department of Epidemiology & Biostatistics, PO Box 7057, 1007 MB Amsterdam, The Netherlands. Electronic address: h.berkhof@vumc.nl. 3. VU University Medical Center, Department of Pathology, PO Box 7057, 1007 MB Amsterdam, The Netherlands. Electronic address: mg.dijkstra@vumc.nl. 4. VU University Medical Center, Department of Pathology, PO Box 7057, 1007 MB Amsterdam, The Netherlands. Electronic address: f.vankemenade@erasmusmc.nl. 5. VU University Medical Center, Department of Pathology, PO Box 7057, 1007 MB Amsterdam, The Netherlands. Electronic address: pjf.snijders@vumc.nl. 6. VU University Medical Center, Department of Pathology, PO Box 7057, 1007 MB Amsterdam, The Netherlands. Electronic address: dam.heideman@vumc.nl. 7. VU University Medical Center, Department of Pathology, PO Box 7057, 1007 MB Amsterdam, The Netherlands. Electronic address: cjlm.meijer@vumc.nl.
Abstract
BACKGROUND: High-risk human papillomavirus (hrHPV) DNA positive women require triage testing to identify those with high-grade cervical intraepithelial neoplasia or cancer (≥CIN2). OBJECTIVE: Comparing three triage algorithms (1) E7 mRNA testing following HPV16/18/31/33/45/52/58 genotyping (E7 mRNA test), (2) HPV16/18 DNA genotyping and (3) cytology, for ≥CIN2 detection in hrHPV DNA-positive women. STUDY DESIGN: hrHPV DNA-positive women aged 18-63 years visiting gynecology outpatient clinics were included in a prospective observational cohort study. From these women a cervical scrape and colposcopy-directed biopsies were obtained. Cervical scrapes were evaluated by cytology, HPV DNA genotyping by bead-based multiplex genotyping of GP5+6+-PCR-products, and presence of HPV16/18/31/33/45/52/58 E7 mRNA using nucleic acid sequence-based amplification (NASBA) in DNA positive women for respective HPV types. Sensitivities and specificities for ≥CIN2 were compared between E7 mRNA test and HPV16/18 DNA genotyping in the total group (n=348), and E7 mRNA test and cytology in a subgroup of women referred for non-cervix-related gynecological complaints (n=133). RESULTS: Sensitivity for ≥CIN2 of the E7 mRNA test was slightly higher than that of HPV16/18 DNA genotyping (66.9% versus 60.9%; ratio 1.10, 95% CI: 1.0002-1.21), at similar specificity (54.8% versus 52.3%; ratio 1.05, 95% CI: 0.93-1.18). Neither sensitivity nor specificity of the E7 mRNA test differed significantly from that of cytology (sensitivity: 68.8% versus 75.0%; ratio 0.92, 95% CI: 0.72-1.17; specificity: 59.4% versus 65.3%; ratio 0.91, 95% CI: 0.75-1.10). CONCLUSION: For detection of ≥CIN2 in hrHPV DNA-positive women, an algorithm including E7 mRNA testing following HPV16/18/31/33/45/52/58 DNA genotyping performs similar to HPV16/18 DNA genotyping or cytology.
BACKGROUND: High-risk human papillomavirus (hrHPV) DNA positive women require triage testing to identify those with high-grade cervical intraepithelial neoplasia or cancer (≥CIN2). OBJECTIVE: Comparing three triage algorithms (1) E7 mRNA testing following HPV16/18/31/33/45/52/58 genotyping (E7 mRNA test), (2) HPV16/18 DNA genotyping and (3) cytology, for ≥CIN2 detection in hrHPV DNA-positive women. STUDY DESIGN: hrHPV DNA-positive women aged 18-63 years visiting gynecology outpatient clinics were included in a prospective observational cohort study. From these women a cervical scrape and colposcopy-directed biopsies were obtained. Cervical scrapes were evaluated by cytology, HPV DNA genotyping by bead-based multiplex genotyping of GP5+6+-PCR-products, and presence of HPV16/18/31/33/45/52/58 E7 mRNA using nucleic acid sequence-based amplification (NASBA) in DNA positive women for respective HPV types. Sensitivities and specificities for ≥CIN2 were compared between E7 mRNA test and HPV16/18 DNA genotyping in the total group (n=348), and E7 mRNA test and cytology in a subgroup of women referred for non-cervix-related gynecological complaints (n=133). RESULTS: Sensitivity for ≥CIN2 of the E7 mRNA test was slightly higher than that of HPV16/18 DNA genotyping (66.9% versus 60.9%; ratio 1.10, 95% CI: 1.0002-1.21), at similar specificity (54.8% versus 52.3%; ratio 1.05, 95% CI: 0.93-1.18). Neither sensitivity nor specificity of the E7 mRNA test differed significantly from that of cytology (sensitivity: 68.8% versus 75.0%; ratio 0.92, 95% CI: 0.72-1.17; specificity: 59.4% versus 65.3%; ratio 0.91, 95% CI: 0.75-1.10). CONCLUSION: For detection of ≥CIN2 in hrHPV DNA-positive women, an algorithm including E7 mRNA testing following HPV16/18/31/33/45/52/58 DNA genotyping performs similar to HPV16/18 DNA genotyping or cytology.
Authors: Corina N A M van den Heuvel; Diede L Loopik; Renée M F Ebisch; Duaa Elmelik; Karolina M Andralojc; Martijn Huynen; Johan Bulten; Ruud L M Bekkers; Leon F A G Massuger; Willem J G Melchers; Albert G Siebers; William P J Leenders Journal: Mod Pathol Date: 2019-09-19 Impact factor: 7.842
Authors: Roosmarijn Luttmer; Maaike G Dijkstra; Peter J F Snijders; Johannes Berkhof; Folkert J van Kemenade; Lawrence Rozendaal; Theo J M Helmerhorst; René H M Verheijen; W Abraham Ter Harmsel; W Marchien van Baal; Peppino G C M Graziosi; Wim G V Quint; Johan W M Spruijt; Dorenda K E van Dijken; Daniëlle A M Heideman; Chris J L M Meijer Journal: Mod Pathol Date: 2016-05-06 Impact factor: 7.842
Authors: Lise M A De Strooper; Viola M J Verhoef; Johannes Berkhof; Albertus T Hesselink; Helena M E de Bruin; Folkert J van Kemenade; Remko P Bosgraaf; Ruud L M Bekkers; Leon F A G Massuger; Willem J G Melchers; Renske D M Steenbergen; Peter J F Snijders; Chris J L M Meijer; Daniëlle A M Heideman Journal: Gynecol Oncol Date: 2016-03-03 Impact factor: 5.482
Authors: Lise M A De Strooper; Johannes Berkhof; Renske D M Steenbergen; Birgit I Lissenberg-Witte; Peter J F Snijders; Chris J L M Meijer; Daniëlle A M Heideman Journal: Int J Cancer Date: 2018-04-27 Impact factor: 7.396