Human papillomavirus E7 protein detection as a method of triage to colposcopy of HPV positive women, in comparison to genotyping and cytology. Final results of the PIPAVIR study

Abstract

The objective of the presented cross-sectional-evaluation-screening study is the clinical evaluation of high-risk(hr)HPVE7-protein detection as a triage method to colposcopy for hrHPV-positive women, using a newly developed sandwich-ELISA-assay. Between 2013-2015, 2424 women, 30-60 years old, were recruited at the Hippokratio Hospital, Thessaloniki/Greece and the Im Mare Klinikum, Kiel/Germany, and provided a cervical sample used for Liquid Based Cytology, HPV DNA genotyping, and E7 detection using five different E7-assays: "recomWell HPV16/18/45KJhigh", "recomWell HPV16/18/45KJlow", "recomWell HPV39/51/56/59", "recomWell HPV16/31/33/35/52/58" and "recomWell HPVHRscreen" (for 16,18,31,33,35,39,45,51,52,56,58,59 E7), corresponding to different combinations of hrHPVE7-proteins. Among 1473 women with eligible samples, those positive for cytology (ASCUS+ 7.2%), and/or hrHPV DNA (19.1%) were referred for colposcopy. Cervical Intraepithelial Neoplasia grade 2 or worse (CIN2+) was detected in 27 women (1.8%). For HPV16/18-positive women with no triage, sensitivity, positive predictive value (PPV) and the number of colposcopies needed to detect one case of CIN2+ were 100.0%, 11.11% and 9.0 respectively. The respective values for E7-testing as a triage method to colposcopy ranged from 75.0-100.0%, 16.86-26.08% and 3.83-5.93. Sensitivity and PPV for cytology as triage for hrHPV(non16/18)-positive women were 45.45% and 27.77%; for E7 test the respective values ranged from 72.72-100.0% and 16.32-25.0%. Triage of HPV 16/18-positive women to colposcopy with the E7 test presents better performance than no triage, decreasing the number of colposcopies needed to detect one CIN2+. In addition, triage of hrHPV(non16/18)-positive women with E7 test presents better sensitivity and slightly worse PPV than cytology, a fact that advocates for a full molecular screening approach.

Cigarette Smoking Promotes Infection of Cervical Cells by High-Risk Human Papillomaviruses, but not Subsequent E7 Oncoprotein Expression

“…Demographic characteristics of the study population have been described previously [ 9 ]. Briefly, the current analysis was conducted on 1473 women aged 30–60 years old who were enrolled for the PIPAVIR project and for whom there was a valid result for hrHPV DNA genotyping and E7 protein detection.…”

“…The PIPAVIR project was a study conducted between August 2012 and August 2015, aiming at the development and initial clinical assessment of a novel ELISA hrHPVE7 oncoprotein detection method for cervical cancer screening. The study design has been described in detail previously [ 9 ]. Briefly, participants were non-pregnant women aged 30–60, without a history of cervical intraepithelial neoplasia (CIN), who visited the Family Planning Centre, Hippokratio Hospital of Thessaloniki, Greece and the Department of Gynecology and Obstetrics in Im Mare Klinikum, Kiel, Germany and gave their written informed consent to participate.…”

“…A sandwich ELISA method was developed during the PIPAVIR project to detect hrHPVE7 protein, as a result of a collaboration between the laboratories of Innsbruck University and Mikrogen GmbH, Neuried, Germany [ 9 ]. The detection strategy for hrHPVE7 was based on five different assays: “recomWell HPV 16/18/45 KJhigh”, “recomWell HPV 16/18/45 KJlow”, “recomWell HPV 39/51/56/59”, “recomWell HPV 16/31/33/35/52/58” and “recomWell HPV HR screen” (for 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 and 59 E7).…”

Cigarette Smoking Promotes Infection of Cervical Cells by High-Risk Human Papillomaviruses, but not Subsequent E7 Oncoprotein Expression

“…The study design has been described in detail previously [9]. Briefly, participants had been not pregnant women aged 30-60, without a history of cervical intraepithelial neoplasia (CIN), who visited the Family Planning Centre, Hippokratio Hospital of Thessaloniki, Greece and the Department of Gynecology and Obstetrics in Im Mare Klinikum, Kiel, Germany and gave their written informed consent to participate.…”

“…A sandwich ELISA method was developed during the PIPAVIR project to detect hrHPVE7 protein, as a result of a collaboration between the laboratories of Innsbruck University and Mikrogen GmbH, Neuried, Germany [9]. The detection strategy for hrHPVE7 was based on five different assays: "recomWell HPV 16/18/45 KJhigh", "recomWell HPV 16/18/45 KJlow", "recomWell HPV 39/51/56/59", "recomWell HPV 16/31/33/35/52/58" and "recomWell HPV HR screen" (for 16,18,31,33,35,39,45, 51, 52, 56, 58 and 59 E7).…”