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.