Abstract Background : Integration of the high-risk Human Papilloma Virus (HPV) in the cell genome is considered to be a key event in the development of cervical cancer and as one of its most important risk factor. Detecting HPV integration may therefore provide a useful marker for the identification of high-grade lesions and lesions at risk of progression. Molecular combing associated to specific Genomic Morse Code (GMC) is a powerful and innovative approach that allow accurate detection and quantification of integrated HPV sequence into the host genome. Objectives : The aim of the EXPL-HPV-002 study is to evaluate the integration of 14 high-risk HPV as a biomarker of the severity and the progression of cervical lesions. Such a «triage biomarker» would help to reduce the number of unnecessary colposcopies, to avoid over-treatment of lesions that spontaneously regress and to better target the lesions requiring treatment. Methods : EXPL-HPV-002 is a prospective study conducted in 2 clinical sites in Czech republic. So far, 688 patients aged 25-65, referred to colposcopy after an abnormal Pap-smear, were enrolled in the study. Among them 60% were found HPV high-risk (HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68). The study is divided in 2 Phases : (I) a transversal phase using data collected at first visit (colposcopy images +/- histology, pap-smear for HPV genotyping and molecular combing) to study the association between HPV integration status versus colposcopy and histology grades. (II) a longitudinal phase using data collected in follow-up visits : cytology at 6, 18 and 30 months and colposcopy +/- histology at 12, 24 and 36 months. A pap-smear collected at 12, 24 and 36 months allows to perform genotyping and molecular combing. HPV integration status is analyzed in comparison with the evolution of lesions, viral clearance and HPV genotype. HPV genotyping and molecular combing are performed in central laboratories, histology data are reviewed by central reading. Conclusions : The transversal phase of the clinical study is achieved while the longitudinal phase data collection is still ongoing. Results of the diagnostic phase show that the HPV integration monitored by Genomic Vision’s technology is a reliable biomarker that can significantly differentiate normal subjects from women with a risk to develop precancerous lesions or cancer. Preliminary results on prognostic value of the test will be presented as well. Citation Format: Florence Mahé, Stéphanie Bouchilloux, Frederic Fer, Aaron Bensimon, Vladimir Dvorak, Pavel Ventruba, Ruth Tachezy, Simona Kubickova, Marketa Trnkova. Association between integration of high-risk HPV genomes, detected by molecular combing, and the severity and clinical outcome of cervical lesions [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-228.