High-risk human papillomavirus (HR-HPV) are involved in cervical cancer development. Integration of HR-HPV DNA in cellular genomes is considered as a major event in cervical cancer development. Several techniques have been used to evaluate viral integration but most of them give an imperfect reflect of HPV physical status. Molecular Combing is a powerful innovative technology which allows direct and high-resolution visualization of HR-HPV genome integration pattern.
The aim of the IDAHO study is to evaluate the integration of 5 HR-HPV (16/18/31/33/45) by Molecular Combing as a biomarker of the severity and/or of the progression of cervical lesions.
The IDAHO prospective multicentric study will enroll 3,500 women aged 25-65 in 8 French University Hospitals, referred to colposcopy after an abnormal Pap smear. The first patient has been included in December 2015. The study will be divided into two phases: (1) transversal phase; at first visit, a colposcopy +/- biopsy will be performed, as well as a Pap smear for HPV genotyping and Molecular Combing; HPV integration status will be associated to colposcopy results and histological grades; (2) longitudinal phase; women with HPV positive and low-grade histological lesions will be followed-up by cytology at 6, 18 and 30 months, and by colposcopy +/- histology at 12, 24 and 36 months. A Pap smear taken at 12, 24 and 36 months will allow to perform HPV genotyping and Molecular Combing. HPV integration status will be associated to the evolution of the lesion / infection. HPV genotyping (Innolipa) and Molecular Combing will be performed in central labs. All histological data will be reviewed by a central reading.
The IDAHO study will evaluate the diagnostic and prognostic values of HR-HPV integration status detected by Molecular Combing and could lead to identify a biomarker that can specifically differentiate between women with a high risk of developing cervical precancerous lesions or cancer and who therefore require treatment, from women with a low risk who require appropriate monitoring. Molecular Combing technology will be presented, as well as the detailed design of the IDAHO study.