28 December 2021

Cervical cancer remains a public health problem worldwide. Although we know that Human papillomaviruses (HPV) are the causative agent of the disease, there are still unknowns about how the virus induces carcinogenesis in women. Recent approaches have focused on studying the cervicovaginal microbiome and its association with HPV infections. However, profiling the microbiome to investigate the disease requires sequencing techniques that discriminate between microbial species, which current methods generally cannot achieve with high confidence. 

Hoping to improve microbiome profiling to fully understand HPV-induced cervical lesions, the group led by Willem Melchers, theme Women's cancers, and consisting of  Karolina Andralojc, theme Infectious diseases and global health and Mariano Molina from the Department of Medical Microbiology, in collaboration with William Leenders from the Department of Biochemistry, the CMBI, and the Departments of Pathology and Obstetrics and Gynecology, developed the method circular probe-based RNA sequencing (CiRNAseq). The results were published in the Journal BMC Biology on 16 December 2021.

They described the design and validation of probes that bind regions of interest in the ribosomal genes of more than 300 microbial species that are highly relevant for the cervicovaginal environment. They conducted in vitro experiments and demonstrated that CiRNAseq could perform DNA and RNA profiling and identify microbial communities and genera with high sensitivity. Lastly, they profiled a cohort of cervical smears that were either HPV negative without lesions or HPV positive with high-grade lesions and confirmed the well-described microbiome change that occurs upon HPV infection.

The cervicovaginal microbiome is associated with HPV infection, persistence, and carcinogenesis. This study demonstrates the potential of CiRNAseq for high-resolution microbiome profiling, which is essential to decipher the microbiome's role in women's cervical health and disease. They are currently analyzing the relationship between the microbiome and HPV in cross-sectional and longitudinal studies, aiming to elucidate viral carcinogenesis in women. 

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