Metatranscriptome analysis in human papillomavirus negative cervical cancers

Human papillomavirus (HPV) negative cancers are associated with symptomatic detection, late-stage diagnosis, and worse prognosis. It is thus essential to investigate all possible infectious agents and biomarkers that could early identify these HPV negative cancers. We aimed to analyze and compare the metatranscriptome present in HPV positive and HPV negative cervical cancers. We analyzed the whole RNA sequencing files from 223 HPV negative cervical cancers (negativity established after confirming cervical cancer diagnosis, sample adequacy and subjecting specimens to PCR and unbiased RNA sequencing), 223 HPV positive tumors and 11 blank paraffin block pools (used as controls) using Kraken2 software. Overall, 84 bacterial genera were detected, with 6/84 genera showing a positive median number of reads/sample and being present in both cervical tumor groups (HPV positive and negative). Viral reads belonged to 63 different viral genera, with 6/63 genera showing a positive median annotated read/sample value. No significant difference among genera was detected except for the presence of alpha-papillomaviruses. Metatranscriptome of bacteria and viruses present in HPV positive and HPV negative cervical cancers show no significant difference, except for HPV. Further studies are needed to early identify this biologically distinct group of cervical cancers.