Integrated analysis of virus and host transcriptomes in cervical cancer in Asian and Western populations

Race may influence vulnerability to HPV variants in viral infection and perisistence. Integrated analysis of the virus and host transcriptomes from different populations provides an unprecedented opportunity to understand these racial disparities in the prevalence of HPV and cervical cancers. We performed RNA-Seq analysis of 90 tumors and 39 adjacent normal tissues from cervical cancer patients at Zhejiang University (ZJU) in China, and conducted a comparative analysis with RNA-Seq data of 286 cervical cancers from TCGA. We found a modestly higher rate of HPV positives and HPV integrations in TCGA than in ZJU. In addition to LINC00393 and HSPB3 as new common integration hotspots in both cohorts, we found new hotspots such as SH2D3C and CASC8 in TCGA, and SCGB1A1 and ABCA1 in ZJU. We described the first, to our knowledge, virus-transcriptome-based classification of cervical cancer associated with clinical outcome. Particularly, patients with expressed E5 performed better than those without E5 expression. However, the constituents of these virus-transcriptome-based tumor subtypes differ dramatically between the two cohorts. We further characterized the immune infiltration landscapes between different HPV statuses and revealed significantly elevated levels of regulatory T cells and M0 macrophages in HPV positive tumors, which were associated with poor prognosis. These findings increase our understanding of the racial disparities in the prevalence of HPV and its associated cervical cancers between the two cohorts, and also have important implications in the classification of tumor subtypes, prognosis, and anti-cancer immunotherapy in cervical cancer.