Integrated Analysis of Virus and Host Transcriptomes in Cervical Cancer in Asian and Western Populations

Abstract Background: Race may influence vulnerability to HPV and have an effect on cervical cancer survival independent of socioeconomic status. Integration of the virus and host transcriptomes from different populations provides an unprecedented opportunity to understand these racial disparities in the prevalence of HPV and its associated cervical cancers in addition to fundamentally advancing the knowledge of HPV-induced cervical carcinogenesis and progression. Methods: 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. Results: We found a significantly 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 populations, 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 that is highly predictive of 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 populations. 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. Conclusions: These findings increase our understanding of the racial disparities in the prevalence of HPV and its associated cervical cancers between Asian and Western populations, and also have important implications in the classification of tumor subtypes, prognosis, and anti-canc