Introduction: Virus infection is a risk factor for most cancers, including cervical squamous carcinoma (CESC). The molecular features of human papillomavirus (HPV)-positive CESC can be used as biomarkers in risk assessment, prognosis, and choosing therapy options. Aim: This study aimed to evaluate the effect of HPV on gene expression in CESC. Material and Methods: Cancer and HPV-associated differentially expressed genes (DEGs) in CESC with |log2FC| ≥ 0.5 and p-value < 0.001 were retrieved from the public OncoDB database. Enrichr database was used for the functional evaluation of genes. Results: 628 (615 upregulated and 13 downregulated) genes showed differential expression between HPV-positive and HPV-negative CESC. 325 HPV-associated upregulated genes were among the CESC-related upregulated ones with enriched pathways such as DNA replication and cell cycle. 10 downregulated genes were common in HPV and CESC-associated DEGs. HPV infection reversed the expression of 51 CESC-associated downregulated genes which enriched in some pathways like necroptosis and JAK-STAT signaling. We found three downregulated genes (i.e., TEX264, DNAJC30, and MRPS17) that were especially associated with HPV-positive CESC. Moreover, 239 upregulated HPV-associated DEGs were not among the CESC-associated DEGs. Discussion: 4.8% of CESC-associated DEGs were modified by HPV infection of which 4.6% was upregulated and contributed to cancer through pathways such as DNA replication, DNA repair, cellular senescence, apoptosis, cell cycle, TNF signaling, and JAK-STAT signaling pathway. 13 downregulated genes in HPV-positive CESC can be applied to the development of targeted therapy for HPV-positive patients. Overall, gene expression profiling disturbance is an underlying cancer-promoting mechanism of HPV.
