HPVTIMER: A shiny web application for tumor immune estimation in human papillomavirus-associated cancers

The tumor immune microenvironment (TIME) is closely associated with tumor formation, particularly linked to the human papillomavirus (HPV), and regulates tumor initiation, proliferation, infiltration, and metastasis. With the rise of immunotherapy, an increasing amount of sample data used for TIME exploration is available in databases. However, no currently available web tool enables a comprehensive exploration of the TIME of HPV-associated cancers by leveraging these data. We have developed a web tool called HPV-associated Tumor Immune MicroEnvironment ExploreR (HPVTIMER), which provides a comprehensive analysis platform that integrates over 10,000 genes and 2290 tumor samples from 65 transcriptome data sets across 8 cancer types sourced from the Gene Expression Omnibus (GEO) database. The tool features four built-in analysis modules, namely, the differential expression analysis module, correlation analysis module, immune infiltration analysis module, and pathway analysis module. These modules enable users to perform systematic and vertical analyses. We used several analytical modules in HPVTIMER to briefly explore the role of CDKN2A in head and neck squamous cell carcinomas. We expect that HPVTIMER will help users explore the immune microenvironment of HPV-associated cancers and uncover potential immune regulatory mechanisms and immunotherapeutic targets. HPVTIMER is available at . HPV-associated Tumor Immune MicroEnvironment ExploreR (HPVTIMER) integrates transcriptomic data from the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database for HPV-associated cancers to allow users to perform various analyses, including differential expression analysis, correlation analysis, pathway analysis, and immune infiltration analysis based on HPV infection status.Highlightsimage HPVTIMER provides multiple analysis modules for exploring differences between HPV-positive and HPV-negative samples, based on transcriptome data, such as differential expression analysis, correlation analysis, immune infiltration analysis, and pathway enrichment analysis.The immune infiltration analysis module provides users with seven specific algorithms, including CIBERSORT, CIBERSORT absolute mode, MCP-counter (or mMCP-counter for mice), EPIC, xCell, quanTIseq, and TIMER.HPVTIMER provides users with meta-analysis, which can be used to explore correlations between gene expression/pathway single-sample gene set enrichment analysis (ssGSEA) scores/immune infiltration scores and differences in immune infiltration scores between HPV-positive/negative samples.