Genes, pathways and vulvar carcinoma - New insights from next-generation sequencing studies

In this review, we summarize the existing literature on next generation sequencing (NGS) studies in vulvar squamous cell carcinoma (VSCC). A total of 201 VSCC tumor samples were investigated in five studies published between 2017 and 2019. Findings on somatic mutations in human papillomavirus (HPV)-DNA positive (HPV+) and HPV-DNA negative (HPV-) disease were extracted and submitted to pathway and drug candidate analyses. The general genetic findings show cell cycle activity aberrations common to both HPV+ and HPV- VSCC. In silico analyses of somatic mutations detected in NGS studies pointed to PI3K-Akt pathway as the main pathway dysregulated in both HPV+ and HPV- VSCC tumors. In addition, pathways specific for HPV+ VSCC, i.e. AMPK, Prolactin, mTOR and Chemokine pathways as well as pathways unique for HPV- disease, i.e. GnRH, Neurotrophin, Oxytocin, Notch pathways were identified. These observations provide a rationale for incorporating novel specific therapeutic strategies in vulvar cancer. In this review, based on the Drug Gene Interaction database analysis of the NGS data, we listed potential drugs for this disease. The candidates revealed in our analysis provide new therapeutic opportunities in VSCC.