Human papillomavirus (HPV)-related lower genital cancers, including cervical cancer, anal squamous cell carcinoma (SCC), vaginal cancer, vulvar cancer, and penile cancer, pose a significant health burden, with approximately 45,000 new cases diagnosed annually. Current effective treatment modalities include chemoradiotherapy, systemic chemotherapy, and immune checkpoint inhibitors (ICIs). The tumor microenvironment in HPV-related cancers is characterized by immune evasion mechanisms, including the modulation of immune checkpoints such as PD-L1/PD-1. HPV oncoproteins E5, E6, and E7 play crucial roles in this process, altering the expression of immune inhibitory molecules and the recruitment of immune cells. ICIs, such as programmed cell death protein 1 (PD-1) inhibitors, have shown efficacy in enhancing the immune response against HPV-associated tumors by blocking proteins that allow cancer cells to evade immune surveillance. Recent studies have demonstrated that HPV-positive tumors exhibit a more favorable response to ICI-based therapies compared to HPV-negative tumors. The integration of ICIs into treatment regimens for HPV-related cancers has been supported by several clinical trials. The inclusion of ICIs in the treatment approach for HPV-related lower genital cancers presents a promising opportunity for improving patient outcomes. Ongoing research and clinical trials are advancing our understanding of the immune microenvironment and the therapeutic potential of immunotherapy for these cancers.

Although the COVID‐19 pandemic is now considered over, the virus remains prevalent, and regular, on‐time vaccination is recommended. Traditional and RNA‐based vaccines have proven lifesaving for millions worldwide; however, their long‐term efficacy remains unknown. The unmet need is to identify interventions that mitigate the severity of SARS‐CoV‐2 infection and associated health complications, including damage to multiple organs. Pro‐inflammatory cytokines, including tumor necrosis factor (TNF), play a crucial role in the pathogenesis of COVID‐19 and the progression to multiple organ failure. The present study describes the role of Mixed Lineage Kinase 3 (MLK3), a TNF downstream target and mitogen‐activated protein kinase upstream regulator, in SARS‐CoV‐2‐induced kidney injury. MLK3 activity was higher in SARS‐CoV‐2‐infected K18‐hACE2 mice and in human kidneys, and it positively correlated with kidney injury. MLK3 transcriptionally upregulated TMPRSS2 expression via the NFATc1, and genetic or pharmacological inhibition of MLK3 mitigated SARS‐CoV‐2 pseudovirus entry into kidney cells. SARS‐CoV‐2 spike glycoprotein receptor binding domain (Spike‐RBD) activated MLK3, thereby regulating IL‐17A. Heat shock protein 70 (Hsp70) interacts with MLK3 and regulates Spike‐RBD‐induced IL‐17A production and ultimately apoptosis in kidney cells. Our results suggest that MLK3 inhibitors could serve as a therapeutic intervention in COVID‐19 patients with acute kidney injury.