New Insights into HPV-Linked Cancers: Targeting Immune Cells to Boost Treatment Effectiveness

New research from the Keck School of Medicine of USC has shed light on the mechanisms behind human papillomavirus (HPV)-linked cancers, specifically the role of a signaling protein, Interleukin-23 (IL-23), in undermining the body's defenses. The study found that blocking IL-23 boosts the effectiveness of experimental treatments for HPV-linked cancers in mice.

Researchers used a combination of cell cultures, mouse studies, and genomic analyses to uncover IL-23's role in cancers caused by HPV16. They discovered that HPV's E6 and E7 proteins prompt nearby cells to release IL-23, preventing the body's T-cells from attacking the tumor. Blocking IL-23 with antibodies already FDA-approved for treating psoriasis and other conditions significantly increased the effectiveness of a therapeutic vaccine, allowing T-cells to find and kill cancer cells.

Key Takeaways:

• The most common cancer-causing strain of HPV, HPV16, undermines the body's defenses by reprogramming immune cells surrounding the tumor.
• Blocking Interleukin-23 (IL-23) with antibodies significantly increased the effectiveness of a therapeutic vaccine in mice, allowing T-cells to find and kill cancer cells.
• HPV16 causes more than half of cervical cancer cases and roughly 90% of HPV-linked throat cancers.
• Researchers are developing "therapeutic vaccines," which can be taken after HPV exposure to trigger an immune response against infected cells.
• The study offers insight into why therapeutic vaccines for HPV have had limited success and identifies a potential strategy to improve their effectiveness.
• Combining experimental vaccines with IL-23 neutralizing antibodies could significantly increase their effectiveness.

Statistics:

• HPV16 causes more than half of cervical cancer cases.
• Roughly 90% of HPV-linked throat cancers are caused by HPV16.
• IL-23 neutralizing antibodies are already FDA-approved for treating psoriasis and other conditions.
• The study's findings may have implications for cancers not related to HPV, such as testicular and bladder cancers, where IL-23 is also found at high levels.

Sources:

• W. Martin Kast, PhD, Professor of Molecular Microbiology & Immunology, Obstetrics & Gynecology, and Otolaryngology, Keck School of Medicine of USC, and Walter A. Richter Cancer Research Chair (2025)
• National Institutes of Health (funding source)
• Journal for ImmunoTherapy of Cancer (publication of the study)
• FDA-approved IL-23 neutralizing antibodies for treating psoriasis and other conditions