Imagine your skin as a bustling city. Each cell is a hardworking citizen, repairing sun damage and keeping the peace. But lurking in the shadows is a virus long thought to be a harmless drifter: beta-HPV (human papillomavirus).
For years, we've known UV rays were the main villain behind a common skin cancer called cutaneous squamous cell carcinoma (cSCC). Beta-HPV? Just a sidekick, helping those UV rays pile up DNA damage.
But now, researchers at the National Institutes of Health (NIH) have uncovered a shocking twist: Beta-HPV can be the mastermind, directly causing cSCC when the immune cells malfunction.
This changes everything when considering how we can treat these cancers. If beta-HPV can drive cancer on its own in people with weak immune systems, doctors might need new ways to treat or prevent cSCC, like targeting the virus itself or boosting immune defenses.
Since cSCC is one of the most common cancers worldwide, this discovery could help protect millions, especially those with immune-related conditions.
Detailing exactly how scientists made this new discovery, the study chronicles the case of a 34-year-old woman who arrived at the NIH Clinical Center with a stubborn skin tumor on her forehead. The tumor kept coming back, even after surgeries and immunotherapy. Her doctors suspected a rare genetic disorder that made her vulnerable to UV damage and weakened her immune system's T cells.
But then the NIH researchers conducted a sophisticated genetic analysis. What they found was unexpected: A beta-HPV virus had snuck into her skin cells' DNA. It wasn't just hanging out; it was actively producing viral proteins, helping the cancer grow, even though her cells could repair UV damage just fine.
Turns out, her immune system couldn't activate its T cells to fight off the virus. That's why beta-HPV was able to multiply unchecked and cause multiple HPV-related diseases.
Researchers then crafted a personalized stem cell transplant to swap out her faulty T cells for healthy ones. But this wasn't easy; she was already immunocompromised, so the procedure had to be handled with extreme care.
"Thankfully, the transplant went smoothly," explained Andrea Lisco, from the NIH's National Institute of Allergy and Infectious Diseases. "Afterward, all her HPV-related diseases, including the recurrent, aggressive cSCC, resolved and have not recurred during the more than three years since the transplant. The finding suggests that other people with defective T-cell responses may also be susceptible to cancer caused directly by beta-HPV."
The study was published in The New England Journal of Medicine.
Source: National Institutes of Health
