Rare HPV-Driven Skin Cancer Linked to Immune Deficiency, Successfully treated with Stem Cell Transplant
Bethesda, MD – In a groundbreaking case study published today in The new England Journal of Medicine, researchers at the National Institutes of Health (NIH) have identified beta-HPV as the direct cause of an aggressive skin cancer in an immunocompromised woman, and demonstrated a successful treatment using a stem cell transplant. This revelation challenges conventional understanding of cutaneous squamous cell carcinoma (cSCC) and highlights the critical role of a functioning immune system in preventing cancer progress, even from typically benign viruses.
The Case: The patient, whose immune system was severely weakened, developed multiple cSCC lesions despite having limited exposure to UV radiation – the traditionally recognized primary driver of the disease. Detailed inquiry revealed a genetic defect impacting the ZAP70 protein, crucial for the proper function of her T cells, effectively preventing them from attacking the beta-HPV virus. while her immune system retained the ability to repair DNA damage from UV exposure, the compromised T cell function allowed the beta-HPV to infect skin cells and initiate cancerous growth. She was also concurrently being treated for other HPV-related conditions, including warts on her skin and within her mouth.
Beyond UV: The Role of Beta-HPV and Immune Function
For decades, UV radiation has been considered the primary culprit in the development of cSCC, the second most common type of skin cancer. However, this case demonstrates that in individuals with significantly weakened immune systems, certain viruses – specifically beta-HPV – can directly contribute to cancer formation. Beta-HPV is a common virus, typically harmless in people with healthy immune systems.
This finding doesn’t diminish the importance of sun protection, but expands the understanding of cSCC etiology. It suggests that a subset of cSCC cases, particularly those occurring in immunocompromised individuals, may require a different diagnostic and therapeutic approach.
Successful treatment and future Implications
Recognizing the underlying immune deficiency, the patient underwent a bone marrow stem cell transplant to replace her dysfunctional T cells with healthy ones. Following the transplant, the aggressive skin cancer resolved completely, and no recurrence was observed during a three-year follow-up period. Her other HPV-related illnesses also cleared up.
“This discovery and successful outcome would not have been possible without the combined expertise of virologists, immunologists, oncologists and transplant specialists,” stated Dr.Lisco, a researcher involved in the study.
The research underscores the growing need for personalized cancer treatments. Conventional, “one-size-fits-all” approaches may be less effective than therapies tailored to the specific underlying causes of a patient’s cancer. It’s plausible that other individuals with similar immune deficiencies and cSCC may exist, highlighting the importance of considering viral contributions in these cases.
Hopeful Trends in HPV-Related Cancer Prevention
This breakthrough arrives alongside encouraging progress in combating other HPV-related cancers. The widespread implementation of vaccination programs against alpha-HPV has led to a dramatic decline in deaths from cervical and throat cancers. while a worldwide cancer cure remains a distant goal, overall cancer survival and recovery rates continue to improve, including for cSCC.
“this discovery could completely change how we think about the development, and consequently the treatment, of cSCC in people who have a health condition that compromises immune function,” Dr. Lisco concluded.Key Takeaways:
beta-HPV as a Direct Cause: Researchers have definitively linked beta-HPV to cSCC development in an immunocompromised patient.
Immune System crucial: A functioning immune system, specifically T cells, is vital for controlling beta-HPV and preventing cancer.
Stem Cell Transplant Effective: A stem cell transplant successfully restored immune function and eradicated the cancer.
Personalized Medicine Needed: The case highlights the need for tailored cancer treatments based on individual patient factors.
Expanding Understanding of cSCC: This research broadens the understanding of cSCC beyond UV radiation as the sole cause.
Source: Ye et al., The New England Journal of Medicine*, 2025. https://doi.org/10.1056/NEJMoa2502114
