Very common virus found to drive cancer growth by hijacking the body's cells

Most people carry skin loving strains of human papillomavirus (HPV) without any trouble, and for years, those strains were treated as bystanders in skin cancer.

New evidence shows that one of these viruses can directly help start and sustain a tumor when the immune system is hamstrung.

Cutaneous squamous cell carcinoma, a cancer that forms from the outer layer of the skin, is widespread and often undercounted in national registries.

One estimate pegs basal and squamous cell skin cancers at about 5.4 million diagnoses in the United States each year, which underscores how common this problem is for families and clinics alike.

HPV and cancer cells

Andrea Lisco, M.D., Ph.D., of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health (NIAID), worked with a cross institute team to study a 34-year-old woman with a recurring tumor on her forehead.

The group documented betapapillomavirus type 19 (beta-HPV) embedded in the tumor’s DNA.

They reported that restoring T-cell function with a donor stem cell transplant coincided with complete remission of her HPV related diseases in long-term follow up.

The tumor had resisted repeat surgeries and a course of immunotherapy, then it stopped returning after the transplant. That clinical turnaround lined up with the biology the team uncovered in the lab.

“This discovery could completely change how we think about the development, and consequently the treatment, of cutaneous squamous cell carcinoma (cSCC) in people who have a health condition that compromises immune function,” Lisco explained, describing why this case matters for patients whose immune systems are impaired, and for the clinicians who treat them.

Common virus, uncommon twist

The virus at the center of this case belongs to beta-HPV, a group of skin-dwelling, non-cancer strains usually considered part of the normal skin community. These viruses rarely cause disease in people with healthy immune systems.

The cancer itself is cSCC. It starts in keratinocytes, the cells that build the tough outer layer of skin.

Researchers detected integration of the viral genome into the tumor’s DNA, which is a hallmark seen in other virus linked cancers like those caused by alpha HPV types in the cervix and throat.

In this patient, the virus produced its own proteins inside tumor cells, a signal that the infection was not just a passenger.

T-cells, cancer, and HPV

The team traced the woman’s problem to her T-cells, white blood cells that recognize infected or abnormal cells and help coordinate clearing them.

Her T-cells could not properly activate against the skin virus, which allowed the infection to take hold and keep the tumor going.

Genetic testing showed a defect in ZAP70, a signaling protein that helps T-cells respond when their receptors bind a target.

ZAP70 deficiency is a rare combined immunodeficiency that disrupts T-cell development and signaling.

In laboratory tests, the woman’s cells could still repair ultraviolet light damage, the classic driver of cSCC. That finding pointed to the virus plus the immune defect as the key pairing in this case.

Transplant changed the picture

Doctors used an allogeneic hematopoietic stem cell transplant (HPSCT) to rebuild the patient’s immune system with healthy donor cells.

That approach can reconstitute T-cells that respond to infections and tumor antigens.

After transplant, the viral diseases cleared, and the stubborn skin cancer stopped recurring over the multi year follow up reported by the team.

The discovery also clarified the driving biology, because fixing the immune response removed the conditions that let virus powered growth persist.

“This discovery and successful outcome would not have been possible without the combined expertise of virologists, immunologists, oncologists and transplant specialists, all working under the same roof,” said Lisco.

The quote highlights a model where one campus allows many specialties to work together in real time.

What this means for care

For patients with aggressive cSCC and signs of immune dysfunction, clinicians may consider whether viral drivers are at play, especially when usual treatments fail.

It also raises the prospect of tests that look for viral reads in tumor tissue when the clinical puzzle points that way.

Monitoring remains important, since cSCC can recur or spread in a subset of cases, and most recurrences appear within three years after initial treatment, according to the National Cancer Institute’s evidence based skin cancer treatment (PDQ).

Close follow up can catch early regrowth and support timely management.

The case underscores a precision strategy, treating the underlying immune problem when it is present instead of only focusing on the tumor.

That lens can be relevant for selected patients who have repeat disease and a clear immune deficit.

HPV vaccine and cancer prevention

This case involves a beta strain, not the alpha strains that are the main targets of current HPV vaccines. Even so, the power of prevention is clear in population data.

Among screened U.S. women aged 20 to 24, cervical precancer incidence fell by roughly 79 percent from 2008 to 2022, consistent with the effect of vaccination programs, according to the CDC.

That success story shows how cutting off viral causes upstream can reduce cancer risk down the line.

Real world trends like those help explain why public health continues to push routine vaccination at ages 11 to 12. Reducing the pool of infections shifts future cancer burdens for communities.

What makes beta-HPV different

Alpha HPV viruses, which infect mucosal tissues, are well known for their ability to integrate into host DNA and drive cancers such as cervical and throat cancer.

Beta strains typically live on the skin as part of the normal flora and are usually harmless in healthy hosts.

In this patient, beta HPV19 acted differently because T-cell signaling was compromised. That combination created an opening for the virus to insert into the tumor genome and to express proteins that supported cell growth.

The observation challenges the assumption that beta HPV only assists ultraviolet damage. It suggests the virus can sometimes play a direct part when immune surveillance is weak.

Questions that remain

How often beta HPV behaves this way in immunocompromised patients is not yet known. Future work will need to test more tumors in similar clinical settings to gauge frequency.

Another open question is whether antiviral strategies or immune targeted therapies could help in cases where beta HPV helps sustain a tumor. Trials can clarify which patients benefit and how to balance risks and gains.

“It suggests that there may be more people out there with aggressive forms of cSCC who have an underlying immune defect and could benefit from treatments targeting the immune system,” said Lisco.

The study is published in The New England Journal of Medicine.

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