New Insights Uncovered About Skin Cancer

Researchers at the National Institutes of Health have identified a new factor contributing to skin cancer, as outlined in a recent case report published in the New England Journal of Medicine.

The new suspect is a strain of human papillomavirus (HPV) typically found on the skin. While it was known to be associated with skin cancer, it wasn’t previously recognized as a direct cause.

Skin cancer arises from DNA damage in skin cells, primarily due to ultraviolet (UV) radiation from sunlight. HPV may exacerbate the build-up of UV-damaged DNA, leading to cancerous changes. However, in this particular case report, doctors observed that the virus itself could instigate the development of cancerous lesions.

The findings stem from a 34-year-old woman with a compromised immune system. Specialists indicated that it’s improbable for HPV to have a similar effect in individuals with a robust immune system.

Dr. Andrea Lisco, who is the head of the mucosal and cutaneous viral immunopathogenesis unit at the NIH and the patient’s physician, explained, “The virus acted in an uncontrolled manner, integrating itself into skin cells, which then became cancerous.”

This woman had 43 lesions of cutaneous squamous cell carcinoma — the second most common skin cancer type, following melanoma — on her face, hands, and legs. After surgical removal and immunotherapy, her cancer unfortunately recurred. When Lisco and her team examined new tumors, they discovered that they were driven by a group of HPVs known as beta HPV.

It turns out that around 90% of people carry some form of beta HPV, generally residing harmlessly on the skin without integrating into the DNA of skin cells.

As Lisco pointed out, “We come into contact with these viruses daily, but our immune systems usually keep us safe.”

There are different HPV strains, primarily alpha HPVs, associated with various cancers. These reside on mucous membranes, integrating into DNA and leading to cancers of the cervix, anus, and head and neck.

This patient had a genetic disorder that weakened her T-cells, which are crucial for immune defense. This deficiency allowed the beta HPV on her skin to behave more like alpha HPV, merging its DNA into her skin cells and resulting in cancer.

Dr. Anthony Oro, a dermatology professor at Stanford Medicine who wasn’t involved in the case, remarked, “It’s tough to directly apply the findings from one unique patient to the broader population.” However, he noted, “It suggests that in cases where T-cell function fails, beta HPVs might contribute to skin cancer and potentially other cancers too.”

The patient underwent a stem cell transplant, aiming to replace her defective T-cells with healthy ones to inhibit HPV replication.

Dr. Lisco stated, “This patient needed a brand-new immune system.” And it turned out to be successful; three years later, she has not had any recurrence of skin cancer.

Dr. Anthony Rossi, a dermatologist at Memorial Sloan Kettering Cancer Center who also wasn’t involved in this case, commented, “This offers valuable insights into how HPV interacts with the immune system.”

It’s been known for some time that beta HPVs can cause skin changes like warts. But this finding was unique — that a beta HPV could integrate into DNA and lead to cancer.

Other researchers had speculated about the implications based on studies using mice, but this new report confirms that such occurrences can happen in humans. The exact number of people at risk remains uncertain.

Dr. Oro cautioned, “This is just one individual with a rather unique immunological profile which allowed the beta HPV to proliferate.”

It’s important to mention that prior biopsies of squamous skin cancers have not shown HPV, indicating that not every case is caused by the virus. Dr. Lisco affirmed that the prevailing view — that HPV plays a passive role in skin cancer by aiding UV damage but does not actively promote cancer growth — still holds true for most individuals.

Preventive measures against UV exposure remain crucial, Lisco added, recommending sunscreen and protective clothing. He also stressed that immunocompromised individuals should be monitored more closely, as they can be up to 100 times more likely to develop squamous cell carcinoma.

The Gardasil HPV vaccine, which protects against multiple strains of alpha HPV, has been shown to reduce rates of cervical and head and neck cancers. However, its effectiveness against other strains like beta HPV is still unclear.

Rossi mentioned, “Even if this particular strain isn’t covered by the vaccine, there’s a theory about cross-reactivity among HPV strains.”

Most individuals will encounter HPV at some point in their lives, with scientists identifying roughly 200 different strains. So far, research has predominantly focused on alpha HPV due to its established cancer links.

Dr. Oro concluded, “This suggests that other types of HPV could also play a significant role, especially when the immune system isn’t functioning properly.”