Cutaneous HPV May Be a Predictor of Cutaneous Squamous Cell Carcinoma Risk

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In an article published by Rollison et al in Cancer Research, researchers demonstrated a link between the presence of cutaneous human papillomavirus (HPV) and the incidence of cutaneous squamous cell carcinomas. They also identified key characteristics of infection that may contribute to development of the disease.

Keratinocyte carcinomas, including basal cell and squamous cell carcinomas, are the most common types of cancer in the United States, with approximately 5.4 million cases diagnosed each year. Despite their low mortality rate, keratinocyte carcinomas are associated with significant medical problems caused by treatment and health-care costs. Therefore, new biomarkers are needed to aid in identifying patients at risk of developing keratinocyte carcinomas.

The identification of biomarkers that are associated with the development of keratinocyte carcinomas is an important component of disease management. This can pinpoint patients who may be at a higher risk of cancer and help promote individualized prevention strategies, such as more frequent or specialized skin cancer screenings. Previous studies have suggested that infections with cutaneous HPV may also be associated with keratinocyte carcinoma development; however, these studies had several limitations and were not conclusive.

“Unlike mucosal HPV types known to cause cervical, head and neck, and anogenital cancers, the role of cutaneous HPV types in the development of cancer is less clear,” said Dana Rollison, PhD, lead study investigator and Associate Center Director of Data Science at Moffitt Cancer Center. 

Unlike mucosal HPV types known to cause cervical, head and neck, and anogenital cancers, the role of cutaneous HPV types in the development of cancer is less clear.
— Dana Rollison, PhD

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Study Details and Findings

Researchers wanted to analyze the potential contribution of cutaneous HPV to keratinocyte carcinoma development. They looked at biomarkers of past and recent infection with cutaneous HPV beta and gamma types, as well as recent ultraviolet (UV) light exposure.

The researchers recruited 1,008 participants aged 60 years or older. The participants had blood, eyebrow hair, and forearm skin swabs taken and analyzed for the presence of cutaneous HPV. The patients underwent total body skin examinations every 6 to 12 months and were monitored for a median of 792 days for the development of new basal cell and squamous cell carcinomas.

The results showed that the presence of beta HPV at baseline, particularly in the skin swabs, significantly predicted the development of squamous cell carcinomas. However, the presence of antibodies to beta HPV, which indicates past HPV infections, was not associated with squamous cell carcinomas.

Interestingly, the researchers found that most of the beta HPV types found in the skin swabs were not present in the squamous cell carcinoma tumors that eventually developed. Additionally, they discovered that less than 5% of squamous cell carcinoma tumors contained beta HPV types, but those that contained beta HPV occurred more frequently in areas of UV skin damage compared to squamous cell carcinoma tumors without beta HPV, suggesting that UV exposure and HPV may act in a cooperative manner to promote squamous cell carcinoma development. The researchers did not find any links between beta HPV and the development of basal cell carcinomas or between gamma HPV and the development of squamous cell or basal cell carcinomas.

These combined observations suggest that beta HPV could ultimately prove to be a useful biomarker to help identify people at an increased risk of developing cutaneous squamous cell carcinomas.

Disclosure: This study was supported by the National Cancer Institute. For full disclosures of the study authors, visit

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