HPV Infection Implicated in Nonmelanoma Skin Cancers

A new study finds cutaneous human papillomavirus (HPV) infection can increase the risk of squamous-cell carcinoma, a nonmelanoma skin cancer. Published in the Journal of Infectious Diseases, the research shows those with a poor tanning ability who sunburn due to sunlight exposure were more likely to have the beta HPV subtype. Among those subjects who were positive for antibodies to cutaneous HPV types alpha and beta, poor or no tanning ability was strongly associated with squamous-cell carcinoma compared to individuals who were negative for these HPV types.

Image shows an individual's nose with squamous-cell carcinoma. Tends to arise from premalignant lesions, actinic keratoses; surface is usually scaly and often ulcerates (as shown here).

“[We] chose to investigate HPV as a risk factor for squamous-cell carcinoma because previous studies had reported finding viral sequences in tumors,” said Dana E. Rollison, PhD, of the department of cancer epidemiology at the H. Lee Moffitt Cancer Center in Tampa, Florida, and lead author of the study. “[There have been] very few large-scale epidemiologic studies that included biomarkers of infection in normal tissues with viral DNA measurements from tumors.”

“Squamous-cell carcinoma cases have higher levels of cutaneous HPV antibodies compared to controls without squamous-cell carcinoma, and DNA from the same types of HPV for which squamous-cell carcinoma cases have antibodies is present in the tumor tissues themselves,” Rollison added.

More than one million cases of nonmelanoma skin cancer-squamous-cell carcinoma and basal-cell carcinoma-are diagnosed in the United States every year, making it the most common cancer. Risk factors include fair hair and skin tone, light eye color, older age, and male sex. Ultraviolet radiation is likely the most common environmental risk factor for both skin cancer types.

The researchers analyzed 204 individuals with basal-cell carcinoma, 156 with squamous-cell carcinoma, and 297 healthy volunteers who had no history of any cancer and were negative for skin cancer following a thorough skin examination. All individuals completed a questionnaire on constitutional and demographic characteristics as well as history of sun exposure. Every individual was tested for the presence of cutaneous HPV antibody in his or her blood sample.

“We report a synergistic effect between tanning ability and cutaneous HPV seroreactivity in that those with poor tanning ability had a greater risk of squamous-cell carcinoma if they were seropositive to cutaneous HPV, compared to those with poor tanning ability who were seronegative,” said Rollison.

Study Results

The study found statistically significant differences in HPV serotypes present among those with skin cancer: HPV alpha and basal-cell carcinoma (P = .01), HPV beta and squamous-cell carcinoma (P = .01), and HPV gamma and both basal-cell carcinoma (P = .0002) and squamous-cell carcinoma (P = .03). Those individuals with squamous-cell carcinoma but not basal-cell carcinoma had higher cumulative sunlight exposure. Both squamous-cell carcinoma and basal-cell carcinoma subjects had sensitivity to sunlight exposure that resulted in sunburn, poor ability to tan, and a history of sunburn associated with blistering.

A poor ability to tan was associated with a higher risk of squamous-cell carcinoma among those who tested positive for the alpha HPV type. A modest risk of squamous-cell carcinoma was seen in those who were negative for the alpha HPV subtype.

The researchers hypothesize that exposure to ultraviolet radiation may interact with cutanous HPV in a synergistic manner to spur nonmelanoma skin cancer development. Ultraviolet radiation is able to locally suppress immune function within the skin, but a full detailed mechanism of how the two pathways are associated with the two skin cancers is still not clear. A possibility is the facilitation of a microenvironment in the skin by ultraviolet radiation that allows cutaneous HPV to replicate. The continuous HPV infection may then promote tumor progression by interfering with the cellular response to UV-induced DNA damage.

Further studies, including larger study cohorts, and identification of how cutaneous HPV infections play a role in sunlight-exposure nonmelanoma skin cancer, are still necessary in order to better characterize higher-risk individuals and develop better prevention strategies, conclude the authors.

“We are seeking to conduct a prospective cohort study in order to investigate the development of skin cancers after documented infection with cutaneous HPV,” said Rollison.