HPV AND SQUAMOUS SKIN CANCER RISK

uly 9, 2010 — Human papillomaviruses (HPVs) have been associated with the development of skin cancer in organ-transplant recipients and those with epidermodysplasia verruciformis. Now, a new study provides evidence that HPV plays a role in the occurrence of cutaneous squamous cell carcinomas in the general population.

In a large population-based case–control study published online July 7 in BMJ, researchers found that a wide range of genus β HPV types were associated with a risk for squamous cell but not basal cell carcinoma. In addition, there was a trend toward a relation between squamous cell carcinoma risk and the number of genus β HPV types for which a person tested positive.

The authors note that the odds ratio (OR) for squamous cell carcinoma with HPV positivity was higher among individuals who had a history of prolonged glucocorticoid use (OR, 3.21; 95% confidence interval [CI], 1.22 - 8.44) than among those without a history of use (OR, 1.23; 95% CI, 0.97 - 1.55). Although this indicates that immunosuppression can enhance this risk, it did not reach statistical significance.

It has been hypothesized that HPV infection plays a role in the pathogenesis of nonmelanoma skin cancer, and papillomaviruses, particularly HPV types 5 and 8, were initially detected in nonmelanoma skin cancers of patients with epidermodysplasia verruciformis. In addition, the authors explain, clinic-based studies have shown a higher prevalence of antibodies to HPV in people with squamous cell carcinoma than in control subjects. These studies, however, lacked adequate statistical power.

"We sought to investigate the role of genus β human papillomaviruses on risk of nonmelanoma skin cancers in the general population," lead author Margaret R. Karagas, PhD, professor of community and family medicine at Dartmouth Medical School in Hanover, New Hampshire, told Medscape Medical News.

Positivity to HPV Raises the Risk

In this study, Dr. Karagas and colleagues were able to obtain information on the HPV status of 2366 cases and controls (663 people with squamous cell carcinoma, 898 people with basal cell carcinoma, 805 control subjects). All study participants were residents of New Hampshire and were between 25 and 74 years of age.

The authors found that men had a slightly higher proportion of antibodies positive for genus β HPV types than women, but the difference was not statistically significant (48% in men vs 42% in women; P = .11). However, no trends were observed in antibody prevalence when the cohort was analyzed by age, level of education, smoking status, skin sensitivity to the sun, or number of painful sunburns.

They observed that the OR for squamous cell carcinoma was elevated for each of the HPV types that were examined, but there was no correlation with basal cell carcinoma. They also found that positivity to at least 1 genus β HPV type was associated with an overall OR of 0.97 (95% CI, 0.80 - 1.19) for basal cell carcinoma and of 1.30 (95% CI, 1.04 - 1.61) for squamous cell carcinoma.

The authors note that they "found a clear increasing trend in risk of squamous cell carcinoma with increasing number of human papillomavirus types positive." The ORs were as follows:

* For 1 positive type, the OR was 0.99 (95% CI, 0.74 - 1.33)
* For 2 or 3 positive types, OR was 1.44 (95% CI, 1.03 - 2.01)
* For 4 to 8 positive types, OR was 1.51 (95% CI, 1.03 - 2.20)
* For more than 8 positive types, OR was 1.71 (95% CI, 1.12 - 2.62).

The ORs for squamous cell carcinoma were slightly higher in patients with histologic evidence of actinic keratoses (OR, 1.59; 95% CI,1.03 - 2.44) than in those without it. They also found that there was a stronger association between HPV and squamous cell carcinoma among patients with a sun-sensitive phenotype, although there was no association with a history of sunburns.

Dr. Karagas plans on continuing research in this area. "There are a wide range of cutaneous human papillomaviruses in addition to those in genus β," she said. "We would like to explore whether other cutaneous human papillomaviruses are associated with risk of nonmelanoma skin cancers."

The study was funded in part by grants from the US National Institutes of Health, the National Cancer Institute, and the European Community. The authors have disclosed no relevant financial relationships.

BMJ. 2010;341:c2986.