ACTINIC keratosis (AK) is a prevalent skin condition that poses significant health and economic challenges due to its potential to progress to keratinocyte carcinoma (KC). Recent research suggests that human papillomavirus (HPV) vaccination may have a therapeutic role in reducing AK burden. The VAXAK trial, a double-blind, randomised, sham-controlled clinical study, investigated this potential benefit in immunocompetent adults with multiple AK lesions. Conducted at Bispebjerg University Hospital in Copenhagen between May 2021 and June 2024, the trial enrolled 70 participants with at least 15 AK lesions in a defined test area.
Participants were randomly assigned to receive either the 9-valent HPV vaccine or a sham vaccine (isotonic sodium chloride solution) at 0, 2, and 6 months. Thick AK lesions were treated with cryotherapy at months 6 and 9, but no other interventions were administered. The study’s primary objective was to assess the percentage reduction in AK lesions from baseline at multiple time points over 12 months. Secondary measures included total AK count, number of thick lesions, new AK development, and KC incidence.
Findings revealed that HPV vaccination consistently resulted in greater reductions in AK burden than the sham vaccine. At month 2, median lesion reduction was 35% in the HPV group compared to 25% in the sham group, a statistically significant difference. By month 6, reductions reached 47% versus 29%, with significant differences continuing through months 9 and 12. Total AK counts remained lower in the vaccinated group throughout the study, with fewer thick lesions observed. However, no notable differences in new AK development or KC incidence were identified between the two groups.
These results suggest that standard HPV vaccination may offer a novel approach to AK management, particularly for individuals with a high disease burden. As AK is a chronic and relapsing condition, HPV-targeted immunisation could serve as an additional tool in reducing lesion count and potentially slowing disease progression. Further research is needed to explore the long-term benefits and potential mechanisms underlying this effect, but these findings provide promising evidence for the role of HPV vaccination in dermatological care.
Reference
Wenande E et al. Human papillomavirus vaccination and actinic keratosis burden: the VAXAK randomized clinical trial. JAMA Dermatol. 2025;DOI:10.1001/jamadermatol.2025.0531.
