HPV Vaccination Is Associated With Reducing Actinic Keratosis Burden

Original Article Title: Human Papillomavirus Vaccination and Actinic Keratosis Burden: The VAXAK Randomized Clinical Trial

Key takeaways of the article:

Actinic keratoses (AKs) are the most common precancerous skin lesions in fair-skinned populations, representing a significant public health burden due to their potential progression to squamous cell carcinoma and the substantial costs associated with their management. Recent evidence has suggested a possible association between human papillomavirus (HPV) and  the development of AKs and keratinocyte carcinomas, raising the intriguing possibility that HPV vaccination could offer therapeutic and preventive benefits for these lesions.

The VAXAK trial was a parallel-design, double-blind, randomized sham-controlled clinical trial conducted at Copenhagen University Hospital in Denmark. The study enrolled 70 immunocompetent adults with 15 or more clinical AK lesions in a defined test area. Participants were randomized 1:1 to receive either the 9-valent HPV vaccine (Gardasil 9) or sham vaccine (saline) administered at 0, 2, and 6 months. The primary outcome was the percentage reduction in baseline AKs assessed at 2, 6, 9, and 12 months.

The results demonstrated consistently greater reductions in AK count in the HPV-vaccinated group compared to the sham group throughout the study period. At month 2, the HPV group showed a 35% median reduction versus 25% in the sham group. By month 6, this difference widened to 47% versus 29%, and at month 12, the HPV group achieved a 58% reduction compared to 47% in the sham group. Additionally, participants receiving HPV vaccination had significantly lower total AK counts and fewer thick (grade II-III) lesions, noting that both groups received lesion-directed cryotherapy for thick AKs at months 6 and 9. Importantly, no significant differences in rates of new AK development or keratinocyte carcinoma incidence were observed during the 12-month follow-up.

In summary, this randomized clinical trial provides the first high-quality evidence that standard HPV vaccination can modestly reduce AK burden in immunocompetent individuals with multiple lesions. While the mechanism remains to be fully elucidated, these findings suggest that HPV-targeted vaccines may represent a potential adjunctive therapeutic approach for managing AKs, a chronic and relapsing condition. Further research with larger cohorts and longer follow-up periods is warranted to confirm these results and assess effects on keratinocyte carcinoma prevention.

Publication Date: April 26, 2026

Reference: Wenande E, Hastrup A, Wiegell S, et al. Human Papillomavirus Vaccination and Actinic Keratosis Burden: The VAXAK Randomized Clinical Trial. JAMA Dermatol. 2025;161(6):605-614. https://doi.org/10.1001/jamadermatol.2025.0531

Summary By: Adam Ali Hussain