Gardasil 9 (HPV vaccine) for actinic keratoses — the off-label evidence

If you have actinic keratoses — rough, scaly patches caused by years of sun damage — or a history of multiple non-melanoma skin cancers, you will know the frustration of the “treatment cycle.” Even with advanced options like laser-assisted photodynamic therapy, some patients keep developing difficult-to-control precancerous changes.

Researchers are studying the HPV vaccine (Gardasil 9) — originally designed to prevent human papillomavirus infection — as a tool to help reduce actinic keratoses. The evidence requires careful interpretation, so this page sticks closely to what the trial actually showed.

What is Gardasil 9?

Gardasil 9 protects against nine strains of the human papillomavirus (HPV). It is well established and has a strong safety record, and in Australia it is routinely given to adolescents through the National Immunisation Program for HPV-related cancers.

Why might an HPV vaccine help with sun damage?

Certain cutaneous (skin) HPV strains are frequently found in actinic keratoses and squamous cell carcinomas. The hypothesis is that these strains may contribute — alongside UV radiation — to the development of these lesions, and that vaccinating may help the immune system recognise and clear abnormal or HPV-affected skin cells. This remains a hypothesis under investigation, not established mechanism.

The evidence: the VAXAK randomised trial

The most rigorous evidence is the VAXAK randomised clinical trial, published in JAMA Dermatology in 2025. It was a double-blind, sham-controlled trial in immunocompetent adults with multiple actinic keratoses. ⁽¹⁾

• Lesion reduction: the vaccinated group had a median 58% reduction in AK lesions at 12 months, versus 47% in the sham group (P = 0.05). The difference was statistically significant earlier, at 6 months (47% vs 29%; P = 0.01). ⁽¹⁾
• A high sham response: the sham group also improved substantially — because trial participants receive attentive care and AKs fluctuate naturally — so the extra benefit attributable to the vaccine was modest. ⁽¹⁾
• No cancer reduction shown: the trial did not demonstrate any reduction in actual squamous or basal cell carcinoma during the 12-month period. ⁽¹⁾
• Short follow-up: one year is a short window for skin-cancer outcomes, so a longer-term effect can neither be confirmed nor excluded on current data. ⁽¹⁾

Who might consider it?

For most people with standard sun damage, field therapy and sun protection remain the priority. The vaccine may be discussed in a specific subset — patients with difficult-to-control actinic keratoses or a high frequency of squamous cell carcinomas — where an additional, modest reduction in lesion burden may be worthwhile. It is an individual decision based on your history.

What “off label” means

Using Gardasil 9 for actinic keratoses or skin cancer prevention is off label. The Therapeutic Goods Administration (TGA) has approved it for specific HPV-related cancers, not for skin cancer. Off-label prescribing is a recognised part of medicine when supported by emerging evidence such as VAXAK — it involves an informed-consent discussion weighing the evidence together.

Risks, cost and limitations

• Side effects: generally mild and short-lived — injection-site soreness, mild fever or headache.
• Uncertain benefit: many patients improve regardless of the vaccine, and it did not stop new lesions entirely.
• Cost: because this use is off label, it is not covered by the PBS — the full three-dose course is an out-of-pocket expense.
• Not a replacement: it is supplementary. Strict sun protection and regular skin checks remain essential.

Discuss your options