Actinic Keratoses

TREATMENT​

Topical Therapies

Imiquimod plus 5-fluorouracil

• Nightly application of a thin layer of imiquimod and 5-FU (any order) until a brisk reaction occurred across at least 80% of applied area (average was 11 days).  At follow up (mean 7 months), all patients experienced at least 75% reduction in AKs (mean 90%). 38316257​​

Photodynamic Therapy (PDT)

Daylight PDT

• These are protocols designed to decreased side effects while maintaining efficacy and also improve convenience for the patient.  Instead of application of a sensitizing agent (usually ALA), a long incubation period, and then exposure to a red or blue light device, the sensitizing agent is applied and then exposed to ambient sunlight.  

• One protocol utilizing ALA demonstrated similar clearance rates between daylight PDT (95.5%) and conventional PDT (96.8%). 30336290  However, the protocol described included microneedling and also was confusingly written, possibly due to a language barrier (Chinese authors).  The protocol included:

  • Application of chemical sunscreen with SPF 30 (15min incubation)​

  • Gentle removal of scales, and crusts

  • Microneedling

  • Application of 10% ALA (30min incubation)

  • 2 hours of daylight exposure. 

HPV Vaccination​​

Human Papillomavirus Vaccination and Actinic Keratosis Burden: The VAXAK Randomized Clinical Trial. JAMA Dermatol. 2025. PMID: 40047786.

• Summary: This single-center, double-blind, randomized, sham-controlled trial (VAXAK) assigned 70 immunocompetent adults (median age ≈ 75 years) who had ≥15 actinic keratoses (AKs) in a 50- to 100-cm² test area to three intramuscular doses of the 9-valent human papillomavirus (HPV) vaccine or normal-saline sham at months 0, 2 and 6. The primary outcome—percentage reduction in baseline AK count—favored the HPV group at month 2 (median 35 % vs 25 %, P = .03) and month 6 (47 % vs 29 %, P = .01) and remained numerically higher through month 12 (58 % vs 47 %, P = .05), accompanied by fewer total and thick (grade II–III) AKs, but there was no difference in new-lesion formation or keratinocyte-carcinoma incidence during 12 months.  All participants received cryotherapy for thick AKs at months 6 and 9, and 76 % underwent additional field-directed therapies outside the test area, potentially diluting or enhancing effects.  Key limitations include small sample size, single geographic site, short follow-up, concurrent AK treatments, reliance on clinical lesion counts (prone to spontaneous regression and observer bias) and group imbalances in Fitzpatrick type and lesion location, which together temper generalizability and inflate uncertainty around cancer-prevention claims.

• Patient Summary: Doctors tested whether the regular HPV ‘cervical-cancer’ vaccine could shrink the number of sun-damage spots called actinic keratoses. Twelve months after three shots, people who got the vaccine had about one-third fewer spots, while those who got salt-water shots had about one-quarter fewer. That means the vaccine helped, but only a little, and it did not stop new spots or skin cancers from appearing during the first year. For now the HPV shot is an experimental add-on—you’d still need sunscreen and the usual creams, freezing or light treatments your dermatologist recommends.

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