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Summary Background Actinic keratoses (AK) frequently occur on sun-exposed skin and are considered as in situ squamous cell carcinoma. To date, no treatment algorithm exists for first or second line therapies due to the lack of comparative studies. Objective This study compared the initial and 12-month clinical clearance, histological clearance, and cosmetic outcomes of topically applied 5% imiquimod (IMIQ) cream, 5% 5-fluorouracil (5-FU) ointment and cryosurgery for the treatment of AK. Patients/methods Patients were randomised to one of the following three treatment groups: one or two courses of cryosurgery (20–40 s per lesion), topical 5-FU (twice daily for 4 weeks), or one or two courses of topical imquimod (three times per week for 4 weeks each). Results Sixty-eight per cent (17/25) of patients treated with cryosurgery, 96% (23/24) of patients treated with 5-FU, and 85% (22/26) of patients treated with IMIQ achieved initial clinical clearance, p = 0·03. The histological clearance rate for cryosurgery was 32% (8/25), 67% (16/24) for 5-FU, and 73% (19/26) in the IMIQ group, p = 0·03. The 12-month follow-up showed a high rate of recurrent and new lesions in the 5-FU and cryosurgery arms. The sustained clearance rate of initially cleared individual lesions was 28% (7/25) for cryosurgery, 54% (13/24) for 5-FU and 73% (19/26) for IMIQ (p

Summary Background Ultraviolet radiation induces DNA damage and is the major risk factor for the development of non-melanoma skin cancer (NMSC). Different mutation rates of p53, p16INK4a and Ha-ras in cutaneous squamous cell carcinoma (SCC) and the earlier stage actinic keratosis (AK) have been reported. Objectives To assess the presence of missense mutations in hotspot exons of p53, p16INK4a and Ha-ras in low-graded AK. Patients/methods Cryo-biopsies of 75 sun-exposed AK lesions and 75 sun-shielded areas of normal skin from 75 AK patients were analysed to identify mutations in p53 (exons 7 and 8), p16INK4a (exon 2) and Ha-ras (exon 1) using polymerase chain reaction (PCR) followed by direct sequencing. As a representative subset of the specimens, ten mutation-negative AK were also micro-dissected in order to exclude the possibility that additional mutations were undetected. Results Eight missense and one nonsense point mutations were found in the 75 AK lesions examined (12%), of which seven (9%) were tumour-specific (i.e. present in AK lesions only) and two (3%) were p16INK4a mutations (i.e. also detected in normal skin). Three of the tumour-specific mutations (42%) were cytosine (C) to thymine (T) transitions at pyrimidine-rich sequences. Tumour-specific mutations were identified in 1% of p16INK4a (exon 2), 1% of Ha-ras (exon 1) and at a higher rate of 7% in p53 (exons 7 and 8), including one nonsense mutation. Conclusions The evaluation of a large number of AK specimens in this study have found a low gene mutation rate in low-graded AK lesions. p53 mutations rather than p16INK4a and/or Ha-ras mutations may be an early event in the development of AK to cutaneous SCC.