The number of keratinocyte skin cancers (KSC)is increasing with an ageing population and continuing recreational sun exposure but the annual figures of incident cancers registered in the UK are a great underestimate (75,000 per year) because of failure to register, particularly basal cell carcinomas (BCCs).
How many skin cancers occur in the UK each year? In Scotland total numbers of tumours are collected from national pathology feeds and in 2012 gave provisional numbers of 14,758 BCCs, 3802 cutaneous squamous cell carcinomas (cSCCs), and 1809 melanomas compared to registry numbers of 7775, 2948, 1176 respectively i.e ratios of total: incident tumours being 1.90, 1.29, and 1.54. This suggests that total skin cancer numbers in the UK are around 260,000 per annum or equal to all other cancers put together. This figure matches a previous pathology study in East of England.
How do we prevent them? Sun avoidance campaigns have been launched in many parts of the world following the lead of Australia, but have run into counter arguments about the role of UVR in vitamin D synthesis. Vitamin D levels may be a result rather than a cause of ill health and RCT evidence of benefit of vitamin D supplementation is currently lacking.
Who is at risk? In addition to the effect of ultraviolet radiation, many patients are at high risk because they have a genetic predisposition to skin cancer such as xeroderma pigmentosum or are globally immunosuppressed such as organ transplant populations.
How do we treat them? Targeted treatments have become available for melanoma (Vemurafenib, Ipilimumab, anti PD1/PD1L) and BCC (Vismedogib) and although surgical removal is effective for many cSCC ,there is a dearth of treatments for metastatic and aggressive disease especially in high risk patients.
What do we know about precancerous lesions? KSC commonly occur on a background of field carcinogenesis with multiple premalignant lesions. The occurence of cSCC following BRaf inhibition suggests that there are clones of mutated Ras and other genes as well as p53 mutant clones in sun- exposed skin
Is genomics going to give us the answer? KSC bear a very high mutational burden and although dysregulation of the Hedgehog pathway is sufficient for basal cell carcinogenesis NOTCH genes are the most highly mutated in squamous cell carcinogenesis. Activating Ras mutations occur in only 11% of cases. However the heavy mutation burden makes it difficult to identify driver mutations or pathways for targeted therapies.