Aims: Keratinocyte carcinoma (KC), which comprises basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and actinic keratosis (AK; precursor of SCC); is the most common cancer diagnosed in Australia and worldwide. Given the rising incidence of KC and associated morbidity and mortality, additional preventative strategies are necessary. Chemoprevention uses pharmaceuticals to inhibit cancer initiation, promotion, and progression. Whilst conventional prevention aims to minimise ultraviolet radiation exposure and promotes sunscreen use, chemoprevention with novel agents such as 5-fluorouracil (5-FU), nicotinamide, imiquimod and cyclooxygenase-2 (COX-2) inhibitors is evolving.
Methods: Three databases were searched (Medline, Embase, Cochrane Central) to retrieve randomised controlled trials. Papers were de-duplicated and a blinded, two-phase screening process utilised by two independent reviewers as per the Cochrane Handbook. Eligibility criteria included general adult populations ≥18 years, oral or topical pharmaceuticals, an appropriate control, and KC outcome. High-risk populations with prior skin cancers were excluded.
Results: A total of 3,444 unique studies were identified, 80 full texts screened, and 11 papers included in the final analysis. Five studies demonstrated statistically significant reductions in SCCs and AKs using sunscreens, but not for BCCs. Nicotinamide reportedly reduces AKs. Use of 5-FU results in fewer superficial BCCs (though imiquimod may be superior), particularly for participants aged ≥85 years. Furthermore, COX-2 inhibitors are shown to offer chemoprevention against both BCCs and SCCs.
Conclusions: Despite the established effectiveness of sunscreen for prevention, oral and topical pharmaceuticals will likely offer additional benefits in reducing the incidence of KC. Further research into these novel agents is warranted.