In the United States, 1 in 5 Americans develop keratinocyte carcinoma (KC) by age 70, placing the disease among the five most expensive cancers based on Medicare expenditure. Current preventative measures have failed to stem rising KC rates, highlighting the need for alternative strategies. Evolving evidence indicates that lasers conventionally used to treat photoaging, may provide protective effects against the development of KC and precursor lesion, actinic keratosis (AK). This review first delves into existing evidence on fractional infrared laser-based KC and AK prevention. Next, the work discusses potential underlying mechanisms that might explain fractional infrared lasers' prophylactic effects. A comprehensive literature search of PubMed and Web of Science databases was conducted from inception to April 2024 using preselected search terms. Interventional human and animal studies, epidemiological analyses, and case reports on fractional infrared laser-based prevention of KC or AK were screened according to predefined inclusion/exclusion criteria. Included evidence demonstrates that ablative fractional lasers reduce and delay development of AK/KC, shown in two controlled trials of photodamaged patients and two murine studies (i.e. Er: YSGG and CO2 lasers). Weaker evidence of KC prevention by nonablative infrared lasers is provided by a retrospective cohort study. In the laser literature, three mechanisms are proposed to drive these prophylactic effects, including the ability of infrared lasers to (i) remove DNA-damaged epidermal cells, (ii) activate the insulin-like growth factor-1 pathway by reducing fibroblast senescence, and (iii) initiate immunomodulating effects. Based on current evidence, infrared fractional lasers show promise particularly for secondary KC prevention in photodamaged populations.
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