A Natural History of Actinic Keratosis and Cutaneous Squamous Cell Carcinoma Microbiomes
ABSTRACTCutaneous squamous cell carcinoma (SCC) is the second-most-common cancer in Australia. The majority of SCCs progress from premalignant actinic keratosis (AK) lesions that form on chronically sun-exposed skin. The role of skin microbiota in this progression is not well understood; therefore, we performed a longitudinal microbiome analysis of AKs and SCCs using a cohort of 13 SCC-prone immunocompetent men. The majority of variability in microbial profiles was attributable to subject, followed by time and lesion type.PropionibacteriumandMalasseziaorganisms were relatively more abundant in nonlesional photodamaged skin than in AKs and SCCs.Staphylococcuswas most commonly associated with lesional skin, in particular, sequences most closely related toStaphylococcus aureus. Of 11S. aureus-like operational taxonomic units (OTUs), six were significantly associated with SCC lesions across seven subjects, suggesting their specific involvement with AK-to-SCC progression. If a causative link exists between certainS. aureus-like OTUs and SCC etiology, therapeutic approaches specifically targeting these bacteria could be used to reduce SCC.IMPORTANCEActinic keratosis (AK) and cutaneous squamous cell carcinoma (SCC) are two of the most common dermatologic conditions in Western countries and cause substantial morbidity worldwide. The role of human papillomaviruses under these conditions has been well studied yet remains inconclusive. One PCR-based study has investigated bacteria in the etiology of these conditions; however, no study has investigated the microbiomes of AK and SCC more broadly. We longitudinally profiled the microbiomes of 112 AK lesions, profiled cross sections of 32 spontaneously arising SCC lesions, and compared these to matching nonlesional photodamaged control skin sites. We identified commonly occurring strains ofPropionibacteriumandMalasseziaat higher relative abundances on nonlesional skin than in AK and SCC lesions, and strains ofStaphylococcus aureuswere relatively more abundant in lesional than nonlesional skin. These findings may aid in the prevention of SCC.