Skin Microbiome Variation: Indicator or Risk Factor for Squamous Cell Carcinoma?

Close-up of the scalp of an elderly patient, showing squamous cell carcinoma (skin cancer)
Close-up of the scalp of an elderly patient, showing squamous cell carcinoma (skin cancer)
Healthy skin microbiome is compared with squamous cell carcinoma (SCC) and actinic keratosis (AK) to characterize the differences between a healthy microbiome and one associated with skin cancer.

There is an imbalance of the skin microbial community composition when comparing healthy skin to squamous cell carcinoma (SCC) but no imbalance in the comparison between healthy skin and pre-malignant actinic keratosis (AK), according to study findings published in The Journal of Investigative Dermatology. Microbial community shifts unique to AK and SCC were found, however.

Skin cancer risk factors that include immune suppression, chronic inflammation, and antibiotic usage imply that the skin microbial community may also be a cancer risk factor and possibly an indicator of skin cancer, the investigators stated. Researchers sought to compare a healthy skin microbiome with SCC and AK with the goal of characterizing the differences between a healthy microbiome and one associated with skin cancer.

To accomplish this, they included 81 patients at the University Hospital Heidelberg, Germany, with SCC and AK, and 25 healthy control individuals (CTRLs) in an  observational analysis of shotgun metagenomes of SCC and AK compared to healthy skin. Skin swabs were taken from healthy skin (HS) matched by age, sex, and sampling site, as well as from SCC, and AK patches. Researchers analyzed 336 samples in all.

Analysis revealed an increase in Staphylococcus aureus in SCC vs HS and a decrease in Cutibacterium acnes in the same comparison. Researchers said this indicated changes that were associated with the progression of the disease in the skin microbiome. There was no increase noted in such unique species comparing AK vs HS.  

Linear discriminant analysis was used to characterize microbes associated with SCC or AK. The possible existence of an antagonistic relationship was examined in S aureus and C acnes. Differentially prevalent genes were identified, and differences in the overall population of gene families were compared between HS and SCC. No differences were noted according to researchers between HS and AK. Researchers also investigated the possibility of predicting the disease progression from HS to AK to SCC which they believed most likely to be found in overlapping gene families that resulted from the surging S aureus.

No study limitations were reported. However, researchers stated that their data was correlative, generating no cause or effect answers of the progression of SCC. They further indicated that their characterization of the SCC and AK skin microbiome can be used to inform future SCC studies.

Researchers concluded that their study, “revealed a transitional microbial dysbiosis from healthy skin to AK to SCC, supporting further investigation of the skin microbiome for use as a biomarker and providing hypotheses for studies investigating how these microbes might influence skin cancer progression.”


Voigt AY, Emiola A, Johnson JS, et al. Skin microbiome variation with cancer progression in human cutaneous squamous cell carcinoma. J Invest Dermatol. Published online April 4, 2022. doi:10.1016/j.jid.2022.03.017