Prevalence of 13 polyomaviruses in actinic keratosis and matched healthy skin samples of immunocompetent individuals

Abstract

Background: Actinic keratosis (AK) is a precursor of cutaneous squamous cell carcinoma (cSCC). UV radiation is the major risk factor for AK, but certain human papillomaviruses (HPVs) of the beta genus are also involved in its development. Differently, the role of polyomaviruses (PyVs) in skin carcinogenesis is still debated. Fiftheen PyVs have been isolated from human tissues so far, including Merkel cell polyomavirus (MCPyV), the aetiological agent of Merkel cell carcinoma.

Methods: The presence of 13 PyVs was assessed in skin samples from AK patients (n = 342). Matched fresh-frozen scrapings from healthy skin (HS) and AK lesions from 242 patients, and formalin-fixed paraffin-embedded AK biopsies from a different cohort of 100 patients were analyzed by multiplex PyVs genotyping assay.

Results: The most frequent lesion site was the scalp in men (27.3%), and the cheek area in women (29.0%). Differences between men and women were significant for the scalp, the cheek area and the lips. Almost all the scrapings were PyV-positive (HS: 89.7%, AK: 94.6%; p = 0.04). The three most frequent PyVs were MCPyV, HPyV6 and JCPyV (HS: 87.2%, 58.7%, 6.6%, respectively; AK: 88.8%, 51.2%, 9.9%, respectively). HPyV9, TSPyV, BKPyV, HPyV7, LIPyV and SV40 were detected in < 2% of the scrapings. In most cases, matched HS and AK scrapings were both positive (MCPyV: 78.1%, HPyV6: 41.7%), or both negative for the individual genotypes (for the remaining PyVs). PyV prevalence in AK biopsies was 22.0%. Only MCPyV (21.0%) and HPyV6 (3.0%) were detected in these samples.

Conclusions: PyV prevalence in HS and AK scrapings was high, but detection of PyVs exclusively in AK scrapings was rare. PyV positivity rate in AK biopsies was modest. Further research is need to reach firm conclusions regarding the role of these viruses in AK development.

Keywords: Actinic keratosis; Luminex-based HPyV assay; Oncoviruses; Polyomaviruses.

Fig. 1

Heatmap for the comparison between healthy skin (HS) and actinic keratosis (AK) samples for each single PyV at individual level. Colors represent: (1) patients with both HS and AK samples negative for any PyV (negHS-negAK, grey); (2) patients with positive HS and negative AK for the virus indicated (posHS-negAK, blue); (3) patients with negative HS and positive AK for the virus indicated (negHS-posAK, green); (4) patients with both HS and AK positive for the virus indicated and showing a higher MFI value in HS than AK (HS > AK, orange), (5) patients with both HS and AK positive for the virus indicated and showing a higher MFI value in AK than HS (AK > HS, red)