Search

Summary: Background: Cutaneous viral infections and immune suppression are risk factors for some forms of nonmelanoma skin cancer; however, their interrelationship is poorly understood. Objectives: To examine cross‐sectional associations between cutaneous viral infections and circulating forkhead‐box P3 (FOXP3)‐expressing T‐regulatory (Treg) cells, suppressive cells that dampen effective antitumour immunity. Materials and methods: Blood, eyebrow hair (EBH) and skin swab (SSW) samples were collected from 352 patients 60 years and older undergoing skin screening, without prevalent skin cancer, while participating in an ongoing prospective cohort study of cutaneous viral infections and skin cancer. DNA corresponding to 98 cutaneous human papillomavirus (HPV) types and five human polyomaviruses (HPyV) was assessed in EBH and SSW. Distinct classes of circulating Treg‐cell subpopulations were defined by flow cytometry including cutaneous lymphocyte antigen (CLA) and CCR4high Treg cells, both previously associated with cutaneous diseases. Age‐ and sex‐adjusted associations between circulating T‐cell populations and infection were estimated using logistic regression. Results: Total Treg‐cell proportion in peripheral blood was not associated with β HPV or HPyV infection. However, the proportion of circulating CLA+ Treg cells was inversely associated with γ HPV EBH infection [odds ratio (OR) 0·54, 95% confidence interval (CI) 0·35–0·84]. Interestingly, circulating Treg cells expressing markers indicative of antigen activation (CD27–CD45RA–FOXP3+CD4+) were also inversely associated with γ HPV infection in SSW (OR 0·55, 95% CI 0·30–0·99) and EBH (OR 0·56, 95% CI 0·36–0·86). Conclusions: Inverse associations between circulating Treg cells and γ HPV infection suggest that localized viral infection may promote immunosuppressive cell migration into skin. What's already known about this topic? Cutaneous viral infections such as the human papillomavirus (HPV) and polyomavirus (HPyV) may play a role in the development of some nonmelanoma skin cancer types, including cutaneous squamous cell carcinoma (cuSCC) and Merkel cell carcinoma (MCC).Immunosuppression is an established risk factor for cuSCC and MCC.The relationship between cutaneous viral infections, immunosuppression and the development of cuSCC and MCC is not well understood. What does this study add? Higher proportions of circulating antigen‐activated CD27–/CD45RA– T‐regulatory (Treg) cells were inversely associated with γ HPV infection in skin swabs and eyebrow hairs, whereas no associations were observed for β human papillomavirus (HPV) or polyomavirus infections.Circulating skin‐homing cutaneous lymphocyte antigen‐positive Treg cells were inversely associated with γ HPV eyebrow hair infection.γ HPV infections may recruit immunosuppressive lymphocytes into the skin, perhaps contributing to cutaneous malignancy development. What is the translational message? In this first study of the associations between Treg cells circulating in the blood and the presence of cutaneous infections with HPVs and HPyVs, circulating immunosuppressive lymphocytes were inversely associated with γ HPV infection.γ HPV infections may recruit immunosuppressive lymphocytes into the skin, perhaps contributing to the development of cutaneous malignancy. Respond to this article Linked Comment: Poyner, Dubois and Haniffa. Br J Dermatol 2019; 180:1294. Plain language summary available online [ABSTRACT FROM AUTHOR]

The article discusses a study that examined genetic factors related to cutaneous ß-human papillomavirus (HPV) infection in cancer-free, immunocompetent individuals and assessed whether the same genetic factors were linked to squamous cell carcinoma (SCC). Tables showing the characteristics of the cases of SCC and healthy controls and the associations of single-nucleotide polymorphisms (SNPs) in epidermodysplasia verruciformis (EVER/TMC) genes with multiple HPV infections are presented.

Linked Article: Hampras et al. Br J Dermatol 2019; 180:1449–1458 [ABSTRACT FROM AUTHOR]

Summary: Approximately three million non‐melanoma skin cancers (NMSCs) are diagnosed worldwide each year, although this number is likely an underestimate given that these cancers are not always recorded in cancer registries. Studies have suggested that skin (cutaneous) infections with human papillomaviruses (HPV) and polyomaviruses (HPyV) may play a role in the development of some NMSC types. Suppression of the immune system is also a risk factor for NMSC. This study, from the U.S.A, aimed to understand the relationship between T‐regulatory (Treg) cells, cells which suppress immune response, and cutaneous viral infections. Blood, skin swabs and eyebrow hairs were collected from 352 patients who underwent skin cancer screening and did not have cancer detected. The researchers examined whether the skin swabs (SSW) and eyebrow hairs (EBH) contained genetic material (DNA) corresponding to 98 cutaneous HPV types (including beta HPV and gamma HPV) and 5 HPyV types. The blood samples were analyzed to determine proportions of different types of Treg cell populations in circulation (in the blood). The researchers found no association between total percent of circulating Treg cells and beta HPV or HPyV infection. However, two types of Treg cells were found at lower levels in those that had gamma HPV infection in their EBH and/or SSW. Those two types were CLA+ Treg cells (known to travel to the skin) and effector CD27‐CD45RA‐FOXP3+CD4+ Treg cells (known to become active when exposed to a foreign viral infection). The study results suggest that gamma HPV infection may stimulate Treg cells to move from circulation into the skin tissues. Linked Article: Hampras et al. Br J Dermatol 2019; 180:1449–1458 [ABSTRACT FROM AUTHOR]