The potential role of infections in melanoma

Introduction Several infectious agents have been implicated in the development of human cancers; however, whether infections contribute to the etiology of melanoma remains unclear. This review evaluated the available evidence regarding potential infectious causes of melanoma. The objective is to determine the evidence available regarding the associations of infectious agents with the development of melanoma. Methods A scoping review of the literature was conducted to identify studies investigating the links between infectious agents and melanoma. Four databases were searched using a combination of keywords and controlled vocabulary for published academic articles. Based on the inclusion criteria, 791 titles and abstracts were screened, and 22 articles were obtained. Inclusion criteria were for studies examining associations between viral infectious agents and melanoma; no language restrictions; and no date range restrictions. The review was broadly inclusive of study types including epidemiologic studies such as meta-analyses, systematic and narrative reviews and observational studies; laboratory and mechanistic studies; and case reports. Studies were grouped into three categories: epidemiologic studies evaluating direct associations between infections and melanoma; laboratory and mechanistic studies investigating potential infection-related carcinogenic pathways for melanoma; and studies examining infections that may predispose to cancers overall, including melanoma. Appropriate-for-study-design criteria were applied to each group of studies to assess and summarize their quality. Results Twenty-two studies met inclusion criteria and were determined to be of moderate to high quality. Infectious agents investigated included human papillomavirus (HPV), Human Herpesvirus 8 (HHV-8), herpes simplex virus type 2 (HSV-2), Epstein–Barr virus (EBV), human immunodeficiency virus (HIV), and the cutaneous microbiome. Three epidemiologic studies directly examined the relationship between infections and melanoma; however, complete study data were available for only one study. These studies had inconsistent results. Seven laboratory and experimental studies demonstrated biologically plausible pathways through which infectious agents, particularly human papillomavirus (HPV) and herpes simplex virus (HSV), may contribute to carcinogenesis. However, the most evidence for biological plausibility was from studies of general cancer biology or non-melanoma skin cancers. Studies examining infections as potential cancer-predisposing conditions generally were the most abundant (12 of 22 studies) and consistently identified HIV-associated immunosuppression as a risk factor for cancers, including increased melanoma incidence and poorer outcomes. Conclusion The available evidence is currently insufficient to determine whether infectious agents are direct causes of melanoma. There are very few epidemiologic studies assessing the associations of infections and melanoma specifically, and these studies demonstrate inconsistent results. Available laboratory and mechanistic studies show biological plausibility for infectious contributions to melanoma-related carcinogenesis; however, direct evidence supporting specific roles in melanoma development remains limited. The largest numbers of studies available have identified that infections such as HIV and their associated immunosuppression that influence cancer risk overall, also influence melanoma risk, indirectly through immune dysfunction. Some available descriptive surveillance databases have shown increased melanoma rates among occupational groups at increased risk of person-to-person infection transmission exposure. Thus, more epidemiologic and laboratory studies are needed to investigate the potential role of infections in melanomas specifically.