title: Cutaneous squamous cell cancer (cSCC) risk and the human leukocyte antigen (HLA) system.
abstract: Cutaneous squamous cell carcinoma (cSCC) is the second most common cancer among Caucasians in the United States, with rising incidence over the past decade. Treatment for non-melanoma skin cancer, including cSCC, in the United States was estimated to cost $4.8 billion in 2014. Thus, an understanding of cSCC pathogenesis could have important public health implications. Immune function impacts cSCC risk, given that cSCC incidence rates are substantially higher in patients with compromised immune systems. We report a systematic review of published associations between cSCC risk and the human leukocyte antigen (HLA) system. This review includes studies that analyze germline class I and class II HLA allelic variation as well as HLA cell-surface protein expression levels associated with cSCC risk. We propose biological mechanisms for these HLA-cSCC associations based on known mechanisms of HLA involvement in other diseases. The review suggests that immunity regulates the development of cSCC and that HLA-cSCC associations differ between immunocompetent and immunosuppressed patients. This difference may reflect the presence of viral co-factors that affect tumorigenesis in immunosuppressed patients. Finally, we highlight limitations in the literature on HLA-cSCC associations, and suggest directions for future research aimed at understanding, preventing and treating cSCC.
authors.affiliation: Epidemiology Division, Department of Health Research & Policy, Stanford University, Stanford, CA 94305, USA.
authors.forename: Pooja
authors.initials: P
authors.lastname: Yesantharao
authors.affiliation: Epidemiology Division, Department of Health Research & Policy, Stanford University, Stanford, CA 94305, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Epidemiology Division, Department of Health Research & Policy, Stanford University, Stanford, CA 94305, USA.
authors.forename: Nilah M
authors.initials: NM
authors.lastname: Ioannidis
authors.affiliation: Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Shadmehr
authors.initials: S
authors.lastname: Demehri
authors.affiliation: Epidemiology Division, Department of Health Research & Policy, Stanford University, Stanford, CA 94305, USA. Electronic address: alicesw@stanford.edu.
authors.forename: Alice S
authors.initials: AS
authors.lastname: Whittemore
authors.affiliation: Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Maryam M
authors.initials: MM
authors.lastname: Asgari
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000453:epidemiology* / Q000235:genetics / Q000276:immunology; D004266:DNA Virus Infections / Q000453:epidemiology*; D005787:Gene Frequency; D055106:Genome-Wide Association Study; D006680:HLA Antigens / Q000235:genetics*; D006801:Humans; D007109:Immunity; D007165:Immunosuppression Therapy; D027383:Papillomaviridae / Q000502:physiology*; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012878:Skin Neoplasms / Q000453:epidemiology* / Q000235:genetics / Q000276:immunology; D014481:United States; D044465:White People
chemical_list: D006680:HLA Antigens
keywords: Cutaneous SCC; HLA; HPV; Immunosuppression