Immunopathogenesis of skin and mucosal Human Papillomavirus (HPV)-related diseases

National Institute Of Allergy And Infectious Diseases

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Abstract

We have been investigating the epidemiological, virological and immunological characteristics of HPV skin and mucosal colonization in immunocompromised hosts. In FY25, we identified the role of a common beta HPV in the pathogenesis of cutaneous squamous cell carcinoma and the role of T cell immunosurveillance in controlling colonization and HPV disease progression in different immunosuppressed hosts. These findings further complement our previous work in models of immunodeficiencies and converged in defining the crucial role of lymphoid effector functions (i.e NK and T cells) and specialized epithelial antigen presenting cells in the control HPV-diseases. Novel next-generation molecular tools for HPV whole genome sequencing have been integrated with microbiome analysis to identify new correlates of disease progression in the skin and mucosal compartment of immunocompromised and immunocompetent individuals. The operational capacity of a new HPV dysplasia clinic at the NIH Clinical Center has been further potentiated to align the studies of HPV viral epidemiology and epithelial barrier immunity with specialized clinical care for diagnosis and management of aggressive HPV-related diseases and cancers.