Treatment of relapsing HPV diseases by restored function of natural killer cells

Andrea Lisco*, Amy P. Hsu, Dimana Dimitrova, Diana M. Proctor, Emily M. Mace, Peiying Ye, Megan V. Anderson, Stephanie N. Hicks, Christopher Grivas, Dima A. Hammoud, Maura Manion, Gabriel J. Starrett, Alvin Farrel, Kerry Dobbs, Isaac Brownell, Christopher Buck, Luigi D. Notarangelo, Jordan S. Orange, Warren J. Leonard, Michael I. OrestesAnju T. Peters, Jennifer A. Kanakry, Julia A. Segre, Heidi H. Kong, Irini Sereti

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


Human papillomavirus (HPV) infections underlie a wide spectrum of both benign and malignant epithelial diseases. In this report, we describe the case of a young man who had encephalitis caused by herpes simplex virus during adolescence and currently presented with multiple recurrent skin and mucosal lesions caused by HPV. The patient was found to have a pathogenic germline mutation in the X-linked interleukin-2 receptor subunit gamma gene (IL2RG), which was somatically reverted in T cells but not in natural killer (NK) cells. Allogeneic hematopoietic-cell transplantation led to restoration of NK cytotoxicity, with normalization of the skin microbiome and persistent remission of all HPV-related diseases. NK cytotoxicity appears to play a role in containing HPV colonization and the ensuing HPV-related hyperplastic or dysplastic lesions.

Original languageEnglish
Pages (from-to)921-929
Number of pages9
JournalNew England Journal of Medicine
Issue number10
StatePublished - 2 Sep 2021
Externally publishedYes


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