The Nine-Headed Monster: Recalcitrant Warts

Graeme M. Lipper, MD


February 12, 2020


This retrospective histologic study found that lesional keratinocytes within warts express PD-L1 and the associated inflammatory infiltrate expresses PD-1. This is similar to what is seen in melanoma, Merkel cell carcinoma, and squamous cell carcinoma—all potentially lethal cancers where upregulation of PD-L1 interferes with the host's ability to mount an effective immune response.

Does HPV escape immune detection by upregulating PD-L1 expression in infected keratinocytes and associated inflammatory cells? And if so, could checkpoint inhibitors used to treat metastatic melanoma and other cancers also help clear refractory warts?

One way to test this hypothesis would be to find a cohort of patients about to receive checkpoint inhibitor immunotherapy who also happen to have warts. Will their warts melt away during treatment? Future histologic studies should also seek to determine whether PD-L1 expression in keratinocytes is unique to HPV-induced warts. What about seborrheic keratoses; inflammatory conditions, such as psoriasis and lichen planus; or dermatophyte infections? Put another way, does HPV directly promote PD-L1 expression, or is this a nonspecific reaction to inflammation?

Given the exorbitant price and potential systemic toxicity of checkpoint inhibitors, such as pembrolizumab and nivolumab, these drugs won't find practical use treating warts in the immediate future. Nevertheless, as new and hopefully cheaper and safer (topical?) drugs are developed to exploit the immune checkpoint pathway, we may gain a powerful new weapon to slay the nine-headed wart monster.

Graeme M. Lipper, MD, is a clinical assistant professor at the University of Vermont Medical College in Burlington, Vermont, and a partner at Advanced DermCare in Danbury, Connecticut.

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