Warts and all: human papillomavirus in primary immunodeficiencies

Area of Science:

• Immunology
• Virology
• Genetics

Background:

• Human papillomavirus (HPV) infection is nearly universal, but severe, persistent infections indicate underlying health issues.
• Pathologic HPV infections are often severe, recurrent, and resistant to treatment, suggesting a link to immune system dysfunction.
• Primary immunodeficiencies are an underappreciated cause of severe and difficult-to-treat HPV infections.

Purpose of the Study:

• To review primary immunodeficiencies associated with severe human papillomavirus (HPV) infections.
• To explore the underlying mechanisms that link specific genetic defects to severe HPV manifestations.
• To highlight the significance of HPV infections as a potential indicator of primary immune defects.

Main Methods:

• Literature review of primary immunodeficiencies and their association with severe HPV infections.
• Analysis of genetic mutations (e.g., EVER1, EVER2, GATA2, CXCR4, DOCK8) linked to extensive HPV.
• Examination of immunological mechanisms contributing to HPV susceptibility and severity.

Main Results:

• Specific genetic mutations, including in EVER1, EVER2, GATA2, CXCR4, and DOCK8, are strongly associated with extensive HPV infections.
• While some immune defects frequently lead to severe HPV, others do so less commonly.
• Severe HPV infections can serve as a clinical manifestation of various primary immune defects.

Conclusions:

• Severe HPV infections are a critical, yet often underrecognized, sign of primary immunodeficiency.
• Understanding the genetic and mechanistic basis of these associations is crucial for diagnosis and management.
• Further research into the interplay between HPV and the immune system in primary immunodeficiency is warranted.