Link between genital warts and the HLA system might lead to new therapeutic targets

A study linked genital warts and human leukocyte antigen systems. Protective and risk alleles could be identified as future antiviral or vaccine targets.

80% of sexually active people may acquire at least one infection by age 45

Genital warts (Condyloma acuminata) present the most widespread sexually transmitted disease worldwide, with more than 80% of sexually active women and men expected to acquire at least one infection by the age of 45 years. They are caused by human papillomavirus (HPV) infections, usually by subtype HPV 6 and 11.

Previous research has already established an association between the human leukocyte antigen system (HLA), part of the immune system involved in antigen presentation, and HPV infections but focused on high-risk HPV subtypes 16 and 18 that may progress to cervical cancer. Dr Pernille Lindsø Andersen (Zealand University Hospital, Denmark) and her team studied a possible association between the HPV types responsible for genital warts and the HLA system. 

A cohort of 65,791 blood donors was examined, with 4,199 participants considered as Condyloma acuminata cases and the remaining 61,592 participants used as a control group. Cases were defined as those registered with a minimum of one redeemed prescription of medication for condyloma acuminata or who had a diagnosis of condyloma acuminata. Genetic information regarding the HLA types and their association with being a case or control was assessed in all participants. 

The risk allele DRQ1*03 was associated with a 25% elevated risk for genital warts

Adjusted for confounders, the researchers were able to identify 12 protective gene variations (odds ratios [OR] 0.4–0.8) and 7 risk alleles (OR 1.1–1.3) of condylomas in their patient cohort. Individuals with risk alleles were less successful at recognising the HPV virus and therefore more likely to present with genital warts – conversely, participants with protective alleles had better immune responses and were more effective at recognising HPV, limiting the likelihood of presenting with condylomas.

Particularly the risk allele DRQ1*03 was associated with a 25% elevated risk for genital warts, supporting the results of a previous study. On the other hand, DRQ1*06:04 was identified as a protective allele, reducing the relative risk for genital warts by 57%. HLA alleles associated with HPV infection may have specific immunological properties related to the presentation of viral antigens. 

“Our research identifies key immunologic features that prove there is a link between the immune system and condylomas,” Dr Lindsø Andersen concluded. Future research should now investigate which viral peptides are immunologically important and might be possible targets for antiviral medication or vaccine development.