The association of HLA-G polymorphism with oral and genital HPV infection in men

Nelli T. Suominen,Stina M. Syrjänen,Anna J. Jaakola,Kari J. Syrjänen,Karolina Louvanto,Seija E. Grénman,Michel Roger,Marie-Claude Faucher

doi:10.1007/s10096-021-04362-8

Abstract

The host genetic factors that influence the natural history of human papillomavirus (HPV) infection in men are not well known. Our aim was to evaluate the role of human leukocyte antigen (HLA)-G polymorphism in oral and genital HPV infection in men. Altogether, 130 men from the Finnish Family HPV Study, with a 6-year follow-up, were included in the analyses. HLA-G alleles were tested by direct sequencing. Oral, urethral, and semen samples were collected and analyzed for 24 different HPV genotypes. Unconditional logistic regression was used to determine associations between HLA-G alleles and genotypes with HPV infection and its outcomes. Overall, eight different HLA-G alleles were identified with 15 different HLA-G genotype combinations. The most common HLA-G allele among the men was G*01:01:01 (86.2%, n = 112) followed by G*01:01:02 (36.2%, n = 47). Allele G*01:01:02 showed to be protective against any- and high-risk (HR) oral HPV (OR range of 0.20–0.24, 95% CI range of 0.06–0.85). Men having allele G*01:01:01 showed a reduced risk for incident (OR 0.30, 95% CI 0.11–0.84) and persistent (OR 0.24, 95% CI 0.08–0.69) oral infections. Allele G*01:01:03 was associated with increased risk for urethral HR-HPV infections (OR 4.94, 95% CI 1.34–18.27). Among self-reported demographic data, genotype G*01:01:01/01:01:03 was associated with an increased risk for oral warts (OR 8.00, 95% CI 1.23–51.89) and allele G*01:03:01 increased the risk of pollen and/or animal allergy (OR 13.59, 95% CI 1.57–117.25). To conclude, HLA-G polymorphism in men largely impacts the outcome of an oral HPV infection and seems to associate with self-reported allergies.

Highlights

Human papillomavirus (HPV) infections are typically asymptomatic, transient, and cleared by the host immune system
HR-HPV was found in 26.7% (23/86), 16.4% (20/122), and 16.4% (21/128) in semen, urethral, and oral samples, respectively, whereas LR-HPV accounted for 10.5% (9/86), 7.4% (9/122), and 3.1% (4/128) of semen, urethral, and oral samples, respectively
Most studies have focused on human leukocyte antigen (HLA)-G polymorphism and HPV-related diseases in women [21, 23,24,25,26,27,28,29]

Summary

Introduction

Human papillomavirus (HPV) infections are typically asymptomatic, transient, and cleared by the host immune system. Anal, penile, and oropharyngeal cancers are attributable to HPV infections [2]. In 2018, 92,887 patients were diagnosed with oropharyngeal carcinoma globally [1]. Oropharyngeal carcinoma is four times more prevalent in men than in women [1]. Around 30% of oropharyngeal cancers, 29,000 cases per year, are caused by HPV; 24,000 of those occur in males [2]. The demographic data of the men were collected by a structured questionnaire at baseline. The baseline demographic data have been reported in detail previously [15]. The questionnaire included a self-reported history of infertility, previous chlamydia and mumps infections, asthma, allergy, and atopy. Men were questioned about their history of HPV-related symptoms and signs of genital, skin, and oral warts

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