HPV-6 molecular variants association with the development of genital warts in men: The HIM Study

Flores-Díaz, Ema; Sereday, Karen A.; Ferreira, Silvaneide; Sirak, Bradley; Baggio, Maria Luiza; Galan, Lenice; Silva, Roberto C.; Lazcano‐Ponce, Eduardo; Giuliano, Anna R.; Villa, Luísa Lina; Sichero, Laura

doi:10.1093/infdis/jiw600

Cited by 17 publications

(19 citation statements)

References 33 publications

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“…Concerning HLA‐DQB1*03:01 allele, identified as a risk factor for OLI, previous studies showed conflicting results: Whereas in chronic hepatitis, this allele has been correlated in some instances with HCV clearance (Huang et al ., ; Thio et al ., ; El‐Bendary et al ., ), other authors have reported a link between HLA‐DQB1*03:01 and HPV6 infection (Chen et al ., ). Notably, this HPV subtype, despite being considered as low risk for cervical cancer, is established to cause genital lesions and to be found in the semen (Lyu et al ., ; Flores‐Díaz et al ., ). In our cohort, no association of HLA‐DQB1*03:01 with HPV was not detected.…”

Section: Discussionmentioning

confidence: 97%

Semen quality is affected by HLA class I alleles together with sexually transmitted diseases

et al. 2019

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Background: The human leukocyte antigen (HLA) locus includes several genes with key roles in antigen presentation and immune response, some of them inclusively found to be associated with non-obstructive azoospermia. Still, HLA connections to other infertility phenotypes such as semen hyperviscosity (SHV), asthenozoospermia (AST), and oligozoospermia (OLI) have been often neglected. Objectives: In this work, we aimed to evaluate the association of HLA class I and II genes with SHV, AST, and OLI phenotypes while exploring a possible role in an adaptive immune response to sexually transmitted diseases (STD). Materials and methods: Whole-exome sequencing was performed in a Portuguese cohort of 71 infertility cases and 68 controls, followed by HLA typing using a specific software-HLA*PRG:LA tool. Molecular screenings of seven STD were carried out in a subset of 72 samples (30 cases and 42 controls). Results: Statistical tests uncovered three protective alleles: HLA-A*11:01, associated with all forms of male infertility (p = 0.0006); HLA-DQB1*03:02 with SHV and OLI (P SHV = 0.0303, P OLI = 0.0153); and HLA-A*29:02 with OLI (p = 0.0355), which was found to interfere in sperm number together with HPV (p = 0.0313). Five risk alleles were also identified: two linked with SHV (HLA-B*50:01, p = 0.0278; and HLA-C*06:02, p = 0.0461), another one with both SHV and OLI (HLA-DQA1*05:01, P SHV = 0.0444 and P OLI =0.0265), and two with OLI (HLA-C*03:03, p = 0.0480; and HLA-DQB1*03:01, p = 0.0499). Here, HLA-C*03:03 carriers tend to be HPV infected. Conclusions: The application of HLA*PRG:LA tool to the study of male infertility provided novel insights for an HLA correlation with semen quality, namely among SHV and OLI phenotypes. The discovery of an HLA-A*29:02/HPV crosstalk, together with former reports of HLA alleles conferring resistance-susceptibility to diverse human pathogens, raises the hypothesis of a mechanistic link between male infertility, HLA polymorphism, and host response to STD.

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Section: Discussionmentioning

confidence: 97%

Semen quality is affected by HLA class I alleles together with sexually transmitted diseases

et al. 2019

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“…The median time to GW detection was 17.1 months; however, it was shortest among men with HPV types 6 or 11 infections (median of 7.7 months). Interestingly, while HPV-6 nucleotide variability was associated with GW development [73], there was a lack of association between any particular HPV-11 variant and increased risk of GW [74]. Recent sexual behavior was strongly associated with GW incidence, whereas frequent condom use was protective [15].…”

Section: Hpv Genital Infection and Associated Diseases: The Him Studymentioning

confidence: 99%

Human Papillomavirus and Genital Disease in Men: What We Have Learned from the <b><i>HIM Study</i></b>

2019

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It is currently recognized that in addition to the major impact of human papillomavirus (HPV) infection in females, HPV causes considerable disease in men at the genitals, anal canal, and oropharynx. Specifically, genital HPV infections may progress to genital warts and penile carcinoma. Although studies concerning the natural history of HPV infections and associated neoplasias have mainly focused on women, during the last 2 decades considerable attention has been given in further understanding these infections in men. The HIM (HPV infection in men) Study, the only prospective multicenter study of male HPV natural history, consisted of a large prospective international cohort study in which men from Brazil, the United States, and Mexico were enrolled. The design and protocols of this study allowed unraveling crucial information regarding the relationship between HPV infection and clinical consequences in men, and associated risk factors at each of the anatomic sites where HPV is known to cause cancer in men.

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“…DNA from HPV 6-and HPV 11-positive cervical swabs were submitted to PCR for amplification of a fragment of the L2 and E2/NCR2 regions, respectively (4,5). Reaction products were sequenced in an ABI PRISM 3130XL GeneticAnalyzer (Applied Biosystems) using the BigDye Terminator v3.1 Cycle Sequencing Kit (Applied Biosystems).…”

Section: Characterization Of Hpv Variantsmentioning

confidence: 99%

Lack of Association between Human Papillomavirus Types 6 and 11 Genetic Variants and Cervical Abnormalities: The Ludwig–McGill Cohort Study

Sichero

El‐Zein

Ferreira

et al. 2019

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: Human papillomavirus (HPV) types 6 and 11 are mainly associated with the development of genital warts and recurrent respiratory papillomatosis. We examined intratypic genetic variability of both viral types with the development of cervical cytologic abnormalities in Brazilian women.Methods: We used PCR sequencing to characterize variants of HPVs 6 and/or 11 in cervical swabs from women in the Ludwig-McGill Cohort Study. We used a binomial generalized estimating equations (GEE) model with logit link to estimate odds ratios (OR) and 95% confidence intervals (CI) for the associations between HPV 6 and 11 variants and cytologic abnormalities.Results: B1 and B3 HPV6 and A2 HPV11 variants were the most common isolates identified. Compared with HPV6negative women, the ORs among women harboring HPV6 B1 or B3 variants were 6.3 (95% CI, 2.3-17.0) and 2.3 (95% CI, 0.6-9.7) for atypical cells of undetermined significance (ASCUS)/low squamous intraepithelial lesions (LSIL), respectively, and 1.7 (95% CI, 0.6-5.1) and 1.2 (95% CI, 0.3-4.7) for ASCUS/LSIL/high squamous intraepithelial lesions (HSIL). Respective ORs were 5.0 (95% CI, 1.7-14.6) and 2.8 (95% CI, 1.0-8.1) upon comparing women with HPV11 A2 variants to HPV11-negative women. All associations disappeared when adjusting for coinfections with high-risk HPV types.Conclusions: Our data do not support an association between low-risk HPVs 6 and 11 genetic variability and cervical abnormalities.Impact: Risk of cervical cytologic abnormalities is not affected by intratypic polymorphism in HPVs 6 and 11.

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HPV-6 molecular variants association with the development of genital warts in men: The HIM Study

Abstract: HPV-6 B1 variants are more prevalent in genital swabs that precede GW development, and confer an increased risk for GW. Further research is warranted to understand the possible involvement of B1 variants in the progression to clinically relevant lesions.

Cited by 17 publications

References 33 publications

Semen quality is affected by HLA class I alleles together with sexually transmitted diseases

Semen quality is affected by HLA class I alleles together with sexually transmitted diseases

Human Papillomavirus and Genital Disease in Men: What We Have Learned from the <b><i>HIM Study</i></b>

Lack of Association between Human Papillomavirus Types 6 and 11 Genetic Variants and Cervical Abnormalities: The Ludwig–McGill Cohort Study

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