Top

Published in:

Open Access 01-12-2021 | Infertility | Research article

HLA-G polymorphism impacts the outcome of oral HPV infections in women

Authors: Anna Jaakola, Michel Roger, Marie-Claude Faucher, Kari Syrjänen, Seija Grénman, Stina Syrjänen, Karolina Louvanto

Published in: BMC Infectious Diseases | Issue 1/2021

Abstract

Backround

Human leukocyte antigen (HLA)-G may have an important role in the natural history of human papillomavirus (HPV) infection. Our aim was to evaluate the role of HLA-G in the outcome of genital and oral HPV infections in women.

Methods

Analyses included 306 women from the Finnish Family HPV-study and were followed-up for six years. Genital and oral samples were tested for 24 different HPV types with multiplex HPV genotyping. HLA-G alleles were determined through direct DNA-sequencing. Unconditional logistic regression was used to determine the associations between HLA-G genotypes and HPV infection outcomes.

Results

Ten HLA-G alleles were identified. Most common HLA-G genotypes were the wild type G*01:01:01/01:01:01 (31.3%) followed by G*01:01:01/01:01:02 (26.8%). G*01:01:01/01:01:01 genotype was associated with increased risk of oral HPV infections by any HPV type or single-type with OR = 1.86 (95% CI 1.14–3.04, P = 0.01) and 2.22 (95% CI 1.14–3.71, P = 0.02), respectively. G*04:01+ allele and the G*01:01:01/01:04:01 genotype both protected from any and single oral HPV infections; OR = 0.46 (95% CI 0.23–0.89, P = 0.02) and 0.53 (95% CI 0.23–0.97, P = 0.03), respectively. G*01:01:02/01:04:01 genotype increased significantly the risk of infertility and its treatments, with respective OR = 5.06 (95% CI 1.22–21.02, P = 0.03) and OR = 9.07 (95% CI 1.22–39.50, P = 0.03). Both HLA-G alleles and genotypes showed several significant associations with the outcomes of oral HPV infections, but none of them had any impact on the outcomes of genital HPV infections in these women.

Conclusions

The host HLA-G genotypes appear to impact the outcomes of oral HPV infections in women but have little if any effect on genital HPV status or infection outcomes.

Syrjanen K, Hakama M, Saarikoski S, et al. Prevalence, incidence, and estimated life-time risk of cervical human papillomavirus infections in a nonselected Finnish female population. Sex Transm Dis. 1990;17(1):15–9. https://doi.org/10.1097/00007435-199017010-00004.CrossRefPubMed

Tam S, Fu S, Xu L, Krause KJ, Lairson DR, Miao H, et al. The epidemiology of oral human papillomavirus infection in healthy populations: a systematic review and meta-analysis. Oral Oncol. 2018;82:91–9. https://doi.org/10.1016/j.oraloncology.2018.04.005.CrossRefPubMed

Hirth J. Disparities in HPV vaccination rates and HPV prevalence in the United States: a review of the literature. Hum Vaccin Immunother. 2019;15(1):146–55. https://doi.org/10.1080/21645515.2018.1512453.CrossRefPubMed

Walboomers JM, Jacobs MV, Manos MM, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 1999;189(1):12–9. https://doi.org/10.1002/(SICI)1096-9896(199909)189:1<12::AID-PATH431>3.0.CO;2-F.CrossRefPubMed

de Sanjose S, Serrano B, Tous S, et al. Burden of Human Papillomavirus (HPV)-Related Cancers Attributable to HPVs 6/11/16/18/31/33/45/52 and 58. JNCI Cancer Spectr. 2019;2:pky045.CrossRef

Tan G, Duan M, Li Y, et al. Distribution of HPV 16 E6 gene variants in screening women and its associations with cervical lesions progression. Virus Res. 2019;273:197740. https://doi.org/10.1016/j.virusres.2019.197740.CrossRefPubMed

Duan R, Qiao Y, Clifford G, Zhao F. Cancer burden attributable to human papillomavirus infection by sex, cancer site, age, and geographical area in China. Cancer Med. 2020;9(1):374–84. https://doi.org/10.1002/cam4.2697.CrossRefPubMed

Timbang MR, Sim MW, Bewley AF, Farwell DG, Mantravadi A, Moore MG. HPV-related oropharyngeal cancer: a review on burden of the disease and opportunities for prevention and early detection. Hum Vaccin Immunother. 2019;15(7-8):1920–8. https://doi.org/10.1080/21645515.2019.1600985.CrossRefPubMedPubMedCentral

Kreimer AR, Chaturvedi AK, Alemany L, Anantharaman D, Bray F, Carrington M, et al. Summary from an international cancer seminar focused on human papillomavirus (HPV)-positive oropharynx cancer, convened by scientists at IARC and NCI. Oral Oncol. 2020;108:104736. https://doi.org/10.1016/j.oraloncology.2020.104736.CrossRefPubMedPubMedCentral

10.

Frazer IH. Immunology of papillomavirus infection. Curr Opin Immunol. 1996;8(4):484–91. https://doi.org/10.1016/S0952-7915(96)80035-5.CrossRefPubMed

11.

Xu HH, Yan WH, Lin A. The Role of HLA-G in Human Papillomavirus Infections and Cervical Carcinogenesis. Front Immunol. 2020;11:1349.CrossRef

12.

Ferguson R, Ramanakumar AV, Richardson H, Tellier PP, Coutlée F, Franco EL, et al. Human leukocyte antigen (HLA)-E and HLA-G polymorphisms in human papillomavirus infection susceptibility and persistence. Hum Immunol. 2011;72(4):337–41. https://doi.org/10.1016/j.humimm.2011.01.010.CrossRefPubMed

13.

Ferguson R, Ramanakumar AV, Koushik A, Coutlée F, Franco E, Roger M, et al. Human leukocyte antigen G polymorphism is associated with an increased risk of invasive cancer of the uterine cervix. Int J Cancer. 2012;131(3):E312–9. https://doi.org/10.1002/ijc.27356.CrossRefPubMed

14.

Li XJ, Zhang X, Lin A, Ruan YY, Yan WH. Human leukocyte antigen-G (HLA-G) expression in cervical cancer lesions is associated with disease progression. Hum Immunol. 2012;73(9):946–9. https://doi.org/10.1016/j.humimm.2012.07.041.CrossRefPubMed

15.

Dong DD, Yang H, Li K, et al. Human leukocyte antigen-G (HLA-G) expression in cervical lesions: association with cancer progression, HPV 16/18 infection, and host immune response. Reprod Sci. 2010;17(8):718–23. https://doi.org/10.1177/1933719110369183.CrossRefPubMed

16.

Delves PJ, Roitt IM. The immune system. Second of two parts. N Engl J Med 2000;343:108–117, 2, DOI: https://doi.org/10.1056/NEJM200007133430207.

17.

Morandi F, Rizzo R, Fainardi E, Rouas-Freiss N, Pistoia V. Recent advances in our understanding of HLA-G biology: lessons from a wide Spectrum of human diseases. J Immunol Res. 2016;2016:4326495.PubMedPubMedCentral

18.

Complete sequence and gene map of a human major histocompatibility complex. The MHC sequencing consortium. Nature. 1999;401(6756):921–3. https://doi.org/10.1038/44853.

19.

Sheu J, Shih I. HLA-G and immune evasion in cancer cells. J Formos Med Assoc. 2010;109(4):248–57. https://doi.org/10.1016/S0929-6646(10)60050-2.CrossRefPubMed

20.

Ferreira LMR, Meissner TB, Tilburgs T, Strominger JL. HLA-G: at the Interface of maternal-fetal tolerance. Trends Immunol. 2017;38(4):272–86. https://doi.org/10.1016/j.it.2017.01.009.CrossRefPubMed

21.

Zheng N, Wang CX, Zhang X, du LT, Zhang J, Kan SF, et al. Up-regulation of HLA-G expression in cervical premalignant and malignant lesions. Tissue Antigens. 2011;77(3):218–24. https://doi.org/10.1111/j.1399-0039.2010.01607.x.CrossRefPubMed

22.

Yoon BS, Kim YT, Kim JW, Kim SH, Kim JH, Kim SW. Expression of human leukocyte antigen-G and its correlation with interleukin-10 expression in cervical carcinoma. Int J Gynaecol Obstet. 2007;98(1):48–53. https://doi.org/10.1016/j.ijgo.2007.03.041.CrossRefPubMed

23.

Metcalfe S, Roger M, Faucher MC, Coutlee F, Franco EL, Brassard P. The association between human leukocyte antigen (HLA)-G polymorphisms and human papillomavirus (HPV) infection in Inuit women of northern Quebec. Hum Immunol. 2013;74(12):1610–5. https://doi.org/10.1016/j.humimm.2013.08.279.CrossRefPubMed

24.

Simoes RT, Goncalves MA, Castelli EC, et al. HLA-G polymorphisms in women with squamous intraepithelial lesions harboring human papillomavirus. Mod Pathol. 2009;22(8):1075–82. https://doi.org/10.1038/modpathol.2009.67.CrossRefPubMed

25.

Rintala M, Grenman S, Puranen M, Syrjanen S. Natural history of oral papillomavirus infections in spouses: a prospective Finnish HPV family study. J Clin Virol. 2006;35(1):89–94. https://doi.org/10.1016/j.jcv.2005.05.012.CrossRefPubMed

26.

Louvanto K, Rintala MA, Syrjanen KJ, Grenman SE, Syrjanen SM. Genotype-specific persistence of genital human papillomavirus (HPV) infections in women followed for 6 years in the Finnish family HPV study. J Infect Dis. 2010;202(3):436–44. https://doi.org/10.1086/653826.CrossRefPubMed

27.

Snijders PJ, van den Brule AJ, Schrijnemakers HF, Snow G, Meijer CJ, Walboomers JM. The use of general primers in the polymerase chain reaction permits the detection of a broad spectrum of human papillomavirus genotypes. J Gen Virol. 1990;71(Pt 1):173–81. https://doi.org/10.1099/0022-1317-71-1-173.CrossRefPubMed

28.

Rautava J, Syrjanen S. Biology of human papillomavirus infections in head and neck carcinogenesis. Head Neck Pathol. 2012;6(Suppl 1):S3–15.CrossRef

29.

Louvanto K, Roger M, Faucher MC, Syrjanen K, Grenman S, Syrjanen S. HLA-G and vertical mother-to-child transmission of human papillomavirus infection. Hum Immunol. 2018;79(6):471–6. https://doi.org/10.1016/j.humimm.2018.03002.

30.

Alves BM, Prellwitz IM, Siqueira JD, Meyrelles ÂR, Bergmann A, Seuánez HN, et al. The effect of human leukocyte antigen G alleles on human papillomavirus infection and persistence in a cohort of HIV-positive pregnant women from Brazil. Infect Genet Evol. 2015;34:339–43. https://doi.org/10.1016/j.meegid.2015.06.027.CrossRefPubMed

31.

Craenmehr MHC, Nederlof I, Cao M, et al. Increased HLA-G Expression in Term Placenta of Women with a History of Recurrent Miscarriage Despite Their Genetic Predisposition to Decreased HLA-G Levels. Int J Mol Sci. 2019;20. https://doi.org/10.3390/ijms20030625.

32.

Kuroshli Z, Gourabi H, Bazrgar M, Sanati M, Zamani EM. The relationship between HLA-G gene polymorphisms and repeated implantation failure in infertile couples undergoing assisted reproductive technique. Iran J Allergy Asthma Immunol. 2015;14:535–42.PubMed

33.

Kovats S, Main EK, Librach C, Stubblebine M, Fisher SJ, DeMars R. A class I antigen, HLA-G, expressed in human trophoblasts. Science. 1990;248(4952):220–3. https://doi.org/10.1126/science.2326636.CrossRefPubMed

34.

Kaariainen H, Muilu J, Perola M, Kristiansson K. Genetics in an isolated population like Finland: a different basis for genomic medicine? J Community Genet. 2017;8(4):319–26. https://doi.org/10.1007/s12687-017-0318-4.CrossRefPubMedPubMedCentral

Title: HLA-G polymorphism impacts the outcome of oral HPV infections in women
Authors: Anna Jaakola
Michel Roger
Marie-Claude Faucher
Kari Syrjänen
Seija Grénman
Stina Syrjänen
Karolina Louvanto
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Infertility
Human Papillomavirus
Infertility
Published in: BMC Infectious Diseases / Issue 1/2021
Electronic ISSN: 1471-2334
DOI: https://doi.org/10.1186/s12879-021-06079-7

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

HLA-G polymorphism impacts the outcome of oral HPV infections in women

Abstract

Backround

Methods

Results

Conclusions

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Backround

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2021

Investigation of SARS-CoV-2 in tear and conjunctival secretions of hospitalized patients with clinically-confirmed COVID-19 pneumonia

A highly effective and inexpensive standardized treatment of multidrug-resistant tuberculosis: a multicenter prospective study in China

The impact of comorbidities and their stacking on short- and long-term prognosis of patients over 50 with community-acquired pneumonia

Case report: aseptic meningitis secondary to varicella-zoster virus (VZV) without an exanthem post MMR vaccination

Informing the public health response to COVID-19: a systematic review of risk factors for disease, severity, and mortality

The serotype distribution of Streptococcus agalactiae (GBS) carriage isolates among pregnant women having risk factors for early-onset GBS disease: a comparative study with GBS causing invasive infections during the same period in Denmark

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page