The Immunomodulation Role of Vaginal Microenvironment On Human Papillomavirus Infection

Authors

  • Cen Ma Department of Obstetrics and Gynecology Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, China.
  • Lingyan Sun Department of Obstetrics and Gynecology Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, China.
  • Li Li Department of Obstetrics and Gynecology Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, China.
  • Wenxin Xu Department of Obstetrics and Gynecology Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, China.

DOI:

https://doi.org/10.31661/gmj.v12i.2991

Keywords:

Human papillomavirus, Vaginal microenvironment, Lactobacillus acidophilus, Cervical Cancer, Cervical Intraepithelial Neoplasia

Abstract

Background: Evidence suggests the role of the vaginal microbiome and microenvironment in the immunity state. The human papillomavirus (HPV) infection is widely dependent on the healthy vaginal microenvironment. Hence, this study aimed to investigate the role of the vaginal microenvironment in the rate of high-risk HPV (hr-HPV) infection. Materials and Methods: This cross-sectional study was performed on 512 women with hr-HPV positive (n=212) or negative (n=300) infection. The vaginal samples of women were examined regarding yeas and Gardnerella vaginalis infection. Also, Lactobacillus acidophilus, pH, and enzyme activity (such as catalase, proline aminopeptidase, and leucocyte esterase) were compared between the two groups. Also, the histopathological study was performed on the vaginal samples. Results: The higher rate of yeast and G. vaginalis infections as well as decreased L. acidophilus, were significantly observed in women with hr-HPV positive infection (P<0.001). Also, histopathological findings indicated that cervical intraepithelial neoplasia grade I-III and cervical cancer lesions were markedly higher in hr-HPV positive group compared with control women. Conclusion: The hr-HPV infection was markedly correlated to vaginal microenvironments, and it could a risk factor for the elevation of the rate of high-grade cervical lesions.

References

Thun MJ, DeLancey JO, Center MM, Jemal A, Ward EM. The global burden of cancer: priorities for prevention. Carcinogenesis. 2010; 31(1): 100-10. https://doi.org/10.1093/carcin/bgp263PMid:19934210 PMCid:PMC2802672 Torcia MG. Interplay among Vaginal Microbiome, Immune Response and Sexually Transmitted Viral Infections. Int J Mol Sci. 2019; 20(2): 266. https://doi.org/10.3390/ijms20020266PMid:30641869 PMCid:PMC6359169 Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, et al. Cancer statistics in China, 2015. CA Cancer J Clin. 2016;66(2):115-32. https://doi.org/10.3322/caac.21338PMid:26808342 Shvartsman E, Hill JE, Sandstrom P, MacDonald KS. Gardnerella Revisited: Species Heterogeneity, Virulence Factors, Mucosal Immune Responses, and Contributions to Bacterial Vaginosis. Infect Immun. 2023; 91(5): e00390-22. https://doi.org/10.1128/iai.00390-22PMid:37071014 PMCid:PMC10187134 Norenhag J, Du J, Olovsson M, Verstraelen H, Engstrand L, Brusselaers N. The vaginal microbiota, human papillomavirus and cervical dysplasia: a systematic review and network meta-analysis. BJOG. 2020;127(2):171-80. https://doi.org/10.1111/1471-0528.15854PMid:31237400 Pańczyszyn A, Boniewska-Bernacka E, Głąb G. Telomere length in leukocytes and cervical smears of women with high-risk human papillomavirus (HR HPV) infection. Taiwan J Obstet Gynecol. 2020;59(1):51-5. https://doi.org/10.1016/j.tjog.2019.11.007PMid:32039800 Manley KM, Luker R, Park C. An audit of liquid-based cytology samples reported as high-risk human papillomavirus and borderline nuclear change in endocervical cells. Cytopathology. 2020;31(2):130-5. https://doi.org/10.1111/cyt.12803PMid:31995849 Wright Jr TC, Cox JT, Massad LS, Carlson J, Twiggs LB, Wilkinson EJ. 2001 Consensus guidelines for the management of women with cervical intraepithelial neoplasia. J Low Genit Tract Dis. 2003;7(3):154-67. https://doi.org/10.1097/00128360-200307000-00002PMid:17051063 Chao X, Sun T, Wang S, Tan X, Fan Q, Shi H, et al. Research of the potential biomarkers in vaginal microbiome for persistent high-risk human papillomavirus infection. Ann Transl Med. 2020; 8(4): 100. https://doi.org/10.21037/atm.2019.12.115PMid:32175393 PMCid:PMC7049000 Lv P, Zhao F, Xu X, Xu J, Wang Q, Zhao Z. Correlation between Common Lower Genital Tract Microbes and High-Risk Human Papillomavirus Infection. Can J Infect Dis Med Microbiol. 2019; 2019: 9678104. https://doi.org/10.1155/2019/9678104PMid:31885754 PMCid:PMC6893239 Bhatla N, Singhal S. Primary HPV screening for cervical cancer. Best Pract Res Clin Obstet Gynaecol. 2020;65:98-108. https://doi.org/10.1016/j.bpobgyn.2020.02.008PMid:32291178 Thomason JL, Gelbart SM, Wilcoski LM, Peterson AK, Jilly BJ, Hamilton PR. Proline aminopeptidase activity as a rapid diagnostic test to confirm bacterial vaginosis. Obstet Gynecol. 1988;71(4):607-11. Chacko MR, Kozinetz CA, Hill R, Collins K, Dunne M, Hergenroeder AC. Leukocyte esterase dipstick as a rapid screening test for vaginitis and cervicitis. J Pediatr Adolesc Gynecol. 1996;9(4):185-9. https://doi.org/10.1016/S1083-3188(96)70028-1PMid:8957772 Calderón E, Rivera R, Gordillo S, Conde-Glez C. Evaluation of a Fast Test to Identify the Presence of Proline Aminopeptidase in Women With Bacterial Vaginosis. Infect Dis Obstet Gynecol. 1997; 5(3): 226-31. https://doi.org/10.1002/(SICI)1098-0997(1997)5:3 Weston G, Dombrowski C, Harvey MJ, Iftner T, Kyrgiou M, Founta C, et al. Use of the Aptima mRNA high-risk human papillomavirus (HR-HPV) assay compared to a DNA HR-HPV assay in the English cervical screening programme: a decision tree model based economic evaluation. BMJ Open. 2020;10(3):e031303. https://doi.org/10.1136/bmjopen-2019-031303PMid:32152154 PMCid:PMC7064071 Vos RA, Pasmans H, Tymchenko L, Janga-Jansen AV, Baboe-Kalpoe S, Hulshof K, et al. High seroprevalence of multiple high-risk human papillomavirus types among the general population of Bonaire, St. Eustatius and Saba, Caribbean Netherlands. Vaccine. 2020;38(13):2816-26. https://doi.org/10.1016/j.vaccine.2020.02.017PMid:32088019 Castle PE, Varallo JE, Bertram MM, Ratshaa B, Kitheka M, Rammipi K. High-risk human papillomavirus prevalence in self-collected cervicovaginal specimens from human immunodeficiency virus (HIV)-negative women and women living with HIV living in Botswana. PLoS One. 2020;15(2):e0229086. https://doi.org/10.1371/journal.pone.0229086PMid:32053659 PMCid:PMC7018080 Santella B, Schettino MT, Franci G, De Franciscis P, Colacurci N, Schiattarella A, et al. Microbiota and HPV: The role of viral infection on vaginal microbiota. J Med Virol. 2022; 94(9): 4478-84. https://doi.org/10.1002/jmv.27837PMid:35527233 PMCid:PMC9544303 Wei ZT, Chen HL, Wang CF, Yang GL, Han SM, Zhang SL. Depiction of Vaginal Microbiota in Women With High-Risk Human Papillomavirus Infection. Front Public Health. 2020; 8: 587298. https://doi.org/10.3389/fpubh.2020.587298PMid:33490017 PMCid:PMC7820762 Dareng EO, Ma B, Adebamowo SN, Famooto A, Ravel J, Pharoah PP, et al. Vaginal microbiota diversity and paucity of Lactobacillus species are associated with persistent hrHPV infection in HIV negative but not in HIV positive women. Sci Rep. 2020; 10: 19095. https://doi.org/10.1038/s41598-020-76003-7PMid:33154533 PMCid:PMC7644686 Sangpichai S, Patarapadungkit N, Pientong C, Ekalaksananan T, Chaiwiriyakul S, Thongbor R, et al. Chlamydia trachomatis infection in high-risk human papillomavirus based on cervical cytology specimen. Asian Pac J Cancer Prev. 2019; 20(12): 3843-7. https://doi.org/10.31557/APJCP.2019.20.12.3843PMid:31870131 PMCid:PMC7173371 Zhao S, Zhao XL, Hu SY, Wang Y, Remila R, Xu XQ, et al. Comparison of high-risk human papillomavirus infection rate and genotype distribution between Han and Mongolian women. Zhonghua Liu Xing Bing Xue Za Zhi. 2019;40(11):1439-44. Cao M, Wang Y, Wang D, Duan Y, Hong W, Zhang N, et al. Increased High-Risk Human Papillomavirus Viral Load Is Associated With Immunosuppressed Microenvironment and Predicts a Worse Long-Term Survival in Cervical Cancer Patients. Am J Clin Pathol. 2020;153(4):502-12. https://doi.org/10.1093/ajcp/aqz186PMid:31819948 Kang HJ, Chu KB, Kim MJ, Park H, Jin H, Lee SH, et al. Evaluation of CpG-ODN-Adjuvanted Toxoplasma gondii Virus-Like Particle Vaccine upon One, Two, and Three Immunizations. Pharmaceutics. 2020; 12(10): 989. https://doi.org/10.3390/pharmaceutics12100989PMid:33086673 PMCid:PMC7588908 Nikouyan N, Farhadi A, Gorzin AA, Geramizadeh B, Okhovat MA, Seyyedi N, et al. A fluorometric hybridization assay for detecting and genotyping high-risk human papillomavirus 16 and 18 in archival tissues of cervical specimens. Braz J Microbiol. 2020; 51(1): 161-8. https://doi.org/10.1007/s42770-019-00137-8PMid:31707717 PMCid:PMC7058809 Chan PK, Cheung TH, Li WH, Mei YY, Chan MY, Yim SF, et al. Attribution of human papillomavirus types to cervical intraepithelial neoplasia and invasive cancers in Southern China. Int J Cancer. 2012;131(3):692-705. https://doi.org/10.1002/ijc.26404PMid:21976212 Kyrgiou M, Mitra A, Moscicki AB. Does the vaginal microbiota play a role in the development of cervical cancer?. Transl Res. 2017; 179: 168-82. https://doi.org/10.1016/j.trsl.2016.07.004PMid:27477083 PMCid:PMC5164950

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Published

2023-05-20

Issue

Vol. 12 (2023): 2023

Section

Original Article

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https://creativecommons.org/licenses/by/4.0/