Investigating the correlation between oncogenic HPV, sexually transmitted disease, and vaginal microbiota in patients with normal Pap smear
-
Farah Farzaneh
,
Khatereh Hekmatnia
,
Maryam Sadat Hosseini
,
Maliheh Arab
,
Maryam Talayeh
,
Mahshid Vasef
,
Samaneh Yavari
,
Hossein Keyvani
Abstract
Background and Objectives: This study investigated the correlation between high-risk (HR) human papillomavirus (HPV), sexually transmitted disease (STD), and vaginal microbiota in patients with a normal Pap smear.
Materials and Methods: For women who were referred for their routine cervical cancer screening, in addition to co-testing, some samples were taken from the vaginal and cervical environment to check the presence of the most common STD pathogens. The diagnosis of the organisms was done by means of PCR and microbial cultures.
Results: HR HPV was detected in 67 women, and STD was positive in 80% of them, while in HR HPV negative women, this was 67%. The HPV positive group reported a significantly higher rate of STD history (92% vs. 82%) and frequency of intercourse weekly (86% vs. 3.96%) (p<0.05). Lactobacilli, streptococcus, and staphylococcus concentrations were significantly lower in the HPV positive group compared to the HPV negative group (p<0.007; OR = 4.17). Ureaplasma urealyticum and Ureaplasma parvum were significantly (p<0.001) more prevalent in the HPV positive group compared to the HPV negative group.
Conclusion: This study showed that the existence of other STDs and the composition of the vaginal and cervical microbiome play an important role in either the clearance or the progression of high-risk HPV.
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13. Zhang T, Yu Z, Song D, Chen Y, Yao T, Peixoto E, et al. Sexual behavior transition and acute and early HIV infection among men who have sex with men: evidence from an open cohort in China, 2011–2019. Arch Sex Behav 2022; 51: 3557-3568.
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15. Ravel J, Gajer P, Abdo Z, Schneider GM, Koenig SS, McCulle SL, et al. Vaginal microbiome of reproductive-age women. Proc Natl Acad Sci U S A 2011; 108 Suppl 1(Suppl 1): 4680-4687.
16. Kovachev S. Defence factors of vaginal lactobacilli. Crit Rev Microbiol 2018; 44: 31-39.
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18. Dou P, Fang F, Qin R, Nie J, Chen X, Yin X, et al. Vaginal flora in HPV infection: a cross-sectional analysis. J Obstet Gynaecol 2024; 44: 2361847.
19. Tantengco OAG, Nakura Y, Yoshimura M, Nishiumi F, Llamas-Clark EF, Yanagihara I. Co-infection of human papillomavirus and other sexually transmitted bacteria in cervical cancer patients in the Philippines. Gynecol Oncol Rep 2022; 40: 100943.
20. Kops NL, Bessel M, Horvath JDC, Domingues C, de Souza FMA, Benzaken AS, et al. Factors associated with HPV and other self-reported STI coinfections among sexually active Brazilian young adults: cross-sectional nationwide study. BMJ Open 2019; 9(6): e027438.
21. Gallegos-Bolaños J, Rivera-Domínguez JA, Presno-Bernal JM, Cervantes-Villagrana RD. High prevalence of co-infection between human papillomavirus (HPV) 51 and 52 in Mexican population. BMC Cancer 2017; 17: 531.
22. Paesi S, Aver L, Barea F, Vanni A, Roesch-Ely M. Human papillomavirus and infections of the lower genital tract in women with abnormal cervical cytological examination. Sci Med 2013; 23: 41-46.
23. Zangeneh M, Veisi F, Najafi S, Hematti M. Evaluation of the effect of vaginal probiotic products in eliminating HPV virus in women. J Sabzevar Univ Med Sci 2024; 31: 714-723.
24. Eshtad E, Yaghoubi A, Khazaei M. The role of microbiota on women's reproductive health: defense mechanisms, pathogenesis, and its importance in uterine adhesion: A systematic review. Iran J Obstet Gynecol Infert 2024; 27: 81-100.
25. Gao W, Weng J, Gao Y, Chen X. Comparison of the vaginal microbiota diversity of women with and without human papillomavirus infection: a cross-sectional study. BMC Infect Dis 2013; 13: 271.
2. O'Hanlon DE, Moench TR, Cone RA. In vaginal fluid, bacteria associated with bacterial vaginosis can be suppressed with lactic acid but not hydrogen peroxide. BMC Infect Dis 2011; 11: 200.
3. Liu P, Yang X, Zhao H, Liang L, Chen M, Yin A. High burden of human papillomavirus infection among men in Guangzhou, South China: Implications for HPV vaccination strategies. Hum Vaccin Immunother 2024; 20: 2337161.
4. Tosado-Rodríguez E, Mendez LB, Espino AM, Dorta-Estremera S, Aquino EE, Romaguera J, et al. Inflammatory cytokines and a diverse cervicovaginal microbiota associate with cervical dysplasia in a cohort of Hispanics living in Puerto Rico. PLoS One 2023; 18(12): e0284673.
5. Chen Y, Qiu X, Wang W, Li D, Wu A, Hong Z, et al. Human papillomavirus infection and cervical intraepithelial neoplasia progression are associated with increased vaginal microbiome diversity in a Chinese cohort. BMC Infect Dis 2020; 20: 629.
6. Lin W, Zhang Q, Chen Y, Dong B, Xue H, Lei H, et al. Changes of the vaginal microbiota in HPV infection and cervical intraepithelial neoplasia: a cross-sectional analysis. Sci Rep 2022; 12: 2812.
7. Liu Y, Li R, Liu J, Liang X, Su M, Wang S, et al. Exploring the role of the vaginal microbiome in HPV infection dynamics: A prospective cohort study. iScience 2025; 28: 112476.
8. Yin Z, Feng T, Xu Q, Dai W, Ni M, Ni J, et al. Monitoring of Cell-free human papillomavirus DNA in metastatic or recurrent cervical cancer: clinical Significance and treatment implications. bioRxiv 2024; 10.1101/2024.09.16.613189.
9. Gargiulo Isacco C, Balzanelli MG, Garzone S, Lorusso M, Inchingolo F, Nguyen KC, et al. Alterations of vaginal microbiota and chlamydia trachomatis as crucial co-causative factors in cervical cancer genesis procured by HPV. Microorganisms 2023; 11: 662.
10. Gonçalves-Nobre JG, Matos A, Carreira M, Santos AC, Veiga LC, Ginete C, et al. The interplay between HPV, other sexually transmissible Infections, and genital microbiome on cervical microenvironment (MicroCervixHPV study). Front Cell Infect Microbiol 2024; 13: 1251913.
11. Plisko O, Zodzika J, Jermakova I, Pcolkina K, Prusakevica A, Liepniece-Karele I, et al. Prediction of high-grade cervical precancerous abnormalities: The role of personal factors, vaginal microflora, sexually transmitted infections, and high-risk human papillomavirus. PLoS One 2024; 19(11): e0313004.
12. Qing W, Shi Y, Chen R, Zou YA, Qi C, Zhang Y, et al. Species-level resolution for the vaginal microbiota with short amplicons. mSystems 2024; 9(2): e0103923.
13. Zhang T, Yu Z, Song D, Chen Y, Yao T, Peixoto E, et al. Sexual behavior transition and acute and early HIV infection among men who have sex with men: evidence from an open cohort in China, 2011–2019. Arch Sex Behav 2022; 51: 3557-3568.
14. Mitra A, MacIntyre DA, Marchesi JR, Lee YS, Bennett PR, Kyrgiou M. The vaginal microbiota, human papillomavirus infection and cervical intraepithelial neoplasia: what do we know and where are we going next? Microbiome 2016; 4: 58.
15. Ravel J, Gajer P, Abdo Z, Schneider GM, Koenig SS, McCulle SL, et al. Vaginal microbiome of reproductive-age women. Proc Natl Acad Sci U S A 2011; 108 Suppl 1(Suppl 1): 4680-4687.
16. Kovachev S. Defence factors of vaginal lactobacilli. Crit Rev Microbiol 2018; 44: 31-39.
17. Ağar E, Aker SS. Association of HPV and sexually transmitted infections among patients with genital warts and asymptomatic individuals: a crosssectional study. Eur J Gynaecol Oncol 2023; 44: 145-155.
18. Dou P, Fang F, Qin R, Nie J, Chen X, Yin X, et al. Vaginal flora in HPV infection: a cross-sectional analysis. J Obstet Gynaecol 2024; 44: 2361847.
19. Tantengco OAG, Nakura Y, Yoshimura M, Nishiumi F, Llamas-Clark EF, Yanagihara I. Co-infection of human papillomavirus and other sexually transmitted bacteria in cervical cancer patients in the Philippines. Gynecol Oncol Rep 2022; 40: 100943.
20. Kops NL, Bessel M, Horvath JDC, Domingues C, de Souza FMA, Benzaken AS, et al. Factors associated with HPV and other self-reported STI coinfections among sexually active Brazilian young adults: cross-sectional nationwide study. BMJ Open 2019; 9(6): e027438.
21. Gallegos-Bolaños J, Rivera-Domínguez JA, Presno-Bernal JM, Cervantes-Villagrana RD. High prevalence of co-infection between human papillomavirus (HPV) 51 and 52 in Mexican population. BMC Cancer 2017; 17: 531.
22. Paesi S, Aver L, Barea F, Vanni A, Roesch-Ely M. Human papillomavirus and infections of the lower genital tract in women with abnormal cervical cytological examination. Sci Med 2013; 23: 41-46.
23. Zangeneh M, Veisi F, Najafi S, Hematti M. Evaluation of the effect of vaginal probiotic products in eliminating HPV virus in women. J Sabzevar Univ Med Sci 2024; 31: 714-723.
24. Eshtad E, Yaghoubi A, Khazaei M. The role of microbiota on women's reproductive health: defense mechanisms, pathogenesis, and its importance in uterine adhesion: A systematic review. Iran J Obstet Gynecol Infert 2024; 27: 81-100.
25. Gao W, Weng J, Gao Y, Chen X. Comparison of the vaginal microbiota diversity of women with and without human papillomavirus infection: a cross-sectional study. BMC Infect Dis 2013; 13: 271.
| Files | ||
| Issue | Vol 17 No 5 (2025) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijm.v17i5.19892 | |
| Keywords | ||
| Human papillomavirus DNA tests Sexually transmitted diseases Bacterial Microbiota Uterine cervical neoplasms Cellular microenvironment | ||
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Farzaneh F, Hekmatnia K, Hosseini MS, Arab M, Talayeh M, Vasef M, Yavari S, Keyvani H. Investigating the correlation between oncogenic HPV, sexually transmitted disease, and vaginal microbiota in patients with normal Pap smear. Iran J Microbiol. 2025;17(5):835-840.
