Correlation between human papillomavirus infection and vaginal microecological environment, and the effect of Lactobacillus vaginal capsules combined with recombinant human interferon α-2b gel on human papillomavirus infection.
Correlación entre la infección por el virus del papiloma humano y el entorno microecológico vaginal, y el efecto de cápsulas vaginales de Lactobacillus combinada con gel de interferón α-2b humano recombinante sobre la infección por el virus del papiloma humano.
Palabras clave:
infección por virus del papiloma humano, microecología vaginal, vaginosis bacteriana, cápsula vaginal de Lactobacillus, gel recombinante humano de interferón α-2b
Resumen
Este estudio analizó principalmente la correlación entre la infección por el virus del papiloma humano (VPH) y el entorno microecológico vaginal, y exploró el efecto de cápsulas vaginales de Lactobacillus combinadas con gel de interferón humano recombinante α-2b sobre la infección por VPH. Se seleccionaron 500 pacientes que se sometieron a examen ginecológico en nuestro hospital de junio de 2021 a junio de 2023 y se las dividió en un grupo positivo para VPH y un grupo negativo para VPH. En relación con el grupo VPH negativo, el grupo VPH positivo presentó mayor tasa anormal de Lactobacillus, catalasa, neuraminidasa, prolina aminopeptidasa y limpieza (p<0,05) y mayor tasa positiva de vaginosis bacteriana (BV) (p<0,05). El análisis multivariado de regresión logística mostró que la catalasa, la prolina aminopeptidasa y la BV fueron factores de riesgo para la infección por VPH (p<0,05). Además, 180 pacientes VPH positivos se dividieron aleatoriamente en un grupo control (GC) y un grupo de observación (OG). Al CG se le administró gel recombinante humano de interferón − -2b, y al OG se le administró gel recombinante humano de interferón − -2b más cápsulas vaginales de Lactobacillus. En relación con el GC, el OG presentó mayor tasa efectiva total (p<0,05), menor inflamación (p<0,01), mejor función inmune (p<0,01) y mayor proporción de densidad de flora vaginal de grado II-III y diversidad de flora vaginal de grado II-III (p< 0,001). Colectivamente, el VPH se correlaciona significativamente con el entorno microecológico vaginal, y la catalasa, la prolina aminopeptidasa y el BV se relación estrechamente con la infección por VPH. Además, las cápsulas vaginales de Lactobacillus más el gel de interferón α-2b recombinante humano tienen eficacia clínica efectiva, lo que puede reducir la inflamación, promover la función inmune, mejorar el entorno microecológico vaginal, y es seguro en el tratamiento de pacientes con infección por VPH.
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Kaur K, Kush P, Pandey RS, Madan J, Jain UK, Katare OP. Stealth lipid coated aquasomes bearing recombinant human interferon-α-2b offered prolonged release and enhanced cytotoxicity in ovarian cancer cells. Biomed Pharmacother 2015; 69: 267-276. https://doi.org10.1016/j.biopha.2014.12.007.
Yu J, Lu X, Tong L, Shi X, Ma J, Lv F, et al. Interferon-α-2b aerosol inhalation is associated with improved clinical outcomes in patients with coronavirus disease-2019.Br J Clin Pharmacol 2021; 87(12): 4737-4746. https://doi.org10.1111/bcp.14898.
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Dolina JS, Lee J, Brightman SE, McArdle S, Hall SM, Thota RR, et al. Linked CD4+/CD8+ T cell neoantigen vaccination overcomes immune checkpoint blockade resistance and enables tumor regression. J Clin Invest 2023; 133(17). https://doi.org10.1172/jci164258.
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Kanca H, Tez G, Bal K, Ozen D, Alcigir E, Atalay Vural S. Intratumoral recombinant human interferon alpha-2a and vincristine combination therapy in canine transmissible venereal tumour. Vet Med Sci 2018; 4(4): 364-372. https://doi.org10.1002/vms3.119.
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Rahangdale L, Mungo C, O’Connor S, Chibwesha CJ, Brewer NT. Human papillomavirus vaccination and cervical cancer risk. Bmj 2022; 379: e070115. https://doi.org10.1136/bmj-2022-070115.
Sucato A, Buttà M, Bosco L, Di Gregorio L, Perino A, Capra G. Human Papillomavirus and male infertility: What do we know? Int J Mol Sci 2023; 24(24). https://doi.org10.3390/ijms242417562.
Nelson CW, Mirabello L. Human papillomavirus genomics: Understanding carcinogenicity. Tumour virus research 2023; 15: 200258. https://doi.org10.1016/j.tvr.2023.200258.
Oyouni AAA. Human papillomavirus in cancer: Infection, disease transmission, and progress in vaccines. J Infect Public Health 2023; 16(4): 626-631. https://doi. org10.1016/j.jiph.2023.02.014.
Zhang Z, Ma Q, Zhang L, Ma L, Wang D, Yang Y, et al. Human papillomavirus and cervical cancer in the microbial world: exploring the vaginal microecology. Front Cell Infect Microbiol 2024; 14: 1325500. https://doi.org10.3389/ fcimb.2024.1325500.
Zang L, Feng R, Huang Y, Huang J, Hu Y. Relationship between vaginal microecology and human papillomavirus infection as well as cervical intraepithelial neoplasia in 2,147 women from Wenzhou, the southeast of China. Front Oncol 2023; 13: 1306376. https://doi.org10.3389/fonc.2023.1306376.
Ye J, Qi X. Vaginal microecology and its role in human papillomavirus infection and human papillomavirus associated cervical lesions. Apmis 2023. https://doi.org10.1111/apm.13356.
Fan Z, Han D, Fan X, Zeng Y, Zhao L. Analysis of the correlation between cervical HPV infection, cervical lesions and vaginal microecology. Front Cell Infect Microbiol 2024; 14: 1405789. https://doi.org10.3389/fcimb.2024.1405789.
Zhao HD, Feng XL, Zhao Y, Li N. Randomized controlled study: Sophora flavescens gel in treatment of cervical HPV infection]. Zhongguo Zhong Yao Za Zhi 2016; 41(21): 4072-4075. https://doi.org10.4268/cjcmm20162129.
Mändar R, Sõerunurk G, Štšepetova J, Smidt I, Rööp T, Kõljalg S, et al. Impact of Lactobacillus crispatus-containing oral and vaginal probiotics on vaginal health: a randomised double-blind placebo controlled clinical trial. Benef Microbes 2023; 14(2): 143-152. https://doi.org10.3920/bm2022.0091.
Li M, Zhao C, Zhao Y, Li J and Wei L. Immunogenicity, efficacy, and safety of human papillomavirus vaccine: Data from China. Front Immunol 2023; 14: 1112750. https://doi.org10.3389/fimmu.2023.1112750
.
Piña-Sánchez P. Human papillomavirus: challenges and opportunities for the control of cervical cancer. Archi Med Res 2022; 53(8): 753-769. https://doi.org10.1016/j.arcmed.2022.11.009.
Le D, Coriolan Ciceron A, Jeon MJ, Gonzalez LI, Jordan JA, Bordon J, Long B. Cervical cancer prevention and high-risk HPV self-sampling awareness and acceptability among women living with HIV: A qualitative investigation from the patients’ and providers’ perspectives. Curr Oncol 2022; 29(2): 516-533. https://doi.org10.3390/curroncol29020047.
Ye J, Zheng L, He Y, Qi X. Human papillomavirus associated cervical lesion: pathogenesis and therapeutic interventions. MedComm (2020) 2023; 4(5): e368. https://doi.org10.1002/mco2.368.
Chen X, Lu Y, Chen T, Li R. The female vaginal microbiome in health and bacterial vaginosis. Front Cell Infect Microbiol 2021; 11: 631972. https://doi.org10.3389/fcimb.2021.631972.
Li X, Wu J, Wu Y, Duan Z, Luo M, Li L, Li S, Jia Y. Imbalance of vaginal microbiota and immunity: two main accomplices of cervical Cancer in Chinese women. Int J Womens Health 2023; 15: 987-1002. https://doi.org/10.2147/ijwh.S406596.
Zheng JJ, Miao JR, Wu Q, Yu CX, Mu L, Song JH. Correlation between HPV-negative cervical lesions and cervical microenvironment. Taiwan J Obstet Gynecol 2020; 59(6): 855-861. https://doi.org10.1016/j.tjog.2020.08.002.
Deka N, Hassan S, Seghal Kiran G, Selvin J. Insights into the role of vaginal microbiome in women’s health. J Basic Microbiol 2021; 61(12): 1071-1084. https://doi. org10.1002/jobm.202100421.
Scillato M, Spitale A, Mongelli G, Privitera GF, Mangano K, Cianci A, et al.. Antimicrobial properties of Lactobacillus cell-free supernatants against multidrug-resistant urogenital pathogens. MicrobiologyOpen 2021; 10(2): e1173. https://doi. org10.1002/mbo3.1173.
Preci DP, Almeida A, Weiler AL, Mukai Franciosi ML, Cardoso AM. Oxidative damage and antioxidants in cervical cancer. Int J Gynecol Cancer 2021; 31(2): 265-271. https://doi.org10.1136/ijgc-2020-001587.
Li J, Jiang L, Wang C, Meng J, Wang H, Jin H. Investigation of the relationship between the changes in vaginal microecological enzymes and human papillomavirus (HPV) infection. Medicine (Baltimore) 2024; 103(6): e37068. https://doi.org10.1097/md.0000000000037068.
Cruz-Gregorio A, Aranda-Rivera AK, Ortega-Lozano AJ, Pedraza-Chaverri J, Mendoza-Hoffmann F. Lipid metabolism and oxidative stress in HPV-related cancers. Free Radic Biol Med 2021; 172: 226-236. https://doi.org10.1016/j.freeradbiomed.2021.06.009.
Ntuli L, Mtshali A, Mzobe G, Liebenberg LJ, Ngcapu S. Role of immunity and vaginal microbiome in clearance and persistence of human papillomavirus infection. Front Cell Infect Microbiol 2022; 12: 927131. https://doi.org/10.3389/fcimb.2022.927131.
Martins BCT, Guimarães RA, Alves RRF, Saddi VA. Bacterial vaginosis and cervical human papillomavirus infection in young and adult women: a systematic review and meta-analysis. Revista de saude publica 2023; 56: 113. https://doi.org10.11606/s1518-8787.2022056004412.
Guo YL, You K, Qiao J, Zhao YM, Geng L. Bacterial vaginosis is conducive to the persistence of HPV infection. Int J STD AIDS 2012; 23(8): 581-584. https://doi. org10.1258/ijsa.2012.011342.
Xu X, Zhang Y, Yu L, Shi X, Min M, Xiong L, et al. . A cross-sectional analysis about bacterial vaginosis, high-risk human papillomavirus infection, and cervical intraepithelial neoplasia in Chinese women. Sci Rep 2022; 12(1): 6609. https://doi.org10.1038/s41598-022-10532-1.
Kaur K, Kush P, Pandey RS, Madan J, Jain UK, Katare OP. Stealth lipid coated aquasomes bearing recombinant human interferon-α-2b offered prolonged release and enhanced cytotoxicity in ovarian cancer cells. Biomed Pharmacother 2015; 69: 267-276. https://doi.org10.1016/j.biopha.2014.12.007.
Yu J, Lu X, Tong L, Shi X, Ma J, Lv F, et al. Interferon-α-2b aerosol inhalation is associated with improved clinical outcomes in patients with coronavirus disease-2019.Br J Clin Pharmacol 2021; 87(12): 4737-4746. https://doi.org10.1111/bcp.14898.
Khan WA. Recombinant interferon Alpha- 2b is ahigh-affinity antigen for Type 1d diabetes autoantibodies. Can J Diabetes 2017; 41(2): 217-223. https://doi.org10.1016/j. jcjd.2016.10.001.
Yang A, Yang C, Yang B. Use of hydro-xychloroquine and interferon alpha-2b for the prophylaxis of COVID-19. Med Hypotheses 2020; 144: 109802. https://doi. org10.1016/j.mehy.2020.109802.
Mahajan G, Doherty E, To T, Sutherland A, Grant J, Junaid A, et al. Vaginal microbiome-host interactions modeled in a human vagina-on-a-chip. Microbiome 2022; 10(1): 201. https://doi.org10.1186/s40168-022-01400-1.
Ang XY, Mageswaran UM, Chung YLF, Lee BK, Azhar SNA, Roslan NS, et al. Probiotics reduce vaginal candidiasis in pregnant women via modulating abundance of Candida and Lactobacillus in vaginal and cervicovaginal regions. Microorganisms 2022; 10(2). https://doi.org10.3390/microorganisms10020285.
Koirala R, Gargari G, Arioli S, Taverniti V, Fiore W, Grossi E, et al. Effect of oral consumption of capsules containing Lacto-bacillus paracasei LPC-S01 on the vaginal microbiota of healthy adult women: a randomized, placebo controlled, double-blind crossover study. FEMS microbiology ecology 2020; 96(6). https://doi.org10.1093/femsec/fiaa084.
Marrazzo JM, Cook RL, Wiesenfeld HC, Murray PJ, Busse B, Krohn M, Hillier SL. Women’s satisfaction with an intravaginal Lactobacillus capsule for the treatment of bacterial vaginosis. J Women’s Health (2002) 2006; 15(9): 1053-1060. https://doi.org10.1089/jwh.2006.15.1053.
Yamaguchi M, Mtali YS, Sonokawa H, Takashima K, Fukushima Y, Kouwaki T, Oshiumi H. HPV vaccines induce trained immunity and modulate pro-inflammatory cytokine expression in response to secondary Toll-like receptor stimulations. Microbiol Immmunol, 2024; 68(2): 65-74. https://doi.org10.1111/1348-0421.13108.
Wu DW, Tsai LH, Chen PM, Lee MC, Wang L, Chen CY, Cheng YW, Lee H. Loss of TIMP-3 promotes tumor invasion via elevated IL -6 production and predicts poor survival and relapse in HPV-infected non-small cell lung cancer. Am J Pathol 2012; 181(5): 1796-1806. https://doi.org10.1016/j.aj-path.2012.07.032.
Dobrohotova YE, Korotkikh IN, Kuzmenko AV, VKV Gyaurgiev TA. [The efficiency of probiotics in the prevention of recurrent lower urinary tract infections and bacterial vaginosis]. Urologiia (Moscow, Russia : 1999) 2021(4): 30-34.
Joshi S, Anantharaman D, Muwonge R, Bhatla N, Panicker G, Butt J, et al. Evaluation of immune response to single dose of quadrivalent HPV vaccine at 10-year post-vaccination. Vaccine 2023; 41(1): 236-245. https://doi.org10.1016/j.vaccine.2022.11.044.
Dolina JS, Lee J, Brightman SE, McArdle S, Hall SM, Thota RR, et al. Linked CD4+/CD8+ T cell neoantigen vaccination overcomes immune checkpoint blockade resistance and enables tumor regression. J Clin Invest 2023; 133(17). https://doi.org10.1172/jci164258.
Ang XY, Roslan NS, Ahmad N, Yusof SM, Abdullah N, Nik Ab Rahman NN, et al. Lactobacillus probiotics restore vaginal and gut microbiota of pregnant women with vaginal candidiasis. Benef Microbes 2023; 14(5): 421-431. https://doi.org10.1163/18762891-20220103.
Shahid S, Nawaz Chaudhry M, Mahmood N and Sheikh S. Mutations of the human interferon alpha-2b gene in brain tumor patients exposed to different environmental conditions. Cancer Gene Ther 2015; 22(5): 246-261. https://doi.org/10.1038/cgt.2015.12.
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Publicado
2025-06-06
Cómo citar
Sun, Y., Li, L., Xu, W., & Ma, C. (2025). Correlation between human papillomavirus infection and vaginal microecological environment, and the effect of Lactobacillus vaginal capsules combined with recombinant human interferon α-2b gel on human papillomavirus infection.: Correlación entre la infección por el virus del papiloma humano y el entorno microecológico vaginal, y el efecto de cápsulas vaginales de Lactobacillus combinada con gel de interferón α-2b humano recombinante sobre la infección por el virus del papiloma humano. Investigación Clínica, 66(2), 131-146. https://doi.org/10.54817/IC.v66n2a01
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