Inflammation and Stem Cell Stochasticity of HPV-induced Cervical Cancer: Epigenetics based Biomarkers through Microbiome and Metabolome for Personalized Medicine: A Systematic Review

doi:10.2174/0109298673257429231108072717

. 2025;32(12):2390-2408.

doi: 10.2174/0109298673257429231108072717.

Inflammation and Stem Cell Stochasticity of HPV-induced Cervical Cancer: Epigenetics based Biomarkers through Microbiome and Metabolome for Personalized Medicine: A Systematic Review

Yufei Zheng¹, Junqi Liu^{1

2}, Narasimha Murthy Beeraka^{3

4

5}, Prasath Manogaran^{6

7}, Hemanth Vikram Poola Ramachandrappa³, Lakshmi Durga Yarramsetty Naga⁸, Shaik Mohammed Suhail⁸, Bhupalam Pradeepkumar³, Mikhail Y Sinelnikov^{4

9

10}, Greeshma Mandya Venkata¹¹, Mahesh Padukudru Anand¹¹, Namratha Mandya Parashivamurthy⁸, Gurupadayya Bannimath¹², Jie Zhao¹³, Ruitai Fan^{1

2}

Affiliations

¹ Department of Radiation Oncology, Cancer Center, The First Affiliated Hospital of Zhengzhou University, 1 Jianshedong Str., Zhengzhou, 450052, China.
² Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, 1 Jianshedong Str., Zhengzhou, 450052, China.
³ Raghavendra Institute of Pharmaceutical Education and Research (RIPER), Anantapuramu, Chiyyedu, Andhra Pradesh, 515721, India.
⁴ Department of Human Anatomy, I.M. Sechenov First Moscow State Medical University (Sechenov University), 8/2 Trubetskaya Street, Moscow, 119991, Russian Federation.
⁵ Herman B. Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, 1044 W. Walnut Street, R4-168, Indianapolis, IN 46202, Indiana.
⁶ Department of Biotechnology, Bharathiar University, Maruthamalai Road Coimbatore - 641046 Tamil Nadu, India.
⁷ Department of Clinical and Translational Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, West Virginia, USA.
⁸ Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research (JSS AHER), Mysuru, Karnataka, India.
⁹ Sinelab Biomedical Research Centre, Minnesota, 55905, USA.
¹⁰ Research Institute of Human Morphology, Russian Scientific Center of Surgery, Moscow, 119991, Russia.
¹¹ Department of Pulmonary Medicine, JSS Medical College, JSS Academy of Higher Education & Research (JSS AHER), Mysuru, Karnataka, India.
¹² Department of Pharmaceutical chemistry, JSS College of Pharmacy, JSS Academy of Higher Education & Research (JSS AHER), Mysuru, Karnataka, India.
¹³ Internet Medical and System Applications of National Engineering Laboratory, Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.

PMID: 38018189
DOI: 10.2174/0109298673257429231108072717

Inflammation and Stem Cell Stochasticity of HPV-induced Cervical Cancer: Epigenetics based Biomarkers through Microbiome and Metabolome for Personalized Medicine: A Systematic Review

Yufei Zheng et al. Curr Med Chem. 2025.

. 2025;32(12):2390-2408.

doi: 10.2174/0109298673257429231108072717.

Authors

Affiliations

¹ Department of Radiation Oncology, Cancer Center, The First Affiliated Hospital of Zhengzhou University, 1 Jianshedong Str., Zhengzhou, 450052, China.
² Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, 1 Jianshedong Str., Zhengzhou, 450052, China.
³ Raghavendra Institute of Pharmaceutical Education and Research (RIPER), Anantapuramu, Chiyyedu, Andhra Pradesh, 515721, India.
⁴ Department of Human Anatomy, I.M. Sechenov First Moscow State Medical University (Sechenov University), 8/2 Trubetskaya Street, Moscow, 119991, Russian Federation.
⁵ Herman B. Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, 1044 W. Walnut Street, R4-168, Indianapolis, IN 46202, Indiana.
⁶ Department of Biotechnology, Bharathiar University, Maruthamalai Road Coimbatore - 641046 Tamil Nadu, India.
⁷ Department of Clinical and Translational Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, West Virginia, USA.
⁸ Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research (JSS AHER), Mysuru, Karnataka, India.
⁹ Sinelab Biomedical Research Centre, Minnesota, 55905, USA.
¹⁰ Research Institute of Human Morphology, Russian Scientific Center of Surgery, Moscow, 119991, Russia.
¹¹ Department of Pulmonary Medicine, JSS Medical College, JSS Academy of Higher Education & Research (JSS AHER), Mysuru, Karnataka, India.
¹² Department of Pharmaceutical chemistry, JSS College of Pharmacy, JSS Academy of Higher Education & Research (JSS AHER), Mysuru, Karnataka, India.
¹³ Internet Medical and System Applications of National Engineering Laboratory, Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.

PMID: 38018189
DOI: 10.2174/0109298673257429231108072717

Abstract

Background: Chemoresistance by stemness in HPV-induced cervical carcinogenesis has significant implications for the overall disease-specific survival of the patients. To date, there are no reports related to the implications of significant aspects of inflammation and microbiome-mediated epigenetics in cervical cancers.

Objective: The current systematic review delineates the significant aspects of the inflammation-related pathophysiology, cervical cancer diagnosis based on the HPV-indued stemness, and microbiome-mediated epigenetic markers to develop personalized therapies to target the stemness-acquired indefinitely dividing cancer stem cells.

Methods: We performed a systematic review without a meta-analysis. We searched several public databases, such as Pubmed, ReleMed, National Library of Medicine, and Scopus, related to inflammation, metabolomics, microbiome-mediated epigenetic markers, and HPV-induced stemness.

Results and conclusion: The review significantly described the correlation between microbial inflammation and stem cell stochasticity of HPV-Induced cervical cancer and the expression of epigenetics-based biomarkers through microbiome and metabolome to foster the cervical cancer progression. These are major risk factors that can cause cervical dysplasia with substantial therapy resistance in cervical cancer patients. The qualitative and quantitative examination of the spatial transcriptomic expression of these stemness markers in the dividing cervical cancer stem cells has significant implications in the clinical sector to develop early personalized medicine to prevent cervical precancerous lesions depending on the prognosis of the cervical cancer patients. Mainly, the combinatorial regimen of current therapeutic modalities, along with microbiome-related therapies with future landscape of epigenetics-modulated therapies, may enhance overall disease-specific survival by modulating the stochastic dynamics of basal epithelial cells across the cervical region.

Keywords: HPV; Microbiome-epigenetic markers; cervical cancer; inflammation; metabolome.; microbiome; stemness.

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References

1. Sung H.; Ferlay J.; Siegel R.L.; Laversanne M.; Soerjomataram I.; Jemal A.; Bray F.; Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021,71(3),209-249 - DOI - PubMed
1. Arbyn M; Weiderpass E; Bruni L; de Sanjosé S; Saraiya M; Ferlay J; Bray F; Estimates of incidence and mortality of cervical cancer in 2018: A worldwide analysis. Lancet Glob Health 2020,8(2),e191-e203
1. Walboomers J.M.; Jacobs M.V.; Manos M.M.; Bosch F.X.; Kummer J.A.; Shah K.V.; Snijders P.J.; Peto J.; Meijer C.J.; Muñoz N.; Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 1999,189(1),12-19 - DOI - PubMed
1. Baker T.S.; Newcomb W.W.; Olson N.H.; Cowsert L.M.; Olson C.; Brown J.C.; Structures of bovine and human papillomaviruses. Analysis by cryoelectron microscopy and three-dimensional image reconstruction. Biophys J 1991,60(6),1445-1456 - DOI - PubMed
1. Bennett J.E.; Dolin R.; Blaser M.J.; Mandell, douglas, and bennett's principles and practice of infectious diseases E-book 2019

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[1] Sung H.; Ferlay J.; Siegel R.L.; Laversanne M.; Soerjomataram I.; Jemal A.; Bray F.; Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021,71(3),209-249 - DOI - PubMed

[2] Sung H.; Ferlay J.; Siegel R.L.; Laversanne M.; Soerjomataram I.; Jemal A.; Bray F.; Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021,71(3),209-249 - DOI - PubMed

[3] Arbyn M; Weiderpass E; Bruni L; de Sanjosé S; Saraiya M; Ferlay J; Bray F; Estimates of incidence and mortality of cervical cancer in 2018: A worldwide analysis. Lancet Glob Health 2020,8(2),e191-e203

[4] Arbyn M; Weiderpass E; Bruni L; de Sanjosé S; Saraiya M; Ferlay J; Bray F; Estimates of incidence and mortality of cervical cancer in 2018: A worldwide analysis. Lancet Glob Health 2020,8(2),e191-e203

[5] Walboomers J.M.; Jacobs M.V.; Manos M.M.; Bosch F.X.; Kummer J.A.; Shah K.V.; Snijders P.J.; Peto J.; Meijer C.J.; Muñoz N.; Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 1999,189(1),12-19 - DOI - PubMed

[6] Walboomers J.M.; Jacobs M.V.; Manos M.M.; Bosch F.X.; Kummer J.A.; Shah K.V.; Snijders P.J.; Peto J.; Meijer C.J.; Muñoz N.; Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 1999,189(1),12-19 - DOI - PubMed

[7] Baker T.S.; Newcomb W.W.; Olson N.H.; Cowsert L.M.; Olson C.; Brown J.C.; Structures of bovine and human papillomaviruses. Analysis by cryoelectron microscopy and three-dimensional image reconstruction. Biophys J 1991,60(6),1445-1456 - DOI - PubMed

[8] Baker T.S.; Newcomb W.W.; Olson N.H.; Cowsert L.M.; Olson C.; Brown J.C.; Structures of bovine and human papillomaviruses. Analysis by cryoelectron microscopy and three-dimensional image reconstruction. Biophys J 1991,60(6),1445-1456 - DOI - PubMed

[9] Bennett J.E.; Dolin R.; Blaser M.J.; Mandell, douglas, and bennett's principles and practice of infectious diseases E-book 2019

[10] Bennett J.E.; Dolin R.; Blaser M.J.; Mandell, douglas, and bennett's principles and practice of infectious diseases E-book 2019

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Inflammation and Stem Cell Stochasticity of HPV-induced Cervical Cancer: Epigenetics based Biomarkers through Microbiome and Metabolome for Personalized Medicine: A Systematic Review

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Inflammation and Stem Cell Stochasticity of HPV-induced Cervical Cancer: Epigenetics based Biomarkers through Microbiome and Metabolome for Personalized Medicine: A Systematic Review

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