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Review

HPV-Driven Cervical Carcinogenesis: Genetic and Epigenetic Mechanisms and Diagnostic Approaches

by
Evangelia Legaki
1,
Theofania Lappa
1,
Konstantina-Lida Prasoula
1,
Zoi Kardasi
1,
Emmanouil Kalampokas
2,
Theodoros Kalampokas
3,
Maria G. Roubelakis
1,
Ekaterina Charvalos
4 and
Maria Gazouli
1,*
1
Laboratory of Biology, Department of Basic Biological Science, School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece
2
Unit of Gynecologic Oncology, Second Department of Obstetrics and Gynecology, Aretaieion Hospital, 11528 Athens, Greece
3
Unit of Obstetrics and Gynecology, Second Department of Obstetrics and Gynecology, Aretaieion Hospital, 11528 Athens, Greece
4
Department of Molecular Diagnosis, Reprogenetica, Dios 44, 15235 Vrilissia, Greece
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2026, 27(2), 803; https://doi.org/10.3390/ijms27020803
Submission received: 14 December 2025 / Revised: 1 January 2026 / Accepted: 7 January 2026 / Published: 13 January 2026
(This article belongs to the Special Issue Molecular Advances in Gynecologic Cancer, 2nd Edition)
Versions Notes

Abstract

Cervical cancer remains a major global public health concern, with persistent infection by high-risk human papillomavirus (hrHPV) types recognized as the primary etiological factor. This review explores the multifactorial nature of the disease, focusing on the complex interplay between host genetic susceptibility and epigenetic alterations that drive cervical carcinogenesis. Evidence from genome-wide association studies (GWAS) is discussed, highlighting the contribution of specific genetic loci, predominantly within the HLA region, to susceptibility to HPV infection and disease progression. In parallel, the review examines the molecular mechanisms by which the viral oncoproteins E6 and E7 promote genetic instability and epigenetic reprogramming, including histone modifications and dysregulation of non-coding RNAs. Particular emphasis is placed on DNA methylation, affecting both the viral genome and host genes such as FAM19A4, CADM1, PAX1, and MAL, as a promising biomarker for triage and detection of high-grade intraepithelial lesions (CIN2+). Finally, the review evaluates currently available methylation-based assays and self-sampling devices, highlighting their potential to enhance diagnostic accuracy and increase participation in cervical cancer screening programs.
Keywords: cervical cancer; HPV; genetics; epigenetics; DNA methylation cervical cancer; HPV; genetics; epigenetics; DNA methylation

Share and Cite

MDPI and ACS Style

Legaki, E.; Lappa, T.; Prasoula, K.-L.; Kardasi, Z.; Kalampokas, E.; Kalampokas, T.; Roubelakis, M.G.; Charvalos, E.; Gazouli, M. HPV-Driven Cervical Carcinogenesis: Genetic and Epigenetic Mechanisms and Diagnostic Approaches. Int. J. Mol. Sci. 2026, 27, 803. https://doi.org/10.3390/ijms27020803

AMA Style

Legaki E, Lappa T, Prasoula K-L, Kardasi Z, Kalampokas E, Kalampokas T, Roubelakis MG, Charvalos E, Gazouli M. HPV-Driven Cervical Carcinogenesis: Genetic and Epigenetic Mechanisms and Diagnostic Approaches. International Journal of Molecular Sciences. 2026; 27(2):803. https://doi.org/10.3390/ijms27020803

Chicago/Turabian Style

Legaki, Evangelia, Theofania Lappa, Konstantina-Lida Prasoula, Zoi Kardasi, Emmanouil Kalampokas, Theodoros Kalampokas, Maria G. Roubelakis, Ekaterina Charvalos, and Maria Gazouli. 2026. "HPV-Driven Cervical Carcinogenesis: Genetic and Epigenetic Mechanisms and Diagnostic Approaches" International Journal of Molecular Sciences 27, no. 2: 803. https://doi.org/10.3390/ijms27020803

APA Style

Legaki, E., Lappa, T., Prasoula, K.-L., Kardasi, Z., Kalampokas, E., Kalampokas, T., Roubelakis, M. G., Charvalos, E., & Gazouli, M. (2026). HPV-Driven Cervical Carcinogenesis: Genetic and Epigenetic Mechanisms and Diagnostic Approaches. International Journal of Molecular Sciences, 27(2), 803. https://doi.org/10.3390/ijms27020803

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