A Review on the Relationship Between p53 Gene and Viruses in Endometriosis

• Alaa Mahdy Obaid Khzal

  Department of Pathological Analyses, College of Science, University of Kufa, Najaf

Ten percent of pre-menopausal women suffer from endometriosis which manifests as a chronic inflammatory disorder due to complicated and poorly understood pathogenesis. The relationship between P53 tumor suppressor genes and viral infections as causes of endometriosis needs complete evaluation in research. Studies conducted at the molecular level reveal endometriotic lesions display major P53 expression variations while functional regulation and defensive abilities change from somatic mutations and DNA polymorphisms in addition to epigenetic influences that block tumor-suppression operations. Multiple investigations have established that endometriotic tissues carry human papillomavirus (HPV) Epstein-Barr virus (EBV) and cytomegalovirus (HCMV) viral DNA sequences with varying frequency percentages. The proposed mechanisms study how viral oncoproteins activate P53 pathways in endometriosis development by damaging cell death systems and through their influence on inflammatory processes and genomic instability creation and cell motility changes. The review examines how such biological interactions impact endometriosis diagnosis and treatment options. Currently missing components of known analysis become apparent in this research as it points out needed study techniques for understanding the sophisticated relationship between sun-induced skin damage and Human Papillomavirus infections.

Highlights: 

1. Endometriosis involves disrupted P53 function due to mutations, polymorphisms, and epigenetics.

2. Viral DNA from HPV, EBV, and HCMV is found in endometriotic tissues, implicating infections in disease progression.

3. Viral oncoproteins may alter P53 pathways, affecting inflammation, cell death, and genomic stability.

Keywords: Endometriosis, P53 Tumor Suppressor, Human Papillomavirus, Viral Oncoproteins, Inflammation

[1] J. J. Zeng, G. Q. Li, Y. Ji, L. Sun, and A. B. Wang, "Influence of HPV Infection on Expression Levels of P53 and CDC2 Proteins in Cancer Tissues of Patients With Endometrial Cancer," 2021.

[2] E. Cicinelli et al., "Altered Gene Expression Encoding Cytokines, Growth Factors and Cell Cycle Regulators in the Endometrium of Women With Chronic Endometritis," Diagnostics, vol. 11, no. 3, p. 471, 2021.

[3] J. Lamceva, R. Uljanovs, and I. Strumfa, "The Main Theories on the Pathogenesis of Endometriosis," Int. J. Mol. Sci., vol. 24, no. 5, p. 4254, 2023.

[4] T. Maruyama, "A Revised Stem Cell Theory for the Pathogenesis of Endometriosis," J. Pers. Med., vol. 12, no. 2, p. 216, 2022.

[5] H. Wang, M. Guo, H. Wei, and Y. Chen, "Targeting P53 Pathways: Mechanisms, Structures and Advances in Therapy," Signal Transduct. Target Ther., vol. 8, no. 1, p. 92, 2023.

[6] J. E. Zawacka-Pankau, "The Role of P53 Family in Cancer," Cancers, vol. 14, no. 3, p. 823, 2022.

[7] D. A. Hareza, J. R. Wilczyński, and E. Paradowska, "Human Papillomaviruses as Infectious Agents in Gynecological Cancers: Oncogenic Properties of Viral Proteins," Int. J. Mol. Sci., vol. 23, no. 3, p. 1818, 2022.

[8] Y. Han, Z. Liu, and T. Chen, "Role of Vaginal Microbiota Dysbiosis in Gynecological Diseases and the Potential Interventions," Front. Microbiol., vol. 12, p. 643422, 2021.

[9] A. Tresa et al., "Clinical Profile and Survival Outcome of Endometrial Cancer With P53 Mutation," Indian J. Surg. Oncol., vol. 13, no. 3, pp. 580–586, 2022.

[10] M. Köbel et al., "Interpretation of P53 Immunohistochemistry in Endometrial Carcinomas: Toward Increased Reproducibility," Int. J. Gynecol. Pathol., vol. 38, Suppl. 1, pp. S123–S131, 2019.

[11] H. E. Marei et al., "P53 Signaling in Cancer Progression and Therapy," Cancer Cell Int., vol. 21, no. 1, p. 703, 2021.

[12] J. Casanova et al., "Abnormal P53 High-Grade Endometrioid Endometrial Cancer: A Systematic Review and Meta-Analysis," Cancers, vol. 17, no. 1, p. 38, 2024.

[13] Y. Yang, S. F. Wu, and W. Bao, "Molecular Subtypes of Endometrial Cancer: Implications for Adjuvant Treatment Strategies," Int. J. Gynaecol. Obstet., vol. 164, no. 2, pp. 436–459, 2024.

[14] E. D. Serbes et al., "Retinoblastoma Protein Loss in P53 Abnormal Endometrial Carcinoma: Histologic and Clinicopathological Correlates," Mod. Pathol., vol. 38, no. 3, p. 100660, 2025.

[15] L. Huang, D. Sheng, X. Fan, R. Gao, and Y. Miao, "Molecular Characterization, Function, Tissue Differential Expression, and Single-Nucleotide Polymorphism of Buffalo TP53 Gene," Arch. Anim. Breed., vol. 67, no. 2, pp. 217–230, 2024.

[16] H. Kobayashi et al., "Rethinking the Pathogenesis of Endometriosis: Complex Interactions of Genomic, Epigenetic, and Environmental Factors," J. Obstet. Gynaecol. Res., vol. 50, no. 10, pp. 1771–1784, 2024.

[17] P. J. Wydorski et al., "Exposure to the Extremely Low-Frequency Electromagnetic Field Induces Changes in the Epigenetic Regulation of Gene Expression in the Endometrium," Theriogenology, vol. 217, pp. 72–82, 2024.

[18] A. S. Laganà et al., "The Pathogenesis of Endometriosis: Molecular and Cell Biology Insights," Int. J. Mol. Sci., vol. 20, no. 22, p. 5615, 2019.

[19] A. Santoro et al., "Mesonephric-Like Adenocarcinoma of the Endometrium: Detailed Molecular Characterization of the First Case Showing a Morphological Continuum," Virchows Arch., pp. 1–6, 2025.

[20] T. H. Vu et al., "Apolipoprotein-B mRNA-Editing Complex 3B Could Be a New Potential Therapeutic Target in Endometriosis," Sci. Rep., vol. 14, no. 1, p. 24968, 2024.

[21] J. Korbecki et al., "Involvement in Tumorigenesis and Clinical Significance of CXCL1 in Reproductive Cancers: Breast Cancer, Cervical Cancer, Endometrial Cancer, Ovarian Cancer and Prostate Cancer," Int. J. Mol. Sci., vol. 24, no. 8, p. 7262, 2023.

[22] J. G. Delenko et al., "Quercetin, a Senolytic, Enhances Endometrial Stromal Cell Decidualization Through AKT and P53 Signaling and Reveals the Potential Role of Senescent Stromal Cells in Endometriosis," medRxiv, 2023.

[23] E. Kalampokas et al., "Current Approaches to the Management of Patients With Endometrial Cancer," Cancers, vol. 14, no. 18, p. 4500, 2022.

[24] H. K. Chang et al., "Nectin-4 as a Predictive Marker for Poor Prognosis of Endometrial Cancer With Mismatch Repair Impairment," Cancers, vol. 15, no. 10, p. 2865, 2023.

[25] H. Asif et al., "Analysis of Endometrial Carcinoma TCGA Reveals Differences in DNA Methylation in Tumors From Black and White Women," Gynecol. Oncol., vol. 170, pp. 1–10, 2023.

[26] N. M. Abdelmaksoud et al., "The Role of miRNAs in the Pathogenesis and Therapeutic Resistance of Endometrial Cancer: A Spotlight on the Convergence of Signaling Pathways," Pathol. Res. Pract., vol. 244, p. 154411, 2023.

[27] P. Javadian, C. Washington, S. Mukasa, and D. M. Benbrook, "Histopathologic, Genetic and Molecular Characterization of Endometrial Cancer Racial Disparity," Cancers, vol. 13, no. 8, p. 1900, 2021.

[28] A. H. Chuwa and D. H. Mvunta, "Prognostic and Clinicopathological Significance of Survivin in Gynecological Cancer," Oncol. Rev., vol. 18, p. 1444008, 2024.

[29] C. N. Chao et al., "Clinical and Molecular Analysis of JCPyV and BKPyV Infection and Associated Risk of Urothelial Carcinoma Development in the Upper Tract," Virol. J., vol. 22, no. 1, p. 32, 2025.

[30] L. Nazari et al., "HPV Infection and Endometrial Polyps: Insights From a Case-Control Study," BMC Womens Health, vol. 24, no. 1, p. 598, 2024.

[31] X. Tang et al., "CDC42 Deficiency Leads to Endometrial Stromal Cell Senescence in Recurrent Implantation Failure," Hum. Reprod., vol. 39, no. 12, pp. 2768–2784, 2024.

[32] L. Ye, X. Wang, and B. Li, "Expression Profile of Epithelial-Mesenchymal Transition-Related Genes as a Prognostic Biomarker for Endometrial Cancer," J. Cancer, vol. 12, no. 21, p. 6484, 2021.

[33] R. Vargas et al., "Leveraging the P53 Signaling Pathway as a Radio-Sensitization Strategy in Endometrial Cancer," bioRxiv, 2022.

[34] J. Delenko et al., "Quercetin Enhances Decidualization Through AKT-ERK-P53 Signaling and Supports a Role for Senescence in Endometriosis," Reprod. Biol. Endocrinol., vol. 22, no. 1, p. 100, 2024.

[35] G. Ji et al., "HADHA Promotes Apoptosis and Inflammatory Response in Bovine Endometrial Epithelial Cells by Regulating Transcription and Metabolism," Int. J. Biol. Macromol., 2025, Art. no. 140980.

[36] S. Choi, Y. Y. Jung, and H. S. Kim, "Serous Carcinoma of the Endometrium With Mesonephric-Like Differentiation Initially Misdiagnosed as Uterine Mesonephric-Like Adenocarcinoma: A Case Report," Diagnostics, vol. 11, no. 4, p. 717, 2021.

[37] I. Sakamoto et al., "In Response to P53 Immunohistochemical Staining and TP53 Gene Mutations in Endometrial Cancer: Does Null Pattern Correlate With Prognosis?," Am. J. Surg. Pathol., vol. 48, no. 3, pp. 374–375, 2024.

[38] K. Michalova et al., "Next-Generation Sequencing in the Molecular Classification of Endometrial Carcinomas: Experience With 270 Cases," Virchows Arch., pp. 1–12, 2024.

[39] F. Kazanci et al., "Homologous Recombination Deficiency Gene Panel Analysis Results in Synchronous Endometrial and Ovarian Cancers," Rev. Assoc. Med. Bras., vol. 70, no. 10, p. e20240534, 2024.

[40] F. Blanc-Durand et al., "Clinical Utility of Comprehensive Liquid Molecular Profiling in Patients With Advanced Endometrial Cancer," Cancer, vol. 130, no. 19, pp. 3311–3320, 2024.

[41] A. Stan et al., "Detection of Driver Mutations and Genomic Signatures in Endometrial Cancers Using Artificial Intelligence Algorithms," PLoS One, vol. 19, no. 2, p. e0299114, 2024.