Evaluation of Vimentin as a Marker of Cervical Carcinogenesis in Women Infected with Human Papillomavirus and Chlamydia trachomatis with Cervical Pathology
-
Sheba Joseph Magaji
,
Maryam Aminu
,
Muhammad Hassan I. Doko
,
Adekunle Olanrewaju Oguntayo
,
Saad A. Ahmed
,
Jigo D. Yaro
,
Murtala Abubakar
,
Kamarudeen Owolabi Sani
,
Victor Godwin Nelson
,
Ovye Engom Alaba
Abstract
Background: Among the co-factors contributing to human papillomavirus (HPV)-related cervical carcinogenesis, genital chlamydial infection is considered a very strong risk factor. The molecular mechanisms by which this organism contributes to HPV-related cervical carcinogenesis remain unknown. This study aimed to evaluate the role of vimentin in cervical carcinogenesis in women infected with human papillomavirus and Chlamydia trachomatis.
Materials and Methods: A total of 200 formalin-fixed paraffin-embedded (FFPE) cervical tissue samples were collected from women with pre-invasive and invasive cervical disease in northern Nigeria during July 2022 to September 2023. Samples were screened for both high-risk human papillomavirus (hrHPV) and C. trachomatis antigen using GeneXpert® and rapid tests, respectively. Samples that were positive for hrHPV, C. trachomatis, and cervical cancer underwent immunohistochemistry assay for vimentin detection.
Results: The results showed that 47 (23.5%) samples had hrHPV, while 17 (8.5%) samples had C. trachomatis antigen. A total of 103 samples were assayed for vimentin expression, of which 16 (15.5%) samples expressed vimentin at varying degrees. It was observed that vimentin expression increased significantly with increasing tumor severity.
Conclusion: The strong statistical association between vimentin expression and hrHPV-C. trachomatis co-infection in cervical carcinogenesis suggests the potential application of vimentin expression assays for early detection of cervical cancer, monitoring disease progression, and implementing prompt treatment approaches. This study findings implicate epithelial-mesenchymal transition (EMT) as a possible molecular mechanism for cervical carcinogenesis in women infected with hrHPV and C. trachomatis and highlight vimentin as a poor prognostic indicator, given its observed correlation with tumor severity.
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15. Sousa B, Paredes J, Milanezi F, et al. P-cadherin, vimentin and ck14 for identification of basal-like phenotype in breast carcinomas: An immunohistochemical study. Histol Histopathol. 2010; 25(8): 963-74.
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17. Lin J, Lu J, Wang C, et al. The prognostic values of the expression of vimentin, TP53, and podoplanin in patients with cervical cancer. Cancer Cell Int. 2017; 17: 80.
18. Guerendiain D, Moore C, Wells L, et al. Formalin-fixed paraffin embedded (FFPE) material is amenable to HPV detection by the Xpert®HPV assay. J Clin Virol. 2016; 77:55–59.
19. Centre for Disease Control and Prevention. Chlamydia: Pathogenesis and Microbiology 2023. Available at: https://www2a.cdc.gov/stdtraining/selfstudy/chlamydia/chlamydia_pathogenesis_self_study_from_cdc.html. Accessed: September 8th 2023.
20. Koskela P, Anttila T, Bjørge, T, et al. Chlamydia trachomatis infection as a risk factor for invasive cervical cancer. Int J Cancer. 2000; 85(1):35-39.
21. Petrosky E, Bochinni JA, Hariri S, et al. Use of 9-valent Human papillomavirus vaccine: Updated HPV vaccination recommendations of the advisory committee on immunisation practices. In: Centre for Disease Control and Prevention. MMWR Morb Mortal Wkly Rep. 2015;64(11):300-4.
22. Malik AI. The role of Human Papillomavirus (HPV) in the aetiology of cervical cancer. J Pak Med Assoc. 2005; 55(12): 553-558.
23. Zhu H, Shen Z, Luo H, et al. Chlamydia trachomatis infection-associated risk of cervical cancer: a meta-analysis. Medicine (Baltimore) 2016; 95: e3077.
24. Madaan N, Pandhi D, Sharma V, et al. Association of abnormal cervical cytology with coinfection of Human Papillomavirus and Chlamydia trachomatis. Indian J Sex Transm Dis AIDS. 2019; 40(1): 57-63.
25. Sangpichai S, Patarapadungkit N, Pientong C, et al. C. trachomatis infection in high-risk Human Papillomavirus based on cervical cytology specimen. Asian Pac J Cancer Prev. 2019; 20(12): 3843-3847.
26. Zadora PK, Chumduri C, Imami K, et al. Integrated phosphoproteome and transcriptome analysis reveals chlamydia-induced epithelial-to-mesenchymal transition in host cells. Cell Rep. 2019; 26(5): 1286-1302.e8.
27. Knowlton AE, Fowler LJ, Patel RK, et al. Chlamydia induces anchorage independence in 3T3 Cells and detrimental cytological defects in an infection model. PLoS One. 2013; 8(1):e54022.
28. Discacciati MG, Gimenes F, Pennacchi PC, et al. MMP-9/RECK imbalance: A mechanism associated with high-grade cervical lesions and genital infection by Human Papillomavirus and Chlamydia trachomatis. Cancer Epidemiol Biomarkers Prev. 2015; 24(10): 1539-47.
29. Chen H, Luo L, Wen Y, et al. Chlamydia trachomatis and Human Papillomavirus Infection in women from Southern Hunan province in China: a large observational study. Front Microbiol. 2020; 11: 827.
30. Franchini AAP, Iskander B, Anwer F, et al. The role of Chlamydia trachomatis in the pathogenesis of cervical cancer. Cureus. 2022; 14(1): e21331.
31. Dmello C, Sawant S, Alam H, et al. Vimentin regulates differentiation switch via modulation of keratin 14 levels and their expression together correlates with poor prognosis in oral cancer patients. PLoS One. 2017; 12(2): e0172559.
32. Dmello C, Sawant S, Chaudhari PR, et al. Aberrant expression of vimentin predisposes oral premalignant lesion derived cells towards transformation. Exp Mol Pathol. 2018; 105(3): 243–251.
33. Shibue T, Weinberg RA. EMT, CSCs, and drug resistance: The mechanistic link and clinical implications. Nat Rev Clin Oncol. 2017; 14(10): 611–629.
34. Lamouille S, Xu J, Derynck R. Molecular Mechanisms of Epithelial-Mesenchymal Transition. Nat Rev Mol Cell Biol. 2014; 15(3): 178–96.
35. Mahesh PP, Retnakumar RJ, Mundayoor S. Downregulation of vimentin in macrophages infected with Mycobacterium tuberculosis is mediated by reactive oxygen species. Sci Rep. 2016; 6: 21526.
36. Jung S, Yi L, Kim J, et al. The role of vimentin as a methylation biomarker for early diagnosis of cervical cancer. Mol Cells. 2011; 31(5): 405-11.
37. Yokoi E, Mabuchi S, Takahashi R, et al. Impact of histological subtype on survival in patients with locally advanced cervical cancer that were treated with definitive radiotherapy; adenocarcinoma/adenosquamous carcinoma versus squamous cell carcinoma. J Gynecol Oncol. 2017; 28(2):e19.
38. Pan X, Yang W, Wen Z, et al. Does adenocarcinoma have a worse prognosis than squamous cell carcinoma? A real-world study with a propensity score matching Analysis. J Gynecol Oncol. 2020; 31(16): e80.
39. Lee JY, Kim YT, Kim S, et al. Prognosis of cervical cancer in the era of concurrent chemoradiation form national database in Korea: A comparison between squamous cell carcinoma and adenocarcinoma. PLoS One. 2015; 10(12):e0144887.
40. Zhou J, Wu SG, Sun JY, et al. Comparison of clinical outcome of squmaous cell carcinoma, adenocarcinoma and adenosquamous carcinoma of the uterine cervix after definitive radiotherapy: A population-based analysis. J Cancer Res Clin Oncol. 2017; 143(1): 115-122.
41. Jonska-Gmyek J, Gmyrek L, Zolciak-Siwinska A, et al. Adenocarcinoma histology is a poor prognostic factor in locally advanced cervical cancer. Curr Med Res Opin. 2019;35(4):595-601.
42. Aoki D. Annual report of gynecologic oncology committee, Japan society of obstetrics and gynaecology, 2013. J Obstet and Gynaecol Res. 2014; 40(2): 338-48.
43. Nazik Elmalaika O S H, , Babiker AY, Albuti AS, et al. Clinicopathological significance of vimentin and cytokeratin protein in the genesis of squamous cell carcinoma of cervix. Obstet Gynecol Int. 2016:2016:8790120.
44. Al-Saad S, Al-Shibli K, Donnem T, et al. The prognostic impact of NF-
2. National Cancer Institute. Cervical Cancer Treatment (2022). Available from: www.cancer.gov/types/cervical/patient/cervical -treatment-pdq. Retrieved: September 24th, 2023.
3. American Sexual Health Association. HPV and Cervical Cancer (2021). Available from: www.ashasexualhealth.org/stdsstis/hpv. Accessed: July 3rd, 2021.
4. Bruni L, Diaz M, Castellsague X, et al. Cervical Human Papillomavirus prevalence in 5 continents: meta-analysis of 1 million women with normal cytological findings. J Infect Dis. 2010; 202(12):1789–99.
5. Anoruo O, Bristow C, Mody N, et al. Estimated prevalence of human papillomavirus among Nigerian women: A systematic review and meta-analysis. Afr J Reprod Health. 2022; 26 (6):89-96.
6. Ezechi O, Akinsolu F, Salako A, et al. High-risk Human Papillomavirus infection among Nigerian women: A systematic review and meta-analysis. J Int Med Res. 2023; 51(7):3000605231182884.
7. Huh WK. Human Papillomavirus Infection: A Concise Review of Natural History. Obstet Gynecol. 2009; 114(1):139–143.
8. Arnheim DL, Andersson K, Luostarinen T, et al. Prospective seroepidemiologic study of Human Papillomavirus and other risk factors in cervical cancer. Cancer Epidemiol Biomarkers Prev. 2011; 20(12): 2541-50.
9. Beuran M, Negoi I, Paun S, et al. The epithelial to mesenchymal transition in pancreatic cancer: A systematic review. Pancreatology. 2015; 15(3): 217-25.
10. Liu PF, Kang BH, Wu YM, et al. Vimentin is a potential prognostic factor for tongue squamous cell carcinoma among five epithelial-mesenchymal transition-related proteins. PLcoS One. 2017; 12(6): e0178581.
11. Kalluri R, Neilson EG. Epithelial-mesenchymal Transition and its Implications for Fibrosis. J Clin Invest. 2003; 112(12): 1776–84.
12. Thiery JP, Acloque H, Huang RY, et al. Epithelial-mesenchymal transitions in development and disease. Cell. 2009; 139(5): 871-90.
13. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011; 144(5): 646–74.
14. Cannavo I, Loubatier C, Chevallier A, et al. Improvement of DNA extraction for Human Papillomavirus genotyping from formalin-fixed paraffin-embedded tissues. Biores Open Access. 2012;1(6):333-7.
15. Sousa B, Paredes J, Milanezi F, et al. P-cadherin, vimentin and ck14 for identification of basal-like phenotype in breast carcinomas: An immunohistochemical study. Histol Histopathol. 2010; 25(8): 963-74.
16. Yu J, Zhou Q, Zheng Y, et al. Expression of vimentin and ki-67 proteins in cervical squamous cell carcinoma and their relationships with clinicopathological features. Asian Pac J Cancer Prev. 2015; 16(10):4271-5.
17. Lin J, Lu J, Wang C, et al. The prognostic values of the expression of vimentin, TP53, and podoplanin in patients with cervical cancer. Cancer Cell Int. 2017; 17: 80.
18. Guerendiain D, Moore C, Wells L, et al. Formalin-fixed paraffin embedded (FFPE) material is amenable to HPV detection by the Xpert®HPV assay. J Clin Virol. 2016; 77:55–59.
19. Centre for Disease Control and Prevention. Chlamydia: Pathogenesis and Microbiology 2023. Available at: https://www2a.cdc.gov/stdtraining/selfstudy/chlamydia/chlamydia_pathogenesis_self_study_from_cdc.html. Accessed: September 8th 2023.
20. Koskela P, Anttila T, Bjørge, T, et al. Chlamydia trachomatis infection as a risk factor for invasive cervical cancer. Int J Cancer. 2000; 85(1):35-39.
21. Petrosky E, Bochinni JA, Hariri S, et al. Use of 9-valent Human papillomavirus vaccine: Updated HPV vaccination recommendations of the advisory committee on immunisation practices. In: Centre for Disease Control and Prevention. MMWR Morb Mortal Wkly Rep. 2015;64(11):300-4.
22. Malik AI. The role of Human Papillomavirus (HPV) in the aetiology of cervical cancer. J Pak Med Assoc. 2005; 55(12): 553-558.
23. Zhu H, Shen Z, Luo H, et al. Chlamydia trachomatis infection-associated risk of cervical cancer: a meta-analysis. Medicine (Baltimore) 2016; 95: e3077.
24. Madaan N, Pandhi D, Sharma V, et al. Association of abnormal cervical cytology with coinfection of Human Papillomavirus and Chlamydia trachomatis. Indian J Sex Transm Dis AIDS. 2019; 40(1): 57-63.
25. Sangpichai S, Patarapadungkit N, Pientong C, et al. C. trachomatis infection in high-risk Human Papillomavirus based on cervical cytology specimen. Asian Pac J Cancer Prev. 2019; 20(12): 3843-3847.
26. Zadora PK, Chumduri C, Imami K, et al. Integrated phosphoproteome and transcriptome analysis reveals chlamydia-induced epithelial-to-mesenchymal transition in host cells. Cell Rep. 2019; 26(5): 1286-1302.e8.
27. Knowlton AE, Fowler LJ, Patel RK, et al. Chlamydia induces anchorage independence in 3T3 Cells and detrimental cytological defects in an infection model. PLoS One. 2013; 8(1):e54022.
28. Discacciati MG, Gimenes F, Pennacchi PC, et al. MMP-9/RECK imbalance: A mechanism associated with high-grade cervical lesions and genital infection by Human Papillomavirus and Chlamydia trachomatis. Cancer Epidemiol Biomarkers Prev. 2015; 24(10): 1539-47.
29. Chen H, Luo L, Wen Y, et al. Chlamydia trachomatis and Human Papillomavirus Infection in women from Southern Hunan province in China: a large observational study. Front Microbiol. 2020; 11: 827.
30. Franchini AAP, Iskander B, Anwer F, et al. The role of Chlamydia trachomatis in the pathogenesis of cervical cancer. Cureus. 2022; 14(1): e21331.
31. Dmello C, Sawant S, Alam H, et al. Vimentin regulates differentiation switch via modulation of keratin 14 levels and their expression together correlates with poor prognosis in oral cancer patients. PLoS One. 2017; 12(2): e0172559.
32. Dmello C, Sawant S, Chaudhari PR, et al. Aberrant expression of vimentin predisposes oral premalignant lesion derived cells towards transformation. Exp Mol Pathol. 2018; 105(3): 243–251.
33. Shibue T, Weinberg RA. EMT, CSCs, and drug resistance: The mechanistic link and clinical implications. Nat Rev Clin Oncol. 2017; 14(10): 611–629.
34. Lamouille S, Xu J, Derynck R. Molecular Mechanisms of Epithelial-Mesenchymal Transition. Nat Rev Mol Cell Biol. 2014; 15(3): 178–96.
35. Mahesh PP, Retnakumar RJ, Mundayoor S. Downregulation of vimentin in macrophages infected with Mycobacterium tuberculosis is mediated by reactive oxygen species. Sci Rep. 2016; 6: 21526.
36. Jung S, Yi L, Kim J, et al. The role of vimentin as a methylation biomarker for early diagnosis of cervical cancer. Mol Cells. 2011; 31(5): 405-11.
37. Yokoi E, Mabuchi S, Takahashi R, et al. Impact of histological subtype on survival in patients with locally advanced cervical cancer that were treated with definitive radiotherapy; adenocarcinoma/adenosquamous carcinoma versus squamous cell carcinoma. J Gynecol Oncol. 2017; 28(2):e19.
38. Pan X, Yang W, Wen Z, et al. Does adenocarcinoma have a worse prognosis than squamous cell carcinoma? A real-world study with a propensity score matching Analysis. J Gynecol Oncol. 2020; 31(16): e80.
39. Lee JY, Kim YT, Kim S, et al. Prognosis of cervical cancer in the era of concurrent chemoradiation form national database in Korea: A comparison between squamous cell carcinoma and adenocarcinoma. PLoS One. 2015; 10(12):e0144887.
40. Zhou J, Wu SG, Sun JY, et al. Comparison of clinical outcome of squmaous cell carcinoma, adenocarcinoma and adenosquamous carcinoma of the uterine cervix after definitive radiotherapy: A population-based analysis. J Cancer Res Clin Oncol. 2017; 143(1): 115-122.
41. Jonska-Gmyek J, Gmyrek L, Zolciak-Siwinska A, et al. Adenocarcinoma histology is a poor prognostic factor in locally advanced cervical cancer. Curr Med Res Opin. 2019;35(4):595-601.
42. Aoki D. Annual report of gynecologic oncology committee, Japan society of obstetrics and gynaecology, 2013. J Obstet and Gynaecol Res. 2014; 40(2): 338-48.
43. Nazik Elmalaika O S H, , Babiker AY, Albuti AS, et al. Clinicopathological significance of vimentin and cytokeratin protein in the genesis of squamous cell carcinoma of cervix. Obstet Gynecol Int. 2016:2016:8790120.
44. Al-Saad S, Al-Shibli K, Donnem T, et al. The prognostic impact of NF-
| Files | ||
| Issue | Vol 19 No 3 (2025) | |
| Section | Original Article(s) | |
| Keywords | ||
| hrHPV; Chlamydia trachomatis; Vimentin; FFPE; Cervical cancer | ||
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How to Cite
1.
Magaji S, Aminu M, Doko M, Oguntayo A, Ahmed S, Yaro J, Abubakar M, Sani K, Nelson V, Alaba O. Evaluation of Vimentin as a Marker of Cervical Carcinogenesis in Women Infected with Human Papillomavirus and Chlamydia trachomatis with Cervical Pathology. Int J Hematol Oncol Stem Cell Res. 2025;19(3):223-236.
