Low presence of papillomavirus and its lack of correlation with clinicopathological factors in breast cancer: a case control study
-
Manoochehr Makvandi
,
Mohammad Rashno
,
Ebrahim Faghihloo
,
Shahram Bagheri
,
Saeed Hesam
,
Habibollah Mirzaei
,
Ali Ramezani
Abstract
Background and Objectives: Breast cancer is currently the most commonly diagnosed neoplasm in women worldwide. There is evidence that human papillomavirus (HPV) infection may play a key role in breast cancer aggressiveness, but results are conflicting across studies. The aim of this study was to investigate the presence of the HPV viral genome in benign and malignant breast tissue samples and its clinicopathological characteristics of cancer.
Materials and Methods: In this case-control study, 100 formalin-fixed paraffin-embedded (FFPE) of breast cancer and 100 blocks of non-cancerous breast tissue were selected as a control group from the pathology department of Imam Khomeini Hospital in Ahvaz from 2020-2022. The presence of HPV was detected using nested PCR including MY09/11 primers and sequencing were performed for virus genotyping.
Results: The present study enrolled 100 subjects each in two cancer and control groups with a mean age of 52.81±13.23 and 35.77±11.65, respectively. The risk of cancer in HPV-infected patients is almost 5 times higher than in HPV-negative individuals, it is not statistically significant (OR =4.99, 95% CI 0.35 to 72.15, p=0.238). The prevalence of HPV in the cancer and control groups was 7% and 1%, respectively and HPVs detected in two groups were of the HPV 16 genotype. Although the chance of ER and PR expression, lymphvascular involvement, perineural invasion, and higher tumor grade was higher in HPV-positive subjects than in HPV-negative subjects, this was not statistically significant (OR>1, p>0.05).
Conclusion: Based on studies reporting the existence of sequences of different high-risk HPV types (oncogenes) in breast cancer tissues, this study confirmed the hypothesis of a possible infectious cause in the development of breast cancer. So far, however, the results have been controversial and inconclusive. Further studies with large sample sizes are needed to demonstrate the link between HPV and breast cancer.
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5. Gupta I, Ulamec M, Peric-Balja M, Ramic S, Al Moustafa AE, Vranic S, et al. Presence of high-risk HPVs, EBV, and MMTV in human triple-negative breast cancer. Hum Vaccin Immunother 2021; 17: 4457-4466.
6. Paver EC, Currie AM, Gupta R, Dahlstrom JE. Human papilloma virus related squamous cell carcinomas of the head and neck: diagnosis, clinical implications and detection of HPV. Pathology 2020; 52: 179-191.
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8. Sher G, Salman NA, Kulinski M, Fadel RA, Gupta VK, Anand A, et al. Prevalence and type distribution of high-risk human Papillomavirus (HPV) in breast cancer: a qatar based study. Cancers (Basel) 2020; 12: 1528.
9. Szymonowicz KA, Chen J. Biological and clinical aspects of HPV-related cancers. Cancer Biol Med 2020; 17: 864-878.
10. Lawson JS, Glenn WK. Catching viral breast cancer. Infect Agent Cancer 2021; 16: 37.
11. Venceslau EM, Bezerra MM, Lopes ACM, Souza ÉV, Onofre ASC, de Melo CM, et al. HPV detection using primers MY09/MY11 and GP5+/GP6+ in patients with cytologic and/or colposcopic changes. J Bras Patol Med Lab 2014; 50: 280-285.
12. Li J, Ding J, Zhai K. Detection of human papillomavirus DNA in patients with breast tumor in China. PLoS One 2015; 10(8): e0136050.
13. Makvandi M, Jalilian S, Faghihloo E, Khanizadeh S, Ramezani A, Bagheri S, et al. Prevalence of human Papillomavirus and co-infection with Epstein-Barr Virus in oral and oropharyngeal Squamous Cell Carcinomas. Asian Pac J Cancer Prev 2022; 23: 3931-3937.
14. Dureh N, Choonpradub C, Tongkumchum P. An alternative method for logistic regression on contingency tables with zero cell counts. Songklanakarin J Sci Technol 2016; 38: 171-176.
15. Ghittoni R, Accardi R, Chiocca S, Tommasino M. Role of human papillomaviruses in carcinogenesis. Ecancermedicalscience 2015; 9: 526.
16. Islam S, Dasgupta H, Roychowdhury A, Bhattacharya R, Mukherjee N, Roy A, et al. Study of association and molecular analysis of human papillomavirus in breast cancer of Indian patients: Clinical and prognostic implication. PloS One 2017; 12(2): e0172760.
17. Williams VM, Filippova M, Soto U, Duerksen-Hughes PJ. HPV-DNA integration and carcinogenesis: putative roles for inflammation and oxidative stress. Future Virol 2011; 6: 45-57.
18. Maldonado-Rodríguez E, Hernández-Barrales M, Reyes-López A, Godina-González S, Gallegos-Flores PI, Esparza-Ibarra EL, et al. Presence of human papillomavirus DNA in Malignant Neoplasia and non-malignant breast disease. Curr Issues Mol Biol 2022; 44: 3648-3665.
19. Rezaee Azhar I, Yaghoobi M, Mossalaeie MM, Kollaee Darabi A, Nejadeh AH, Jamshidi M, et al. Prevalence of human papilloma virus (HPV) genotypes between outpatients males and females referred to seven laboratories in Tehran, Iran. Infect Agent Cancer 2022; 17: 7.
20. Jamdar F, Farzaneh F, Navidpour F, Younesi S, Balvayeh P, Hosseini M, et al. Prevalence of human papillomavirus infection among Iranian women using COBAS HPV DNA testing. Infect Agent Cancer 2018; 13: 6.
21. Malhone C, Longatto-Filho A, Filassi JR. Is human Papilloma Virus associated with breast cancer? A review of the molecular evidence. Acta Cytol 2018; 62: 166-177.
22. Khodabandehlou N, Mostafaei S, Etemadi A, Ghasemi A, Payandeh M, Hadifar S, et al. Human papilloma virus and breast cancer: the role of inflammation and viral expressed proteins. BMC Cancer 2019; 19: 61.
23. Sigaroodi A, Nadji SA, Naghshvar F, Nategh R, Emami H, Velayati AA. Human papillomavirus is associated with breast cancer in the north part of Iran. ScientificWorldJournal 2012; 2012: 837191.
24. Haghshenas MR, Mousavi T, Moosazadeh M, Afshari M. Human papillomavirus and breast cancer in Iran: a meta-analysis. Iran J Basic Med Sci 2016; 19: 231-237.
25. Malekpour Afshar R, Balar N, Mollaei HR, Arabzadeh SA, Iranpour M. Low prevalence of human papilloma virus in patients with breast cancer, Kerman; Iran. Asian Pac J Cancer Prev 2018; 19: 3039-3044.
26. Simões PW, Medeiros LR, Pires PDS, Edelweiss MI, Rosa DD, Silva FR, et al. Prevalence of human papillomavirus in breast cancer: a systematic review. Int J Gynecol Cancer 2012; 22: 343-347.
27. Li N, Bi X, Zhang Y, Zhao P, Zheng T, Dai M. Human papillomavirus infection and sporadic breast carcinoma risk: a meta-analysis. Breast Cancer Res Treat 2011; 126: 515-520.
28. Bae J-M, Kim EH. Human papillomavirus infection and risk of breast cancer: a meta-analysis of case-control studies. Infect Agent Cancer 2016; 11: 14.
29. Khan N, Castillo A, Koriyama C, Kijima Y, Umekita Y, Ohi Y, et al. Human papillomavirus detected in female breast carcinomas in Japan. Br J Cancer 2008; 99: 408-414.
30. Fernandes A, Bianchi G, Feltri AP, Pérez M, Correnti M. Presence of human papillomavirus in breast cancer and its association with prognostic factors. Ecancermedicalscience 2015; 9: 548.
31. Herrera-Goepfert R, Vela-Chávez T, Carrillo-García A, Lizano-Soberón M, Amador-Molina A, Oñate-Ocaña LF, et al. High-risk human papillomavirus (HPV) DNA sequences in metaplastic breast carcinomas of Mexican women. BMC Cancer 2013; 13: 445.
32. Ahmed HG, Bensumaidea SH, Alshammari FD, Alenazi FSH, BA AL, Alturkstani MZ, et al. Prevalence of human papillomavirus subtypes 16 and 18 among Yemeni patients with Cervical Cancer. Asian Pac J Cancer Prev 2017; 18: 1543-1548.
33. Gebregzabher E, Seifu D, Tigneh W, Bokretsion Y, Bekele A, Abebe M, et al. Detection of high-and low-risk HPV DNA in archived breast carcinoma tissues from ethiopian women. Int J Breast Cancer 2021; 2021: 2140151.
34. Cavalcante JR, Pinheiro LGP, Almeida PRC, Ferreira MVP, Cruz GA, Campelo TA, et al. Association of breast cancer with human papillomavirus (HPV) infection in Northeast Brazil: molecular evidence. Clinics (Sao Paulo) 2018; 73: e465.
35. Mobini Kesheh M, Keyvani H. The Prevalence of HPV Genotypes in Iranian population: an update. Iran J Pathol 2019; 14: 197-205.
36. Salman NA, Davies G, Majidy F, Shakir F, Akinrinade H, Perumal D, et al. Association of high risk human papillomavirus and breast cancer: a UK based study. Sci Rep 2017; 7: 43591.
37. Antonsson A, Spurr TP, Chen AC, Francis GD, McMillan NA, Saunders NA, et al. High prevalence of human papillomaviruses in fresh frozen breast cancer samples. J Med Virol 2011; 83: 2157-2163.
38. Doosti M, Bakhshesh M, Zahir ST, Shayestehpour M, Karimi-Zarchi M. Lack of evidence for a relationship between high risk human papillomaviruses and breast cancer in Iranian patients. Asian Pac J Cancer Prev 2016; 17: 4357-4361.
2. Haghshenas MR, Mousavi T, Kheradmand M, Afshari M, Moosazadeh M. Efficacy of human Papillomavirus L1 protein vaccines (Cervarix and Gardasil) in reducing the risk of cervical intraepithelial neoplasia: A Meta-analysis. Int J Prev Med 2017; 8: 44.
3. Feng Y, Spezia M, Huang S, Yuan C, Zeng Z, Zhang L, et al. Breast cancer development and progression: Risk factors, cancer stem cells, signaling pathways, genomics, and molecular pathogenesis. Genes Dis 2018; 5: 77-106.
4. Chen C-J, Hsu W-L, Yang H-I, Lee M-H, Chen H-C, Chien Y-C, et al. Epidemiology of virus infection and human cancer. Recent Results Cancer Res 2014; 193: 11-32.
5. Gupta I, Ulamec M, Peric-Balja M, Ramic S, Al Moustafa AE, Vranic S, et al. Presence of high-risk HPVs, EBV, and MMTV in human triple-negative breast cancer. Hum Vaccin Immunother 2021; 17: 4457-4466.
6. Paver EC, Currie AM, Gupta R, Dahlstrom JE. Human papilloma virus related squamous cell carcinomas of the head and neck: diagnosis, clinical implications and detection of HPV. Pathology 2020; 52: 179-191.
7. Giraldi L, Collatuzzo G, Hashim D, Franceschi S, Herrero R, Chen C, et al. Infection with Human Papilloma Virus (HPV) and risk of subsites within the oral cancer. Cancer Epidemiol 2021; 75: 102020.
8. Sher G, Salman NA, Kulinski M, Fadel RA, Gupta VK, Anand A, et al. Prevalence and type distribution of high-risk human Papillomavirus (HPV) in breast cancer: a qatar based study. Cancers (Basel) 2020; 12: 1528.
9. Szymonowicz KA, Chen J. Biological and clinical aspects of HPV-related cancers. Cancer Biol Med 2020; 17: 864-878.
10. Lawson JS, Glenn WK. Catching viral breast cancer. Infect Agent Cancer 2021; 16: 37.
11. Venceslau EM, Bezerra MM, Lopes ACM, Souza ÉV, Onofre ASC, de Melo CM, et al. HPV detection using primers MY09/MY11 and GP5+/GP6+ in patients with cytologic and/or colposcopic changes. J Bras Patol Med Lab 2014; 50: 280-285.
12. Li J, Ding J, Zhai K. Detection of human papillomavirus DNA in patients with breast tumor in China. PLoS One 2015; 10(8): e0136050.
13. Makvandi M, Jalilian S, Faghihloo E, Khanizadeh S, Ramezani A, Bagheri S, et al. Prevalence of human Papillomavirus and co-infection with Epstein-Barr Virus in oral and oropharyngeal Squamous Cell Carcinomas. Asian Pac J Cancer Prev 2022; 23: 3931-3937.
14. Dureh N, Choonpradub C, Tongkumchum P. An alternative method for logistic regression on contingency tables with zero cell counts. Songklanakarin J Sci Technol 2016; 38: 171-176.
15. Ghittoni R, Accardi R, Chiocca S, Tommasino M. Role of human papillomaviruses in carcinogenesis. Ecancermedicalscience 2015; 9: 526.
16. Islam S, Dasgupta H, Roychowdhury A, Bhattacharya R, Mukherjee N, Roy A, et al. Study of association and molecular analysis of human papillomavirus in breast cancer of Indian patients: Clinical and prognostic implication. PloS One 2017; 12(2): e0172760.
17. Williams VM, Filippova M, Soto U, Duerksen-Hughes PJ. HPV-DNA integration and carcinogenesis: putative roles for inflammation and oxidative stress. Future Virol 2011; 6: 45-57.
18. Maldonado-Rodríguez E, Hernández-Barrales M, Reyes-López A, Godina-González S, Gallegos-Flores PI, Esparza-Ibarra EL, et al. Presence of human papillomavirus DNA in Malignant Neoplasia and non-malignant breast disease. Curr Issues Mol Biol 2022; 44: 3648-3665.
19. Rezaee Azhar I, Yaghoobi M, Mossalaeie MM, Kollaee Darabi A, Nejadeh AH, Jamshidi M, et al. Prevalence of human papilloma virus (HPV) genotypes between outpatients males and females referred to seven laboratories in Tehran, Iran. Infect Agent Cancer 2022; 17: 7.
20. Jamdar F, Farzaneh F, Navidpour F, Younesi S, Balvayeh P, Hosseini M, et al. Prevalence of human papillomavirus infection among Iranian women using COBAS HPV DNA testing. Infect Agent Cancer 2018; 13: 6.
21. Malhone C, Longatto-Filho A, Filassi JR. Is human Papilloma Virus associated with breast cancer? A review of the molecular evidence. Acta Cytol 2018; 62: 166-177.
22. Khodabandehlou N, Mostafaei S, Etemadi A, Ghasemi A, Payandeh M, Hadifar S, et al. Human papilloma virus and breast cancer: the role of inflammation and viral expressed proteins. BMC Cancer 2019; 19: 61.
23. Sigaroodi A, Nadji SA, Naghshvar F, Nategh R, Emami H, Velayati AA. Human papillomavirus is associated with breast cancer in the north part of Iran. ScientificWorldJournal 2012; 2012: 837191.
24. Haghshenas MR, Mousavi T, Moosazadeh M, Afshari M. Human papillomavirus and breast cancer in Iran: a meta-analysis. Iran J Basic Med Sci 2016; 19: 231-237.
25. Malekpour Afshar R, Balar N, Mollaei HR, Arabzadeh SA, Iranpour M. Low prevalence of human papilloma virus in patients with breast cancer, Kerman; Iran. Asian Pac J Cancer Prev 2018; 19: 3039-3044.
26. Simões PW, Medeiros LR, Pires PDS, Edelweiss MI, Rosa DD, Silva FR, et al. Prevalence of human papillomavirus in breast cancer: a systematic review. Int J Gynecol Cancer 2012; 22: 343-347.
27. Li N, Bi X, Zhang Y, Zhao P, Zheng T, Dai M. Human papillomavirus infection and sporadic breast carcinoma risk: a meta-analysis. Breast Cancer Res Treat 2011; 126: 515-520.
28. Bae J-M, Kim EH. Human papillomavirus infection and risk of breast cancer: a meta-analysis of case-control studies. Infect Agent Cancer 2016; 11: 14.
29. Khan N, Castillo A, Koriyama C, Kijima Y, Umekita Y, Ohi Y, et al. Human papillomavirus detected in female breast carcinomas in Japan. Br J Cancer 2008; 99: 408-414.
30. Fernandes A, Bianchi G, Feltri AP, Pérez M, Correnti M. Presence of human papillomavirus in breast cancer and its association with prognostic factors. Ecancermedicalscience 2015; 9: 548.
31. Herrera-Goepfert R, Vela-Chávez T, Carrillo-García A, Lizano-Soberón M, Amador-Molina A, Oñate-Ocaña LF, et al. High-risk human papillomavirus (HPV) DNA sequences in metaplastic breast carcinomas of Mexican women. BMC Cancer 2013; 13: 445.
32. Ahmed HG, Bensumaidea SH, Alshammari FD, Alenazi FSH, BA AL, Alturkstani MZ, et al. Prevalence of human papillomavirus subtypes 16 and 18 among Yemeni patients with Cervical Cancer. Asian Pac J Cancer Prev 2017; 18: 1543-1548.
33. Gebregzabher E, Seifu D, Tigneh W, Bokretsion Y, Bekele A, Abebe M, et al. Detection of high-and low-risk HPV DNA in archived breast carcinoma tissues from ethiopian women. Int J Breast Cancer 2021; 2021: 2140151.
34. Cavalcante JR, Pinheiro LGP, Almeida PRC, Ferreira MVP, Cruz GA, Campelo TA, et al. Association of breast cancer with human papillomavirus (HPV) infection in Northeast Brazil: molecular evidence. Clinics (Sao Paulo) 2018; 73: e465.
35. Mobini Kesheh M, Keyvani H. The Prevalence of HPV Genotypes in Iranian population: an update. Iran J Pathol 2019; 14: 197-205.
36. Salman NA, Davies G, Majidy F, Shakir F, Akinrinade H, Perumal D, et al. Association of high risk human papillomavirus and breast cancer: a UK based study. Sci Rep 2017; 7: 43591.
37. Antonsson A, Spurr TP, Chen AC, Francis GD, McMillan NA, Saunders NA, et al. High prevalence of human papillomaviruses in fresh frozen breast cancer samples. J Med Virol 2011; 83: 2157-2163.
38. Doosti M, Bakhshesh M, Zahir ST, Shayestehpour M, Karimi-Zarchi M. Lack of evidence for a relationship between high risk human papillomaviruses and breast cancer in Iranian patients. Asian Pac J Cancer Prev 2016; 17: 4357-4361.
| Files | ||
| Issue | Vol 15 No 4 (2023) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijm.v15i4.13513 | |
| Keywords | ||
| Breast malignant tumor; Human papillomavirus; Prognostic factors; Nested polymerase chain reaction; Prevalence | ||
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Makvandi M, Rashno M, Faghihloo E, Bagheri S, Hesam S, Mirzaei H, Ramezani A. Low presence of papillomavirus and its lack of correlation with clinicopathological factors in breast cancer: a case control study. Iran J Microbiol. 2023;15(4):585-593.
