HUMAN PAPILLOMA VIRUS (HPV) AS A POTENTIAL CO-FACTOR IN BREAST CANCER - A RETROSPECTIVE CASE-CONTROL STUDY
DOI:
https://doi.org/10.48165/abr.2025.27.01.57Keywords:
Breast cancer, hormone receptor status, human papilloma virus, molecular detectionAbstract
Human papillomavirus (HPV) is an increasingly debated etiological factor in breast cancer, with growing evidence suggesting its potential role as an early trigger in breast carcinogenesis. This retrospective case–control study investigated the prevalence and genotypic distribution of HPV DNA in breast carcinoma tissues compared with non-malignant breast tissues to evaluate a possible association between HPV infection and breast cancer. The study was conducted from 1 January 2024 to 15 March 2025 and included 230 formalin-fixed paraffin-embedded (FFPE) breast tissue specimens collected from Azadi Teaching Hospital, Kirkuk General Hospital, and private laboratories in Kirkuk city, Iraq. Among these, 130 samples were diagnosed as breast cancer cases, while 100 samples represented benign breast lesions as controls. Clinical and pathological data—including tumour grade, tumour stage, estrogen receptor (ER), progesterone receptor (PR), and HER-2/neu status—were obtained from medical records. Molecular detection of HPV was performed using High- and Low-Risk PapillomaStrip assays and polymerase chain reaction (PCR). HPV DNA was detected at a significantly higher frequency in breast cancer tissues than in controls (P < 0.0001). HPV type 32 was the most prevalent genotype, identified in 24.6% of breast cancer samples compared to 3% of control samples. HPV positivity was predominantly observed in high-grade (grade III) and advanced-stage tumours. No significant association was found between HPV positivity and tumour laterality, ER status, or PR status. However, HPV-positive cases demonstrated a significantly higher proportion of HER-2 positivity than HPV-negative cases. In conclusion, HPV infection was more prevalent among breast cancer patients, particularly in HER-2–positive, high-grade, and advanced-stage tumours, suggesting a potential role of HPV in aggressive breast cancer progression.
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Abdulla, A. K., Al-Barzinji, R. M. G., & Taher, C. A. (2024). Open reading frame 8 gene sequence variation of coronavirus in patients from Erbil City, Iraq. Gomal Journal of Medical Sciences, 22(1), 44–51.
Bahram Arif, K., & Shareef Abdul-Kareem, S. (2023). Exploring breast cancer characteristic features and their influences on survival rates. Medical & Clinical Research, 8(10), 1–5.
Boumba, A. L. M., Malanda Mboungou Moudiongui, D., Ngatali, S. F. C., Takale, R. P., Moukassa, D., & Peko, J. F. (2021). Oncogenic human papillomavirus in breast cancer: Molecular prevalence in a group of Congolese patients. Access Microbiology, 3(3), 000216. https://doi.org/10.1099/acmi.0.000216
Elagali, A. M., Suliman, A. A., Altayeb, M., Dannoun, A. I., Parine, N. R., & Sakr, H. I. (2021). Human papillomavirus, gene mutation and estrogen and progesterone receptors in breast cancer: A cross-sectional study. Pan African Medical Journal, 38(1), 1–10.
El-Sheikh, N., Mousa, N. O., Tawfeik, A. M., Saleh, A. M., Elshikh, I., Deyab, M., et al. (2021). Assessment of human papillomavirus infection and risk factors in Egyptian women with breast cancer. Breast Cancer, 15, 1178223421996279. https://doi.org/10.1177/1178223421996279
Eslamifar, A., Ramezani, A., Azadmanesh, K., Bidari-Zerehpoosh, F., Banifazl, M., & Aghakhani, A. (2015). Assessment of the association between human papillomavirus infection and breast carcinoma. Iranian Journal of Pathology, 10(1), 41–46.
Gao, G., Chernock, R. D., Gay, H. A., Thorstad, W. L., Zhang, T. R., & Wang, H. (2013). A novel RT-PCR method for quantification of human papillomavirus transcripts in archived tissues and its application in oropharyngeal cancer prognosis. International Journal of Cancer, 132(4), 882–890.
Gumus, M., Yumuk, P., Salepci, T., Aliustaoglu, M., Dane, F., & Ekenel, M. (2006). HPV DNA frequency and subset analysis in human breast cancer patients’ normal and tumoral tissue samples. Journal of Experimental & Clinical Cancer Research, 25(4), 515–521.
Heng, B., Glenn, W., Ye, Y., Tran, B., Delprado, W., & Lutze-Mann, L. (2009). Human papillomavirus is associated with breast cancer. British Journal of Cancer, 101(8), 1345–1350.
Islam, M. S., Chakraborty, B., & Panda, C. K. (2020). Human papillomavirus profiles in breast cancer: Future management. Annals of Translational Medicine, 8(10), 650. https://doi.org/10.21037/atm-19-2756
Istifo, N., Al-Zobaidy, M., & Abass, K. (2024). Long-term effect of fluoxetine and memantine on biochemical markers of Alzheimer’s disease in scopolamine-induced mice. Regulatory Mechanisms in Biosystems, 15(2), 226–229.
Kalantari, N., Ghaffari, S., Bayani, M., Elmi, M. M., Moslemi, D., & Nikbakhsh, N. (2015). Preliminary study on association between toxoplasmosis and breast cancer in Iran. Asian Pacific Journal of Tropical Biomedicine, 5(1), 44–47.
Karachalios, C., Petousis, S., Margioula-Siarkou, C., & Dinas, K. (2023). Human papillomaviruses and breast cancer: A systematic review and meta-analysis. Oncology Letters, 27(2), 75. https://doi.org/10.3892/ol.2023.14208
Khan, N., Castillo, A., Koriyama, C., Kijima, Y., Umekita, Y., & Ohi, Y. (2008). Human papillomavirus detected in female breast carcinomas in Japan. British Journal of Cancer, 99(3), 408–414.
Khodabandehlou, N., Mostafaei, S., Etemadi, A., Ghasemi, A., Payandeh, M., & Hadifar, S. (2019). Human papillomavirus and breast cancer: The role of inflammation and viral expressed proteins. BMC Cancer, 19(1), 61. https://doi.org/10.1186/s12885-019-5286-0
Kudela, E., Kudelova, E., Kozubik, E., Rokos, T., Pribulova, T., & Holubekova, V. (2022). HPV-associated breast cancer: Myth or fact? Pathogens, 11(12), 1510. https://doi.org/10.3390/pathogens11121510
Mahmood, A. R., Abdulla, A. K., & Hussein, N. M. (2021). Molecular detection of Toxoplasma gondii specific repeat element in blood of recurrent aborted women by real-time PCR. Periodicals of Engineering and Natural Sciences, 9(4), 708–714.
Mohammed, H. A., Shakoor, J. A., Mahmood, N. A., Kumait, A. S., & Kareem, A. M. (2023). Prevalence of cancer cases among population of Kirkuk, Iraq from 2016–2020. Rawal Medical Journal, 48(1), 3. https://doi.org/10.5455/rmj20221119075443
Nascimento, K. C. G., São Marcos, B. D. F., Fontes, P. H. B., Isídio, B. E. D. O., Leão, S. L., & da Silva, G. R. P. (2024). HPV detection in breast tumors and associated risk factors in north-eastern Brazil. Cells, 13(13), 1132. https://doi.org/10.3390/cells13131132
Ngan, C., Lawson, J. S., Clay, R., Delprado, W., Whitaker, N. J., & Glenn, W. K. (2015). Early human papillomavirus oncogenic influences in breast cancer. Breast Cancer, 9, 35–42.
Ren, C., Zeng, K., Wu, C., Mu, L., Huang, J., & Wang, M. (2019). Human papillomavirus infection increases the risk of breast carcinoma: A systematic review and meta-analysis. Gland Surgery, 8(5), 486–493.
Sher, G., Salman, N. A., Kulinski, M., Fadel, R. A., Gupta, V. K., & Anand, A. (2020). Prevalence and type distribution of high-risk human papillomavirus in breast cancer: A Qatar-based study. Cancers, 12(6), 1528. https://doi.org/10.3390/cancers12061528
Zhao, G., Chang, J., & Wei, K. (2024). Correlation between breast cancer and human papillomavirus infection. Heliyon, 10(17), e37027.

