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Tracing Human Papilloma Virus in Breast Tumors of Iranian Breast Cancer Patients

Detection of different human papilloma virus (HPV) types from breast tumor postulated that this virus may also play a role in etiology of breast cancer. HPV was also linked the clinicopathological characteristics of the breast cancer and suggested as a prognostic marker for breast cancer (1,2). After approval by ethical committee of Tehran University of Medical Sciences, 67 frozen samples from operated breast cancer patients were included in this study. The stage of the tumors was defined based on TNM classification. HPV typing carried out as previously described (3). Moreover, different tumor markers including estrogen and progesterone receptors as well as expression of P53 protein, and over expression of HER-2 ⁄ nue were defined using immunohistochemistry. We used Pearson chi-square test (fisher exact test whenever applicable) for statistical analyses. Among the samples studied, 30% of breast tumors were positive for HPV infection. The prevalence of HPV 16, 11 ⁄ 6, and 31 ⁄ 33 were 14.9%, 11.94%, and 2.99% respectively. There was no association between age at diagnosis and HPV infection (p-value = 0.7). However, we found statistically significant inverse association between tumor stage and HPV infection (p-value = 0.03).This association was pertained mainly to the lymph node involvement (p-value = 0.05) than to the tumor size. In addition, HPV was more prevalent among patients who were negative for estrogen receptor (ER negative) (p-value = 0.04). The association between HPV infection and breast cancer was supported by several studies (1,2,4), although others failed to find such association (5–8). To confirm a causal role of HPV on etiology of breast cancer, it is important to understand how HPV infection reaches into the breast tissue. Association of anogenital cancers with HPV infection has been linked to the sexual transmission of the virus. Follow-up studies among patients with a diagnosis of carcinoma in situ of cervix showed a considerably higher risk of anogenital cancer in these patients and confirmed that the sexual transmission of infection is reasonable in these cancers. Transmission from cervix to breast tissue through blood stream, a mechanical path where virus is scrubbed through the skin, or sexual activity have been suggested (9,10). However, because patients with carcinoma in situ of cervix were not in excess risk for breast cancer, transmission through cervix was questioned. Moreover, none of the patients included in this study had cervical ⁄ intraepithelial neoplasia. In line with some previous reports (9), we found that HPV infection was more common among patients with lower stage of the tumor. In addition, we found that HPV-DNA was more common among patients who were negative for estrogen receptor. But there was no association with other tumor markers, i.e., progesterone receptor, P53, and HER-2 ⁄ neu. Previous studies on association of HPV histochemical markers are also conflicting. Due to limited power in almost all previous studies, decision about a link between these markers and HPV infection and prognostic value of the HPV infection on breast cancer warrant further studies. This study adds valuable data to the recent series of evidence on association between HPV and breast cancer. However, further epidemiological studies with sufficient power are still needed to establish a real association.