High-risk human papillomavirus (HPV) DNA sequences in metaplastic breast carcinomas of Mexican women

Abstract

BackgroundMetaplastic carcinoma, an uncommon subtype of breast cancer, is part of the spectrum of basal-like, triple receptor-negative breast carcinomas. The present study examined 20 surgical specimens of metaplastic breast carcinomas, for the presence of high-risk Human papillomavirus (HPV), which is suspected to be a potential carcinogenic agent for breast carcinoma.MethodsMastectomy specimens from patients harboring metaplastic breast carcinoma, as defined by the World Health Organization (WHO), and who attended the Instituto Nacional de Cancerologia in Mexico City, were retrieved from the files of the Department of Pathology accumulated during a 16-year period (1995–2008). Demographic and clinical information was obtained from patients’ medical records. DNA was extracted from formalin-fixed, paraffin-embedded tumors and HPV type-specific amplification was performed by means of Polymerase chain reaction (PCR). Quantitative Real-time (RT) PCR was conducted in HPV positive cases. Statistically, the association of continuous or categorical variables with HPV status was tested by the Student t, the Chi square, or Fisher’s exact tests, as appropriate.ResultsHigh-risk HPV DNA was detected in eight (40%) of 20 metaplastic breast carcinomas: seven (87.5%) HPV-16 and one (12.5%) HPV-18. Mean age of patients with HPV-positive cases was 49 years (range 24–72 years), the same as for HPV-negative cases (range, 30–73 years). There were not striking differences between HPV + and HPV– metaplastic carcinomas regarding clinical findings. Nearly all cases were negative for estrogen, progesterone and Human epidermal growth factor receptor 2 (HER2), but positive for Epidermal growth factor receptor (EGFR).ConclusionsHigh-risk HPV has been strongly associated with conventional breast carcinomas, although the subtle mechanism of neoplastic transformation is poorly understood. In Mexican patients, the prevalence of HPV infection among metaplastic breast carcinomas is higher than in non-metaplastic ones, as so the HPV viral loads; notwithstanding, HPV viral loads show wide variation and remain even lower than cervical and other non-cervical carcinomas, making it difficult to assume that HPV could play a key role in breast carcinogenesis. Further studies are warranted to elucidate the meaning of the presence of high-risk HPVDNA in breast carcinomas.

Presence of human papillomavirus in breast cancer and its association with prognostic factors

“…In Latin America, the rate is a little lower. It is reporting between 5–40% of positivity [ 26 , 27 , 28 , 34 ], particularly in the case of Herrera et al (2013) [ 34 ], who report a 40% of positivity. Their samples were from metaplastic breast tumours, a subset of breast tumours, characterised for being more aggressive and worse prognosis.…”

“…It is worth noting that several authors have suggested that the presence of HPV is associated with smaller breast tumours [ 24 , 27 , 32 , 34 ], when compared with negative tumours for viral infection. In this work, despite the fact that we found no statistical significant relationship, HPV-positive breast tumours were found mainly among the groups T1 and T2 lesions with a maximum size of 50 mm.…”

“…Currently, the mechanism of HPV infection in the breast is uncertain. Due to the fact that the HPV life cycle occurs in epithelial layers, bloodstream viraemia is not a possible event [ 34 ]. The following two hypotheses are considered: (1) infection via the nipple skin, as demonstrated in the work of DeVilliers et al (2005) [ 20 ], which indicate the presence of the HPV genome in the tumour tissue, as in the nipple, proposing a retrograde ductular pattern of viral spread.…”

Cystatin E/M Suppresses Tumor Cell Growth through Cytoplasmic Retention of NF-κB

“…However, only those in a subset develop cervical cancer. Recently, HPVs have been implicated in the development of head and neck, lung, and breast cancers (8)(9)(10).…”

The most important questions in cancer research and clinical oncology

“…A study from Singapore showed a high prevalence of infection with high-risk HPV in breast cancer patients [45]. A Mexican study detected high-risk HPV DNA in 8 (40.0%) of 20 metaplastic breast carcinomas [7 (87.5%) with HPV-16 infection and 1 (12.5%) with HPV-18 infection)] [46]. Another study from China, using paraffin-embedded breast cancer tissue samples, detected HPV18 E6 and HPV18 E7 in approximately 30% of the samples [47].…”