High-risk human papillomavirus infections in breast cancer in Syrian women and their association with Id-1 expression: a tissue microarray study

Abstract

High-risk human papillomaviruses (HPVs) could be important risk factors for breast carcinogenesis and metastasis. Based on this hypothesis, we recently studied the effect of E6/E7 onco-proteins of high-risk HPV type 16 in two non-invasive human breast cancer cell lines, BT20 and MCF7; we reported that E6/E7 converts these cell lines to invasive cells. This is accompanied by an overexpression of Id-1, which is an important regulator of breast metastasis. In this investigation, we examined the presence of highrisk HPVs (16, 18, 31, 33 and 35) and the expression of their E6 onco-protein as well as their correlation with Id-1 gene expression, using polymerase chain reaction (PCR) and tissue microarray (TMA) analysis, respectively, in a cohort of 113 Syrian breast cancer patients. We found that high-risk HPV types 16, 18, 31, 33 and 35 are present in 8.84, 9.73, 7.07, 55.75 and 37.16% of our samples, respectively, which represent invasive breast cancers. Overall, 69 (61.06%) of the 113 samples are HPV positive; among these specimens 24 tissues (34.78%) are coinfected with more than one HPV type. Furthermore, we report that the expression of the E6 onco-protein of these high-risk HPVs is correlated with Id-1 overexpression in the majority of invasive breast cancer tissue samples. Our data suggest that high-risk HPV infections are associated with human breast cancer progression in Syrian women.

Human papilloma virus is associated with breast cancer

“…Previous studies have demonstrated the presence of HPV high-risk types 16, 18 and 33 in breast cancer specimens from diverse populations around the world: Italy, Norway, China, Japan, USA, Austria, Brazil, Australia, Taiwan, Turkey, Greece, Korea, Mexico, Hungary and Syria (Lonardo et al, 1992;Hennig et al, 1999;Yu et al, 1999;Liu et al, 2001;Damin et al, 2004;Widschwendter et al, 2004;de Villiers et al, 2005;Kan et al, 2005;Tsai et al, 2005;Gumus et al, 2006;Kroupis et al, 2006;Lawson et al, 2006;Choi et al, 2007;Akil et al, 2008;Khan et al, 2008;Kulka et al, 2008;MendizabalRuiz et al, 2009). The prevalence of HPV positive breast cancer in these studies was reported to vary from 4% in Mexican to 86% in American women.…”

Does the Syrian population have to wait for the new generation of human papillomaviruses vaccine?

“…6 Herein, we report that high-risk HPVs type 45, 51, 52 and 58 are frequently present in colorectal cancer in this population (p < 0.001, p < 0.001, p < 0.001 and p < 0.0001, respectively) ( Table 1), in some cases multiple types of HPV infections were detected. Therefore and based on previous studies, [6][7][8] and our present data on colorectal cancer, we conclude that the most frequent high-risk HPV types, in the Syrian population, are 16, 33, 35, 45, 52 and 58 (Table 1). In parallel, it is important to mention that our preliminary data of HN cancers in the Syrian population show that 43% of these cancers are positives for high-risk HPVs; while, genotyping of high-risk HPVs is presently under investigation by our group, we believe that data of this analysis will be similar to our data of cervical and colorectal cancers (Ghabreau et al, in preparation).…”

“…However, a new generation of broad spectrum HPV vaccines, protecting against multiple high-risk HPV types is emerging. At present, a phase III trial is running to assess the carcinomas in the Syrian population, [6][7][8] we firmly believe that the new generation of high-risk HPVs vaccine will present the best protection for the Syrian people against HPV viruses. This great advancement could reduce the development of cervical, colorectal, breast and HN cancers by more than 50%, as well as decrease their progression to a metastatic form which is responsible for the majority of cancer-related deaths.…”

“…5 We recently conducted several studies regarding the presence of high-risk HPVs in human cervical, colorectal and breast cancers in the Syrian population, [6][7][8] we found that high-risk HPV types, 16, 18, 31, 33 and 35 are present in these cancers, and the majority of high-risk HPV positive cancers are invasive carcinomas; this phenotype is accompanied by overexpression of numerous genes such as Id-1, Fascin and P-cadherin, which are important regulators of cell invasion and metastasis. [6][7][8] In this current study, we used the same samples and protocol as our recent investigation of colorectal cancers and HPVs. The samples were analyzed for HPVs by multiplex PCR using PGMY09/11 L1 primer pools and specific primers for E7 gene of HPV types 45, 51, 52 and 58, as previously described by our…”

Presencia del virus del papiloma humano y del virus de Epstein-Barr en biopsias de cáncer de mama como posibles factores de riesgo

“…Actualmente se conocen bien varios factores de riesgo asociados con el cáncer de mama, pero en la mayoría de las mujeres afectadas no es posible identificar ningún factor en particular relacionado con el desarrollo de la enfermedad 3 . En las últimas décadas se ha considerado como factor importante en el desarrollo de cán-cer la acción de un grupo de virus que provocan tumores, tanto en modelos experimentales como en humanos 4,5 . El virus del papiloma humano (VPH) es el agente etiológico del cáncer de cuello uterino, y el virus de Epstein-Barr (VEB) está asociado principalmente con el carcinoma nasofaríngeo y el linfoma de Burkitt.…”