Analysis of the presence of cutaneous and mucosal papillomavirus types in ductal lavage fluid, milk and colostrum to evaluate its role in breast carcinogenesis

Cazzaniga, Massimiliano; Gheit, Tarik; Casadio, Chiara; Khan, Noureen; Macis, Debora; Valenti, Francesco; Miller, Mara Jo; Sylla, Bakary S.; Akiba, Suminori; Bonanni, Bernardo; Decensi, Andrea; Veronesi, Umberto; Tommasino, Massimo

doi:10.1186/1753-6561-3-s5-s5

Cited by 5 publications

(6 citation statements)

References 25 publications

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“…In four out of six women (one IC and three IP) the same HPV type was harbored in both ND and breast tissue ( Table 1). The notion that HPV DNA can be found in breast fluids has previously been reported in colostrum, milk and ductal lavage [3,4]. Therefore, our data confirm that HPV is present in the breast tissue but does not seem strictly related to malignancy per se, as it is more represented in IPs.…”

Section: Hpv Dna In Pathologic and Physiologic Ndsupporting

confidence: 77%

“…A plethora of pathogens has been found in triple negative breast cancer, the most aggressive breast cancer phenotype, including mucosal and cutaneous HPVs [2]. The presence of HPV DNA has been reported in biological fluids such as milk and colostrum of lactating women as well as in ductal lavages from women at increased risk of breast cancer [3,4]. The presence of HPV DNA has never been investigated in nipple discharge, a spontaneous or induced biological fluid which is examined to exclude the presence of malignant cells in women with any palpable lump or mammographic abnormalities.…”

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confidence: 99%

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Liquid Biopsy in the Diagnosis of HPV DNA in Breast Lesions

et al. 2017

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Aim: HPV DNA has never been investigated in nipple discharges (ND) and serum-derived extracellular vesicles, although its presence has been reported in ductal lavage fluids and blood specimens. Materials & methods: We analyzed 50 ND, 22 serum-derived extracellular vesicles as well as 51 pathologic breast tissues for the presence of 16 HPV DNA types. Results: We show that the presence of HPV DNA in the ND is predictive of HPV DNA-positive breast lesions and that HPV DNA is more represented in intraductal papillomas. We also show the presence of HPV DNA in the serum-derived extracellular vesicles. Conclusion: Our data supports the use of liquid biopsy to detect HPV DNA in breast pathology. The presence of HPV DNA in breast cancer has been widely investigated in the last three decades [1], but few data are available on its presence in benign breast lesions, in other words, intraductal papilloma (IP). A plethora of pathogens has been found in triple negative breast cancer, the most aggressive breast cancer phenotype, including mucosal and cutaneous HPVs [2]. The presence of HPV DNA has been reported in biological fluids such as milk and colostrum of lactating women as well as in ductal lavages from women at increased risk of breast cancer [3,4]. The presence of HPV DNA has never been investigated in nipple discharge, a spontaneous or induced biological fluid which is examined to exclude the presence of malignant cells in women with any palpable lump or mammographic abnormalities. Interestingly, HPV DNA has recently been described in the blood of cervical cancer affected women [5]. Recent literature also shows that viral nucleic acids are cargoed by circulating extracellular vesicles (EVs), which are membrane-derived vesicles involved in cell-to-cell communication [6,7].We first searched for the presence of 16 high-risk mucosal HPV DNA in the virome of breast tissues and their biological fluids, in other words, nipple discharges (ND) and serum-derived EVs, of women with benign or malignant breast cancer lesions. Then, we searched if a noninvasive approach, the liquid biopsy, could be useful in the diagnosis of HPV DNA-positive breast lesions.

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Section: Hpv Dna In Pathologic and Physiologic Ndsupporting

confidence: 77%

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confidence: 99%

Liquid Biopsy in the Diagnosis of HPV DNA in Breast Lesions

et al. 2017

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“…For the detection of all Hr-HPV types, all pHr-HPV types, Lr-HPV type 70, and ␤-globin, the PCR was performed as described previously (9), but with some modifications: a Mastercycler (Eppendorf, Germany) was used, dUTP was omitted, and reverse primers were biotinylated to allow later detection with a Luminex reader. In addition, the E7 forward primers for HPV-16 (5Ј-TTATGAGCAATTAAATGACAGCTCAG-3Ј) and HPV-39 (5Ј-GGTTTGCAGTTGCACACCACGG-3Ј) were slightly modified, resulting in a higher analytical sensitivity compared to that achieved with the previous version (4,9).…”

Section: Methodsmentioning

confidence: 99%

Abundance of Multiple High-Risk Human Papillomavirus (HPV) Infections Found in Cervical Cells Analyzed by Use of an Ultrasensitive HPV Genotyping Assay

et al. 2010

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PCR methods enable the detection of a large variety of human papillomavirus (HPV) genotypes that infect the anogenital tract. However, PCR with consensus primers, general primers, and, to a lesser extent, broadspectrum primers may underrepresent the true prevalence of HPV, especially the true prevalence of multiple infections. We compared the rate of HPV positivity determined by a broad-spectrum PCR with primers BSGP5؉ and BSGP6؉ (BS-PCR) coupled to an established bead-based multiplex HPV genotyping (MPG) assay with the rate of HPV positivity determined by a multiplex PCR with type-specific primers (TS-PCR) coupled to a newly developed MPG assay for 735 selected cervical scraping samples. While the primers used for the BS-PCR are located within the L1 region of the HPV genome, the primers used for the TS-PCR target the E7 gene. The overall rates of positivity for the 19 HPV types included in both assays were 60.9% and 72.2% by the BS-PCR and the TS-PCR, respectively, and the two assays found multiple infections in 34.8% and 58.0% of the specimens, respectively. Both HPV detection assays allowed the semiquantitative detection of HPV types and identified the same dominant HPV type in 66.6% of the multiple infections. In conclusion, the TS-PCR-MPG assay significantly increased the rate of detection of HPV DNA and the number of infections with multiple HPV types detected and demonstrated that the prevalence of low-copy-number HPV infections in the anogenital tract may be strongly underestimated by conventional HPV amplification methods, especially in cases of multiple infections. As a consequence, PCR-TS-MPG appears to be highly suited for analysis of the significance of multiple infections in the development of cervical cancer and for the study the natural history and the latency of HPV.Human papillomaviruses (HPV) are DNA viruses that infect cutaneous and mucosal epithelia. Until now, approximately 100 HPV genotypes have been fully characterized on the basis of the isolation of complete genomes (7), and there is evidence that a larger number exist (1). There are approximately 45 known mucosal HPV types; and these are further divided into three groups on the basis of their epidemiological association with cervical cancer: high-risk HPV (Hr-HPV) types (types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 82), putative high-risk HPV (pHr-HPV) types (types 26, 53, and 66), and low-risk HPV (Lr-HPV) types (e.g., types 6, 11, 40, 42, 43, 44, and 70) (18). Hr-HPV types are causally associated with several malignant diseases, of which cervical cancer has particular significance, being the second most common cancer in women worldwide and the main cancer of women in most developing countries (18). Hr-HPV type DNA has been detected in 99.7% of cervical cancer tissue specimens (26), and persistent infection with an oncogenic HPV type, particularly HPV type 16 (HPV-16) or HPV-18, is recognized as a necessary cause of cervical cancer. HPV genotyping is of importance for the study of the natural history of infectio...

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“…Recent identification of HPV by PCR in breast milk, ductal lavage and colostrum specimens is not cited by Lawson et al (Sarkola et al, 2008;Cazzaniga et al, 2009). Human papilloma virus was detected in 4 and 14% of non-selected breast milk specimens.…”

Section: Sirmentioning

confidence: 99%

Regarding: Koilocytes indicate a role for human papilloma virus in breast cancer

Sandstrom

2010

Br J Cancer

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Analysis of the presence of cutaneous and mucosal papillomavirus types in ductal lavage fluid, milk and colostrum to evaluate its role in breast carcinogenesis

Cited by 5 publications

References 25 publications

Liquid Biopsy in the Diagnosis of HPV DNA in Breast Lesions

Liquid Biopsy in the Diagnosis of HPV DNA in Breast Lesions

Abundance of Multiple High-Risk Human Papillomavirus (HPV) Infections Found in Cervical Cells Analyzed by Use of an Ultrasensitive HPV Genotyping Assay

Regarding: Koilocytes indicate a role for human papilloma virus in breast cancer

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