Human papillomavirus DNA in sera of cervical cancer patients as tumor marker

Widschwendter, Andreas; Blassnig, Anya; Wiedemair, Annemarie; Müller‐Holzner, Elisabeth; Müller, Hannes M.; Marth, Christian

doi:10.1016/j.canlet.2003.09.006

Cited by 51 publications

(60 citation statements)

References 22 publications

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“…The presence of viral DNA in the peripheral blood fraction (PBF), plasma and serum is not an unusual event in tumour patients. Recently, HPV DNA was detected in serum and/or PBF of individuals with cervical, head/neck or schistosomiasis-associated bladder cancer and women suffering from cervical carcinomas (Ho et al, 2005;Widschwendter et al, 2003). It has been postulated that HPV DNA is involved in carcinogenesis in breast tissue in some patients suffering from cervical cancer (Widschwendter et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Detection of bovine papillomavirus type 2 in the peripheral blood of cattle with urinary bladder tumours: possible biological role

Roperto

Brun

Paolini³

et al. 2008

Journal of General Virology

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Bovine papillomavirus type 2 (BPV-2) infection has been associated with urinary bladder tumours in adult cattle grazing on bracken fern-infested land. In this study, we investigated the simultaneous presence of BPV-2 in whole blood and urinary bladder tumours of adult cattle in an attempt to better understand the biological role of circulating BPV-2. Peripheral blood samples were collected from 78 cattle clinically suffering from a severe chronic enzootic haematuria. Circulating BPV-2 DNA was detected in 61 of them and in two blood samples from healthy cows. Fifty of the affected animals were slaughtered at public slaughterhouses and neoplastic proliferations in the urinary bladder were detected in all of them. BPV-2 DNA was amplified and sequenced in 78 % of urinary bladder tumour samples and in 38.9 % of normal samples as a control. Circulating episomal BPV-2 DNA was detected in 78.2 % of the blood samples. Simultaneous presence of BPV-2 DNA in neoplastic bladder and blood samples was detected in 37 animals. Specific viral E5 mRNA and E5 oncoprotein were also detected in blood by RT-PCR and Western blot/immunocytochemistry, respectively. It is likely that BPV-2 can persist and be maintained in an active status in the bloodstream, in particular in the lymphocytes, as a reservoir of viral infection that, in the presence of co-carcinogens, may cause the development of urinary bladder tumours. INTRODUCTIONBovine papillomaviruses (BPVs) are species-specific, double-stranded DNA viruses responsible for cutaneous and mucosal neoplastic lesions. They are small non-enveloped viruses with an icosahedral capsid. Their open reading frames (ORFs) are divided into early (E) and late (L) regions. The early region encodes non-structural proteins E1 to E7, of which, E5, E6 and E7 are known to be oncoproteins. The late region encodes structural proteins L1 and L2 forming the capsid. Bovine papillomavirus type 2 (BPV-2) is classified in the genus Deltapapillomavirus, species 4, the biological properties of which are characterized by the induction of fibropapillomas in cattle and sarcoids in equids (Brandt et al., 2008;Chambers et al., 2003;de Villiers et al., 2004). BPV-2 infection in the presence of environmental carcinogens, such as ptaquiloside (PT) of bracken fern (Pteridium aquilinum), has been associated with urinary bladder neoplastic lesions in adult cattle, in which chronic enzootic haematuria (CEH) is the most important clinical sign (Campo, 1997; Campo et al., 1992;Hopkins, 1986).The effect of the route of viral infection, and the synergistic relationship between BPV-2 and immunosuppressive and oncogenic compounds present in the bracken fern in the malignant progression of bladder lesions (Campo, 1997; Campo et al., 1992; Jarrett et al., 1978;Reddy & Fialkow, 1983;Stocco dos Santos et al., 1998) are not well-known, thus deserving further investigations.To date, the BPV-2 genome has been detected in lymphocytes during latent papillomavirus infection in cattle (Campo et al., 1994). In addition, the occurrence of horiz...

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Section: Discussionmentioning

confidence: 99%

Detection of bovine papillomavirus type 2 in the peripheral blood of cattle with urinary bladder tumours: possible biological role

Roperto

Brun

Paolini³

et al. 2008

Journal of General Virology

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“…Serum samples were taken on the date of diagnosis and before initial treatment. These serum samples were taken from a prior study investigating the presence of serum human papillomavirus DNA in cervical cancer patients (12). Major clinical and histopathological characteristics of patients are given in Table 1.…”

Section: Methodsmentioning

confidence: 99%

DNA Methylation in Serum and Tumors of Cervical Cancer Patients

Widschwendter

Müller

Fiegl

et al. 2004

Clinical Cancer Research

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118

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Purpose: Promoter hypermethylation has been recognized to play an important role in carcinogenesis. Numerous studies have demonstrated tumor-specific alterations, such as aberrant promoter hypermethylation, in DNA recovered from plasma or serum of patients with various malignancies. The aim of this study was to investigate the methylation status of various genes in cervical cancer patients and their association with clinicopathological characteristics and outcome of the disease.Experimental Design: The methylation status of CALCA, hTERT, MYOD1, PGR (progesterone receptor), and TIMP3 was investigated in serum samples from 93 cervical cancer patients and 19 corresponding tissue samples using the MethyLight technique.Results: Aberrant promoter hypermethylation was detected in any of these genes in 87% (81 of 93) of the serum samples studied. Methylation of MYOD1 was detected more frequently in advanced stage. All of the genes found to be methylated in serum samples were also methylated in the corresponding tissue sample, except in one patient. Patients with unmethylated MYOD1 serum DNA had significantly better disease-free (P ‫؍‬ 0.04) and overall survival (P ‫؍‬ 0.02) in comparison with patients with methylated MYOD1.Conclusions: To the best of our knowledge, this is, thus far, the largest study investigating aberrant promoter hypermethylation in serum samples from cancer patients and the first study investigating methylation patterns in sera of cervical cancer patients. Our results suggest that serological detection of MYOD1 promoter hypermethylation may be of potential use as a prognostic marker for discriminating cervical cancer patients at high risk for lymph node metastasis or relapse. Additional studies, including a panel of additional genes, are necessary to elucidate the role of aberrant methylation in serum as a tool for surveillance of cervical cancer.

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“…PVs are described as epitheliotropic, although their presence has been detected in different tissues and cells (Freitas et al, 2003;Yaguiu et al, 2006;Lindsey et al, 2009;Silva et al, 2011). Recently, human and bovine PV DNA have been shown to be detectable in peripheral blood mononuclear cells (Freitas et al, 2003;Bodaghi et al, 2005;Roperto et al, 2008Roperto et al, , 2011 and plasma and serum (Widschwendter et al, 2003;Freitas et al, 2007). The expression of structural and non-structural genes, as well as their corresponding proteins, has been demonstrated in the lymphocytes of cattle with bladder cancer (Roperto et al, , 2011.…”

Section: Introductionmentioning

confidence: 99%

Detection and expression of Bovine papillomavirus in blood of healthy and papillomatosis-affected cattle

Silva¹,

Albuquerque²,

Pontes³

et al. 2013

Genet. Mol. Res.

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ABSTRACT. Papillomaviruses (PV) are double-stranded DNA viruses that can cause benignant and malignant tumors in amniotes. There are 13 types of bovine papillomavirus (BPV-1 to -13); they have been found in reproductive tissues and body fluids. Normally these viruses are detected in epithelial tissue. We looked for BPV in the blood of healthy cattle and cattle with papillomatosis, using PCR and RT-PCR. BPV types 1 and 2 were detected in 8/12 blood samples of asymptomatic bovines and in 8/9 samples from cattle with papillomatosis. Six of 8 asymptomatic samples positive for BPV also showed expression for BPV. Five of 6 samples were positive for E2 expression, while 3/6 samples were positive for E5 expression. Five of 8 symptomatic samples positive for BPV also showed BPV expression. Five of 5 were positive for E2 expression, while 1/5 was positive for E5 expression. Two of 6 blood samples of asymptomatic cattle and 1/5 symptomatic blood samples scored positive for both E2 and E5 expression. This is the first ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 12 (3): 3150-3156 (2013) BPV expression in cattle blood 3151 study showing expression of BPV genes in the blood of asymptomatic and papillomatosis-affected animals.

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Human papillomavirus DNA in sera of cervical cancer patients as tumor marker

Cited by 51 publications

References 22 publications

Detection of bovine papillomavirus type 2 in the peripheral blood of cattle with urinary bladder tumours: possible biological role

Detection of bovine papillomavirus type 2 in the peripheral blood of cattle with urinary bladder tumours: possible biological role

DNA Methylation in Serum and Tumors of Cervical Cancer Patients

Detection and expression of Bovine papillomavirus in blood of healthy and papillomatosis-affected cattle

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