Merkel Cell Carcinomas Arising in Autoimmune Disease Affected Patients Treated with Biologic Drugs, Including Anti-TNF

Rotondo, John Charles; Bononi, Ilaria; Puozzo, Andrea; Govoni, Marcello; Foschi, Valentina; Lanza, Giovanni; Gafà, Roberta; Gaboriaud, Pauline; Touzé, Françoise Antoine; Selvatici, Rita; Martini, Fernanda; Tognon, Mauro

doi:10.1158/1078-0432.ccr-16-2899

Cited by 58 publications

(86 citation statements)

References 46 publications

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“…HPV genotypes were determined by direct sequencing analysis in HPV-positive middle ear samples. qPCR amplicons were purified using the QIAquick PCR Purification Kit (Qiagen) [52]. Purified qPCR amplicons were sequenced with automated ABIPrism 3730xl Genetic Analyser (Applied Biosystems) [53].…”

Section: Hpv Genotypingmentioning

confidence: 99%

High Human Papillomavirus DNA loads in Inflammatory Middle Ear Diseases

et al. 2020

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Background. Previous studies reported human papillomaviruses (HPVs) in middle ear tumors, whereas these viruses have been poorly investigated in chronic inflammatory middle ear diseases. We investigated HPVs in non-tumor middle ear diseases, including chronic otitis media (COM). Methods. COM specimens (n = 52), including chronic suppurative otitis media (CSOM) (n =38) and cholesteatoma (COMC) (n = 14), as well as normal middle ear (NME) specimens (n = 56) were analyzed. HPV sequences and DNA loads were analyzed by quantitative-PCR. HPV genotyping was performed by direct sequencing. Results. HPV DNA was detected in 23% (12/52) of COM and in 30.4% (17/56) of NME (p > 0.05). Specifically, HPV DNA sequences were found in 26.3% (10/38) of CSOM and in 14.3% (2/14) of COMC (p > 0.05). Interestingly, the HPV DNA load was higher in COMC (mean 7.47 copy/cell) than in CSOM (mean 1.02 copy/cell) and NME (mean 1.18 copy/cell) (P = 0.03 and P = 0.017 versus CSOM and NME, respectively). HPV16 and HPV18 were the main genotypes detected in COMC, CSOM and NME. Conclusions. These data suggest that HPV may infect the middle ear mucosa, whereas HPV-positive COMCs are associated with higher viral DNA loads as compared to NME.Pathogens 2020, 9, 224 2 of 10 mucosa sampled from CSOM patients [11]. However, the etiology of CSOM remains to be determined. The relationship between HPV infection and inflammation has been previously reported [12]. It has been shown that persistent infection with high-risk HPVs leads to an increase in pro-inflammatory cytokines, including IL-6, TNF-α and MIP-1α [13]. In addition, high-risk HPV type 16 (HPV16) is able to increase the expression of cyclooxygenase-2 (COX-2), a key enzyme in the synthesis of prostaglandins, which are important mediators of inflammation [14,15]. Until now, only a single study has reported HPV DNA sequences in CSOM, whereby different HPV genotypes, including HPV16, HPV18 and HPV6, have been detected in 30.7% of CSOM [4].COMC is a form of expanding growth consisting of keratinizing squamous cell epithelium [16]. There is great interest in the etiopathogenesis of HPV-associated cholesteatoma because HPV commonly infects the stratified epithelium [17,18]. However, conflicting data have been reported for HPV in COMC [10,[19][20][21]. HPV sequences have been detected in COMC with different prevalence, ranging from 3% to 70% [10,[19][20][21]. Moreover, no specific HPV genotypes have been associated with COMC, as high-and low-risk HPVs, such as HPV16, HPV18 and HPV6 and HPV11, have been detected [10,[19][20][21].There is emerging evidence that HPV infection can occur in different anatomical sites. Since HPV infects epithelia [22], all anatomical sites covered with epithelial tissue are potentially exposed to HPV infection. Apart from pluristratified tissues of the cervix [23], vulva [24] and oral pharynx [25], HPV sequences have been detected in simple epithelia from several anatomical sites such as lung [26], upper respiratory tract [27], larynx [28] and nose [29]. Since the middle ear muc...

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Section: Hpv Genotypingmentioning

confidence: 99%

High Human Papillomavirus DNA loads in Inflammatory Middle Ear Diseases

et al. 2020

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“…Each DNA sample was quantified and evaluated for its PCR suitability using a spectrophotometric reading (NanoDrop 2000, Thermo Scientific, Monza, Italy) and by amplifying the β-globin, respectively [27]. DNAs were isolated with a sample of salmon sperm DNA and sample lacking DNA (H2O), and subjected to PCR techniques [13].…”

Section: Dna Isolationmentioning

confidence: 99%

“…MCPyV and HPV genomic sequences in SA and VI chorionic villi and PBMCs were investigated using qualitative PCR. DNA from samples was analyzed by PCR with primers targeting MCPyV large T antigen (LT) region (Table 1) [13]. The pUC57MC1 recombinant plasmid carrying DNA from the MCC350 strain (GenBank sequence EU375803) was used as a positive control [15].…”

Section: Viral Dna Detectionmentioning

confidence: 99%

“…Merkel cell polyomavirus (MCPyV) is the viral agent associated with the Merkel cell carcinoma (MCC), which is a rare but aggressive tumor of the skin [13]. Recently, IgG antibodies against MCPyV were detected at a high prevalence, of up to 80%, in healthy subjects and patients affected by MCC [14].MCPyV DNA sequences were detected in buffy coats and sera of healthy subjects, with a prevalence of 22% and 2.6%, respectively [15], [16].…”

Section: Introductionmentioning

confidence: 99%

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DNA Sequences of Small DNA Tumor Viruses, Merkel Cell Polyomavirus and Human Papillomavirus, in Spontaneous Abortion Specimens

Tagliapietra¹,

Rotondo²,

Bononi³

et al. 2018

Preprint

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Background. The role of viruses in spontaneous abortion (SA) in not completely known. Methods. Merkel cell polyomavirus (MCPyV) and Human papillomavirus (HPV), two small DNA tumor viruses, were investigated in SA. MCPyV/HPV DNAs were investigated by PCR and droplet-digital/quantitative PCRs (ddPCR/qPCR) in chorionic villi and peripheral blood mononuclear cells (PBMCs) from SA females (n=100), the cases, and voluntary interruption (VI, n=100) of pregnancy females, the controls. Results. MCPyV DNAs were detected in 4% and 5% of SA and VI chorionic villi, respectively, with a mean DNA load of 1.99 copy/104 cells in SA and 3.02 copy/10,000 cells in VI (p>0.05). HPV DNAs were detected in 2% of VI chorionic villi, with a mean DNA load of 7.12 copy/cell. Two cases in the VI samples were HPV-45 positive. In PBMCs, MCPyV DNA was detected in 9% and 14% of SA and VI samples, with a mean viral DNA load of 2.09 and 4.70 copy/10,000 cells in SA and VI samples, respectively (p>0.05). None of PBMCs samples tested HPV-positive. Conclusions. MCPyV and HPV DNAs were quantified, for the first time, by ddPCR/qPCR in SA and VI chorionic villi and PBMCs. Data of the present study may help to better understand the role of MCPyV/HPV in SA.

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“…Host immunosuppression is the critical cofactor in BKPyV and JCPyV pathology, with pharmacological immunosuppression to prevent graft rejection essential for BKPyV reactivation in KTx recipients, while PML is observed in HIV/AIDS patients or under immunosuppressive and immunomodulatory medication. Similarly, immunosuppressed states including AIDS [7], solid organ transplantation [8] and haematological malignancies are associated with increased incidence of MCC [9].…”

Section: Introductionmentioning

confidence: 99%