Merkel Cell Polyomavirus in Cutaneous Squamous Cell Carcinoma of Immunocompetent Individuals

Abstract

Squamous cell carcinoma (SCC) is the second most frequently diagnosed skin cancer. It has a higher incidence in immunosuppressed individuals such as organ transplant recipients and human immunodeficiency virus (HIV) carriers. Recently, a newly described polyoma virus, Merkel cell polyomavirus (MCPyV), was found in Merkel cell carcinoma (MCC), a rare aggressive skin cancer also associated with immunosuppression. We hypothesized that MCPyV would be present in SCCs. To test for the presence of MCPyV in immunocompetent SCC patients, we used PCR primer sets directed against the large T (LT) antigen and VP1 gene of MCPyV. We detected MCPyV in 15% (26/177) of SCC DNA samples and 17% (11/63) of adjacent skin DNA samples from 21 of 58 (36%) individuals studied. We did not detect MCPyV in any matched normal blood DNA (0/57), but observed the presence of MCPyV DNA in 1 of 12 normal mouthwash DNAs. All sequenced SCC samples had a common mutation truncating the LT antigen that provides indirect evidence of viral integration. The presence of MCPyV in approximately 15% of SCCs from immunocompetent individuals warrants evaluation of MCPyV as an etiologic agent in the carcinogenesis of SCC.

Human Merkel cell polyomavirus: virological background and clinical implications

“…It has also been reported that low levels of MCPyV sequence can be amplified from many human tissues where it may undergo low-level replication or latency (1,39,43,44). MCPyV DNA has also been detected in the oral cavity, with prevalence ranging from 8% to as high as 60% (34,35,39). The sensitivity of the detection of MCPyV DNA is affected by variations in the number of cells present in different samples.…”

“…MCPyV DNA has been detected at varying levels of frequency (0-100%) in skin samples, and in anal and penile swabs (1,9,20,21,26,(32)(33)(34)(35)(36)(37)(38). The MCPyV viral load on the skin surface varies from less than 1 copy per 1000 cells to 1000 copies per cell (9,26,30,(39)(40)(41).…”

Low prevalence of Merkel cell polyomavirus with low viral loads in oral and maxillofacial tumours or tumour-like lesions from immunocompetent patients: Absence of Merkel cell polyomavirus-associated neoplasms

“…MCPyV has been detected in MCC patients and appears to play a key role in tumourigenesis; ~80% of MCCs harbour MCPyV (1). Using quantitative polymerase chain reaction (qPCR), MCPyV has been detected in malignant and benign tumours (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). Moreover, certain investigators have reported that low viral loads of MCPyV have also been detected in normal human tissue samples, including skin, liver and respiratory secretions, suggesting that this virus is widespread in the human body (7,17).…”

First Report of Three Major Oncogenic Viruses: Human Papillomavirus, Epstein-Barr Virus And Merkel Cell Polyomavirus in Penile Cancer

“…Falchook and colleagues (2013) [16] reported the presence of HPVMCPyV in a SCC from a patient with melanoma treated with the BRAF inhibitor dabrafenib. In another study involving SCC, Dworkin and colleagues (2009) [13] demonstrated a higher proportion of HPV DNA among the MCPyV-positive group (87%) in comparison to the MCPyV-negative group (57%), although a clear correlation between these two viruses could not be established. Mittledorf and colleagues (2012) [17] reported HPV6 and MCPyV DNA in a combined MCCinvasive SCC.…”

“…Particularly, non-melanoma skin cancers have been studied, especially squamous cell carcinoma and basal cell carcinoma. The prevalence of MCPyV in SCC ranges from 13% to 38% [13][14][15].…”