Detection of Merkel cell polyomavirus in cervical squamous cell carcinomas and adenocarcinomas from Japanese patients

Abstract

BackgroundMerkel cell polyomavirus (MCPyV) was identified originally in Merkel cell carcinoma (MCC), a rare form of human skin neuroendocrine carcinoma. Evidence of MCPyV existence in other forms of malignancy such as cutaneous squamous cell carcinomas (SCCs) is growing. Cervical cancers became the focus of our interest in searching for potentially MCPyV-related tumors because: (i) the major histological type of cervical cancer is the SCC; (ii) the uterine cervix is a common site of neuroendocrine carcinomas histologically similar to MCCs; and (iii) MCPyV might be transmitted during sexual interaction as demonstrated for human papillomavirus (HPV). In this study, we aimed to clarify the possible presence of MCPyV in cervical SCCs from Japanese patients. Cervical adenocarcinomas (ACs) were also studied.ResultsFormalin-fixed paraffin-embedded tissue samples from 48 cervical SCCs and 16 cervical ACs were examined for the presence of the MCPyV genome by polymerase chain reaction (PCR) and sequencing analyses. PCR analysis revealed that 9/48 cervical SCCs (19%) and 4/16 cervical ACs (25%) were positive for MCPyV DNA. MCPyV-specific PCR products were sequenced to compare them with reference sequences. The nucleotide sequences in the MCPyV large T (LT)-sequenced region were the same among MCPyV-positive cervical SCCs and AC. Conversely, in the MCPyV viral protein 1 (VP1)-sequenced region, two cervical SCCs and three cervical ACs showed several nucleotide substitutions, of which three caused amino acid substitutions. These sequencing results suggested that three MCPyV variants of the VP1 were identified in our cases. Immunohistochemistry showed that the LT antigen was expressed in tumor cells in MCPyV-positive samples. Genotyping of human HPV in the MCPyV-positive samples revealed that infected HPVs were HPV types 16, 31 and 58 for SCCs and HPV types 16 and 18 for ACs.ConclusionsThis study provides the first observation that MCPyV coexists in a subset of HPV-associated cervical cancers from Japanese patients. The prevalence of MCPyV in these lesions was close to that observed in the cutaneous SCCs. Further worldwide epidemiological surveys are warranted to determine the possible association of MCPyV with pathogenesis of cervical cancers.

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

“…Murakami et al reported that MCPyV was present in 13% cases of cutaneous SCCs from Japanese patients; this indicates that cutaneous SCC in Japanese patients is infrequently associated with MCPyV (13). Imajoh et al reported that MCPyV was present in 19% of cervical SCCs from Japanese patients; this suggested that MCPyV may be a cofactor of human papillomavirus for tumour initiation and/or progression (14).…”

“…Cutaneous SCC is the second most frequent type of skin cancer (23), and cervical SCC is the major type of uterine cervical cancer (14). In SCC of the skin or uterine cervix, absence or lower frequency of MCPyV has been detected compared with MCCs (9-14).…”

“…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

“…Of interest, Epstein-Barr virus (EBV) is among the sexually transmitted viruses that might be a cofactor in cancer development [6] and also Merkel cell polyomavirus (MCPyV), the agent of a subset of Merkel cell carcinoma, a rare and aggressive neoplasia, which has been frequently detected in squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). Recent studies found HPV-positive SCC cervical cancers and adenocarcinomas to be also positive for MCPyV [7,8]. Nevertheless, the occurrence of MCPyV in other genital cancers is unknown, as well as in co-infection with other viruses.…”

Phylogenetic analysis of Merkel cell polyomavirus based on full-length LT and VP1 gene sequences derived from neoplastic tumours in Japanese patients

“…First, we recently detected MCPyV DNA in cutaneous squamous cell carcinoma (SCC), cervical cancer, chronic lymphocytic leukaemia and non-small cell lung cancer in Japanese patients (Hashida et al, 2013a, b;Imajoh et al, 2012aImajoh et al, , 2012bImajoh et al, , 2013Murakami et al, 2011), and found that the sequences of the large T-antigen (LT) and viral protein 1 (VP1) genes were different from reference sequences of the MCPyV MCC350 isolate derived from a North American Hattori et al (2013) reported that one partial LT sequence (designated NU3) derived from Japanese MCC was genetically distinct from Caucasian strains. However, these results were based on sequence analyses of small gene segments, so studies of full-length gene sequences are needed to achieve a better understanding of the phylogenetic relationships between the two different populations.…”