Viruses in cancers among the immunosuppressed

Abstract

Most cancer forms known to be caused by viruses are increased among the immunosuppressed, but several cancer forms without established viral etiology are also increased, notably nonmelanoma skin carcinoma (NMSC). We followed all 13,429 solid organ transplantation patients in Sweden for cancer occurrence after transplantation. We requested these tumor specimens and sequenced the first 89 specimens received (62 NMSCs, 27 other cancers). The sequences were analyzed for viruses based on two bioinformatics algorithms (paracel-blast (sensitive for detection of known viruses) and hidden Markov model (HMM; sensitive for distantly related viruses)). Among the 62 NMSCs, the virus family detected in the largest proportion of specimens was Mimiviridae (9/62 NMSCs). The majority of the virus-related reads belonged to Papillomaviridae. The HMM analysis identified 86 additional previously not described viral contigs related to 11 virus families, with reads related to Mimiviridae being the most common (detected in 28/62 NMSCs) with the most prevalent contig (Mimivirus SE906, 1937 bp) detected in 17/62 NMSCs. Among the 27 other cancers, viral sequences were detected in only 5 specimens by blast analysis, compared to in all 27 specimens by HMM (Mimiviridae, Poxviridae, Phycodnaviridae and virus-related sequences yet unclassified to any family). 99% of the virus reads belonged to a single previously not described sequence (Mimivirus SE996, 911 bp). A multitude of viruses is readily detectable in specimens with cancers occurring among the immunosuppressed, with sequences related to Mimiviridae being the most prevalent. Further research would be needed to elucidate the biological significance of the viruses.

Genomic and metagenomic signatures of giant viruses are ubiquitous in water samples from sewage, inland lake, waste water treatment plant, and municipal water supply in Mumbai, India

“…Giant viruses have been primarily studied to ascertain their true classification 8 and evolutionary significance 9,48,49 . More recently, GVs have been detected in humans, associated with respiratory illness 50 , cancer 51 . In addition to isolation of GVs, metagenomic studies have contributed significantly to our understanding of NCLDV diversity and abundance, and also their detection in environments that are shared with human communities 5 .…”

Author's reply to: Human papillomavirus type 197 is not associated with skin tumors

“…1 Apart from that different specimen series may differ, we also raised the possibility of biological contamination (i.e., contamination already before the sample arrives at the lab). 2 This phenomenon was most clearly shown for an HPV88-positive skin cancer that contained >1 million viral copies/cell and where the tumor appeared to have contaminated the fingers on the other arm of the patient. 3 We have also pointed out that many skin cancers that are positive for low amounts of HPV DNA appear to lack any detectable viral transcription, 4 suggesting that their presence may not reflect an infection but rather be a deposition caused by the patient or at the dermatology clinic, arguing that studies on HPV infections of the skin should focus on detection of viral RNA transcripts.…”

De novo sequence assembly requires bioinformatic checking of chimeric sequences

“…Current advancements in next-generation sequencing technologies have enabled researchers to obtain sequence information from all genomes present in a specimen, without prior knowledge of what genomes are present [1][2][3][4][5]. This metagenomic approach has revolutionized the field of virology in particular, since the lack of an appropriate phylogenetic marker (e.g.…”

“…Of particular interest is the virome study of non-melanoma skin cancers (NMSCs), as this cancer presents a 100-fold increased incidence among the immunosuppressed patients [1], but has not been associated with any pathogen yet. Metagenomics studies of viral DNA in NMSCs have reported that Human papillomavirus (HPV) comprises >95% of viral reads [4], and putative persistence of the same HPV types in different skin tumors diagnosed over time from the same patient has also been reported [17], making HPV a very good causative candidate for this type of cancer.…”