Skip to main content
Premium Trial:

Request an Annual Quote

HPV, Polyomavirus Infections Likely Minor Bladder Cancer Contributors, Study Suggests

NEW YORK (GenomeWeb) – Neither the human papillomavirus (HPV) nor the human polyomavirus (HPyV) appear to be common contributors to urothelial bladder carcinoma (UBC) development, according to a genetic screen by a team from the UK and the Netherlands.

As they reported online yesterday in Scientific Reports, the researchers used quantitative PCR to screen for the BK virus (BKV), JC virus (JCV), or other polyomaviruses, and for the high-risk HPV types HPV16 and HPV18 in DNA extracted from almost 700 UBC tumors. Their analyses uncovered HPV16 in less than 1 percent of the tumors, while HPV18 DNA did not turn up in any of the tumor samples.

HPyVs were a bit more common, appearing in some 7 percent of the bladder cancer cases considered, including 23 BKV-positive samples and half a dozen samples with confirmed JCV. And the HPyV-positive samples appeared to show enhanced T antigen expression relative to HPyV-negative samples. Even so, the team concluded these viruses were not common enough to account for most UBC cases.

"Although our results cannot completely exclude a causative role for these viruses in the pathogenesis of UBC, it is clear that high levels of virus are not persistent driving factors in UBC," senior author Richard Bryan, a cancer and genomic sciences researcher at the University of Birmingham, and his co-authors wrote.

Past studies have implicated viral infections as contributors to several cancer types — from the infamous role of HPV in cervical cancer or head and neck cancers to liver cancer cases stemming from hepatitis virus infections. But the team noted that there has been ongoing debate over the potential of finding oncogenic viruses in bladder cancers such as UBC.

"[M]ore than 50 studies on HPV and UBC have failed to come to a consensus," the authors wrote, noting that "potentially oncogenic viruses such as [Epstein-Barr virus] and human polyomaviruses have received less attention."

Building on recent studies that described HPV and/or HPyV DNA or mutational signatures in UBC, the researchers did qPCR with primers targeting E6 and E7 genes to screen for HPV16 and HPV18, respectively, in 689 fresh-frozen UBC tumors. They similarly used the qPCR approach to screen the UBC tumor set for BKV and JCV.

When viral-positive samples were detected by qPCR, the team turned to Sanger sequencing and RT-PCR or immunohistochemistry to verify the presence of HPV or HPyV.

On the HPV side, the researchers saw just one HPV16-positive sample, which was subsequently confirmed using RT-PCR-based E6 and E7 oncogene expression profiling. None of the UBC samples contained detectable HPV18 DNA, they reported.

"Due to limits of analytical sensitivity, our data cannot rule out the presence of extremely low levels of HPV16 or HPV18 in bladder tumors, but it is clear that the majority of bladder tumors do not contain HPV16 or HPV18," the authors wrote. "Thus, for HPV16 or HPV18 to play a significant role in bladder cancer, we have to envisage the scenario that the virus initiates an oncogenic effect which persists after the virus is eliminated."

The team's polyomavirus analysis suggested that more than 90 percent of the samples were HpyV-negative. Nevertheless, at least 49 of the UBC tumors appeared to harbor some HPyV DNA, including 23 tumors with BKV DNA and six that were JCV-positive — viruses peppered across tumors from different disease stages, tumor grades, or patient ages.

"[W]hilst we report that up to 7 percent of UBCs may be positive for HPyV, we have only unequivocally demonstrated that 4 percent of UBCs contain HPyV DNA sequences," the authors wrote, noting that "[i]t may be worth considering alternative primers or even a probe-based capture and next-generation sequencing approach to improve assay sensitivity and specificity in the future."

The Scan

Support for Moderna Booster

An FDA advisory committee supports authorizing a booster for Moderna's SARS-CoV-2 vaccine, CNN reports.

Testing at UK Lab Suspended

SARS-CoV-2 testing at a UK lab has been suspended following a number of false negative results.

J&J CSO to Step Down

The Wall Street Journal reports that Paul Stoffels will be stepping down as chief scientific officer at Johnson & Johnson by the end of the year.

Science Papers Present Proteo-Genomic Map of Human Health, Brain Tumor Target, Tool to Infer CNVs

In Science this week: gene-protein-disease map, epigenomic and transcriptomic approach highlights potential therapeutic target for gliomas, and more