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HPV

Published On January 15, 2020

CLINICAL RESEARCH

Where Is the Next HPV Vaccine?

At least 10% of cancers are probably caused by a viral infection. But researchers struggle to replicate the success they have had with cervical cancer.

A review paper published in The Lancet in summer 2019 showed the dramatic impact of human papillomavirus (HPV) vaccines. In more than 60 million study subjects and across 14 countries, the vaccines have reduced infections from the most dangerous, cancer-causing strains of the virus by as much as 83%. In conjunction with better screening, this in turn has led to fewer cases of cervical cancer.

HPV is far from the only virus that causes cancer. So-called oncoviruses are probably behind one in 10 cases, according to a recent special issue of Philosophical Transactions of the Royal Society B. So why haven’t more cancer vaccines made it to the market?

One problem is identifying with 100% certainty that a particular virus is responsible for cancer. BK virus, for instance, infects more than 90% of U.S. children by age 10. In test animals, infection with BKV has been linked with various cancers, and in cell cultures, a researcher can watch it turn rodent cells cancerous. But while researchers suspect that it plays a role in cancers of the urinary tract (where, along with the kidney, the virus resides in the human body), no one has been able to map a clear connection.

Another suspect is cytomegalovirus, or CMV, a common type of herpesvirus. In a paper published in 2002, researchers from the Veterans Affairs Medical Center in Birmingham, Ala., found evidence of this virus in every one of 27 samples of glioblastoma, the deadliest form of brain tumor. Later studies didn’t turn up such neat results, and a controversy over CMV's possible link to cancer is still ongoing.  

But research has shown that patients with high-grade CMV infection live 20 fewer months than those with a low-grade infection, and a recent study from Duke University showed that a treatment targeting CMV can extend the life of patients with glioblastoma more than 40 months. Proof that CMV infection actually causes this brain cancer, however, remains elusive.

One proponent of further study is Harald zur Hausen, the virologist who won the 2008 Nobel Prize in Physiology or Medicine for his work with HPV. In April 2019, zur Hausen published a paper suggesting that viruslike structures—circular single-stranded DNA—found in red meat and dairy products might raise the risk of colon and breast cancers. He began his work after noting a remarkable geographic coincidence: India, a country where beef is not widely consumed, had a low rate of breast and colon cancers.

While other researchers have looked at the link between red meat and cancer before, zur Hausen and his colleague Ethel-Michele de Villiers focused on bovine milk and meat factors (BMMFs), bacterial plasmids found in cows. While not strictly viruses, BMMFs are closely related to a specific group of bacterial plasmids and are relatively simple self-replicating strands of DNA that require a host to survive. They offer a tantalizing picture of how such structures, when they enter the human body, might become linked to cancer.

“BMMFs are adapted to independent growth in human cells, inducing chronic inflammation that persists for decades,” zur Hausen says. That inflammation causes mutations in adjacent cells, part of “a substantial amount of evidence” that viruses and similar structures might play a key and as yet unexplained role in the disease.

Zur Hausen also points out, however, that people shouldn’t avoid red meat and dairy products in 2020 just because BMMFs are associated with cancer. “We are all infected with these agents anyway,” he says, “so don’t worry about it. The infections persist, that is the point, and whether we ingest them now will not modify respective risks of cancers.”

Targeting oncoviruses and BMMFs—even if their connection to cancer is made clearer—may still be quite a way off. There aren’t yet vaccines to protect against even proven culprits, including Merkel cell polyomavirus, which is linked to an aggressive skin cancer, and Kaposi's sarcomaassociated herpesvirus. Creating a vaccine takes time and a major investment by pharmaceutical companies, and candidate vaccines must undergo lengthy human trials. If zur Hausen is proved correct, however, such evidence would bring new urgency to finding vaccines that would provide a broad—and lifesaving—precaution.