Kristy Heilenday Illustrations

What if a cancer that claims hundreds of thousands of lives each year could be virtually eradicated?

Although significant obstacles remain, it appears to be a real possibility for cervical cancer. And across UVA, research focused on prevention and screening—and a promising new discovery that could lead to a new approach to treatment—helps move the world closer to that reality.

Cervical cancer was once the leading cause of cancer deaths among women in the U.S., until the widespread introduction of the Pap screening test in the mid-20th century led to a dramatic drop in its incidence. Then, in the 1970s, scientists established the link between HPV—the human papillomavirus—and cervical cancer, determining that a few high-risk strains of this common virus were responsible for most cases of the disease.

Infection with HPV is widespread among sexually active people; in some cases, high-risk strains of the virus can lead not only to cervical cancer but also to genital warts and some other, less-common cancers. However, as Professor Anindya Dutta in the School of Medicine explains, cervical cancer is actually an “accident” of HPV infection, when DNA from the virus—for reasons that are not fully understood—becomes incorporated into human chromosomes.

While studying such HPV-infected cancer cells in his lab, Dutta and his team made an unexpected discovery: An enzyme known as USP46 appears to play a role in helping these cells proliferate.

“It is something specifically happening in HPV-transformed cancer cell lines,” Dutta says. “USP46 seems to be very important for multiplication for HPV-transformed cancer cells.”

Dutta says it may be possible to create a drug narrowly targeted to “jam” the activity of USP46 and “attack HPV cancer but leave the rest of the proliferating cells in the body alone.” His team is now searching for chemical inhibitors that could be likely candidates for that role. 

With more than 570,000 new cases and 311,000 deaths around the world from cervical cancer last year, there remains a need for effective treatment. But preventing the disease is the ultimate goal, one that is conceivably within reach thanks to the recent introduction of a screening test to detect, and vaccines to prevent, infection by the high-risk strains of HPV.

Gardasil 9, the vaccine available in the U.S., targets seven high-risk sexually transmitted HPV types that “together account for 90 percent of cervical cancers,” explains Dr. Mark Stoler, professor emeritus of pathology and clinical gynecology in the School of Medicine, who was extensively involved in clinical trials of the vaccine and works on the long-term follow-up studies. “This is the most effective vaccine ever developed,” he says. “If you get the vaccine, you don’t get infected with the virus.”

In Australia, about 80 to 90 percent of the targeted school-age population now receives the vaccination, Stoler says. Such a high rate of vaccination, he explains, actually breaks the chain of transmission: “Eventually those strains of HPV die out,” he says. “It becomes too rare in the population.” Researchers recently estimated that with vaccination and continued screening, cervical cancer could be virtually eradicated from the country within a decade.

Unfortunately, that scenario is not mirrored elsewhere, including in the U.S., where only 49 percent of teenagers have received the full course of HPV vaccination, and, despite the availability of HPV and Pap screening, the American Cancer Society estimates there will be more than 13,000 new diagnoses and 4,000 deaths from cervical cancer this year.

While vaccine reluctance is part of the problem in some high-income countries, the global incidence of cervical cancer reflects disparities in access to vaccination, screening and care, says Emma Mitchell (Nurs ’08, ’11), an assistant professor and co-director of global initiatives in the School of Nursing. Many of the most at-risk women live in middle- and lower-income countries, particularly in Africa and Central and South America. Yet even in the U.S., women in marginalized groups and in rural areas also experience barriers to access.

In her research in rural Virginia and in Central America, Mitchell is examining those barriers “and how we can use innovative technology to transcend or mitigate” them. One project is evaluating providing women with at-home, mail-in HPV self-collection kits to test for infection with high-risk types.

Yet testing isn’t enough. Countries with the highest incidence of cervical cancer are also those where many women lack access to basic health care services, such as Pap screening. Even in the U.S., Mitchell found that a large number of women in the collection-kits study lacked a primary-care doctor. Even among those who had such a doctor, “all were overdue for cervical screenings and none were told they were.”

Could Australia’s success be replicated around the globe? Maybe—with a global commitment.

UVA researchers are doing their part in that effort.

“I would love to become irrelevant in my lifetime,” Mitchell says.