“We have to flood the market to let women and young girls and boys know that they should get vaccinated,” said Meneses, Ph.D., associate professor of biological sciences, who dedicates his laboratory to studying the basic processes that establish HPV infection.

HPV and Black Women

This past month, a study published in the journal Cancer highlighted the impact of the virus, which affects 14 million Americans each year, according to the Centers for Disease Control and Prevention (CDC). Researchers found that the death rate from cervical cancer, an HPV-related cancer, is higher among black women than previously suspected. According to the study, black women were dying of cervical cancer at twice the rate of white women. Among black women over the age of 20, the rate of cervical cancer death was 10.1 deaths per 100,000 women while the rate for white women was 4.7 per 100,000 women.

One major emphasis of the Cancer study is that HPV-related cancers like cervical cancer is up to 93 percent preventable by pap smears and HPV vaccinations, according to the CDC.

“There might be something biological where some groups are more susceptible, but I think there are some groups who may also be less good at preventative medicine,” said Meneses. “Once they go to get a check-up, it’s almost too late.”

Meneses, who has spent his career examining the process of initial viral entry and trafficking to better understand HPV, said HPV vaccines are mostly marketed as antiviral vaccines when in fact they should also be viewed as anticancer vaccines.

Taking Preemptive Measures

Currently, Gardasil, Gardasil 9, and Cervarix are the only vaccines approved by the Food and Drug Administration to help prevent HPV infection. Both Gardasil and Gardasil 9 have been approved for use in men, women, girls, and children. Cervarix has been approved for use in girls and women for the prevention of HPV-caused cervical cancer.

“We need to make sure that the vaccines are hitting enough people to prevent the disease from spreading from person to person,” said Meneses. “Right now, the vaccines are being taken by approximately 40 percent of young girls, and you almost need 80 percent to ensure the protection.”

While there are preemptive measures in place to combat the disease, access to affordable health care continues to be a potential limiting factor for minority women.

“If you’re not very wealthy or don’t have good health care, you’re probably not going to get the vaccine,” he said. “And if you’re not getting the vaccine early on, you’re going to be getting an HPV infection and that’s going to already predispose you to having cervical cancer.”

Meneses said the challenge that doctors face today is getting people to understand that tactical practices such as screenings and vaccinations are the first line of defense against HPV-related cancers.

“This is one of those diseases from the perspectives of a scientist that you can almost eradicate from the world because it’s virally mediated,” he said. “You could eventually cover enough people that it doesn’t present a problem anymore, but obviously that’s in an ideal world.”

Related stories:

Professors Collaborate to Detect HPV

https://now.fordham.edu/science/fordham-professors-collaborate-to-detect-hpv/

Student Researchers Seek Cure for HPV

https://now.fordham.edu/science/video-faculty-and-student-researchers-seek-cure-for-hpv-virus/

If it follows the usual pattern of viral infections, it will eventually take over the cell, turning it into an engine for making more viruses and infecting other cells.

Except it doesn’t.

The virus stalls. The infection stops and the cell survives.

This scenario plays out all the time in the laboratory of Patricio I. Meneses, Ph.D., associate professor of biology, who has spent nearly 10 years figuring out how to short-circuit the virus in this controlled laboratory setting.

Today, he’s looking for a way to short-circuit it outside of the lab—that is, in people who catch the virus. The result, he hopes, will be a treatment that saves thousands of lives.
That’s because the virus in question is HPV, or human papillomavirus, which is responsible for 99 percent of cervical cancers, as well as many oral cancers and most anal cancers.

Despite the development of HPV vaccines within the last six years, cervical cancer still kills an estimated 250,000 women annually, most of them in the developing world, according to the World Health Organization.

Given these numbers, Meneses is doubly driven: to understand the virus, but also to prevent deaths that often have significant social costs.

“Many of these women are in their early 30s … so not only are we losing these women to cancer, but the family structure is completely destroyed, both at home and in the community, and in the country itself, especially in places like sub-Saharan Africa,” he said. “You’re losing all these women who can make a difference, both in the social structure and the direction of the local environment, the local government. The social impact is huge.”

Two HPV vaccines, Cervarix and Gardasil, counteract the two most common strains of HPV, but not the remaining 13 strains that cause 30 percent of cervical cancer cases.

Meneses is searching for an inexpensive treatment, affordable for those in less-developed countries, that would stop all strains of the virus. He envisions a treatment that’s easy to make and deliver, such as a small molecule—taken in pill form, perhaps—that slips inside an infected cell and prevents HPV from taking it over.

For this project, Meneses is drawing on a longstanding interest in how viruses work. While studying gene therapy as a graduate student in the 1990s, he took part in a study of the use of viruses to deliver genes that would replace genes that were linked to cancer. He pursued postdoctoral study of HPV at Harvard after learning about the virus’s ability to lie dormant in the cervix for years after entering the body.

“The biology of how a virus infects a cell is surely phenomenal,” he said. “It’s such a small agent—the virus is infinitesimal in its size—and yet it can do so much. You may end up working 10 years of your life on a five-minute span of the lifetime of a virus, but that five-minute span is really crucial. A lot happens in that five minutes.”

His research—funded by a grant from the American Cancer Society, and one from the National Cancer Institute—belongs to the field of proteomics, or the study of the makeup of proteins, which are the essential stuff of cells.

Two proteins form the outer shell of the HPV virus, enclosing the DNA within. When the virus enters a healthy cell, these proteins “hijack” the cell’s proteins, which normally move nutrients and oxygen toward the cell’s nucleus, and force them to carry the virus’s DNA instead.

In the course of this takeover, the HPV proteins mingle their amino acids with the healthy proteins inside of the cell.

This is the phase that Meneses is studying. He has found that when he mutates four of the HPV proteins’ amino acids, the virus stalls somewhere in the jungle of proteins inside the cell. To find out exactly where it breaks down, he and his team are conducting a variety of experiments involving these altered HPV viruses, which they manufacture and set loose on cultured human cells.

It’s challenging work because he has to pinpoint the few amino acid interactions that faltered, somewhere amid the thousands of proteins inside the cell. Once he succeeds, however, the result could be a targeted treatment that prevents these interactions and stops the infection.

In taking on this wily virus, Meneses sees new possibilities for advancing our understanding of nature.

“Viruses are the greatest survivors,” he said. “They’ve been around for centuries, and they have managed a way to still be around by adapting. So I think there is a lot to learn as to how nature works in general” by studying them, he said.

Meneses estimates that any breakthrough in his work is two to five years away. He noted, however, that there is another anti-HPV weapon that isn’t used often enough, especially in underdeveloped countries: the simple pap smear, which can detect cervical cancer in its early stages. “If you catch (cervical cancer) early, it’s very treatable,” Meneses said.

If it follows the usual pattern of viral infections, it will eventually take over the cell, turning it into an engine for making more viruses and infecting other cells.

Except it doesn’t.

The virus stalls. The infection stops and the cell survives.

This scenario plays out all the time in the laboratory of Patricio I. Meneses, Ph.D., associate professor of biology, who has spent nearly 10 years figuring out how to short-circuit the virus in this controlled laboratory setting.

Today, he’s looking for a way to short-circuit it outside of the lab—that is, in people who catch the virus. The result, he hopes, will be a treatment that saves thousands of lives.

That’s because the virus in question is HPV, or human papillomavirus, which is responsible for 99 percent of cervical cancers, as well as many oral cancers and most anal cancers.

Despite the development of HPV vaccines within the last six years, cervical cancer still kills an estimated 250,000 women annually, most of them in the developing world, according to the World Health Organization.

Given these numbers, Meneses is doubly driven: to understand the virus, but also to prevent deaths that often have significant social costs.

“Many of these women are in their early 30s … so not only are we losing these women to cancer, but the family structure is completely destroyed, both at home and in the community, and in the country itself, especially in places like sub-Saharan Africa,” he said. “You’re losing all these women who can make a difference, both in the social structure and the direction of the local environment, the local government. The social impact is huge.”

Two HPV vaccines, Cervarix and Gardasil, counteract the two most common strains of HPV, but not the remaining 13 strains that cause 30 percent of cervical cancer cases.

Meneses is searching for an inexpensive treatment, affordable for those in less-developed countries, that would stop all strains of the virus. He envisions a treatment that’s easy to make and deliver, such as a small molecule—taken in pill form, perhaps—that slips inside an infected cell and prevents HPV from taking it over.

For this project, Meneses is drawing on a longstanding interest in how viruses work. While studying gene therapy as a graduate student in the 1990s, he took part in a study of the use of viruses to deliver genes that would replace genes that were linked to cancer. He pursued postdoctoral study of HPV at Harvard after learning about the virus’s ability to lie dormant in the cervix for years after entering the body.

“The biology of how a virus infects a cell is surely phenomenal,” he said. “It’s such a small agent—the virus is infinitesimal in its size—and yet it can do so much. You may end up working 10 years of your life on a five-minute span of the lifetime of a virus, but that five-minute span is really crucial. A lot happens in that five minutes.”

His research—funded by a grant from the American Cancer Society, and one from the National Cancer Institute—belongs to the field of proteomics, or the study of the makeup of proteins, which are the essential stuff of cells.

Two proteins form the outer shell of the HPV virus, enclosing the DNA within. When the virus enters a healthy cell, these proteins “hijack” the cell’s proteins, which normally move nutrients and oxygen toward the cell’s nucleus, and force them to carry the virus’s DNA instead.

In the course of this takeover, the HPV proteins mingle their amino acids with the healthy proteins inside of the cell.

This is the phase that Meneses is studying. He has found that when he mutates four of the HPV proteins’ amino acids, the virus stalls somewhere in the jungle of proteins inside the cell. To find out exactly where it breaks down, he and his team are conducting a variety of experiments involving these altered HPV viruses, which they manufacture and set loose on cultured human cells.

It’s challenging work because he has to pinpoint the few amino acid interactions that faltered, somewhere amid the thousands of proteins inside the cell. Once he succeeds, however, the result could be a targeted treatment that prevents these interactions and stops the infection.

In taking on this wily virus, Meneses sees new possibilities for advancing our understanding of nature.

“Viruses are the greatest survivors,” he said. “They’ve been around for centuries, and they have managed a way to still be around by adapting. So I think there is a lot to learn as to how nature works in general” by studying them, he said.

Meneses estimates that any breakthrough in his work is two to five years away. He noted, however, that there is another anti-HPV weapon that isn’t used often enough, especially in underdeveloped countries: the simple pap smear, which can detect cervical cancer in its early stages. “If you catch (cervical cancer) early, it’s very treatable,” Meneses said.