Feature

HPV over 3 decades: A preventable epidemic

To mark our 30th anniversary, Infectious Diseases in Children will be examining some of the infectious diseases that have defined and changed the field over the past 3 decades.

Nearly every adult in the United States has been infected at some time with a subtype of HPV, according to researchers. Experts have long warned of the link between certain types of the virus and cervical, oropharyngeal, penile, anal, vaginal and other types of cancer.

Michelle Berlin

As prevalent as HPV is, the more dangerous strains are the primary concern for clinicians and their patients.

“The question is which patients end up getting cancer and which ones don’t,” Michelle Berlin, MD, MPH, a professor of obstetrics and gynecology at Oregon Health and Science University and co-director of the university’s Center for Women’s Health, told Infectious Diseases in Children. “Fortunately, most people don’t. The problem is we don’t have any way to predict ahead of time who will [become infected] who will not. It’s unbelievably common.”

Despite the effectiveness of vaccines against high-risk HPV types, immunization rates among American youth are, according to experts, frustratingly low.

According to the CDC, in 2016, 49.5% of girls and 37.5% of boys in the U.S. were up to date in receiving the HPV vaccine. They included those who had received three doses under former recommendations or had been properly vaccinated according to the more recent two-dose regimen. Berlin said health care providers must seek to increase those rates.

Lisa Rahangdale

“That is the key issue, and that is what I spend a lot of time dealing with right now,” said Berlin, who considers vaccines the most important development regarding HPV over the past 30 years. “I think the major issue at this point is that the public doesn’t correctly perceive that HPV vaccine is a cancer-prevention vaccine.”

Berlin said the HPV vaccine has too often been regarded as an immunization against a sexually transmitted infection rather than as a cancer prevention tool. However, officials are working to correct that misconception.

“There are a lot of resources now being devoted by the National Cancer Institute, the American Cancer Society, the CDC — a lot of people on the ground — to make sure that parents and kids understand that this is to help prevent cancer, period,” she said.

A weapon against infection

In the 1990s, researchers discovered that proteins forming the outer HPV shell could create virus-like particles (VLPs) that look much like the virus but are not infectious. VLPs, which can prompt the immune system to create antibodies that stop HPV, were used to develop the vaccines Gardasil, (HPV quadrivalent recombinant, Merck), Cervarix (HPV bivalent recombinant, GlaxoSmithKline) and Gardasil 9 (HPV nine-valent recombinant, Merck).

Cervarix and Gardasil target HPV types associated with cervical and anal cancer, along with genital warts — another potential HPV-related morbidity, according to Lisa Rahangdale, MD, MPH, an associate professor of obstetrics and gynecology and associate dean of admissions at the University of North Carolina School of Medicine.

“The Cervarix vaccine covers high-risk HPV subtypes 16 and 18, and the Gardasil 9 vaccine prevents both low-risk HPV subtypes 6 and 11, which can cause genital warts, and high-risk HPV subtypes 16, 18, 31, 33, 45, 52 and 58, which cause cervical dysplasia and cancer,” she explained.

Rahangdale said vaccine coverage of those nine subtypes has been one of the most significant victories researchers and developers have achieved against HPV.

The option of a two-dose, as opposed to a three-dose, immunization series for many children and adolescents is another step forward, she added.

“The benefit of the two-dose schedule is convenience, cost and increased likelihood of completion,” Rahangdale said.

The efficacy of HPV vaccines has also been well-documented. According to the CDC, clinical trials have shown that HPV vaccines are nearly 100% effective in preventing cervical precancers and genital warts. A CDC study published in July showed a large decrease in HPV infections.

The researchers assessed NHANES data on HPV among two age groups of young women from before and after the introduction of the quadrivalent vaccine in 2006. They found that, in a group of those aged 14 to 19 years, the virus’ prevalence decreased from 11.5% in the period of 2003 to 2006 to 3.3% in the period from 2011 to 2014.

In a group of those aged 20 to 24 years, prevalence fell from 18.5% in the period from 2003 to 2006 to 7.2% in the period from 2011 to 2014.

The decline in HPV infections since the vaccines’ advent has been impressive, according to Lauri Markowitz, MD, a medical epidemiologist with the CDC’s division of viral diseases.

“HPV vaccination is protecting against cancer-causing infections even better than we expected,” Markowitz said. “Since the introduction of the first HPV vaccine, infections with HPV types that cause most of these cancers and genital warts have decreased by 71% in teen girls and 61% in young women.”

Although public health officials want to greatly increase the proportion of teens completing the recommended vaccination series, Markowitz noted that most parents are at least starting the process.

“Most U.S. parents are getting the first dose of HPV vaccine for their children,” she said. “Six out of 10 U.S. parents are choosing to get the HPV vaccine for their children, according to the latest National Immunization Survey-Teen report.”

What is next?

With so much data supporting HPV vaccine efficacy, the challenge that remains is increasing their use in the U.S.

“Overall, I think the public forgets that if we’re going to look at the major things that have saved people’s lives in the last 100 years, it’s clean water, clean milk and immunization,” Berlin said. “I think people forget how much of an advance that is.”

There are several approaches to promoting immunization, Berlin added.

“I think one way is to really encourage providers to talk to parents and kids,” she said. “A second way is to try to make it really easy to get this vaccine, like in pharmacies where people can get influenza and shingles vaccines. We’re working hard to try to get the [HPV vaccine] administered in pharmacies as well.”

Making HPV vaccines a part of standard immunizations is also important, Berlin said.

“I think what has happened is that some parents have seen this as an ‘optional’ vaccine, when that’s not the appropriate way to look at it,” she said. “At the appropriate age, I think that we need to think of HPV vaccine as part of the whole package that kids get, just like everything else.”

Berlin said that advances in vaccine technology could possibly reduce the number of required doses to just one.

Markowitz, too, stressed the importance of efficiency.

“CDC encourages clinicians to recommend HPV vaccine the same way and same day they recommend other vaccines for adolescents,” she said.

Markowitz suggested clinicians can “make small changes to their practices” that can include adding reminder/recall notices — messages by telephone, text, letter, postcard or other medium to parents or patients who are due or overdue for an immunization.

“The latest NIS-Teen report also found that HPV vaccination coverage was lower in rural and less urban areas, suggesting that these communities could benefit from additional efforts to increase coverage,” Markowitz added. “CDC will be investigating this difference and potential interventions in future research.”

Rahangdale said there are other factors to consider in preventing and addressing HPV-associated cancers, including giving all women access to screening for cervical cancer, including pap smears with or without HPV testing.

She also mentioned that a therapeutic vaccine is in development that could potentially allow HPV-infected patients to clear the virus.

In addition, she said, “medical therapies — topical or injectable — are in development so that women with cervical precancers or HPV infection may have medical options for treatment rather than just surgical options.”

Although significant progress has been made against HPV-related cervical cancer, more must be done to target other cancers linked to the virus, Berlin said.

“In terms of treatment over the past 30 years, we’ve gone far in being able to help diagnose precancers in women and take care of them before they get cancer,” she said. “That’s in terms of cervical cancer. Not quite so much in other cancers from HPV ... We’re still learning more and more about those.” – by Joe Green

Disclosures: Berlin, Markowitz and Rahangdale report no relevant financial disclosures.

To mark our 30th anniversary, Infectious Diseases in Children will be examining some of the infectious diseases that have defined and changed the field over the past 3 decades.

Nearly every adult in the United States has been infected at some time with a subtype of HPV, according to researchers. Experts have long warned of the link between certain types of the virus and cervical, oropharyngeal, penile, anal, vaginal and other types of cancer.

Michelle Berlin

As prevalent as HPV is, the more dangerous strains are the primary concern for clinicians and their patients.

“The question is which patients end up getting cancer and which ones don’t,” Michelle Berlin, MD, MPH, a professor of obstetrics and gynecology at Oregon Health and Science University and co-director of the university’s Center for Women’s Health, told Infectious Diseases in Children. “Fortunately, most people don’t. The problem is we don’t have any way to predict ahead of time who will [become infected] who will not. It’s unbelievably common.”

Despite the effectiveness of vaccines against high-risk HPV types, immunization rates among American youth are, according to experts, frustratingly low.

According to the CDC, in 2016, 49.5% of girls and 37.5% of boys in the U.S. were up to date in receiving the HPV vaccine. They included those who had received three doses under former recommendations or had been properly vaccinated according to the more recent two-dose regimen. Berlin said health care providers must seek to increase those rates.

Lisa Rahangdale

“That is the key issue, and that is what I spend a lot of time dealing with right now,” said Berlin, who considers vaccines the most important development regarding HPV over the past 30 years. “I think the major issue at this point is that the public doesn’t correctly perceive that HPV vaccine is a cancer-prevention vaccine.”

Berlin said the HPV vaccine has too often been regarded as an immunization against a sexually transmitted infection rather than as a cancer prevention tool. However, officials are working to correct that misconception.

“There are a lot of resources now being devoted by the National Cancer Institute, the American Cancer Society, the CDC — a lot of people on the ground — to make sure that parents and kids understand that this is to help prevent cancer, period,” she said.

A weapon against infection

In the 1990s, researchers discovered that proteins forming the outer HPV shell could create virus-like particles (VLPs) that look much like the virus but are not infectious. VLPs, which can prompt the immune system to create antibodies that stop HPV, were used to develop the vaccines Gardasil, (HPV quadrivalent recombinant, Merck), Cervarix (HPV bivalent recombinant, GlaxoSmithKline) and Gardasil 9 (HPV nine-valent recombinant, Merck).

Cervarix and Gardasil target HPV types associated with cervical and anal cancer, along with genital warts — another potential HPV-related morbidity, according to Lisa Rahangdale, MD, MPH, an associate professor of obstetrics and gynecology and associate dean of admissions at the University of North Carolina School of Medicine.

“The Cervarix vaccine covers high-risk HPV subtypes 16 and 18, and the Gardasil 9 vaccine prevents both low-risk HPV subtypes 6 and 11, which can cause genital warts, and high-risk HPV subtypes 16, 18, 31, 33, 45, 52 and 58, which cause cervical dysplasia and cancer,” she explained.

Rahangdale said vaccine coverage of those nine subtypes has been one of the most significant victories researchers and developers have achieved against HPV.

The option of a two-dose, as opposed to a three-dose, immunization series for many children and adolescents is another step forward, she added.

“The benefit of the two-dose schedule is convenience, cost and increased likelihood of completion,” Rahangdale said.

The efficacy of HPV vaccines has also been well-documented. According to the CDC, clinical trials have shown that HPV vaccines are nearly 100% effective in preventing cervical precancers and genital warts. A CDC study published in July showed a large decrease in HPV infections.

The researchers assessed NHANES data on HPV among two age groups of young women from before and after the introduction of the quadrivalent vaccine in 2006. They found that, in a group of those aged 14 to 19 years, the virus’ prevalence decreased from 11.5% in the period of 2003 to 2006 to 3.3% in the period from 2011 to 2014.

In a group of those aged 20 to 24 years, prevalence fell from 18.5% in the period from 2003 to 2006 to 7.2% in the period from 2011 to 2014.

The decline in HPV infections since the vaccines’ advent has been impressive, according to Lauri Markowitz, MD, a medical epidemiologist with the CDC’s division of viral diseases.

“HPV vaccination is protecting against cancer-causing infections even better than we expected,” Markowitz said. “Since the introduction of the first HPV vaccine, infections with HPV types that cause most of these cancers and genital warts have decreased by 71% in teen girls and 61% in young women.”

Although public health officials want to greatly increase the proportion of teens completing the recommended vaccination series, Markowitz noted that most parents are at least starting the process.

“Most U.S. parents are getting the first dose of HPV vaccine for their children,” she said. “Six out of 10 U.S. parents are choosing to get the HPV vaccine for their children, according to the latest National Immunization Survey-Teen report.”

PAGE BREAK

What is next?

With so much data supporting HPV vaccine efficacy, the challenge that remains is increasing their use in the U.S.

“Overall, I think the public forgets that if we’re going to look at the major things that have saved people’s lives in the last 100 years, it’s clean water, clean milk and immunization,” Berlin said. “I think people forget how much of an advance that is.”

There are several approaches to promoting immunization, Berlin added.

“I think one way is to really encourage providers to talk to parents and kids,” she said. “A second way is to try to make it really easy to get this vaccine, like in pharmacies where people can get influenza and shingles vaccines. We’re working hard to try to get the [HPV vaccine] administered in pharmacies as well.”

Making HPV vaccines a part of standard immunizations is also important, Berlin said.

“I think what has happened is that some parents have seen this as an ‘optional’ vaccine, when that’s not the appropriate way to look at it,” she said. “At the appropriate age, I think that we need to think of HPV vaccine as part of the whole package that kids get, just like everything else.”

Berlin said that advances in vaccine technology could possibly reduce the number of required doses to just one.

Markowitz, too, stressed the importance of efficiency.

“CDC encourages clinicians to recommend HPV vaccine the same way and same day they recommend other vaccines for adolescents,” she said.

Markowitz suggested clinicians can “make small changes to their practices” that can include adding reminder/recall notices — messages by telephone, text, letter, postcard or other medium to parents or patients who are due or overdue for an immunization.

“The latest NIS-Teen report also found that HPV vaccination coverage was lower in rural and less urban areas, suggesting that these communities could benefit from additional efforts to increase coverage,” Markowitz added. “CDC will be investigating this difference and potential interventions in future research.”

Rahangdale said there are other factors to consider in preventing and addressing HPV-associated cancers, including giving all women access to screening for cervical cancer, including pap smears with or without HPV testing.

She also mentioned that a therapeutic vaccine is in development that could potentially allow HPV-infected patients to clear the virus.

In addition, she said, “medical therapies — topical or injectable — are in development so that women with cervical precancers or HPV infection may have medical options for treatment rather than just surgical options.”

Although significant progress has been made against HPV-related cervical cancer, more must be done to target other cancers linked to the virus, Berlin said.

“In terms of treatment over the past 30 years, we’ve gone far in being able to help diagnose precancers in women and take care of them before they get cancer,” she said. “That’s in terms of cervical cancer. Not quite so much in other cancers from HPV ... We’re still learning more and more about those.” – by Joe Green

Disclosures: Berlin, Markowitz and Rahangdale report no relevant financial disclosures.

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