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Vaccines against human papillomavirus have been hailed as a success: they have been shown to decrease the incidence of cervical lesions associated with the HPV types that are in the vaccine.
However,
An expert not involved in the research said the new data “tell us to be a little bit careful.” Although the HPV types not included in the vaccine are rarer and less aggressive, they can still cause cancer.
The data come from the Costa Rica HPV Vaccine Trial, which involved more than 10,000 women aged 18-25 years. The HPV vaccine used in the trial was Cervarix, from GlaxoSmithKline. It covers the two leading causes of cervical cancer, HPV-16 and -18, and provides partial protection against three other genotypes.
After a follow-up of 11 years, among vaccinated women, there was an excess of precancerous cervical lesions caused by genotypes not included in the vaccine, resulting in negative vaccine efficacy for those HPV variants.
The increase wasn’t enough to offset the overall benefit of vaccination when all genotypes were considered, said the researchers, led by Jaimie Shing, PhD, a postdoctoral research fellow at the National Cancer Institute in Bethesda, Md.
Vaccinated women “still had long-term absolute reductions in high-grade lesions,” they pointed out.
The net protection “remained considerable, emphasizing the importance of HPV vaccination for cervical cancer prevention,” the team concluded.
The findings were published online in The Lancet Oncology.
The results are likely the first evidence to date of “clinical unmasking” with HPV vaccination, meaning that protection against the strains covered by the vaccine leaves women more prone to attack from other carcinogenic HPV variants.
This phenomenon “could attenuate long-term reductions in high-grade disease following successful implementation of HPV vaccination programs,” the investigators commented.
Highlighting a need for caution
The take-home message from the trial is that “we have to be careful,” said Marc Steben, MD, co-President of HPV Global Action and a professor at the University of Montreal.
He noted that the Cervarix HPV vaccine used in the trial is not the vaccine that is used now in developed nations.
The current standard HPV vaccine is Gardasil 9 (Merck), which offers broader coverage against nine HPV types (types 6, 11, 16, 18, 31, 33, 45, 52, and 58).
There are 12 main carcinogenic HPV genotypes, so unmasking of other strains is still possible with Gardasil 9, he said.
There is another issue, Dr. Steben added. The success of HPV vaccinations - a nearly 90% reduction in invasive cervical cancer in women who are vaccinated at a young age – has led to questions about the future role of routine cervical cancer screening.
“Some people are saying that if we achieve 90% coverage, we might” eliminate community transmission and no longer need to screen, he said.
These trial results “tell us to be a little bit careful,” Dr. Steben continued. Those HPV types that are less aggressive and rarer than HPV-16 and -18 “can still cause cancer and might be there and surprise us. It could take more time than we thought” to get to the point where screening can be eliminated.
“There might be a little problem if we stop too early,” he said.
Study details
During the period 2004-2005, the investigators randomly assigned 3,727 women aged 18-25 years to receive Cervarix and 3,739 to a control group that received the hepatitis A vaccine; after 4 years, the control group also received Cervarix and exited the study. They were replaced by an unvaccinated control group of 2,836 women. The new control group and the original HPV vaccine group were followed for an additional 7 years.
In years 7-11 of the trial, the investigators found 9.2 additional cervical intraepithelial neoplasias of grade 2 or worse (CIN2+) from HPV types not covered by Cervarix per 1,000 vaccinated women in comparison with unvaccinated participants. This corresponds to –71.2% negative vaccine efficacy against CIN2+ lesions of HPV types not covered by the vaccine.
There were 8.3 additional CIN3+ lesions from nontargeted HPV strains per 1,000 vaccinated women in comparison with unvaccinated participants, which corresponds to –135% negative vaccine efficacy.
Overall, however, there was a net benefit of vaccination, with 27 fewer CIN2+ lesions when all HPV genotypes – vaccine covered or not – were considered per 1,000 vaccinated women over the entire 11 years of follow-up.
There were also 8.7 fewer CIN3+ lesions across all genotypes per 1,000 vaccinated women, but the benefit was not statistically significant.
Among the study limits, the team was unable to evaluate the effect of clinical unmasking on cervical cancer, because women were treated for high-grade cervical lesions before cases could progress to cervical cancer.
The trial was funded by the National Cancer Institute and the National Institutes of Health Office of Research on Women’s Health. GlaxoSmithKline provided the Cervarix vaccine and supported aspects of the trial. Two authors are named inventors on U.S. government–owned HPV vaccine patents with expired licenses to GlaxoSmithKline and Merck. Dr. Steben is an adviser/speaker for many companies, including GlaxoSmithKline and Merck.
A version of this article first appeared on Medscape.com.
Vaccines against human papillomavirus have been hailed as a success: they have been shown to decrease the incidence of cervical lesions associated with the HPV types that are in the vaccine.
However,
An expert not involved in the research said the new data “tell us to be a little bit careful.” Although the HPV types not included in the vaccine are rarer and less aggressive, they can still cause cancer.
The data come from the Costa Rica HPV Vaccine Trial, which involved more than 10,000 women aged 18-25 years. The HPV vaccine used in the trial was Cervarix, from GlaxoSmithKline. It covers the two leading causes of cervical cancer, HPV-16 and -18, and provides partial protection against three other genotypes.
After a follow-up of 11 years, among vaccinated women, there was an excess of precancerous cervical lesions caused by genotypes not included in the vaccine, resulting in negative vaccine efficacy for those HPV variants.
The increase wasn’t enough to offset the overall benefit of vaccination when all genotypes were considered, said the researchers, led by Jaimie Shing, PhD, a postdoctoral research fellow at the National Cancer Institute in Bethesda, Md.
Vaccinated women “still had long-term absolute reductions in high-grade lesions,” they pointed out.
The net protection “remained considerable, emphasizing the importance of HPV vaccination for cervical cancer prevention,” the team concluded.
The findings were published online in The Lancet Oncology.
The results are likely the first evidence to date of “clinical unmasking” with HPV vaccination, meaning that protection against the strains covered by the vaccine leaves women more prone to attack from other carcinogenic HPV variants.
This phenomenon “could attenuate long-term reductions in high-grade disease following successful implementation of HPV vaccination programs,” the investigators commented.
Highlighting a need for caution
The take-home message from the trial is that “we have to be careful,” said Marc Steben, MD, co-President of HPV Global Action and a professor at the University of Montreal.
He noted that the Cervarix HPV vaccine used in the trial is not the vaccine that is used now in developed nations.
The current standard HPV vaccine is Gardasil 9 (Merck), which offers broader coverage against nine HPV types (types 6, 11, 16, 18, 31, 33, 45, 52, and 58).
There are 12 main carcinogenic HPV genotypes, so unmasking of other strains is still possible with Gardasil 9, he said.
There is another issue, Dr. Steben added. The success of HPV vaccinations - a nearly 90% reduction in invasive cervical cancer in women who are vaccinated at a young age – has led to questions about the future role of routine cervical cancer screening.
“Some people are saying that if we achieve 90% coverage, we might” eliminate community transmission and no longer need to screen, he said.
These trial results “tell us to be a little bit careful,” Dr. Steben continued. Those HPV types that are less aggressive and rarer than HPV-16 and -18 “can still cause cancer and might be there and surprise us. It could take more time than we thought” to get to the point where screening can be eliminated.
“There might be a little problem if we stop too early,” he said.
Study details
During the period 2004-2005, the investigators randomly assigned 3,727 women aged 18-25 years to receive Cervarix and 3,739 to a control group that received the hepatitis A vaccine; after 4 years, the control group also received Cervarix and exited the study. They were replaced by an unvaccinated control group of 2,836 women. The new control group and the original HPV vaccine group were followed for an additional 7 years.
In years 7-11 of the trial, the investigators found 9.2 additional cervical intraepithelial neoplasias of grade 2 or worse (CIN2+) from HPV types not covered by Cervarix per 1,000 vaccinated women in comparison with unvaccinated participants. This corresponds to –71.2% negative vaccine efficacy against CIN2+ lesions of HPV types not covered by the vaccine.
There were 8.3 additional CIN3+ lesions from nontargeted HPV strains per 1,000 vaccinated women in comparison with unvaccinated participants, which corresponds to –135% negative vaccine efficacy.
Overall, however, there was a net benefit of vaccination, with 27 fewer CIN2+ lesions when all HPV genotypes – vaccine covered or not – were considered per 1,000 vaccinated women over the entire 11 years of follow-up.
There were also 8.7 fewer CIN3+ lesions across all genotypes per 1,000 vaccinated women, but the benefit was not statistically significant.
Among the study limits, the team was unable to evaluate the effect of clinical unmasking on cervical cancer, because women were treated for high-grade cervical lesions before cases could progress to cervical cancer.
The trial was funded by the National Cancer Institute and the National Institutes of Health Office of Research on Women’s Health. GlaxoSmithKline provided the Cervarix vaccine and supported aspects of the trial. Two authors are named inventors on U.S. government–owned HPV vaccine patents with expired licenses to GlaxoSmithKline and Merck. Dr. Steben is an adviser/speaker for many companies, including GlaxoSmithKline and Merck.
A version of this article first appeared on Medscape.com.
Vaccines against human papillomavirus have been hailed as a success: they have been shown to decrease the incidence of cervical lesions associated with the HPV types that are in the vaccine.
However,
An expert not involved in the research said the new data “tell us to be a little bit careful.” Although the HPV types not included in the vaccine are rarer and less aggressive, they can still cause cancer.
The data come from the Costa Rica HPV Vaccine Trial, which involved more than 10,000 women aged 18-25 years. The HPV vaccine used in the trial was Cervarix, from GlaxoSmithKline. It covers the two leading causes of cervical cancer, HPV-16 and -18, and provides partial protection against three other genotypes.
After a follow-up of 11 years, among vaccinated women, there was an excess of precancerous cervical lesions caused by genotypes not included in the vaccine, resulting in negative vaccine efficacy for those HPV variants.
The increase wasn’t enough to offset the overall benefit of vaccination when all genotypes were considered, said the researchers, led by Jaimie Shing, PhD, a postdoctoral research fellow at the National Cancer Institute in Bethesda, Md.
Vaccinated women “still had long-term absolute reductions in high-grade lesions,” they pointed out.
The net protection “remained considerable, emphasizing the importance of HPV vaccination for cervical cancer prevention,” the team concluded.
The findings were published online in The Lancet Oncology.
The results are likely the first evidence to date of “clinical unmasking” with HPV vaccination, meaning that protection against the strains covered by the vaccine leaves women more prone to attack from other carcinogenic HPV variants.
This phenomenon “could attenuate long-term reductions in high-grade disease following successful implementation of HPV vaccination programs,” the investigators commented.
Highlighting a need for caution
The take-home message from the trial is that “we have to be careful,” said Marc Steben, MD, co-President of HPV Global Action and a professor at the University of Montreal.
He noted that the Cervarix HPV vaccine used in the trial is not the vaccine that is used now in developed nations.
The current standard HPV vaccine is Gardasil 9 (Merck), which offers broader coverage against nine HPV types (types 6, 11, 16, 18, 31, 33, 45, 52, and 58).
There are 12 main carcinogenic HPV genotypes, so unmasking of other strains is still possible with Gardasil 9, he said.
There is another issue, Dr. Steben added. The success of HPV vaccinations - a nearly 90% reduction in invasive cervical cancer in women who are vaccinated at a young age – has led to questions about the future role of routine cervical cancer screening.
“Some people are saying that if we achieve 90% coverage, we might” eliminate community transmission and no longer need to screen, he said.
These trial results “tell us to be a little bit careful,” Dr. Steben continued. Those HPV types that are less aggressive and rarer than HPV-16 and -18 “can still cause cancer and might be there and surprise us. It could take more time than we thought” to get to the point where screening can be eliminated.
“There might be a little problem if we stop too early,” he said.
Study details
During the period 2004-2005, the investigators randomly assigned 3,727 women aged 18-25 years to receive Cervarix and 3,739 to a control group that received the hepatitis A vaccine; after 4 years, the control group also received Cervarix and exited the study. They were replaced by an unvaccinated control group of 2,836 women. The new control group and the original HPV vaccine group were followed for an additional 7 years.
In years 7-11 of the trial, the investigators found 9.2 additional cervical intraepithelial neoplasias of grade 2 or worse (CIN2+) from HPV types not covered by Cervarix per 1,000 vaccinated women in comparison with unvaccinated participants. This corresponds to –71.2% negative vaccine efficacy against CIN2+ lesions of HPV types not covered by the vaccine.
There were 8.3 additional CIN3+ lesions from nontargeted HPV strains per 1,000 vaccinated women in comparison with unvaccinated participants, which corresponds to –135% negative vaccine efficacy.
Overall, however, there was a net benefit of vaccination, with 27 fewer CIN2+ lesions when all HPV genotypes – vaccine covered or not – were considered per 1,000 vaccinated women over the entire 11 years of follow-up.
There were also 8.7 fewer CIN3+ lesions across all genotypes per 1,000 vaccinated women, but the benefit was not statistically significant.
Among the study limits, the team was unable to evaluate the effect of clinical unmasking on cervical cancer, because women were treated for high-grade cervical lesions before cases could progress to cervical cancer.
The trial was funded by the National Cancer Institute and the National Institutes of Health Office of Research on Women’s Health. GlaxoSmithKline provided the Cervarix vaccine and supported aspects of the trial. Two authors are named inventors on U.S. government–owned HPV vaccine patents with expired licenses to GlaxoSmithKline and Merck. Dr. Steben is an adviser/speaker for many companies, including GlaxoSmithKline and Merck.
A version of this article first appeared on Medscape.com.
FROM THE LANCET ONCOLOGY