Although the types of HPV not included in the vaccine are rarer and less aggressive, they can still cause cancer.
There are 12 main cancer-causing genotypes of HPV, so it is still possible to unmask other strains. Photo: Shutterstock.
Vaccines against human papilloma virus (HPV) have been hailed as a success: they have been shown to decrease the incidence of cervical injuries associated with types of HPV found in the vaccine.
However, new evidence suggests that vaccination against hpv makes women more susceptible than their unvaccinated peers to HPV genotypes not covered by the vaccine.
An expert not involved in the research said the new data “tells us to be a little bit careful.” Although HPV types not included in the vaccine they are rarer and less aggressive, they can still cause cancer.
The data comes from the trial of the vaccine contra hpv of Costa Ricain which more than 10,000 women between the ages of 18 and 25 participated. The vaccine contra hpv used in the trial was Cervarixof GlaxoSmith Kline. It covers the two main causes of cervical cancer, HPV 16 and 18, and provides partial protection against three other genotypes.
After 11 years of follow-up, among vaccinated women, there was an excess of precancerous cervical lesions caused by genotypes not included in the vaccineresulting in negative vaccine efficacy for those HPV variants.
The increase was not enough to offset the overall benefit of vaccination when all genotypes were considered, say the researchers, led by Jaimie Shingpostdoctoral researcher at the National Cancer Institute in Bethesda, Maryland.
The vaccinated women “still had long-term absolute reductions in high-grade lesions,” they note.
Net protection “remained considerable, emphasizing the importance of vaccination against hpv for cervical cancer prevention,” the team concludes. The findings were published online June 13 at The Lancet Oncology.
The results are probably the first evidence to date of “clinical unblinding” with vaccination against hpvwhich means that protection against strains covered by the vaccine leaves women more likely to suffer attacks of other carcinogenic variants del VPH.
This phenomenon “could attenuate long-term reductions in high-risk disease degree after successful implementation of vaccination programs against hpv“, comment the researchers.
Highlight the need for caution
The essay’s final message is that “we have to be careful,” he said. Marc Steben, co-president of HPV Global Action and teacher from Faculty of Public Health from University of Montréal.
He pointed out that the vaccine contra hpv Cervarix used in the trial is not the vaccine which is now used in developed countries.
The vaccine contra hpv current standard is Gardasil 9, which offers broader coverage against nine HPV types (types 6, 11, 16, 18, 31, 33, 45, 52, and 58). There are 12 major cancer-causing genotypes of HPV, so it’s still possible to unmask other strains with Gardasil 9, he said.
There is another problem, Steben added. The success of vaccines against hpva nearly 90% reduction in invasive cervical cancer in women who get vaccinated at a young age, has raised questions about the future role of routine cervical cancer screening.
“Some people say that if we get to 90% coverage, we could” eliminate community transmission and testing would no longer be necessary, he said.
The results of these trials “tell us to be a little careful,” Steben continued. Those HPV types that are less aggressive and rarer than hpv 16 and 18 “can still cause cancer and could be there and surprise us. It could take longer than we thought” to get to the point where screening can be eliminated. “There could be a little problem if we stop too soon,” she said.
study details
During 2004-2005, researchers randomly assigned 3,727 women ages 18 to 25 to receive Cervarix and 3,739 to a control group that received Cervarix. the vaccine against hepatitis A; after 4 years, the control group also received Cervarix and dropped out of the study. They were replaced by an unvaccinated control group of 2,836 women. The new control group and the original group of the vaccine contra hpv they were followed for an additional 7 years.
In years 7 to 11 of the trial, the investigators found an additional 9.2 cervical intraepithelial neoplasia grade 2 or worse (CIN2+) of HPV types not covered by Cervarix per 1,000 vaccinated women compared with unvaccinated participants. This corresponds to a negative vaccine efficacy of -71.2% against CIN2+ lesions of HPV types not covered by the vaccine.
There were an additional 8.3 CIN3+ lesions from non-target HPV strains per 1000 vaccinated women compared to unvaccinated participants, corresponding to a negative efficacy of the vaccine -135%.
Overall, however, there was a net benefit of vaccination, with 27 fewer CIN2+ lesions when all HPV genotypes were considered, covered by the vaccine or not, per 1,000 women vaccinated during the full 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.
Within the limits of the study, the team was unable to assess the effect of clinical unblinding on cervical cancer, because the women were treated for high-grade cervical lesions before the cases could progress to cervical cancer.
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