Friday February 20 2015
The HPV vaccine is recommended for all girls age 12 to 13
"New HPV vaccine stops 90% of cervical cancers," the Mail Online reports. The vaccine, which protects against nine common strains of the cancer-causing human papilloma virus (HPV), has proved both safe and effective in a study involving 14,000 women. HPV is one of the major causes of cervical cancer, as well as genital warts.
The current HPV vaccine, Gardasil, which the NHS offers to all girls aged 12 to 13, protects against the two most common strains associated with cervical cancer, as well as an additional two strains known to cause genital warts. Research suggests Gardasil can prevent around 70% of potential cervical cancers.
The new vaccine covers these four strains and five additional ones. This latest study indicates this may provide protection against 90% of cases. And researchers found the new vaccine reduced the incidence of cancer from these extra five strains to 0.1 cases per 1,000 person-years, compared with 1.6 cases per 1,000 person-years.
It is important to note that the study was conducted in women aged 16 to 26, which is much older than the 12 to 13 age group currently offered vaccination, and may affect the results. In addition, the participants were only followed up for 4.5 years. Longer studies including other age groups are now required.
Where did the story come from?
The study was carried out by researchers from universities and institutes in Austria, Norway, Denmark, Germany, the UK, the US, Canada, Brazil, Hong Kong, Mexico, Thailand, Columbia, Taiwan, and Australia.
It was funded by the pharmaceutical company Merck. There are potential conflicts of interest, as many of the authors have affiliations with Merck.
The study was published in the peer-reviewed journal, the New England Journal of Medicine.
The Mail's reporting was confusing as it opened with the incorrect information that the "current vaccine used in the UK, Gardasil, protects against nine HPV strains". If this were the case, there would be no reason to assess the effectiveness of a new vaccine.
The current vaccine actually only protects against two strains that cause 70% of cervical cancers, and two strains that cause genital warts.
And despite the irresponsible suggestion to the contrary, we wouldn't recommend that you decline the offer of a smear test – cervical cancer screening – if recommended.
What kind of research was this?
This was a randomised, double-blind clinical trial comparing the effectiveness of a new vaccine against HPV with the current vaccine.
In the UK, around 3,100 women are diagnosed with cervical cancer each year. A major cause of cervical cancer is infection from the human papilloma virus (HPV). There are more than 100 types of HPV, and at least 15 of them are considered to be high risk.
In the UK, the HPV vaccine, which is offered to all girls aged 12 to 13, gives protection against four types of HPV: 6, 11, 16 and 18. Two of these types – HPV 16 and 18 – are believed to cause more than 70% of cases of cervical cancer.
The vaccine also protects against strains HPV 6 and 11, which are responsible for 90% of genital wart cases.
The new 9vHPV vaccine covers these four strains as well as five others (31, 33, 45, 52 and 58). This has the potential to increase the protection against cervical cancer from 70% to 90%, according to the prevalence of these strains in a global study of 10,575 cases of cervical cancer.
What did the research involve?
Women aged 16 to 26 were given either the current Gardasil vaccine or the new 9vHPV vaccine, and the rates of HPV infection were then compared.
The study recruited 14,215 women from Asia Pacific, Europe, Latin America and North America, and randomly assigned them to receive three doses of the 9vHPV vaccine or three doses of the current HPV vaccine over the course of six months. Their average age was 22 and the age when they first had sexual intercourse was 17.
Women were eligible for the study if they had:
- no history of an abnormal smear test result
- no more than four sexual partners in their lifetime
- no previous abnormality on cervical biopsy
The women had swabs taken for 14 types of HPV on the day they first received the vaccine and then every six months for 4.5 years. They also had a smear at each visit and, if this was abnormal, they had a colposcopy (a more detailed examination of the cervix).
Statistical analyses were performed comparing the outcomes for women who had no evidence of HPV infection when they were first vaccinated or the subsequent seven months. Additional analyses were performed for those who did have HPV infection during this time.
The outcomes measured were incidences of cervical, vaginal and vulval cancers. They did not directly compare the two vaccines for infection with the four types of HPV.
What were the basic results?
For all women who entered the study:
- The incidence of high-grade cervical, vulval and vaginal disease was 14.0 per 1,000 person-years in women given either vaccine. High-grade disease included invasive cancers and abnormal changes that have a high likelihood of developing into invasive cancer.
- In women not initially infected with HPV, the incidence was 2.4 per 1,000 person-years in those given the new 9vHPV vaccine compared with 4.2 per 1,000 person-years for those given the current vaccine. This means the new vaccine was 42.5% more effective (95% confidence interval [CI] 7.9 to 65.9) in women who were not infected with HPV at the time they had the vaccination. In women who were already infected with HPV when they had their first vaccine, there was no difference in incidence.
For women who did not have HPV infection for the first seven months of the study who completed the vaccination course and had no study violations, called the per-protocol efficacy population:
- The incidence of disease from the extra five types of HPV was 0.1 per 1,000 person-years in the 9vHPV group compared with 1.6 per 1,000 person-years in the current vaccine group (1 case versus 30), meaning the vaccine was more effective for these women.
The new 9vHPV caused slightly more pain, swelling and redness than the current vaccine. There were two serious events related to the vaccine in either group.
How did the researchers interpret the results?
The authors concluded that the 9vHPV vaccine provided the same amount of protection as the qHPV vaccine for the four vaccines that they both cover.
It also prevented infection and disease related to the five extra strains in susceptible women when compared with the normal qHPV vaccine. The 9vHPV vaccine did not protect against other strains of the virus.
This double-blind randomised trial has shown that the new HPV vaccine provides increased protection from additional strains of HPV that cause cervical, vulval and vaginal cancers.
Strengths of the study include:
- Blinding of the pathologists to the vaccine type, and blinding of the participants (they didn't know which vaccine they had been given), which reduces any bias – a double-blind randomised controlled trial is considered the gold standard of how best to assess a treatment or intervention.
- The large number of women included in the study, with diverse ethnic backgrounds, makes it likely that the results would be applicable to most women in this age group.
However, there are some limitations:
- It is widely reported in the media that the two vaccines offer the same protection for the original four HPV strains, but there was no direct comparison between the vaccines for their ability to protect against the four types of HPV virus. The comparison was restricted to incidence of invasive cancers and high-grade abnormalities, which may take longer to occur than the 4.5 years of the study's duration. The researchers acknowledge that longer studies are required, however.
- The study group were much older than the age of girls who are currently vaccinated, presumably so that they could provide their own consent to participate. This may have a bearing on the results.
Further studies will be required to address these issues before it is known whether there will be a change in the type of vaccine offered in the UK.
While vaccination is an important component in reducing the risk of these types of cancer, it is important to reduce the risk in other ways, too.
This includes not smoking, as this increases the risk of cervical cancer – chemicals from cigarettes have been found in cervical mucus, and it is thought this damages the cervix. Safe sex, such as using condoms, is also important.
Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.