HPV vaccination to prevent cervical cancer. New evidence from Cochrane.

Sarah Chapman from Cochrane UK blogs about new Cochrane evidence on the safety and effectiveness of HPV vaccination for women to prevent cervical cancer and precancer.

Update on 04 September 2018: Cochrane has conducted an investigation into an article criticising this review. You can read the response from Cochrane’s Editor in Chief, David Tovey, here (there is also a link to the full report).

New Cochrane evidence published yesterday shows that vaccinating young women against human papilloma virus (HPV) does, as hoped, reduce the risk of cervical lesions (‘precancer’). HPV vaccines also appear to be safe. These findings, backed by high quality evidence, are reassuring both for those who have already been vaccinated and those needing to make choices about whether to have it.

What is HPV and why does it matter?

Human papilloma viruses are sexually transmitted. Common in young people, most people who have sexual contact at some time in their lives will be exposed to HPV. In most women, the immune system will clear the virus within a few months. In some, this doesn’t happen, and persistent infection with HPV can cause abnormal, ‘precancerous’ cells that may progress to cancer of the cervix (neck of the womb) if left untreated.

Cervical cancer is the fourth most common cancer in women worldwide, primarily affecting younger women. About 70% of all cervical cancers are caused by two high-risk types of the virus, HPV16 and HPV18. Vaccination before exposure to a virus triggers the immune system to produce antibodies, which protect against infection if the person is exposed to it.

Who is vaccinated against HPV?

In the UK, all girls can be vaccinated against HPV free on the NHS, from the age of 12 up to their 18th birthday, and in England girls aged 12 to 13 are routinely offered it in school. Here, take-up is high, but in Denmark, Ireland and Japan confidence in HPV vaccination has plummeted, following alleged cases of neurological problems and parental fears that vaccinating their daughters could encourage promiscuity. In Japan, vaccination take-up has fallen from more than 70% to less than 1%.

Just for girls?

 Infection with HPV matters for boys and men too, with HPV types 16 and 18 linked to cancers of the mouth, throat, penis and anus. Vaccinating girls helps in that they won’t be passing on HPV, but this still leaves many men unprotected, including those who have sex with men. The Cochrane Review explores the protection offered to women from cervical precancer, but there are increasing calls for boys to be vaccinated too, with some people paying for the vaccine. Last month saw the start of a phased roll-out of a programme in England to offer HPV vaccination to men who have sex with men through sexual health and HIV clinics. This is already offered in other parts of the UK.

New evidence on HPV vaccination and cervical precancer

The new Cochrane Review brings together evidence from 26 studies with over 73,000 women. The majority were under 25 years old, but three studies involved women aged between 25 and 45. Women in the studies were randomly allocated to receive one of two sorts of HPV vaccine targeting HPV 16/18 or a placebo. There were no eligible studies of a newer vaccine that targets nine HPV types.

None of the studies have followed up their participants for long enough to show whether vaccination has had an effect on cervical cancer. Instead, data are available on the development of cervical lesions between three and a half to eight years after vaccination.

The evidence showed that:

  • HPV vaccination in young women aged 15 to 26 reduces the risk of cervical precancer associated with HPV 16/18 from 341 to 157 in 100,000 women, and for any precancer lesions from 559 to 391 in 100,000. This is high-certainty evidence.
  • In women vaccinated between 25 and 45 years, the vaccine works less well, possibly because older women are more likely to have been exposed to HPV. The risk of precancer associated with HPV 16/18 is probably reduced from 145 in 10,000 unvaccinated women to 107 in 10,000 following vaccination. The risk of any precancer is probably similar between the two groups. This is moderate-certainty evidence.
  • The risk of serious adverse events is similar with HVP and control vaccines (placebo or vaccine against other infections). This is high certainty evidence.
  • HPV vaccination probably does not increase the risk of miscarriage but more data are needed about the effects on pregnancy outcomes and very rare side effects.

Welcome news

Professor Peter Openshaw, President of the British Society of Immunology, was among a number of scientific experts who were quick to welcome this new evidence.  He commented that it “paints a reassuring picture, highlighting the huge public health benefits that this vaccine offers to young women”, and stressed the need to “redouble efforts to ensure that HPV vaccination rates in girls remain high and that we continue to actively communicate the benefits of this vaccine to parents and children”.

Part of a bigger picture

The lead author of the Cochrane Review, Dr. Marc Arbyn, from the Unit of Cancer Epidemiology, Belgian Cancer Centre, Sciensano, said: “The findings of this review should be viewed within the context of multiple global surveillance studies, which have been conducted by the Global Advisory Committee on Vaccine Safety from the WHO since the vaccinations were licensed. The committee concluded that the risk-benefit profile of prophylactic HPV vaccines remains favourable and expressed its concerns about unjustified claims of harm that lack biological and epidemiological evidence, and which may affect the confidence of the public. At the same time, the Committee encouraged health authorities to continue surveillance and examination for potential adverse events.”

Screening still matters

Women should remain aware of the importance of screening though, said Dr. Jo Morrison, Consultant in Gynaecological Oncology at the Musgrove Park Hospital, Somerset, UK. “Vaccination aims to prime the immune system to produce antibodies that can block subsequent natural HPV infection. These data show that immunizing against HPV infection protects against cervical precancer, and it is very likely that this will reduce cervical cancer rates in the future. However, it cannot prevent all cervical cancer and it is still important to have regular screening, even if you have been vaccinated.”

Informed choices

My daughters both chose to be vaccinated, a handful of years ago, but as we looked at the information provided to help with their decisions, we were aware that the evidence-base was thin. This Cochrane Review changes that, and should enable young women to make a more informed choice.

References may be found here.

Sarah Chapman has nothing to disclose.

Page last updated 04 September 2018.

 

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Sarah Chapman

About Sarah Chapman

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Sarah's work as a Knowledge Broker at Cochrane UK focuses on disseminating Cochrane evidence through social media, including Evidently Cochrane blogs, blogshots and the ‘Evidence for Everyday’ series for nurses, midwives, allied health professionals and patients. A former registered general nurse, Sarah has a particular interest making evidence accessible and useful to practitioners and to others making decisions about health. Before joining Cochrane, Sarah also worked on systematic reviews for the University of Oxford and the Royal College of Nursing Institute, and obtained degrees in History from the University of Oxford and in the history of women’s health and illness in early modern England (MPhil., University of Reading).

3 Comments on this post

  1. Would you agree that the paper “The Cochrane HPV vaccine review was incomplete and ignored important evidence of bias” by
    Lars Jørgensen, Peter C Gøtzsche, Tom Jefferson, makes it necessary to look at the Arbyn et al systematic review in a different and less favourable light?

    The key findings of this paper:
    – The Cochrane human papillomavirus (HPV) vaccine review missed nearly half of the eligible trials.
    – The review was influenced by reporting bias and biased trial designs.
    – Authors of Cochrane reviews should make every effort to identify all trials and the trials’ limitations.

    The concluding comments include:
    “Part of the Cochrane Collaboration’s motto is ‘Trusted evidence’. We do not find the Cochrane HPV vaccine review to be ‘Trusted evidence’, as it was influenced by reporting bias and biased trial designs. We believe that the Cochrane review does not meet the standards for Cochrane reviews or the needs of the citizens or healthcare providers that consult Cochrane reviews to make ‘Informed decisions’, which also is part of Cochrane’s motto”

    The Jørgensen et al assessment is a damning critique of the Arbyn et al systematic review. This systematic review has been used by news agencies, health agencies and governments across the world to reassure the public of the safety and effectiveness of the HPV vaccines and it was published to a great media fanfare and promotion. In contrast, the Jørgensen et al critical assessment has had no media coverage, leaving the public with a false sense of security about the HPV vaccines.

    Jørgensen L, Gøtzsche PC, Jefferson T The Cochrane HPV vaccine review was incomplete and ignored important evidence of bias BMJ Evidence-Based Medicine Published Online First: 27 July 2018. doi: 10.1136/bmjebm-2018-111012

    Caron Ryalls / Reply
    • Sarah Chapman

      An investigation has now been conducted and the report published, along with a response from Cochrane’s Editor in Chief, David Tovey. I have added the link at the top of the blog.

      Sarah Chapman

      Sarah Chapman / (in reply to Caron Ryalls) Reply
  2. The only Gardasil trial that used anything close to a true placebo (protocol 18) included just 1165 subjects in the experimental group and just 584 subjects in the placebo control group. Roughly half of these subjects were boys, and all were 9 to 15 years old.

    Here are the actual (not fraudulently “summarized” by Merck) results of this study:

    https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-005717-23/results

    Serious adverse events (SAEs) were defined as: “any adverse event that results in death, is life threatening, results in a persistent or significant disability/incapacity, results in hospitalization or prolongs an existing hospitalization, is a congenital anomaly/birth defect, is a cancer, is an overdose, or is considered an “other important medical event” based on medical judgment.”

    The results of this study showed 6 serious adverse events out of 1165 (0.52%) for Garsasil injected experimental subjects compared to 0 serious adverse events out of 584 (0.00%) for “saline” injected control subjects. That means more than 1 in 194 subjects injected with Gardasil experienced a severe adverse event compared 0 or 584 injected with “saline.” Including the negative QALY values of 1 in 194 vaccination victims in Gardasil’s cost per QALY studies would have rendered Gardasil’s cost per QALY prohibitive at $500 per vaccine regimen. No wonder Merck quickly moved to experimentally invalidate all of its future Gardasil studies by comparing Gardasil against a confirmed neurotoxin rather than a relatively inert “saline” placebo! What you refuse to quantify by using tiny trials void of meaningful statistical analyses and bad experimental design can’t be used against you in independent cost vs. QALY analyses.

    Could a difference of 6 serious adverse events out of 1165 (0.52%) for Garsasil injected experimental subjects vs. no serious adverse events out of 584 (0.00%) for “saline” injected control subjects be chalked up to mere statistical noise? Perhaps. However, the Fisher Exact Test showed Merck that there was a 81.3% chance that this was actually NOT a random effect. Merck simply could not take a low 18.7% chance on its new and only ready to fast track cash cow, and therefore Merck made all of its subsequent safety studies 100% experimentally invalid by indefensibly making three shots of a known neurotoxin its new comparator “placebo”. Merck felt it was a far better bet to pay a legion of shills to defend its totally invalid experimental design than it was to risk valid experimental results that might have rendered Gardasil’s cost per QALY irrationally expensive or even negative.

    On the off chance that you are just a useful idiot for Merck, I beg you to reconsider the actual results of the only near-placebo trial and how the negative QALY of one of 194 children who suffered severe adverse effects from Gardasil compared to 0 with the control would affect the already strained cost per QALY justifications for mandating a vaccine against a disease that had already significantly declined and was still steadily declining in the USA when Gardasil was first introduced. The incidence rates for invasive cervical cancer had decreased by 54% over the 35 year period before Gardasil, from 13.07/100,000 (1973–1975) to 6.01/100,000 (2006–2007).

    Kelly Duke / Reply

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