Note: this article was updated in February 2016 to include an additional link to the minutes of the MARC meeting of 3 December 2015.
HPV vaccine safety
The safety of Human Papillomavirus (HPV) vaccine has been extensively studied around the globe and has been subject to review by a number of international bodies.
The vaccine was shown to have a good safety profile during large clinical trials involving more than 20,000 people from 30 countries, including New Zealand.
Gardasil® has been approved for use in more than 125 countries, including New Zealand, Australia, the United States, Canada and countries in the European Union.
In New Zealand, as in other countries, there is ongoing monitoring of vaccine safety.
All applications seeking consent to distribute a medicine in New Zealand are evaluated by Medsafe. This evaluation is performed to internationally defined standards and requirements. Gardasil® was evaluated by Medsafe and formal approval of the vaccine was notified in the New Zealand Gazette on 20 July 2006.
The overwhelming evidence is that HPV has at least as good a safety profile as any other childhood vaccine.
In September 2015, Medicines Adverse Reactions Committee (MARC) – which provides expert advice to the Minister of Health on the safety of approved medicines – considered a summary of published observational studies investigating the possible association between HPV vaccine and autoimmune conditions. The Committee found that based on the evidence presented, there is no safety concern.
- Minutes of the 163rd MARC Meeting - 10 September 2015
- Minutes of the 164th MARC Meeting - 3 December 2015
WHO’s Global Advisory Committee on Vaccine Safety (GACVS) released a statement on HPV vaccine safety on 13 June 2013.
How many New Zealanders have received the Gardasil vaccine?
HPV immunisation began in New Zealand on 1 September 2008. More than 200,000 New Zealand girls and young women have received three doses each of Gardasil since then.
How are adverse reactions monitored in NZ?
Medsafe has been closely monitoring the safety of Gardasil since the beginning of the programme.
The Ministry of Health monitors all vaccines after they have been released onto the market, to identify any adverse effects that were not apparent in pre-market testing.
The New Zealand Pharmacovigilance Centre at the University of Otago in Dunedin runs the Centre for Adverse Reactions Monitoring (CARM), which collects suspected medicine adverse reaction reports on behalf of the Ministry. Passive reporting systems like CARM can indicate areas for further research, but do not by themselves show the true rate of adverse effects. CARM and Medsafe have systems in place to identify possible safety problems with medicines and vaccines even though not all suspected adverse reactions are reported.
How many adverse reactions following vaccination with Gardasil have been reported to CARM?
CARM reviews all reports of suspected adverse reactions to medicines to determine the role of the medicine and whether any action needs to be taken by the medicines regulator - Medsafe. Advice is also sought from the Medicines Adverse Reactions Committee (MARC) on these cases.
Of the 568 reports of adverse reactions in relation to Gardasil received by CARM up until 30 June 2015, 41 were considered serious. The seriousness of a report is determined according to internationally agreed criteria and is based on what happens to the patient. For example a report of headache would not be considered serious if it lasted only a few hours and responded to home treatment; a headache would be considered serious if it led to the person being unable to attend work, or required admission to hospital for treatment. Classification of whether an event is serious is independent of whether CARM consider it to be likely to have been caused by the vaccine.
The reactions reported from HPV immunisation are similar to other immunisations. The most common are injection site pain, redness, and swelling. Nausea and fainting have also been reported.
The reports held by CARM represent all events following immunisation, not necessarily only those considered by CARM to be likely to have been caused by the vaccine, and include medication errors (for example accidentally administering a fourth dose).
A report of an adverse reaction does not prove that the vaccine was the cause of that reaction. Events that occur after vaccination (temporal association) do not mean the vaccine was the cause.
The events listed by CARM represent around a quarter of a percent of all recipients of the vaccine, a similar rate to other childhood vaccines. New Zealand health professionals have a high rate of reporting of all adverse medicine reactions, compared with other countries.
Any suspected adverse reactions to any medicine, vaccine or complementary medicine should be reported to CARM. This should be done even if it is not certain that the medicine has caused it, or if the reaction is well recognised, or if other medicines have been given at the same time. Anyone may report a suspected adverse event to CARM.
Anonymised information on suspected adverse reactions to medicines in New Zealand is published on the Medsafe website: Suspected Medicine Adverse Reaction Search (SMARS).
What research has been done into whether there is a link between the Gardasil vaccine and conditions such as Complex regional pain syndrome (CRPS) and Postural Tachycardia Syndrome (POTS)?
HPV vaccines have been subject to post-marketing safety monitoring and regular review by regulatory agencies worldwide, including:
- the World Health Organization’s Global Advisory Committee on Vaccine Safety,
- the European Medicines Authority
- the United States’ Centers for Disease Control,
- the Australian Therapeutic Goods Administration and
- Medsafe, New Zealand’s Medicines and Medical Devices Safety Authority
In making their findings, these regulatory agencies considered reports such as those made to CARM, as well as large studies that included over a million individuals. These studies have found no association between HPV immunisation and a range of health conditions including chronic fatigue syndrome, auto-immune conditions, multiple sclerosis, complex regional pain syndrome, postural orthostatic tachycardia syndrome and sudden death.
On 5 November 2015 the European Medicines Agency (EMA) released its scientific review of the evidence surrounding reports of CRPS and POTS in young women given HPV vaccines. It found no evidence that the overall rates of these syndromes in vaccinated girls were different from expected rates in these age groups. They therefore found no reason to change the way the vaccines are used or amend the current product information.
CRPS and POTS are not new conditions and were occurring in New Zealand before Gardasil vaccine started to be used.
There is likely to remain disagreement, or a lack of certainty, about the causes of these rare conditions. The Ministry of Health encourages parents with concerns to discuss them with their doctor. The doctor will in turn provide information to CARM as appropriate, and then to us, to ensure we do know about potential harms, which we in turn can consider and act on if needed.
What are the benefits of being vaccinated? Are we seeing these in NZ yet?
Each year in New Zealand around 160 women are diagnosed with cervical cancer, around 50 women die from the disease, and many more need treatment for pre-cancerous cervical lesions.
Almost all cervical cancer is caused by HPV.
HPV immunisation protects against the HPV strains responsible for around 70 percent of cervical cancers. These strains can also cause cancers to the genital region, head and neck – these are less common than cervical cancer.
It will take time before we see girls who are young enough to have received the vaccine move into the age range where cervical cancer is more likely to develop, but the Cervical Screening Programme is already reporting a reduction in the number of cervical abnormalities.
In June 2015, the Report of the Parliamentary Review Committee regarding the New Zealand Cervical Screening Programme noted a "significant decline in the proportion of samples reported as HSIL [high-grade squamous intraepithelial lesions] for women in the age cohorts of < 20 and 20–24 years. Women in these age groups were eligible for HPV vaccination (the oldest cohort would have been aged up to 23 years at the time of the latest Monitoring Report)."
The number of reported cases of genital warts has declined steeply for young women since 2009, and, to a lesser extent, for young men as well.
An Australian study has shown a decrease in cervical abnormalities among vaccinated young women
- Effectiveness of quadrivalent Human Papillomavirus vaccine for the prevention of cervical abnormalities: case-control study nested within a population based screening programme in Australia