Human papillomavirus (HPV) vaccine

MHRA's first year safety review of the human papillomavirus (HPV) programme
At the end of the first year of the Cervarix HPV immunisation programme, at least 1.4 million doses have now been given across the UK. The programme has so far been a success and the latest uptake levels continue to be very encouraging.

In September 2009, the Commission on Human Medicines (CHM) considered a one year comprehensive safety review of all the suspected side effects reported via the Yellow Card Scheme for Cervarix vaccine. The total number and nature of suspected side effects reported via the Yellow Card Scheme during the first year of the Cervarix vaccination programme has been very much as expected. Key conclusions from CHM’s review were:

• The vast majority of suspected adverse reactions have related either to the signs and symptoms of recognised side effects listed in the product information or were due to the injection process and not the vaccine itself (ie ‘psychogenic’ in nature).
• No serious new risks have been identified in association with Cervarix despite significant exposure in the UK.
• The balance of risks and benefits of Cervarix remains positive.
  

A summary of this safety review was published in the Drug Safety Update bulletin on 7 October 2009.

Please find below a letter from MHRA’s Chief Executive, Professor Kent Woods, summarising an overview of the safety experience so far and a copy of the Drug Safety Update article. 

MHRA’s Chief Executive, Professor Kent Woods', vaccine letter October 2009 and a summary of the Drug Safety Update bulletin on 7 October 2009. (141Kb)

Following the tragic death of a young girl who had received Cervarix vaccine batch AHPVA043BB, investigations into the quality of the batch were carried out by the manufacturer, GlaxoSmithKline, and two independent Official Medicines Control laboratories (the UK National Institute for Biological Standards and Control and the Belgian National Control Authority). These included tests on retained samples as well as samples received from the girl’s school.

The investigations, which have been completed, revealed no evidence of any quality defect and the batch conformed to its licensed specifications. There remains no evidence to link this tragic event to administration of the vaccine.

Introduction
A routine immunisation programme for human papillomavirus (HPV) started across the UK on 1 September 2008 for 12 to 13 year-old girls (school year 8). The vaccine given is called Cervarix, which protects against infection with HPV types 16 and 18.

Infection with HPV is one of the most common sexually transmitted diseases. Genital infection with a high-risk (or ‘oncogenic’—potentially cancer-causing) HPV virus is the main cause of cervical cancer and is responsible for nearly 3000 cases of cervical cancer every year in the UK: HPV types 16 and 18 cause around 70% of cases.

Immunising girls before they become infected could eventually prevent up to 400 deaths every year in the UK.

As well as routine immunisation of girls in school year 8, there will be a phased catch-up of girls currently aged up to 18 years. In England, 17 to 18 year-old girls will also be offered the vaccine during the coming year, with the remaining girls immunised during 2009 to 2011. The timing of the catch-up programmes may differ in Scotland, Wales and Northern Ireland.

Vaccine safety
The safety and efficacy of Cervarix vaccine has been extensively studied in clinical trials before licensing. The most common side-effects identified are injection-site reactions, fever, headache, fatigue, muscle pain, nausea, vomiting, and diarrhoea, which are listed in the product information (please refer to the Summary of Product Characteristics and Patient Information Leaflet available via the Electronic Medicines Compendium (external link)).

However, as with all vaccines and medicines used in the UK, it is important that the MHRA continues to monitor the safety of Cervarix vaccine during routine use.

Another HPV vaccine called Gardasil is also licensed and on the UK market outside of the national immunisation programme. The MHRA is also responsible for monitoring the safety of Gardasil vaccine.

Reporting of suspected side effects (adverse reactions)
One way that MHRA monitors vaccine safety is through reporting of suspected side effects (adverse reactions) via the Yellow Card Scheme.

Please report suspected adverse reactions that may have occurred after administration of HPV vaccine via the Yellow Card Scheme. You can send Yellow Cards by post, but we strongly encourage you to report online. This will allow us quick access to your Yellow Card report.

When submitting a Yellow Card, please include:

• suspected adverse reaction(s): please report only the main diagnosis as the suspected side-effect - signs and symptoms can be included as additional information if necessary
• vaccine brand name
• vaccine batch number (if available)
• time to onset (if known)
• age and gender of the person who had the adverse reaction
• your contact details, should we need further information.

Many adolescents will be immunised with Cervarix vaccine over a relatively short time. Adherence to the specific guidance outlined below will help us monitor the safety of the vaccine effectively and communicate any information promptly.

Faints and panic attacks
Fainting can occur during, following, or even before vaccination and occurs most commonly in adolescents. Some individuals may also experience panic attacks before vaccination. The clinical features of fainting and panic attacks are described in detail in chapter 8 of the Department of Health's ‘Green Book’ (external link) . Fainting can result in traumatic injury, and local procedures should be in place to observe and manage such events. It is important that any sudden loss of consciousness or generalised reaction is distinguished from a possible anaphylactic (or severe allergic) reaction (see below).

Fainting and panic attacks can occur during any injection procedure. When an episode occurs during or very shortly after vaccination, it is highly unlikely to be a true-side effect of the vaccine itself and is most likely a psychogenic response to the injection process. Only reactions that are suspected to be related to the vaccine (and not those associated with the injection process) should be reported via the Yellow Card Scheme.

If having considered this advice, you wish to report a possible psychogenic response, please include only the main diagnosis or event as the suspected reaction (eg, ‘faint’, ‘vasovagal syncope’, or ‘panic attack’). Any signs or symptoms associated with these events (eg, loss of consciousness, injury, limb jerking or tingling, difficulty in breathing, hyperventilation) should not be reported as a suspected adverse reaction. If necessary, they can be included as ‘additional information’ on the Yellow Card.

Since episodes of mass fainting and/or panic attacks can occur during a large immunisation session we ask that you follow the above guidance to allow an appropriate assessment and a proportionate response to such incidents.

Reporting of anaphylaxis and other allergic reactions
Anaphylaxis is an acute, severe allergic reaction that is a very rare, recognised side-effect of most vaccines. Suspected cases should be reported via the Yellow Card Scheme. Chapter 8 of the Green Book (external link) gives detailed guidance on distinguishing between faints, panic attacks, and the clinical features of anaphylaxis.

If a case of suspected anaphylaxis meets diagnostic criteria, please report it via the Yellow Card Scheme as a case of ‘anaphylaxis’ (or if appropriate ‘anaphylactoid reaction’). Cases of less-severe allergic reactions (ie those that do not have the full clinical features of anaphylaxis) should be reported as ‘allergic reaction’, not ‘anaphylaxis’. Any relevant signs or symptoms should be reported only as 'additional information' on the Yellow Card.

Current safety profile
The number and nature of suspected adverse reactions received so far is very much in line with what we expected to receive at this time. The Commission on Human Medicines reviewed these data on 18 September 2009 and agreed that no new or serious risks have been identified following substantial usage of Cervarix in the UK, and that the balance of benefits and risks remains positive. As with all vaccines, the MHRA and CHM will continue to closely monitor the safety of Cervarix during continued use in the UK.

Further information on the safety experience during the first year of the Cervarix immunisation programme is provided in the following article from the October 2009 issue of Drug Safety Update:
Human papillomavirus (HPV) immunisation programme - first year safety review (81Kb)

Suspected adverse reactions received by the MHRA
The documents below summarise the reports of suspected adverse reactions received by the MHRA in association with Cervarix vaccine as well as HPV vaccine for which the brand was not reported. Please read the introductory information provided with this information to assist in interpretation of the data. 

Cervarix Human papillomavirus (HPV) vaccine (145Kb)
Human papillomavirus (HPV) vaccine (brand unspecified) (92Kb)

Further information

• Published safety and efficacy studies:
• • Harper DM, et al. Lancet 2004; 364: 1757–65 (external link).
  • Harper DM, et al. Lancet 2006; 367 1247–55 (external link).
  • Paavonen J, et al. Lancet 2007; 369: 2135–37  (external link).
    
• For facts on the immunisation programme - NHS Immunisation website (external link).
  
• For further facts on the HPV programme and diseases:
• • Department of Health Green Book on immunisation against infectious disease (external link).
  • Health Protection Agency (external link).
  • Vaccine in pregnancy surveillance (external link).
    
• For facts on the MHRA and the Yellow Card Scheme (external link).
  
• September issue of the MHRA's Drug Safety Update (p 5).
  
• For Cervarix information from the European Medicines Agency (external link).
  
• For Gardasil information from the European Medicines Agency (external link).
  
• Summaries of Product Characteristics and Patient Information Leaflets (external link).