The Committee reviewed the safety of HPV vaccines. By March 2009, >60 million doses of the quadrivalent or bivalent HPV vaccine had been distributed either as part of national immunization programmes in 21 countries or by private physicians. Data from post-marketing surveillance were reviewed from countries that introduced the vaccine early, from regulatory authorities and from manufacturers. Additional data were reviewed from 4 demonstration studies undertaken in developing countries that were conducted by the nongovernmental organization PATH (the Program for Appropriate Technology in Health) and from recently completed and ongoing studies conducted by manufacturers on the vaccination of young males and the concomitant use of HPV vaccine with other vaccines in young girls.

The accumulating evidence on the safety of HPV vaccines is reassuring. The most common adverse events were reactions at the injection site and muscle pain. Allergic reactions have also been reported. The potential risk of injury after vaccination resulting from dizziness and syncope has been added to the label of 1 of the vaccines. Several different signals were observed in countries introducing HPV vaccination but none, other than syncope, was judged to be causally related to vaccination. The limited data on the inadvertent administration of HPV vaccines shortly before pregnancy or during pregnancy are reassuring. They do not establish a relationship between HPV vaccination and miscarriage, but the data are insufficient to rule out a small effect, in particular if conception occurs shortly after vaccination. The Committee considers that further studies should be encouraged, given the limited data.

The Committee noted with satisfaction that studies on HPV immunization have been initiated in Africa, including some among HIV-positive women. As preparation for introducing HPV vaccines, capacity building for surveillance for adverse events is being addressed. While the safety profile of HPV vaccine is reassuring, the collection of high-quality safety data from different geographical locations and epidemiological settings where the vaccine is being introduced remain a high priority.

Full report of GACVS meeting of 17-18 June 2009, published in the WHO Weekly Epidemiological Record on 7 August 2009

The Committee reviewed the latest SAGE recommendations on HPV vaccines as well as data related to their large-scale use as well as publications on early post-marketing surveillance. The post-licensure data from the United States regarding one HPV vaccine (Gardasil) were reassuring; the safety profile was similar to that found in the pre-licensure trials. No evidence of previously undetected serious adverse events had been found that were causally related with use of this vaccine. Of the several new scientific articles on the use of HPV vaccines published since the GACVS meeting in June 2007,³ 3 focused on safety findings with observations on syncope, hypersensitivity, anaphylaxis and central demyelinating diseases. Of note was the finding of a study by Brotherton and colleagues⁴ conducted in New South Wales, Australia following the introduction of Gardasil. They reported 7 cases of anaphylaxis occurring within 30 minutes of vaccination during the administration of 269 000 doses of the vaccine. This rate was significantly higher than had been observed in a comparable school-based programme with meningococcal C vaccination. However, there were no serious sequelae following appropriate management. After careful methodological review, neither this report nor the other reports raised sufficient concern to change previous advice given by GACVS. In particular, there was no convincing evidence in the publication purporting an association between HPV vaccination and central demyelinating diseases.⁵ While allergic reactions and syncope can occur after injection with HPV vaccine, usual safety precautions should suffice.

As many countries have only recently introduced HPV vaccines at the national level, and as plans exist to introduce the vaccines in numerous countries with varying capabilities for monitoring of adverse events following immunization (AEFI), the Committee calls for increased attention to building capacity for post-marketing surveillance in those countries where introduction is being planned. The Committee also agreed to update comprehensively the review of post-marketing safety profile of HPV vaccines at its June 2009 meeting.

³ See No. 28/29, 2007, pp. 255–256.

⁴ Brotherton JML et al. Anaphylaxis following quadrivalent human papillomavirus vaccination. Canadian Medical Association Journal, 2008, 179:525–533.

⁵ Sutton I et al. CNS demyelination and quadrivalent HPV vaccination. Multiple Sclerosis, 19 September 2008. [e-publication ahead of print].

Full report of GACVS meeting of 17-18 December 2008, published in the WHO Weekly Epidemiological Record on 30 January 2009

At the request of the Strategic Advisory Group of Experts on immunization (SAGE), the Committee reviewed the safety of human papillomavirus (HPV) vaccines.

A review of available evidence of the safety of both the 4-valent HPV (Gardasil®) and the 2-valent HPV (Cervarix®) vaccines was presented. Data from pre-licensure randomized controlled trials and post-licensure surveillance reports from the 2 vaccine manufacturers as well as from the European Medicines Evaluation Agency, the United States Food and Drug Administration (FDA) and the United States Centers for Disease Control and Prevention (CDC) were included in the review.

The current evidence on the safety of HPV vaccines is reassuring. The reviewed data covered local and systemic events in short-term, and long-term events up to 6 years after vaccination, including pregnancy events. A common observation was the occurrence of injection site reaction and muscle pain. During adolescent vaccine campaigns, some mass sociogenic illnesses such as post-vaccination dizziness and syncope have been reported. These events have been prevented by observing adolescents for 15 minutes post-vaccination and encouraging good hydration. No concerns with the safety profile were identified.

As with the introduction of any new vaccine, it will be important to conduct surveillance to identify possible, rare unexpected adverse effects, especially as good-quality information on the rates of a variety of diseases before widespread vaccine introduction is generally lacking in the target age group for HPV vaccination (i.e. 9 to 26 years). Also, careful surveillance for specific adverse effects during pregnancy will be important as the target group includes females of reproductive age.

The Committee was advised of studies that are planned, mostly in developed countries, to monitor the occurrence of adverse effects of HPV vaccination. The Committee considered that it would be highly desirable if the protocols for these studies were to be made publicly available to encourage the conduct of similar studies in other locations, including developing countries. The evaluation of adverse effects, especially the long-term events and also the effectiveness of the HPV vaccine, would be greatly facilitated if national registers were maintained of all those who are vaccinated. This is planned in some countries, and the extension of this practice in other locations must be encouraged.

Full report of GACVS meeting of 12-13 June 2007, published in the WHO Weekly Epidemiological Record on 20 July 2007