Gardasil 9 - 9-valent HPV vaccine

What is Gardasil 9 - HPV 9-valent vaccine and what is it used for?

Gardasil 9 is a vaccine used in men and women from nine years of age to protect against the following diseases caused by nine types of human papillomavirus (types HPV 6, 11, 16, 18, 31, 33, 45, 52 and 58 ):

precancerous lesions (growths) and tumors affecting the cervix, vulva or vagina and anus;
genital warts. Gardasil 9 should be administered according to official recommendations.

The vaccine contains purified proteins of the nine types of HPV listed above.

How is Gardasil 9 - HPV 9-valent vaccine used?

Gardasil 9 is a suspension for injection available in vials or pre-filled syringes. Generally Gardasil 9 is administered according to a three-dose regimen, which involves the administration of the second dose two months after the first, while the third dose is given four months after the second. The second dose should always be administered at least one month after the first and the third dose should be administered at least three months after the second. All three doses must be administered within one year.

It is recommended that subjects receiving the first dose of Gardasil 9 complete the three-dose cycle with this same medicine. The vaccine is given by intramuscular injection, preferably in the shoulder or thigh.

The vaccine can only be obtained with a prescription.

How does Gardasil 9 - 9-valent HPV vaccine work?

Human papillomaviruses are viruses that cause condyloma and abnormal tissue growth. There are over 100 types of papillomavirus, some of which are associated with anogenital tumors in both sexes. Almost all cervical carcinomas are caused by an HPV infection. It is estimated that in Europe about 90% of anal cancers, 15% of vulvar cancers, 70% of vaginal cancers and 30-40% of penile cancers are caused by an HPV infection. HPV types 16 and 18 are responsible for a high percentage of cervical and anus tumors, while HPV types 6 and 11 cause the majority of genital warts. Five other types of HPV (31, 33, 45, 52 and 58) are associated with a high risk of cancer, accounting for about 20% of cervical cancers.

All papillomaviruses have an envelope, or "capsid", made up of proteins called "L1 proteins". Gardasil 9 contains the purified L1 proteins for the nine types of HPV listed above, produced by a method known as "recombinant DNA technology" and collected in "virus-like particles" (structures that resemble HPV viruses, such that the body has no difficulty in recognizing them). Such virus-like particles are unable to cause infection or cause disease.

When a patient receives the vaccine, the immune system produces antibodies against L1 proteins. Following vaccination, the immune system is able to produce antibodies more quickly when exposed to real viruses. This production of antibodies helps to protect the body from diseases caused by these viruses.

The vaccine also contains an "adjuvant" (a compound containing aluminum) that stimulates a better response.

What benefit has Gardasil 9 - 9-valent HPV vaccine shown during the studies?

Gardasil 9 can offer protection against all nine types of HPV infection, as demonstrated in four main studies.

The first study examined the effectiveness of Gardasil 9 in over 14, 000 women aged 16 to 26 years. The study evaluated how many of the women treated with Gardasil 9 developed the disease (growths or cancer) following an HPV infection caused by types 31, 33, 45, 52 and 58 compared to the Gardasil vaccine (a vaccine already authorized which confers immunization against types 6, 11, 16 and 18). The study found that 1 out of 6 016 women vaccinated with three doses of Gardasil 9 developed an affection related to types 31, 33, 45, 52 and 58 of HPV compared to 30 women out of 6 017 vaccinated with three doses of Gardasil. It was also found that antibody levels against types 6, 11, 16 and 18 were adequate to protect against these four types of HPV infection. The women were kept under observation for about three and a half years by the administration of the third dose of vaccine.

The second study, conducted on 3066 people, compared the effectiveness of Gardasil 9 in girls and boys aged between 9 and 15 with that of Gardasil 9 in young women aged 16-26. The main measure of effectiveness was the development of antibodies against HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58 one month after the administration of the third dose. The study showed that the vaccine stimulates the production of adequate levels of antibodies against all nine types of HPV in girls and boys aged 9-15 compared to women aged 16-26, for whom protection against the disease had been demonstrated in the first study.

The fourth main study compared the antibody levels against all nine HPV types one month after the third dose in 1, 419 young men aged 16 to 26 years compared to the levels of 1 101 women in the same age group . The study found that Gardasil 9 stimulates similar immunization levels in women and men against all nine types of viruses.

What are the risks associated with Gardasil 9 - 9-valent HPV vaccine?

The third study compared the effectiveness of Gardasil 9 with that of Gardasil in 600 girls aged 9-15. The study evaluated the appearance of antibodies one month after administration of the third dose, showing that patients vaccinated with Gardasil 9 had immunization levels similar to those vaccinated with Gardasil against HPV types 6, 11, 16 and 18. The fourth main study compared the antibody levels against all nine HPV types one month after the third dose in 1, 419 young men aged 16 to 26 years compared to the levels of 1 101 women in the same age group . The study found that Gardasil 9 stimulates similar immunization levels in women and men against all nine types of viruses.

Why has Gardasil 9 - HPV 9-valent vaccine been approved?

The Agency's Committee for Medicinal Products for Human Use (CHMP) decided that Gardasil 9's benefits are greater than its risks and recommended that it be approved for use in the EU. The CHMP has taken into account that Gardasil 9 confers greater protection against the tumor than its precursor, Gardasil, since it protects against five other additional types of HPV (31, 33, 45, 52 and 58), which are considered high risk, although less common than types 16 and 18. Consequently, Gardasil 9 is expected to prevent most cancers and precancerous lesions of the cervix, vagina and vulva, in addition to that the genital warts associated with the HPV virus. As for the undesirable effects, the reactions at the injection site - although manifested by a substantial percentage of subjects - are slightly greater than those observed with Gardasil.

What measures are being taken to ensure the safe and effective use of Gardasil 9 - 9-valent HPV vaccine?

A risk management plan has been developed to ensure that Gardasil 9 is used as safely as possible. Based on this plan, safety information has been included in the summary of product characteristics and the package leaflet for Gardasil 9, including the appropriate precautions to be followed by healthcare professionals and patients.