Updated Recommendations on Human Papillomavirus (HPV) Vaccines: 9-valent HPV vaccine 2-dose immunization schedule and the use of HPV vaccines in immunocompromised populations

1. What

Human papillomavirus (HPV) infections are the most common sexually transmitted infections. There are over 100 types of HPV, and they are broadly classified into high and low risk types.

High-risk HPV types can lead to cervical and anogenital cancers, as well as certain cancers of the head and neck. Low-risk HPV types can cause condylomata acuminata, also called anogenital warts (AGWs).

Gardasil® (HPV4 vaccine) has been authorized for use in Canada since 2006 for the prevention of HPV types 6 and 11 -related AGWs and HPV types 16 and 18 -related cancers. Cervarix® (HPV2 vaccine) has been authorized for use in Canada since 2010 for the prevention of cervical cancer caused by HPV types 16 and 18. Gardasil® 9 (HPV9 vaccine) was authorized with a 3-dose schedule for use in Canada on February 5, 2015 for the prevention of infection caused by HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58, and for prevention of anogenital cancers, related pre-cancerous lesions, and AGWs associated with the HPV types included in the vaccine. The HPV9 vaccine was recommended for use by NACI in July, 2016.

An ongoing phase III study has recently yielded data demonstrating that HPV9 vaccine immunogenicity following a 2-dose immunization schedule was not inferior to a 3-dose schedule in both females and males. The safety profile of a 2-dose schedule was also similar to that of a 3-dose schedule. Gardasil®9 was authorised for use in Canada according to a 2-dose immunization schedule on December 15, 2016.

Several recent studies have also examined the safety and immunogenicity of HPV2 and HPV4 vaccines in immunocompromised populations.

2. Who

Girls and Women

HPV2, HPV4, and HPV9 vaccines are indicated in all females aged 9 to 45 years. HPV2 vaccine is indicated in females 9 to 45 years of age for the prevention of cervical cancer and pre-cancerous lesions associated with the HPV types contained in the vaccine. HPV4 and HPV9 vaccines are indicated for the prevention of the following diseases associated with the HPV types contained in the vaccines:

In females 9 to 45 years of age

• Cervical, vulvar, vaginal cancers and pre-cancerous lesions
• AGWs

In females 9 to 26 years of age

• Anal cancer and pre-cancerous lesions

Boys and Men

HPV4 and HPV9 vaccines are indicated in all males 9 to 26 years of age for the prevention of anal cancers, pre-cancerous lesions and AGWs. HPV2 vaccine is not indicated in males at this time.

HPV vaccines are not indicated in:

• females or males < 9 years of age as no immunogenicity or efficacy data are available in these groups

3. How

HPV vaccines have been authorized by the Canadian federal regulator, Health Canada, to be given as three separate 0.5 mL doses:

• HPV2 vaccine at months 0, 1, and 6,
• HPV4 vaccine at months 0, 2, and 6, and
• HPV9 vaccine at months 0, 2 and 6.

HPV vaccines have also been authorized by the Canadian federal regulator, Health Canada, to be given in two separate 0.5 mL doses in younger immunocompetent individuals:

• HPV2 vaccine at months 0 and 6 in girls aged 9 to 14 years of age at the time of first injection (authorization on July 3, 2014)
• HPV4 vaccine at months 0 and 6 or 0 and 12 in individuals 9 to 13 years of age (authorization on March 10, 2015)
• HPV9 vaccine at months 0 and 5-13 in individuals 9 to 14 years of age (authorization on December 15, 2016)

Based on current evidence, NACI recommends that (see Table 1 for a summary of these recommendations, and the grade of evidence on which these recommendations are based):

• Either a 2 or 3-dose immunization schedule with HPV9 vaccine can be used for immunocompetent females and males 9-14 years of age (as with HPV2 or HPV4 vaccines). In a 2-dose schedule, the second dose should be administered at least 24 weeks after the first dose;
• HPV9 vaccine can be administered according to a 3-dose immunization schedule in males or females ≥15 years (as with HPV2 or HPV4 vaccines);
• A 3-dose schedule should be maintained for HPV2, HPV4, or HPV9 vaccines in immunocompromised populations, immunocompetent HIV infected individuals, and individuals who have not received any dose of HPV vaccine by 15 years of age, ensuring at least 24 weeks between the first and last dose of HPV vaccine.