ARCHIVED - Recommendations on a Human Papillomavirus Immunization Program

11. CIC recommendations

These recommendations represent the first statement by the CIC on the use of quadrivalent HPV vaccine, licensed in Canada in July 2006. They are based on the epidemiology of HPV, the HPV vaccine characteristics, the Canadian disease modeling and economic analysis, as well as on the feasibility and acceptability of HPV immunization programs. Currently, there are no precise epidemiologic data on the general incidence of anogenital condylomas; there are also no data on the effectiveness of HPV vaccines in males. Therefore, the HPV immunization program is recommended for women for cervical cancer prevention only at this time. As more knowledge about the vaccine becomes available, the recommendations can be revised accordingly. A table summarizing the recommendations is included as Appendix 5.

11.1 Goals

To decrease the morbidity and mortality of cervical cancer, its precursors and other HPV-related cancers in women in Canada through combined primary prevention (immunization) and secondary prevention (screening) programs.

11.2 CIC-NACI Working Group recommendations on disease incidence reduction

1. To reduce by 60%^* the CIN 2/3 caused by HPV 16/18 in Canada within 20 years of introduction of an HPV vaccination program^**.
2. To reduce by 60%^* the incidence of cervical cancers (and other HPV-related cancers) caused by HPV 16/18 in Canada within 30 years of introduction of an HPV vaccination program^**.

   ^* These recommendations are based on the following assumptions:

   • Vaccine efficacy is at least 95%, coverage at least 85% for 11-year-old girls, 80% for 14-year-old girls and 75% for 17-year-old girls.
   • Duration of vaccine immunity is life-long.

   ^** Immunization does not replace the need for fully implemented, organized, cervical cancer screening programs.

3. To reduce by 60% mortality due to cervical cancer caused by HPV 16/18 in Canada within 35 years of introduction of an HPV vaccination program^***.

   ^*** This recommendation is based on the following assumptions:

   • There is a lag time between the diagnosis of cervical cancer and the time of death as an outcome.
   • In general, the outcome of therapeutic measures (surgery, chemotherapy, radiation) for cervical cancer is known by 5 years past the time of diagnosis⁽⁸⁵⁾.

11.3 CIC-NACI Working Group recommendations on HPV immunization strategies and programs

A number of models have been developed to predict the long-term impact of various immunization strategies and estimate their cost-benefit ratio (see Appendix 4 for a review of pharmaco-economic evidence supporting the CIC-NACI recommendations). Vaccines are expected to prevent from 15% to 93% of cervical cancer cases, 46% to 66% of high-grade lesions and 20% to 30% of low-grade lesions. The duration of protection has the greatest influence on the impact of vaccination. Much of the potential benefit could be lost if the vaccine's effectiveness lessens over time and thereby merely delays the development of cancer. Consequently, specific evaluation procedures should be put in place to measure the persistence of effectiveness, and strategies should be developed for reaching vaccinated women for booster doses if required.

Principles underlying the recommendations:

• HPV vaccines are highly immunogenic and produce antibody levels much higher than those conferred by natural infection^(13,15).
• The vaccines are beneficial for all young women aged 9-26 years. However, because of their high cost, they must be used with optimal efficiency that is, maximizing the benefits of the resources consumed.
• For maximum vaccine effectiveness, it is preferable to administer HPV vaccines before the onset of sexual activity.
• The immune response in youth aged 9-11 is particularly good, reaching higher levels after two doses than those observed in young women aged 16-26 in whom the clinical efficacy of the vaccine was demonstrated⁽¹⁶⁾.
• It is preferable to administer vaccines in primary school in order to obtain higher vaccination coverage at a lower cost.
• Cost per QALY increases progressively after the age of 14.
• When possible, HPV vaccine can be co-administered with other vaccines (hepatitis B, Tdap) in existing school-based programs.
• Cervical screening will need to be continued after the introduction of the HPV vaccine since the vaccine will protect against certain types of HPV only, and more data on the length of protection and effect of vaccination are needed.

Because of the high prevalence of HPV infection, a routine immunization strategy is preferred over strategies targeting high-risk groups; such strategies are not efficient for HPV immunization and may also be viewed as unethical.

11.3.1 Routine immunization

To decrease the morbidity and mortality associated with cervical cancer, its precursors and other HPV-related cancers in women in Canada, CIC recommends school-based HPV vaccination of one female cohort to be implemented in all Canadian provinces and territories (option 1):

1. To immunize 80% of school-aged girls in either grade 4, 5, 6, 7 or 8 with the required doses of the HPV vaccine within 2 years of program introduction.
2. To immunize 90% of school-aged girls in either grade 4, 5, 6, 7 or 8 with the required doses of the HPV vaccine within 5 years of program introduction.

Particular efforts should be undertaken to achieve high vaccine coverage for routine programs in hard-to-reach and high-risk populations. Catch-up strategies could be extended to these populations.

Although the initial programmatic options examined were for schoolgirls in grades 4, 5, 6 or 7, the Canadian disease modeling and economic analysis indicated that vaccinating the grade 8 schoolgirl cohort is also a cost-effective strategy. Therefore, the grade 8 schoolgirl cohort has been included in the recommendation on routine immunization. When deciding on their routine programs, jurisdictions should consider their own population characteristics, such as the age at sexual debut and the ability to reach girls at different ages to achieve maximum vaccine coverage.

11.3.2 Catch-up immunization

For jurisdictions that wish to consider catch-up programs, these are options for consideration. The following table reflects the pros and cons of various catch-up options compared with a routine program for one school grade alone.

*For all options, the duration of protection will determine the impact on HPV disease incidence and prevalence.

For all strategies, education and awareness campaigns for the population as well as professional education will be needed. However, at the present time, it is not feasible to implement option 3 in Canada.

11.3.3 Immunization schedules

Following the manufacturers' indications for the quadrivalent HPV vaccine, NACI recommends a three-dose schedule (0, 2 and 6 months)(2). Currently, there are research studies under way to assess other HPV immunization schedules. As more information becomes available, Canadian provinces and territories may consider different schedules (e.g. extended schedules, two-dose schedules).

11.3.4 Impact of vaccination on cervical cancer screening

Cervical screening is an essential tool for evaluating the immunization program. While it is not within the CIC's mandate to issue recommendations on cervical cancer screening, the introduction of vaccination is expected to have a major impact ultimately on screening recommendations, and the two activities must now be planned simultaneously. An immunization program should constitute part of a comprehensive cervical cancer prevention program. In addition to determining the impact of vaccines on cancer screening any impact on sexual behaviour should also be evaluated.

Impact of HPV vaccination on screening outcomes: A lower prevalence of cervical lesions will result in a lower positive predictive value of cytology testing. HPV vaccination could also have an impact on the use of new screening tests (e.g. tests to detect the viral DNA of various HPV genotypes). Finally, vaccination will reduce the colposcopy rate by reducing the risk of precancerous lesions^(25,26,86).

CIC recommends the development of a surveillance system to detect a possible replacement in circulating HPV types.

Potential impact of HPV vaccination on women's screening behaviours: An HPV immunization program is expected to reduce the incidence of cervical cancer but will not eradicate the disease. All sexually active women, whether or not they have been vaccinated, should continue to undergo cervical cancer screening. A coordinated set of interventions must be put in place to maintain and improve adherence to screening procedures (surveys on attitudes and behaviour, various educational interventions, follow-up system, etc.). Vaccination and existing cervical cancer prevention programs are complementary, especially in the context of uncertainties regarding duration of vaccine protection.

CIC recommends the development of a national consensus on screening programs in the era of vaccination. Appropriate studies must be conducted to determine what changes may be required in screening schedules and programs as a result of implementation of an HPV vaccination program.

11.4 CIC/NACI Working Group recommendations on program evaluation

Evaluation of the HPV immunization program will be complex, but it is crucial because of its major impact on the health of women and on screening activities, the amounts of money invested and the need to review future strategies as a function of advances in knowledge.

In parallel with implementation of an HPV immunization program, CIC recommends developing a detailed evaluation plan. Vaccination coverage, and the incidence and prevalence of HPV-associated diseases and cervical cancer will have to be monitored. The efficacy and duration of the protection conferred by the vaccine as well as the psychosocial impact of vaccination (for instance, screening adherence in vaccinated women or the knowledge, attitudes and practices of the public and health professionals) will need evaluation.

The development of optimal cervical cancer screening approaches, including the need to define the role of HPV testing, should be an integral part of HPV vaccine program evaluation in order to assess the impact of immunization on HPV infection, cervical cancer and its precursors.

The evaluation of the immunization program will require specific tools. The availability of a registry of HPV vaccine coverage and a registry of cervical cancer, as well as a national HPV sentinel surveillance system, will be important components in this evaluation. Effective linkage between the latter databases will be needed.