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.
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.
* These recommendations are based on the following assumptions:
** Immunization does not replace the need for fully implemented, organized, cervical cancer screening programs.
*** This recommendation is based on the following assumptions:
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:
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.
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):
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.
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.
Table 4: Pros and cons of different publicly funded HPV catch-up immunization programs compared with a routine program for one school grade
Routine program (no catch-up)
Delayed impact on HPV disease incidence and prevalence
At mid-term, lowest impact when compared with other options
Delayed impact on HPV disease incidence and prevalence
At mid-term, minimal impact when compared with other options
At short term, low impact on HPV disease incidence and prevalence
At mid-term medium impact when compared with other options
Quick impact expected on HPV disease incidence and prevalence
Highest impact when compared with other options
|Best cost-effectiveness ratio when compared with other catch-up options||Good cost-effectiveness ratio when compared with other catch-up options||Cost-effectiveness will depend on age groups chosen||The worst cost-effectiveness ratio when compared with other catch-up options; the highest number “need to treat” for one case prevented|
|Feasibility||Best feasibility when compared with other options, especially if partially piggy-backed on existing vaccination programs||Good feasibility when compared with other options, especially if partially piggy-backed on existing vaccination programs||Feasibility will depend on age groups chosen||The lowest feasibility when compared with other options, especially for young adults and teenagers outside school; difficult to obtain high vaccine coverage|
|Accessibility||Best accessibility when compared with other options||Good accessibility||Good accessibility||Low to very low accessibility of some age groups|
|Equity||Less equitable than other options||Equitable for schoolgirls, inequitable for girls outside school||Equitable for schoolgirls, inequitable for girls outside school||Most equitable when compared with other options|
*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.
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).
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.
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.