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Based on the Canada Communicable Disease Report (CCDR) Online publication 15 February 2007;33(ACS-2):1-32

February 15, 2007

Based on study findings, the National Advisory Committee on Immunization (NACI) recently issued the following recommendations for use of the quadrivalent vaccine in Canada:

• Females between 9 and 13 years of age: The vaccine should be given to girls in this age group, before the onset of sexual intercourse, when its efficacy would be greatest.

• Females between 14 and 26 years of age: Females in this age group would benefit from the vaccine, even if they are already sexually active. They may not have been infected with HPV yet and are highly unlikely to have been infected with all four vaccine subtypes. If vaccinated, women in this category need to be aware that they may already be infected with HPV.

• Females between 14 and 26 years of age who have had previous PAP abnormalities, including cervical cancer, or have had genital warts or known HPV infection: Sexually active women in this category would still benefit from the vaccine. They may still not have been infected with the HPV types contained in the vaccine and are very unlikely to have been infected with all four vaccine types. If vaccinated, females should not expect the vaccine to have any effect on existing cervical lesions.

• Immunocompromised persons: The vaccine can be administered to those who are immunosuppressed as a result of disease or medications; however, its immunogenicity and efficacy might be less than that in those who are immunocompetent. • Females >26 years of age and males: No recommendations at this time. In females >26 years of age, studies are ongoing, although use of the vaccine can be considered in individual circumstances. While immunogenicity data are available for males, the efficacy of the vaccine is still unknown.

• Females <9 years of age and pregnancy: Not recommended. Immunogenicity or efficacy is not known in young girls nor is the duration of protection. The data on vaccination in pregnancy are limited and until further information is available, initiation of the vaccine series should be delayed. If a vaccine dose has been administered during pregnancy, there is no indication for any intervention.

Societies Endorse NACI Statement

Several key Canadian societies involved in women’s health care endorsed the new NACI recommendations, noting that they represent a major step forward in reducing the burden of HPV-related disease in Canada. The Society of Gynecologic Oncologists of Canada (GOC) stated in a press release that it “applauds” NACI’s recommendation that “all Canadian girls and women aged nine to 26… be routinely vaccinated with [the quadrivalent vaccine].” Dr. Joan Murphy, Chair, GOC Task Force on Cervical Cancer Prevention and Control, added that because of NACI’s position statement, “vaccination against diseases caused by vaccine-specific HPV types will now become the standard of care for cervical cancer prevention.” In their press statement, Dr. Donald Davis, President, The Society of Obstetricians and Gynecologists of Canada (SOGC), similarly welcomed NACI’s recommendations on HPV vaccination and suggested, “What has to happen now is for the federal, provincial and territorial governments to move quickly to increase access to HPV vaccination [as] the SOGC believes that girls and young women should have access to vaccination, no matter where they live in Canada and regardless of their financial situation.” Despite Dr. Davis’ suggestion, it can take some time before public programs are put into place, putting the onus on physicians to use their judgment in recommending this vaccine to their patients and their families.

Questions and Answers

This question-and-answer session was conducted with Dr. Robert Lotocki, Professor, OB/GYN and Reproductive Sciences, University of Manitoba, Winnipeg; Dr. Joan Murphy, Chair, GOC Task Force on Cervical Cancer Prevention and Control and Associate Professor, OB/GYN, University of Toronto, Ontario; and Dr. Dianne Miller, Associate Professor, OB/GYN, University of British Columbia, Vancouver.

Q: How do you think these new recommendations will change the way physicians practice?

Dr. Murphy: I think they will help physicians sort through some of the dilemmas they have had until now; for instance, what to do with women with post-sexual exposure. Physicians were confused as to whether women who had not been exposed [to sex yet] were [vaccine] candidates, whereas those who had been were not. But even after exposure, the likelihood of women being infected with multiple HPV types is low, so even in women with known HPV infection, the benefit of vaccination is real.

Dr. Miller: This is quite unique in cancer management because we now have the opportunity to do primary prevention of an important cancer and we have never had this opportunity before. Even though our absolute numbers of cervical cancers in Canada are not that large, the number of women who develop precancerous lesions is huge and we put enormous effort into screening, colposcopy and treatment of precancerous lesions. So to have something that prevents the trigger for the development of a cancer is quite phenomenal.

Q: What is the rationale for recommending the vaccine in females at a time when it is highly unlikely they are sexually active?

Dr. Lotocki: Basically, the science shows that these girls are affected by HPV. It may be true that they are not sexually active at age nine, but you have to look at prevention at a time when a female is not sexually mature. Penetration is not even necessary to be exposed to HPV.

Dr. Murphy: Because this is the optimum age when females are very unlikely to be exposed to HPV and secondly, the immune response at this age is felt to be optimal.

Dr. Miller: It is absolutely critical for the vaccine to be given when women are still sexually naive for it to be the most effective. Maybe there are not that many nine-year-olds who are sexually active but certainly quite a number of high school girls are and if we leave it too late, that will decrease the effectiveness of the vaccine. Children also have very robust immune systems so they get a more vigorous immune response to a vaccine than we might as adults. Q: The recommendations state that the vaccine not be given to females over the age of 26 years or to males of any age. Yet if a patient is particularly concerned about HPV infection, what would you do in this situation?

Dr. Lotocki: Your risk of exposure to HPV is about 75% over a lifetime and there are studies coming down the pipeline that show older women around the age of 50 do achieve immune responses to the vaccine, so it is not that it will not be effective against some of the vaccine types in other age groups. HPV infection peaks between the ages of 25 and 30 but there is a second peak around the age of 50 to 55 because of altered sexual behaviour, so vaccination in an older population may prevent that second peak.

Dr. Murphy: From a safety point of view and the known efficacy of the vaccine, there are virtually no downsides to vaccination. So it really is a personal decision and that decision could be patient-driven.

Dr. Miller: All of the studies were done [in women from 16 to 26 years of age] because of the high prevalence of HPV in this population, but the longer somebody is sexually active, the more likely they are to have seen HPV in the past, and that decreases the efficacy of the vaccine. However, as the recommendations suggest, the quadrivalent vaccine covers four HPV subtypes, so even if a woman has been infected with HPV 16, for example, the vaccine should still prevent infection with 6, 11 and 18. This is the reason [the recommendations state] we may still vaccinate women [previously exposed to HPV]. Q: How important is it to have a vaccine that will prevent not only genital warts but also cervical, vaginal and vulvar dysplasias as well as the majority of cervical cancers?

Dr. Lotocki: Looking at the prevention of cervical cancer, we have heard about the vaccine’s efficacy before and it is great. In addition, the vaccine will decrease many precancerous lesions and these lesions cause a lot of distress for women. So the vaccine will have a significant impact in terms of decreasing stress in women with dysplasias and the associated health care burden of managing them. For many women, genital warts are almost as devastating as having a cancer—they are embarrassing, treatments are not very effective and they are uncomfortable—so this is a bonus for young women who may develop warts. Additionally, you may well get broader protection against anogenital and head and neck cancer as well.

Dr. Murphy: We spend tremendous resources looking after women even doing routine PAP smears. When we get abnormal smears, most do not put women at risk but we cannot distinguish all that well between nuisance and sinister lesions. If we can prevent most of these abnormalities from occurring, we can free up tremendous human resources, so in its broadest terms, this vaccine will definitely improve the health of the population.

Dr. Miller: I have seen women die of cervical and vulvar cancer and there are few diseases that I think are as awful in the terminal stages as cervical and vulvar cancer. That being said, I also see a large number of women with precancerous precursors and this affects them not only physically but emotionally, too. Sometimes there is fertility loss associated with treatment, sometimes anxiety about spreading the infection to a partner, so the cost of HPV infection is much more than just cancer. And we have not even touched upon venereal warts and while nobody dies of venereal warts, if we can prevent those as well, it is a tremendous benefit.

Reference: Canada Communicable Disease Report (CCDR) online publication 15 February 2007;33(ACS-2):1-32.