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MEDI-NEWS - Based on Canada Communicable Disease Report (CCDR) January 2012;37:ACS-7.

In 2006, the quadrivalent human papillomavirus vaccine (HPV) was authorized in Canada for use in females between the ages of 9 and 26 years for the prevention of infection caused by HPV types 6, 11, 16 and 18. These types lead to cervical cancer, vulvar and vaginal cancers (along with their precursor lesions) and genital warts. Approximately 2 years later, this indication was expanded to include males in the same age bracket for the prevention of infection caused by the same HPV types as well as for prevention of genital warts caused by HPV types 6 and 11. Shortly afterwards, the quadrivalent vaccine was approved for use in females up to the age of 45. Protection with the same vaccine in females and males between 9 and 26 years of age was expanded to include prevention of anal cancer as well as all precursor lesions. In 2010, the bivalent HPV vaccine against HPV types 16 and 18 was authorized for the prevention of cervical cancer and its precursor lesions in females between the ages of 10 and 25. In January 2012, the National Advisory Committee on Immunization reviewed the epidemiology of HPV among females and males and provided updated information on the quadrivalent vaccine specific to its use in males. Highlights from this review follow.

Chief Medical Editor: Dr. Léna Coïc, Montréal, Quebec

The National Advisory Committee on Immunization (NACI) has issued a strong recommendation for males between 9 and 26 years of age to receive the quadrivalent human papillomavirus (HPV) vaccine for the prevention of anal intraepithelial neoplasia (AIN) of all grades, anal cancer and anogenital warts (AGWs). The evidence supporting this recommendation was judged to be as robust (Grade A) as evidence supporting an earlier recommendation for females between the ages of 9 and 26 years to receive the same quadrivalent vaccine.

NACI also recommended HPV vaccination for females over 26 years of age, granting a grade A recommendation to the quadrivalent vaccine which has demonstrated efficacy in females between 24 and 45 years of age. The bivalent vaccine received a grade B recommendation as efficacy has not been demonstrated in that age group. Both vaccines have been shown to be immunogenic and safe.    

These recommendations reflect those made by the U.S. Advisory Committee on Immunization Practices (ACIP) in October 2011: they recommended routine use of the quadrivalent vaccine in males at the age of 11 or 12 and for males between the ages of 13 and 21 years who had not been previously vaccinated or who had not completed the 3-dose series. The ACIP also noted that males between 22 and 26 years of age may receive the quadrivalent vaccine.

NACI also recommended males who have sex with males (MSM) receive the quadrivalent vaccine from the age of 9 onwards. In contrast, NACI did not recommend males receive the bivalent vaccine, as efficacy end points in males receiving the bivalent vaccine are lacking. 

Incidence of AGWs

In considering the potential inclusion of males in existing female-only routine HPV immunization programs, NACI pointed out that provinces and territories might first consider the public health and economic burden that AGWs alone represent today (over 90% of AGWs are caused by HPV types 6 and 11).

“The public health and economic burden of AGWs in Canada is considerable,” NACI contributors wrote, “particularly among men whose incidence rates and incidence rate ratios compared to females have been increasing in recent years.” According to 2 Canadian studies, the incidence rates of AGWs in men were 154 per 100,000 men in Manitoba in 2004 and 131 per 100,000 men in British Columbia in 2006. Both of these rates were higher than for women at 120 and 121 per 100,000 women in Manitoba and British Columbia, respectively. Both studies also showed that the incidence of AGWs peaked between the ages of 20 and 24 for women and 25 to 29 years of age for men.

In British Columbia, the mean length of a single AGW episode was estimated to be 76 days for men vs. 61 days for women, and the average cost of treatment per episode was about $190—“translating into an estimated annual direct medical cost in British Columbia of approximately $1 million,” NACI noted. From a patient’s perspective, Drolet et al. also showed that a first episode of AGWs produces a quality-adjusted life-year loss equivalent to 9 to 40 days of healthy life lost (Sex Transm Dis 2011;38:949-56). 

Incidence of Cancers

The International Agency for Research on Cancer has concluded that multiple HPV types, including types 16 and 18, cause nearly all cervical cancers. Data also show a causal role of HPV type 16 in cancers of the vulva, vagina, penis, anus, oral cavity and oropharynx as well as an association of HPV type 18 with cancer at most of these sites. Among cancers affecting men, it is estimated that HPV infection is associated with 80 to 90% of anal cancers, 40 to 50% of penile cancers, 35% of oropharyngeal cancer and 25% of oral cavity cancer; the great majority of anal, oral cavity and oropharyngeal cancers are attributable to HPV 16 and 18. Both Canadian and US data indicate that the overall incidence of anal cancer for males and females has increased in the past several decades and that overall survival from anal cancer is lower in males compared to females for all stages of the disease. Recent evidence also supports an association between HPV infection and a subset of cancers of the pharynx and oral cavity, with HPV type 16 again being the most common type. 

As NACI investigators observed, “HPV infection and associated anal disease is highly prevalent among MSM, particularly in those who are HIV-positive.” Increases in anal cancer are similarly being reported among HIV-positive men in the HAART era. These would suggest that increases in anal cancer among MSM may be related to longer life expectancies in HIV-positive men on HAART. Indeed, rates of anal cancer among HIV-positive men are approximately 70 out of 100,000 person-years, which exceed cervical cancer rates among women even in areas of the world with the highest rates of cervical cancer.

HPV-infected males also increase the risk of both precancerous lesions and cervical cancer in their female sexual partners. In one case control study cited by NACI, a fivefold increase in the odds of females developing cervical cancer was observed among women whose partners tested positive for HPV.

The Canadian HITCH (HPV Infection and Transmission among Couples through Heterosexual Activity) (J Infect Dis 2011;204:1723-9) cohort also showed that the prevalence of HPV infection was 56% overall. However, it was higher among those with infected partners at 83% compared to 19% for those whose partners were not infected. 

Some modelling studies suggest that while a quadrivalent HPV vaccine program where females vaccinated prior to 12 years of age would reduce the incidence of AGWs by 83% and of cervical cancer by 78%, “the addition of males to this program would result in a further reduction, with a resulting total decrease of 97% for AGWs and 91% for cervical cancer,” NACI observed.

In the US, adverse events following receipt of the quadrivalent vaccine reported to the Vaccine Adverse Event Reporting System have been consistent with those seen with pre-licensure data.

Questions & Answers

On February 7, 2012, the Federation of Medical Women of Canada (FMWC) called on provincial and territorial governments to provide funding for the vaccination of boys against HPV as part of current school-based vaccination programs. 

This question-and-answer session was conducted with Dr. Vivien Brown, FMWC President (Toronto branch) and affiliated with the Department of Family Medicine, University of Toronto, Ontario.  

Q: Why do you think we need a publicly funded HPV vaccination program for boys?

A: Now that NACI has recommended the vaccine, it becomes standard of care. There is clear evidence the vaccine reduces cancer risk and it is therefore only fair and equitable that men and boys have access to a recommended vaccine. 

Q: You also note that vaccinating girls alone is not enough. Why do you believe that?

A: No vaccine is going to get 100% uptake and we also know that men have male partners who are going to spread HPV as well. So we are not going to achieve a reduction in the virus until we immunize everybody. 

Q: Are there other examples of immunization programs in which only females qualified for a vaccine—for example, the rubella vaccine—where that policy did not work?

A: The rubella vaccine is a great example. We were only worried about rubella in pregnancy so we only immunized women, but it didn’t work because there was too much virus still in the community. We now understand that genital cancers are an infectious disease and by immunizing both partners, we are going to decrease infection in the community and decrease cancer rates as well.  

Q: What about all the males and females who are not eligible for a publicly funded program or who missed it when it was offered in the case of females? Do you feel general practitioners should be making a strong recommendation for HPV vaccination to their patients at risk for HPV who have not yet been vaccinated?

A: Absolutely. When NACI makes a recommendation, it becomes standard of care. Our job as primary care providers is to educate the public and patients we see about the vaccine. Whether the vaccine is implemented in publicly funded schedules or not, its use should be recommended and we should be offering teaching around that vaccine. Patients have a right to say yes or no to it, but if we don’t educate them about issues relating to the vaccine, they do not understand what the issues are. So our role as the primary care provider is to educate patients as to what the recommendations mean to them.