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PRIORITY PRESS - 9th Canadian Immunization Conference (CIC)

Quebec City, Quebec / December 5-8, 2010

Delegates attending a special session here at the CIC on HPV-related disease voted overwhelmingly in favour of public health funding for a human papillomavirus (HPV) vaccination program targeting both males and females, convinced that the burden of disease in males fully justifies broadening the current program to include them. When polled after the presentations, 84% of a large group of attendees voted in favour of a gender-neutral HPV vaccination program across the country. The reasons for this were very compelling.

Disease Prevalence

As discussed by Dr. Marc Steben, Medical Advisor, HPV Scientific Group, STD Unit, Institut national de santé publique du Québec, Quebec City, the clinical spectrum of HPV disease in males includes genital warts (GWs); recurrent respiratory papillomatosis (RRP); penile intraepithelial neoplasia (PIN) and carcinoma; anal intraepithelial neoplasia (AIN) and carcinoma; and some oropharyngeal cancers. “GWs do not cause cancer but they are associated with a significant burden on health care resources,” Dr. Steben observed, “and they are seen more in males than in females.”

Results from the HIM (HPV Detection in Men) study indicated that the prevalence of HPV infection in males between the ages of 18 and 70 was approximately 60% across the 3 countries involved (US, Brazil and Mexico). “Condom use is also unreliable because HPV can be detected in many anatomic sites in the same patient,” Dr. Steben noted. Furthermore, once a patient develops GWs, there are no therapeutic antiviral options; rather, physicians have to rely on methods that destroy the lesion but not the virus, none of which are very successful and all of which are associated with significant recurrence rates. “Treatment options for GWs are associated with discomfort, epithelial erosion, scarring, depigmentation and ulceration,” Dr. Steben added, “and they are embarrassing, painful and uncomfortable for patients as well.”

HPV Consequences and Costs

Over 90% of GWs and all RRP are caused by HPV types 6 and 11, while HPV 16 and 18 are associated with most HPV-related cancers in men, including anal and penile cancer and cancers of the oral cavity and pharynx. In 2008, the estimated number of new cases of HPV-related cancers in US males ranged between 8696 and 11,228—very similar to the burden of cervical cancer in US females which number approximately 11,000/year. Extending HPV vaccination to males to prevent anal cancer is further justified, as Dr. Steben suggested, given the absence of routine screening for anal cancer and the lack of any precancerous diagnostic test, as exists for women.

Cost efficacy of male vaccination depends on vaccine coverage of females and health outcomes. Cost efficacy ratios are below $100,000 at coverage rates up to 75% and when the impact beyond cervical cancer is considered. When all potential HPV-related diseases are included in cost-effectiveness models, the cost of vaccinating both sexes drops dramatically to a mean of $25,664—roughly comparable to a mean of $22,113 when considering the prevention of cervical disease only in girls and women. Cost per quality-adjusted life-year gained by vaccinating boys compares favourably to many other recommended (funded) vaccines. “Vaccination of males would further reduce HPV-related diseases in women and in men and inclusion of males for HPV vaccination should be considered, including cost-effectiveness decisions,” he concluded.

Efficacy in Males

As discussed by Dr. Marina Salvadori, Consultant, Children’s Hospital of Western Ontario, London, immune responses to the HPV vaccine are even more robust in males than they are in females. The main quadrivalent HPV vaccine study in men found that the vaccine was 90.6% effective against HPV 6/11/16/18-related external genital lesions (EGLs) in 1394 per-protocol subjects and 89.3% effective against condyloma; there were no penile lesions in the vaccine group. Among men who have sex with men (MSM), the same study found that the quadrivalent vaccine was 77.5% effective against HPV 6/11/16/18-related AIN, Dr. Salvadori noted.

As speakers here re-emphasized, any HPV-related cancer takes time to develop and the full impact of vaccinating males and females against HPV-related cancer will not be apparent for some time. HPV types leading to GWs, on the other hand, have a relatively short incubation period and the effect of the quadrivalent vaccine can be documented relatively soon after widespread uptake.

The Australian Experience

This is exactly the situation Australia is currently reporting. With rapid and widespread coverage of females 12 to 26 years of age, starting in mid-2007, Australia had already recorded a 59% relative reduction in the incidence of GWs by the end of 2009 among girls and women between 12 and 26 years of age. “Only resident women [who received the vaccine] had this change in GWs; there was no change in the incidence in non-resident women [who did not] and no change in women >26 (who were not eligible for the free vaccine),” Dr. Salvadori told delegates.

In parallel, there was a 39% relative reduction in the incidence of GWs among heterosexual men 12 to 26 years of age, presumably the result of herd immunity; again, there was no change in the incidence of GWs among MSM over the same study interval.

“We absolutely know this vaccine protects men against GWs; we also know it protects MSM from anal cancer and the hope is that it will protect all men against penile, anal and oropharyngeal cancer,” Dr. Salvadori concluded, “and if both groups are vaccinated, the hope is they will protect each other.”

Equity

As reiterated by Dr. Vivien Brown, Lecturer, University of Toronto, and Assistant Professor of Family Medicine, McMaster University, Hamilton, Ontario, HPV infection causes a wide spectrum of diseases in men. “HPV infection and disease in 1 partner significantly contributes to the risk of infection and disease in the other partner,” she stated, “and since HPV is typically asymptomatic, those who are infected can unknowingly transmit it to their partner because it is not something we test for.” In fact, in one Washington-based study, 50% of university-aged females with their first-ever partner tested positive for HPV DNA within 1 to 2 years of being with the same partner. “It is very important that young women and young men understand this—that HPV can be easily transmitted without any signs or symptoms,” Dr. Brown emphasized. As seen in Australia, MSM are not benefitting from the HPV vaccine program because they do not have access to the subsidized vaccine and are often exposed to other unvaccinated men.

She also pointed out that Canada has a public health program that is underutilized. For example, in Ontario, girls receive the vaccine in grade 8. “If you are uncertain in grade 8 and you do not take the vaccine then, you cannot get it from public health in grade 9 and so on. Nor is there a catch-up program in Ontario, so uptake is only 53%, meaning that 47% of grade 8 girls did not get the vaccine when they could have,” Dr. Brown reported. Even in Atlantic Canada where uptake rates approached 80% and where catch-up programs were offered, “We still have a lot of unvaccinated young women,” she added.

Current vaccine uptake is not optimal and will not adequately control disease as was found with rubella. Dr. Brown reminded delegates that countries that offered the rubella vaccine to pregnant women only had to change their policy as surges of rubella attributable to susceptibility among males kept reappearing. She also emphasized that in a country like Canada which prides itself on its health care system, vaccinating males is a more equitable public health policy and recognizes that both genders contribute to the transmission of HPV, and that both can develop clinical manifestations of HPV-related disease.