Human Papillomavirus Vaccination for Men

Advancing Policy and Practice

Peter A Newman; Ashley Lacombe-Duncan


Future Virology. 2014;9(12):1033-1047. 

In This Article

HPV Vaccination Policies

In a global context, WHO data indicate that HPV vaccination had been introduced in 68 countries as of May 2014; few countries with public health insurance offer public funding to cover HPV vaccination programs for males.[39]

Notably, Australia was the first country to initiate government-funded universal HPV vaccination for boys, and began including boys in a national school-based HPV vaccination program in February 2013.[40] The influential US ACIP recommends routine HPV4 vaccination for both boys and girls, with federally financed HPV vaccination for children aged 9–18 years who are uninsured or underinsured provided by the Vaccines for Children (VFC) Program,[29,41] and selective coverage (and policies) by state for those who do not qualify for VFC.[42] The UK national immunization program implemented in 2008 provides universal coverage for girls only,[43] as in most European countries,[44,45] with Austria being the first to initiate a publicly funded gender neutral HPV vaccination program, in 2014.[46] In Canada, 11 of 13 provinces and territories only include girls in publicly funded HPV vaccination; Prince Edward Island provides HPV vaccination to boys free of charge[47] and Alberta's school immunization program included boys as of September 2014,[48] with calls for the inclusion of boys in free immunization programs in other provinces.[49]

Government policy regarding public funding to cover the cost of HPV vaccines for girls but not for boys has highly significant implications for HPV vaccine coverage. In addition to direct barriers to uptake exacerbated by the relatively high out-of-pocket costs for HPV vaccination compared with other routinely used vaccines,[50] the lack of public funding exerts additional influence through HCP. Amid extensive evidence of the substantial influence of HCP on HPV vaccine acceptability for boys as well as for girls,[33,35] HCP decisions to offer the vaccine or not for boys are impacted by HPV vaccination policies, including cost subsidies.[35] HCP may assess that the cost would be a burden for particular patients and their families, particularly in the context of competing healthcare costs, and thereby not suggest it. Parents' attitudes and perceptions about the need for HPV vaccination for boys, in addition to being influenced by HCP, also may be influenced by government policies that provide funding only for vaccination of girls, thus reinforcing the belief that HPV4 is a women's vaccine.

The bulk of the evidence used to inform government policy on whether or not to subsidize the costs of HPV vaccination programs for boys is derived from cost–effectiveness studies. In addition to critiques of the execution of cost–effectiveness studies, several additional lines of argument question the use of cost–effectiveness outcomes as the sole or primary criterion for a policy with such a significant impact on public health. A more comprehensive overview of the state of evidence for extending publicly funded HPV vaccination programs to boys in addition to girls requires attention to and critical review of the assumptions made in choosing the parameters to model cost–effectiveness, consideration of the documented advantages of universal versus targeted vaccination approaches, and attention to health equity concerns, including the role of stigma and discrimination in health policy.


Cost–effectiveness data have played a large role in HPV vaccination policy decision-making. Based on mathematical models suggesting that male HPV4 vaccination programs exceed cost–effectiveness thresholds,[51–53] many countries have chosen to focus exclusively on expanding coverage among women to promote herd immunity[45] and to not extend subsidized coverage to men.[29]

It is difficult to compare cost–effectiveness across countries, given differences in healthcare systems, financing mechanisms, vaccine delivery programs and existing coverage rates for girls, among others. However, a number of common components of cost–effectiveness calculations have been challenged: inconsistent and contested willingness-to-pay thresholds of dollars spent per quality-adjusted life year (QALY) gained and criticisms of the QALY itself; lack of inclusion of noncervical-related outcomes in mathematical models; assumptions that HPV4 vaccination coverage among women is at the level required to confer herd immunity; lack of consideration of differential rates of uptake among underserved racial, ethnic and socioeconomic groups within countries; the exclusion of MSM; and, finally, the assumption of fixed high baseline costs of the HPV4 vaccine.

Decisions based on cost–effectiveness inevitably vary based on QALY calculations, the vaccine's estimated duration of immunity, willingness-to-pay thresholds and the health outcomes included in mathematical models. The QALY itself has been criticized as an inadequate, outdated, and potentially inaccurate cost–effectiveness outcome.[54–56] Rather than a fixed and agreed upon value, willingness-to-pay thresholds of dollars spent per QALY gained vary greatly both within and between countries,[44] as do the types of cost–effectiveness models employed. A primary concern, however, is that cost–effectiveness models are often received by policymakers as providing definitive answers, perhaps deceptive in their apparently simple quantification of what is a highly complex outcome subject to numerous assumptions and unknowns. In fact it has been argued that it is the responsibility of researchers to bring to the attention of policymakers the value of relaxing various QALY assumptions in order to model alternative approaches.[54]

Importantly, QALY focuses on aggregate individual health benefits absent considerations of health equity; as a result, cost–effectiveness studies tacitly rely on policymakers both to question model assumptions and, ideally, to take into account concerns about fairness and ethics in broader deliberations that weigh cost as one input among other compelling societal values.[55] This is not, however, how cost–effectiveness models are generally represented.

In the case of HPV vaccination, cost–effectiveness models to date have largely excluded non-cervical outcomes, thereby underestimating the benefits to men of a universal HPV vaccination program.[57] A recent comprehensive cost–effectiveness study in Norway, for example, revealed several scenarios that would support universal vaccination of boys. Burger et al.[44] expand on previous models by including a range of HPV-related conditions beyond cervical outcomes, such as anal, penile and oropharyngeal cancers and noncancer HPV-related conditions such as genital warts, and further by exploring the impact of different vaccine cost thresholds. Accounting for all HPV-related outcomes, expanding HPV vaccination to boys would be considered cost effective at vaccine costs per dose of US$101, US$62 and US$36, based on willingness-to-pay thresholds of US$83,000, US$50,000 and US$30,000 per QALY gained, respectively.[44] Nevertheless, if one discounts other considerations, such as the merits and ethics of focusing on men's health, increasing vaccination coverage of girls to 90% was more effective and less costly than vaccinating both boys and girls with approximately 70% coverage. A comprehensive cost–effectiveness analysis in Austria that assessed the public health impact of universal HPV vaccination on HPV-associated cancers and genital warts, similarly revealed parameters supporting gender neutral vaccination.[58] Nevertheless, challenges in cost–effectiveness modeling result from the substantial heterogeneity across studies, both within and between countries, in prevalence estimates of HPV among men, including oncogenic HPV types, and HPV prevalence in oral cancers.

Another challenge to cost–effectiveness calculations of HPV4 vaccination for men is that most mathematical models presume a benchmark of coverage among women of 70% or greater, which is necessary to promote herd immunity.[51–53] In Australia, 80% two-dose and 73% three-dose coverage were reported for girls in 2010, 3 years into the school-based HPV4 vaccination program; subsequent declines in genital warts in heterosexual men under (but not over) 30 years of age[59] and lower prevalence of vaccine-targeted genotypes in unvaccinated young women suggest herd immunity.[60] However, actual HPV vaccine coverage for girls remains well below 70% in most countries.[29,45]

Data from the US National Immunization Survey-Teen[32] show that the proportion of girls who had received at least one dose of HPV vaccine increased from 25.1% in 2007 to 53.0% in 2011, with coverage remaining flat in 2012 and then increasing to 57.3% in 2013. The proportion of girls who had received all three doses of the vaccine decreased from 34.8% in 2011 to 33.4% in 2012, with an increase in 2013 to 37.6%.[32] In many other developed countries, HPV vaccine coverage is less than 50% among girls.[51] Coverage estimates in Canada vary by province and territory. After the first 3 years of a school-based vaccination program for girls in Ontario, the most populous province, ≥1-dose coverage increased from 51% in 2007–2008 to 59% in 2009–2010.[61] A large cohort study from Wales, UK, reported 48.5% partial or full uptake among women who had been offered HPV vaccination between 2010 and 2012.[43] A school-based delivery system in Scotland, however, achieved three-dose uptake of over 90% among girls between 2008 and 2010.[62,63] Beyond the need to consider the large heterogeneity in HPV vaccine coverage for girls both within and between countries, these data suggest that considerations of vaccine-delivery method (school based vs provider based) may result in more accurate cost–effectiveness models.

An important and related consideration for HPV vaccination programs is disparities in coverage rates by sociodemographic factors, such as race, ethnicity and socioeconomic status. Young adult women in the USA who had received at least one dose of HPV vaccine were more likely to be non-Hispanic white and to have private health insurance, a usual source of healthcare, and more than high school education; Hispanic women and women with limited access to care consistently had lower rates of HPV vaccination each year from 2008–2012.[64] African–American girls are also less likely to have initiated or completed the three-dose vaccination series compared with whites.[65] In Wales, women who lived in areas of social deprivation were less likely to be vaccinated compared with women in the least deprived areas.[43] However, such disparities were attenuated in Scotland as a result of school-based delivery of the vaccine.[63] Overall, extant data suggest that girls from medically underserved populations, who tend to be at disproportionately high risk for HPV infection, may stand to benefit more from universal male HPV vaccination than girls from general population samples. Racial, ethnic and sociodemographic disparities in vaccine uptake and cancer incidence, while important from a public policy and social justice perspective, are generally not considered in cost–effectiveness studies.

The cost–effectiveness of HPV4 vaccination for men is also enhanced when MSM are considered.[66] While several mathematical modeling studies of HPV vaccination note the exclusion of MSM as a limitation,[44,51,52] a study based exclusively on MSM found vaccination to be extremely cost effective.[66] The benefits were greatest if vaccination occurred by age 12, but even vaccinating MSM at age 20 or 26 years of age was an attractive option based on a willingness to pay threshold of less than US$50,000 per QALY.[66]

Finally, vaccine price is one of the most influential parameters in assessing the cost–effectiveness of adding boys to female-only HPV vaccination programs.[44] The use of fixed baseline vaccine price thresholds, however, limits the ability to consider the impact of alternative pricing on cost–effectiveness, such as cost reductions negotiated by some governments. For example, a mathematical modeling study conducted in the USA indicated that adding male vaccination to a female only vaccination program is an attractive policy in scenarios of 20–30% coverage among girls, but in a scenario of 75% coverage it exceeds accepted QALY thresholds.[52] However, the lowest price per dose considered was US$120.[52] Modeling conducted for Norway more clearly illustrates the impact of vaccine pricing. Based on vaccine pricing that could feasibly be negotiated below the publicly available price, many scenarios were revealed at US$75 and US$50 per dose in which adding boys to universal vaccination programs becomes cost-effective. Reportedly, the Australian decision to add boys to universal, publicly funded vaccination would not have been feasible if the government had not received a substantial price break on HPV4 for boys.[39]

Importantly, investigations assessing the efficacy of a two-dose regimen continue to emerge for bivalent[67–70] and quadrivalent HPV vaccines.[71–73] A move to two-dose regimens would substantially reduce vaccine costs;[74] in combination with vaccine price reductions,[75] this may result in increased cost–effectiveness scenarios that support gender neutral vaccination.

Targeted Versus Universal Vaccination

In addition to critical evaluation of cost–effectiveness models, several lines of argument support the advantages of a universal, gender-neutral approach to vaccination and identify substantial challenges in the implementation of targeted vaccination. Overall, a universal approach through publicly funded HPV vaccination of both males and females would achieve herd immunity more quickly, thereby yielding population health benefits[56] and maximizing the prevention of cervical cancer.[76]

The implementation challenges of a targeted vaccination approach in the USA are revealed in the case of HBV vaccination. A US national survey of adult HBV vaccination practices in primary care settings indicates that despite longstanding vaccination recommendations for adults, only 31% of family physicians and general internists reported routinely assessing for and vaccinating their patients against HBV.[77] Barriers to targeted HBV vaccination were the time consuming process of risk assessment, the sensitivity of the questions, concern that patients may be unwilling to disclose high-risk behaviors and lack of government reimbursement.[77]

More broadly, the history of HBV vaccination in the USA provides important lessons for HPV vaccination. Soon after the HBV vaccine was licensed in 1982, US ACIP recommended vaccination for adults at high risk for HBV infection, which missed a substantial proportion of high-risk, marginalized populations; in turn, targeted vaccination resulted in little or no impact on the transmission of disease.[78] Ultimately, universal childhood and compulsory middle school vaccination against HBV was implemented. As a result, HBV infection declined 75% from 1990–2004, with infection in children comprising 94% of the decline.[78]

In the case of HPV4 vaccination programs, while targeted vaccination of young gay and other men who have sex with men may be cost effective in theory, it is likely to face a number of significant challenges in implementation. First, it requires that individual MSM, including preadolescents or their parents, are aware of their increased risk for HPV infection and anal cancer. Second, it relies on young gay men being adequately interviewed about their sexual health by their HCP and/or their voluntarily disclosing their sexual behaviors to a HCP.

However a recent systematic review and meta-analysis exploring HPV vaccine acceptability among men found no significant difference in HPV vaccine acceptability between gay, bisexual and other MSM – who would benefit most from HPV vaccination – and heterosexual men.[33] In addition, most researchers (similar to many HCP) failed to assess self-identified sexual orientation, thus resulting in a lack of data to enable reliable assessment of potential differences between gay/MSM and heterosexual men. At present the evidence suggests that awareness and identification of elevated risk for HPV and associated cancers is insufficient to support effective targeted vaccination of young gay and other MSM.

Second, and perhaps more significantly, HPV vaccination is recommended for preadolescents, ideally prior to sexual debut. Evidence from two recent studies highlights expectable gaps in attempts to target vaccination for young gay and other MSM. Among over 1000 MSM recruited at community venues in Vancouver, 72.0% of those 26 years of age or younger had disclosed sexual behavior to a HCP; the median time from first sexual contact with a male to disclosure to a HCP was 3 years.[79] Arguably the proportion of young MSM who disclose their sexual orientation to a HCP is likely to be lower in the many contexts of greater stigma and discrimination against sexual minorities than in the relatively accepting context of a major Canadian city. A US study estimated that 90% of young MSM had used healthcare in the last 12 months, among whom 61% disclosed their sexuality to a HCP.[80] Thus existing evidence points to substantial and predictable gaps in the effectiveness of efforts to target HPV vaccination for MSM – likely resulting in missing at least half of the population, and a several year delay in vaccine uptake following sexual debut. These gaps are due in large part to systemic factors, which supports the value of universal HPV vaccination of boys.

Health Equity

In addition to the substantial implementation challenges of targeted vaccination of high-risk populations, a health equity perspective provides further support for universal coverage. One basis of this perspective, as articulated by Burger et al.,[44] is that, "As both genders are responsible for HPV transmission, one may argue on equity grounds that both genders should get vaccinated to share the burden in reducing the risk of HPV-related disease, as well as have equal access to direct vaccine benefits."

An important negative consequence of exclusively targeting women and girls for vaccination is that it conveys or reinforces the message that HPV-related diseases are limited to females, who are thereby represented as responsible for transmitting HPV; the result is the shaming, blaming and stigmatizing of young women, with a disproportionate focus on sexual health as if uniquely a women's issue and on monitoring women's sexual lives.[50,81,82] Young women themselves, regardless of their own HPV vaccination status, indicate a preference that their male partners receive the HPV4 vaccine, as reported in a US survey of 18–26 year old women at an urban university student health clinic.[83]

A second detrimental outcome, from a health equity perspective, of subsidizing HPV vaccination only for girls is that it disregards the importance of men's health,[84] thereby contributing to a broader gendered health gap worldwide that disadvantages men.[85,86] Current healthcare policies demonstrate lack of focus on the sexual health of men, in particular.[57,86] Even those that advocate subsidizing HPV vaccination programs for boys generally invoke preventing cervical cancer in women as the primary rationale, largely overlooking prevention of genital warts, and penile, anal and oropharyngeal cancers in men.[84] In the USA, Healthy People 2020 objectives include increasing HPV vaccine series completion for females aged 13–15 years to 80% by 2020,[87] with no stated objective for HPV vaccination coverage of males.

Third, a health equity perspective brings into consideration the impact of discrimination. Beyond the likely unfeasibility and ineffectiveness of targeting gay and bisexual preadolescents for HPV vaccination, sexual stigma and the devaluation of sex between men may tacitly fuel decisions not to 'waste' money covering men (e.g., the exclusion of MSM in most cost–effectiveness models). A gender-neutral approach to HPV vaccination programs, in addition to promoting gender equity, would be inclusive of gay and other MSM. A health equity argument is also apropos of the devaluation of the sexual lives of people living with HIV, which results in a general lack of sexual health services for this population,[88] and rather a misguided focus on policing their sexual lives,[89] which is antithetical to public health. Thus men at highest risk for HPV infection and subsequent cancers are largely excluded from policy decisions regarding the inclusion of boys in HPV vaccination programs. Notably, in Australia's decision to publicly finance routine vaccination of boys, the greatest impact was expected among MSM, who would be unlikely to benefit from herd immunity as a result of routine vaccination only of girls,[39] and who experience a disproportionately high burden of HPV infection and male HPV-related cancers.