Could the human papillomavirus vaccination be cost-effective in males for the prevention of oropharyngeal cancer?

Abstract

Could the human papillomavirus (HPV) vaccination be cost–effective in males for the prevention of oropharyngeal squamous cell cancer (OPC)? It could be under certain conditions. Research on HPV vaccine has focused mainly on females. However, within the next decade, it is predicted that OPC will surpass cervical cancer as the most common HPV-related cancer, and it is postulated that HPV vaccination may alter the incidence of OPC. The purpose of this editorial is to comment on the potential cost–effectiveness of HPV vaccination in males for OPC prevention by addressing three elements payers often consider when making a decision to fund an intervention and to provide an overview of recent findings regarding the cost–effectiveness of HPV vaccine in males.

Keywords::

• cost–effectiveness analysis
• economic evaluation
• human papillomavirus
• oropharyngeal cancer
• vaccine

Watch out for the newcomer

Within the next decade, it is predicted that oropharyngeal squamous cell cancer (OPC) will surpass cervical cancer as the most common human papillomavirus (HPV)-related cancer [1]. Up to 80% of OPC may be attributable to HPV in developed countries and the incidence of HPV-related diseases such as OPC is increasing (3.6/100,000) [1–4]. OPC, a type of head and neck cancer, is a disease in which cancerous cells grow in the tissue at the base of the tongue, lateral pharyngeal walls, tonsils and soft palate [5]. Treatment with chemoradiation may result in 3-year survival rates of >80% in an advanced stage [6]. It is postulated that HPV vaccination may alter the incidence of OPC.

The vaccine & objective of interest

Quadrivalent HPV vaccine has been shown to be an effective approach in preventing diseases such as cervical cancer, genital warts and potentially OPC [7,8]. A significant association between oral HPV infection and OPC has been established, raising the question of possible benefit for HPV vaccination for the prevention of this disease. Most research on HPV vaccine has focused on females [9], and HPV vaccination in females has been recommended and supported widely as a cost–effective public health program (e.g., 2006 in the US [4] and 2007 in Canada [10]). A confirmed benefit of HPV vaccine for the prevention of HPV-related OPC could lend further weight to the incorporation of HPV vaccination into cancer prevention programs [1,3].

The major question surrounding HPV vaccination currently relates to additional benefits and cost–effectiveness of vaccinating males. Based upon efficacy in sexually active men with reduction of external genital lesions and anal intraepithelial neoplasia by 77.5–91.7% [11], in 2011, the Centers for Disease Control and Prevention Advisory Panel in the US recommended that HPV vaccine be given to males aged 11–12 to prevent genital warts, anal cancer and head and neck cancer [12]. In 2012, the National Advisory Committee on Immunization in Canada recommended HPV vaccination to males aged 9–26 for the prevention of anal intraepithelial neoplasia, anal cancer and anogenital warts [13]. Despite these recommendations, there remain ongoing debates on whether to fund HPV vaccination for males [14].

The purpose of this editorial is to comment on the potential cost–effectiveness of HPV vaccination in males for OPC prevention by addressing the three elements payers often consider when making a decision to fund an intervention (in this case an HPV vaccination program in males) and to provide an overview of the recent findings regarding the cost–effectiveness of HPV vaccine in males.

Big three: effectiveness, cost & value for money

Three elements payers often consider when making a funding decision are effectiveness, cost and value for money. First, when making a decision to fund a program (in this case a HPV vaccination program), a vaccine’s effectiveness and safety are two important factors to consider. An ineffective or unsafe vaccine should not receive funding. Lack of societal acceptance regarding a vaccination program may further influence the program’s effectiveness by adversely affecting uptake rates. Moreover, when discussing a vaccination program, herd immunity is an important component. Based on the concept of herd immunity, vaccinating one part of the population could provide overall population protection, even for those who are not vaccinated [15]. The success of herd immunity depends on achieving a certain uptake rate of vaccination in a given population, in this case, females [15]. Dynamic modeling using information about genital transmission of HPV infection has suggested that a target rate of 80% vaccination in females would be required to achieve herd immunity [9]. Nevertheless, many regions have uptake rates among females below the target rate required to achieve herd immunity [4,14]. Therefore, providing HPV vaccines to males could lead to additional population benefits. Furthermore, HPV vaccination in males would extend the benefit of HPV vaccine to the specific high-risk subgroup of men who have sex with men, where herd immunity from females has no effect. When making a decision to fund a program, decision-makers consider the program’s effectiveness and factors influencing this effectiveness, along with the costs.

Additionally, knowing the cost assists in the decision-making process. In general, one dose of HPV vaccine costs approximately US$500 in North America [2]. In the developed world, this vaccine cost per person may be acceptable, especially for a cancer prevention program (when compared to the price tags of expensive cancer treatments). However, when considering the fact that we have to vaccinate the entire population (i.e., both people who will and will not develop the associated diseases), the cumulative cost may become significant. Generally, the type of costs to consider depends on the perspective of the analysis. For example, the total cost may include cost of treatments associated with the diseases of interest and any related indirect cost. Most costs are likely to be context specific and may increase or decrease the program’s total cost. Based on the chosen perspective, relevant costs should be carefully examined and assessed in relation to the value obtained from the investment.

The third element focuses on the question, ‘What is the value for money?’ To answer this question, value for money may be related to the vaccine’s benefit and/or the decision-makers’ budget. Decision-makers’ willingness-to-pay may depend on the local disease burden. If the burden of disease is significant, decision-makers may have a higher willingness-to-pay threshold than if the burden is not as significant when compared to other concurrent problems. On the other hand, if the patient population is huge, so too would be the budget impact. Value for money is a significant factor affecting funding decisions, especially when the uptake rate and disease burden differ. Decision-makers must weigh the trade-off between providing more support for HPV vaccination to females (in order to increase the uptake rate to obtain the benefit of herd immunity) and extending HPV vaccination to males, keeping in mind that each dollar can be spent only once. Based on the reasoning discussed above, a number of factors should be considered when making a decision to fund a HPV vaccination program in males (a decision that is not answerable by a clinical trial, but that may be examined by a modeling method which incorporates several variables such as uptake rate, cost, target population and herd immunity). We next review recent findings on the cost–effectiveness of HPV vaccine in males.

Recent findings on cost–effectiveness analyses of HPV vaccine in males

Cost–effectiveness analyses of HPV vaccine in males have produced varied results based upon different assumptions [16]; all studies have focused mainly on HPV-related diseases and not specifically on OPC. In general, HPV vaccination in 12-year-old females only led to an incremental cost–effectiveness ratio (ICER) of approximately US$21,000 (2008 USD) per quality-adjusted life year (QALY) in an all-cancer scenario [17]. However, adding males aged 12 years to the female-only vaccination program increased the ICER to almost US$115,000/QALY (approximately a sixfold increase) [9,17]. Expanding the males’ age group to 9–26 would reduce the ICER to approximately US$70,000/QALY [18]. In Austria, vaccinating 65% of males and females was discussed as a possible cost–effective option with an ICER below US$40,000/QALY when including several HPV-associated outcomes [19]. Similarly across studies, cost–effectiveness analyses of HPV vaccine in males were sensitive to factors such as uptake rate and outcomes of interest, which are likely to vary by jurisdiction [9,17]. HPV vaccine in males became economically attractive when the HPV uptake rate in females was low and when the vaccine was targeting more than one HPV-associated outcome [9,17]. To date, published cost–effectiveness analyses assessing male HPV-vaccination have included diseases such as cervical cancer and genital warts, but each used differing assumptions about the cost and incidence of HPV-related cancer, resulting in inconclusive benefit from HPV vaccination in males. No study has primarily focused on OPC. Building on the literature, as a first step, a preliminary cost–effectiveness analysis of HPV vaccination in males specifically for the prevention of OPC was conducted in Canada, focusing only on a male cohort and excluding herd immunity [20]. The goal of this preliminary analysis was to provide an initial finding, which showed that HPV vaccine may be economically attractive under certain contexts. Further research, specifically focusing on OPC, would add insights into the benefit of HPV vaccination in males. In addition, future research on a health intervention with unique characteristics such as vaccine may benefit from a systematic evaluation within the health technology assessment framework [21].

Final thoughts

Could the human papillomavirus vaccination be cost–effective in males for the prevention of OPC? It could be under certain conditions depending on a number of factors. There are common elements to consider when making a decision to fund HPV vaccine in males: the vaccine’s effectiveness, safety, societal acceptance, cost, value for money (e.g., represented by ICER) and additional factors such as herd immunity. The literature on cost–effectiveness of HPV vaccine for males remains equivocal in different regions, depending on the factors mentioned above and on a decision-makers’ willingness-to-pay. Research teams internationally continue to conduct comprehensive and context-specific cost–effectiveness analysis of HPV vaccine in males. In cases where many factors need to be considered when making a decision to fund a program, decision-makers may not only examine a broad range of current evidence but also may focus on evidence specific to their contexts. In the end, one size may not fit all.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.