Cost Effectiveness of HPV Vaccine for Boys

Abstract

Source: Kim JJ, Goldie SJ. Cost effectiveness analysis of including boys in a human papillomavirus vaccination programme in the United States. BMJ. 2009; 339: b3884; doi: 10.1136/bmj.b3884Researchers from Harvard School of Public Health assessed the cost effectiveness of adding preadolescent boys to the human papillomavirus (HPV) vaccination program currently recommended for preadolescent girls in the US. Direct and indirect medical costs associated with HPV vaccination and the costs for screening, diagnosis, and treatment for precancerous and cancerous lesions related to HPV infection were considered. Costs related to cervical, vulvar, vaginal, penile, anal, and oropharyngeal HPV-related cancers and genital warts were also included.For the analyses, transmission of multiple HPV genotypes in the population were simulated, taking into account the impact of immunity after infection. Rates of development of HPV-related precancerous lesions (eg, cervical intra-epithelial neoplasia) and likelihoods of natural regression versus progression of these lesions to invasive cancer were built into the models. In addition, the various models included different assumptions regarding vaccine efficacy, number of years of protection from immunization, and costs of vaccination programs. Vaccination of both sexes was compared with immunization of girls only in the contexts of several different screening programs for cervical cancer. The societal perspective was used for cost attribution. Costs were expressed per quality-adjusted life year (QALY) gained in 2006 US dollars.Using assumptions of 75% vaccination coverage and complete, lifelong protection against HPV types 16 and 18 in girls, the analyses indicated that vaccinating 12-year-old girls consistently cost <$50,000 per QALY gained compared with screening alone, and often far less, across a range of other assumptions. Adding boys to the vaccine program increased cost per QALY to >$100,000 in all but a few scenarios. Vaccinating both girls and boys fell below a threshold of $100,000 per QALY only under scenarios of either 1) high, lifelong efficacy against all types of HPV-related diseases or lower vaccine coverage rates (and thus less vaccine cost), or 2) lower vaccine price. Many scenarios generated costs of >$200,000 per QALY for vaccination of both sexes.The authors conclude that the costs of including boys in an HPV vaccination program exceed established thresholds of good value for money, even under favorable conditions of vaccine protection and health benefits.1HPV types 16 and 18 cause ~70% of cervical cancers worldwide and substantial proportions of anogenital and oropharyngeal tract cancers.2,3 HPV types 6 and 11 cause most anogenital warts and respiratory tract papillomas.4 Both available HPV vaccines appear highly effective in preventing the precancerous lesions associated with cervical cancer.5–7 To date these vaccines are recommended only for females. Should the vaccine now be recommended for males? (The provisional recommendations are available on-line.6 The 2010 Recommended Childhood and Adolescent Immunization Schedule was published in January.8)Most childhood vaccines are designed to prevent acute illness and its complications. Many, such as MMR, cost far less than the health care dollars that would be required to treat those infected without them. Others, such as varicella vaccine, save money when societal costs such as parent time lost from work are considered. HPV vaccination differs because it is predicated primarily on prevention of long-term consequences (eg, cervical and other cancers) of clinically quiescent acute infection. The costs of vaccination are additive to costs of existing screening programs for cervical cancer, which might be reduced in frequency if vaccine use was widespread but not eliminated due to risks from oncogenic HPV types not included in the vaccines.A widely used (but imperfect) method to decide if the cost of this vaccine for boys is worthwhile is to estimate cost of one QALY gained. Costs of various interventions then can be compared. A year spent in perfect health has a value of 1.0, while a year with illness or disability throughout, or in part, has a value between 0 (death) and 1. A threshold of $50,000 is most commonly cited as the point below which an intervention is “cost-effective.”1This study confirms that by this definition vaccinating only girls achieves cost-effectiveness, but adding boys to the program exceeds $100,000 per QALY gained. Although vaccinating boys would lead to reductions in HPV-related diseases in boys and could further reduce cervical cancer by 2% over vaccinating girls alone,9 costs of these benefits seem exceedingly high. Two of three prior studies evaluating the economics of male HPV vaccination that used comparable assumptions reached similar conclusions.9,10 In the third study, the cost of vaccinating both sexes was estimated at $45,056 per QALY, but higher efficacy rates in boys and lower sensitivity values for cytologic screening were assumed.11 It should be noted that the authors of the study were listed as employees of one of the HPV vaccine manufacturers.The QALY-based modeling approach used in the current study is inherently utilitarian and did not consider differential benefits among population subgroups. Some families also may consider the out-of-pocket price of HPV vaccine worthwhile for their sons to reduce their future risk of genital warts and other HPV-related health conditions. Economic modeling analyses like these require many assumptions, and changes in population behaviors, financial resources for health care, and vaccine price all could affect what is, in the end, a value judgment.Most childhood vaccines have been recommended for universal use in the US. So we have had less experience dealing with permissive recommendations, when vaccination is an option to be weighed by physicians, patients, parents and, importantly, payers. Many factors must be weighed: risk factors for infection and its sequelae; individual values; economic circumstances including insurance coverage. For example, for boys who have sex with boys the risks of HPV infection and its sequelae are far, far greater than for the general population, and for such youth we would argue HPV vaccination is indicated – but without a formal ACIP recommendation would it be covered by Medicaid or other payers?For other boys without such risk factors, is protection against HPV worth about $400? Compared with what: a state of the art football helmet, the cost of Weight Watchers, or tuition for a driver’s education course? Rising health care costs require attention to cost: benefit analyses, but critically evaluating the underlying assumptions and methodology of such studies is challenging. As modern vaccinology enables production of new vaccines, we anticipate additional permissive recommendations will be forthcoming from the ACIP and AAP. This will add to the complexity of decision-making for pediatricians who already have difficulty applying a single standard of care to all of their patients, irrespective of their socioeconomic circumstances.