Human papillomavirus vaccination for adults aged 30 to 45 years in the United States: A cost-effectiveness analysis

Abstract

Background: A nonavalent human papillomavirus (HPV) vaccine has been licensed for use in women and men up to age 45 years in the United States. The cost-effectiveness of HPV vaccination for women and men aged 30 to 45 years in the context of cervical cancer screening practice was evaluated to inform national guidelines.

Methods and findings: We utilized 2 independent HPV microsimulation models to evaluate the cost-effectiveness of extending the upper age limit of HPV vaccination in women (from age 26 years) and men (from age 21 years) up to age 30, 35, 40, or 45 years. The models were empirically calibrated to reflect the burden of HPV and related cancers in the US population and used standardized inputs regarding historical and future vaccination uptake, vaccine efficacy, cervical cancer screening, and costs. Disease outcomes included cervical, anal, oropharyngeal, vulvar, vaginal, and penile cancers, as well as genital warts. Both models projected higher costs and greater health benefits as the upper age limit of HPV vaccination increased. Strategies of vaccinating females and males up to ages 30, 35, and 40 years were found to be less cost-effective than vaccinating up to age 45 years, which had an incremental cost-effectiveness ratio (ICER) greater than a commonly accepted upper threshold of $200,000 per quality-adjusted life year (QALY) gained. When including all HPV-related outcomes, the ICER for vaccinating up to age 45 years ranged from $315,700 to $440,600 per QALY gained. Assumptions regarding cervical screening compliance, vaccine costs, and the natural history of noncervical HPV-related cancers had major impacts on the cost-effectiveness of the vaccination strategies. Key limitations of the study were related to uncertainties in the data used to inform the models, including the timing of vaccine impact on noncervical cancers and vaccine efficacy at older ages.

Conclusions: Our results from 2 independent models suggest that HPV vaccination for adult women and men aged 30 to 45 years is unlikely to represent good value for money in the US.

Fig 1. General CISNET-Cervical model schematic.

Both CISNET-Cervical models capture distinct phases of the disease process and interventions, including HPV transmission, cervical cancer natural history, HPV vaccination, and cervical screening, diagnosis, and treatment but differ with respect to the number of health states, HPV genotype categorization, histological cancer types, and data sources used to parameterize the baseline model prior to model calibration to the US setting (Table A in S1 Text). Disease progression in the model is characterized as a sequence of monthly transitions between health states that are descriptive of each patient’s underlying true health, including infection status, grade of CIN, and stage of cancer. CIN, cervical intraepithelial neoplasia; CISNET, Cancer Intervention and Surveillance Modeling Network; HPV, human papillomavirus.

Fig 2. Estimated cervical cancer cases averted.

Compared to status quo human papillomavirus (HPV) vaccination, cervical cancer cases averted were projected to continually increase as vaccination extended to women and men ages 30 years (blue), 35 years (orange), 40 years (grey), and 45 years (yellow). Results were calculated based on model projections over the lifetime of 10-year-old girls born in 1969–2009.