By Rebecca B. Perkins, MD, MSc

Associate Professor, Department of Obstetrics and Gynecology, Boston University School of Medicine/Boston Medical Center, Boston

SYNOPSIS: Researchers found extending the upper limit of HPV vaccination to age 30 to 45 years is not cost-effective.

SOURCE: Kim JJ, Simms KT, Killen J, et al. Human papillomavirus vaccination for adults aged 30 to 45 years in the United States: A cost-effectiveness analysis. PLoS Med 2021; Mar 11.

Human papillomavirus (HPV) vaccination is considered a powerful tool for cancer prevention. Clinical trials and long-term population-level follow-up studies have demonstrated decreases in precancers and cancers.1-3 However, these findings are based largely on HPV vaccination in adolescence, before exposure to oncogenic HPV types.

Recently, HPV vaccination received FDA approval for use in adults age 26 to 45 years, and the CDC Advisory Committee on Immunization Practices recommended shared decision-making in this age group.4 The recommendation is based on study findings of a reduced composite endpoint for genital HPV disease among previously uninfected women, and notes vaccination is not routinely recommended for this age group because of a lack of anticipated population-level benefit.4

The study by Kim et al describes the findings of two microsimulation models of HPV infection. In these models, which have been validated previously against several population-level datasets, individuals can move between states of no infection, infection, precancer, and cancer. HPV-related diseases in the models included cervical, anal, oropharyngeal, vulvar, vaginal, and penile cancers, as well as genital warts. The models compared the cost effectiveness of HPV vaccination in women through age 26 years and in men through age 21 years with vaccination through ages 30, 35, 40, and 45 years. Over a wide range of model assumptions and sensitivity analysis, HPV vaccination at older ages was not cost-effective. Incremental cost-effectiveness ratios (ICERs) ranged from $315,700 to $440,600 per quality-adjusted life year (QALY) gained, which exceeds the commonly accepted upper threshold of $200,000 per QALY. This supports current CDC recommendations not to routinely recommend HPV vaccination for this age group.


This study adds important evidence to help providers, patients, and policymakers decide when to discuss, accept, and reimburse HPV vaccination among patients age 27 to 45 years. The effectiveness of HPV vaccination at preventing precancer and cancers declines in older adolescence, with several studies demonstrating significant drops in effectiveness after age 18.5,6 The people to most likely to benefit from HPV vaccination are those who have not been exposed to oncogenic HPV, and are likely to be exposed in the future. This applies broadly to adolescents who have not begun sexual activity. However, since most people acquire HPV within a few years of beginning intercourse, relatively few adults are in this category.7-9

Primary care clinicians discuss health maintenance with patients, including cancer screenings, flu vaccination, smoking cessation, and cardiovascular disease prevention.10 The Kim et al study supports current guidelines (i.e., clinicians should not discuss HPV vaccination routinely with adult patients).4 Guidance is limited regarding which patients may benefit from HPV vaccination as adults. The American College of Obstetricians and Gynecologists (ACOG) supports CDC recommendations against routine vaccination. ACOG notes women most likely to benefit from vaccination include younger women, those not in committed monogamous relationships, and those recently diagnosed with sexually transmitted infections.11 One specific population that may benefit from HPV vaccination is patients who have been treated for cervical intraepithelial neoplasia, since data indicate post-treatment vaccination may be beneficial to prevent recurrence.12,13 One meta-analysis showed a 64% reduction in recurrence of cervical intraepithelial neoplasia grade 2 or higher.14 The creators of a randomized, controlled trial in the Netherlands are exploring this question, which should provide more definitive data on whether vaccination should be recommended routinely after precancer treatment.15 


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