New real-world data reveal that HPV risk doesn’t end in early adulthood, offering critical insights into lifelong infection patterns and what they mean for vaccination decisions in older women.
Study: Incidence of human papillomavirus infections in women aged 27 years and older in the US: A federated data network study. Image credit: Orawan Pattarawimonchai/Shutterstock.com
A recent International Journal of Infectious Diseases study examined how often unvaccinated US women aged 27 and older developed newly detected anogenital HPV infections. This information could guide vaccination decisions for adults in this age group.
HPV prevalence and prevention in adults
HPV is a group of viruses, some of which are transmitted through sexual contact and can cause genital warts or cancer, such as cervical and oropharyngeal cancers. Most HPV infections are asymptomatic and resolve without intervention, but persistent infections can lead to serious disease.
In the United States, over 42 million people are currently infected with HPV, with about 13 million new cases every year. As the most common sexually transmitted infection in the country, HPV is expected to affect about 85 % of people during their lifetime. Each year, HPV is linked to nearly 45,000 cancer cases and 200,000 cervical precancers, resulting in significant healthcare costs.
Prophylactic HPV vaccination is an important preventive strategy against HPV infection and its related diseases. The Centers for Disease Control and Prevention (CDC)’s Advisory Committee on Immunization Practices (ACIP) recommends routine vaccination with the 9-valent HPV vaccine. This vaccine targets the HPV types responsible for about 90 % of cervical cancer and anogenital warts, and is recommended for all individuals aged 11–12 years, with catch-up vaccination through age 26.
In 2018, the US Food and Drug Administration (FDA) expanded approval of the HPV vaccine to include adults aged 27–45 years. For this older age group, the ACIP recommends shared clinical decision-making regarding vaccination, as the overall benefit may be reduced due to the higher likelihood of prior HPV exposure.
Due to a lack of large, nationally representative studies, the incidence of newly detected HPV infections among unvaccinated individuals aged 27 years or older in the US remains incompletely understood, particularly in large real-world datasets. Such evidence is crucial for informing clinical decisions and immunization policy for adults aged 26 and older.
Assessing HPV incidence among older women in the United States
The current study assessed the five-year cumulative incidence of HPV infection in women aged 27 and older using electronic health records (EHRs) and linked claims data. Two data sources were used: the TriNetX Dataworks-USA network, which provides de-identified electronic health record data from US healthcare organizations, and the Linked EHR plus Closed Claims network, which combines EHRs with claims data for commercial, Medicaid, and Medicare Advantage members.
Both sources contain demographic and clinical information. The Dataworks sample is larger but limited to in-network care; the Linked sample is more comprehensive but smaller. The primary analyses used the Dataworks sample, while the Linked sample was used for secondary analyses.
Eligible participants were women aged 27 or older who had a healthcare visit between January 1, 2012, and January 6, 2024, had at least one year of prior EHR data, and had a negative HPV test result at baseline. Follow-up began at the index date and continued until the earliest occurrence of a positive HPV test, last negative test, HPV vaccination, death, five years of observation, or insurance disenrollment (for the Linked sample only).
HPV infection risk varies by age, race, and region
The study included 305,974 women from the Dataworks-USA network, with a median follow-up of 3.5 years. Most participants underwent a follow-up HPV test about 2.8 years after their initial test, and 29 % had at least five years of follow-up.
Baseline characteristics of the Dataworks sample revealed an average participant age of 44 years. Approximately 69 % of participants were White, and over 80 % were non-Hispanic.
Over five years, HPV incidence peaked at 21.1 % for women aged 27–29, declined to 13.4 % for those aged 30–34, and reached a low of 6.7 % among women aged 55–59, before increasing again in older ages. Black women and women residing in the South had the highest incidence rates. Hispanic women also experienced higher rates compared to non-Hispanic women. Cumulative incidence rose from 1.4 % after one year to 10.3 % after five years, declining until age 59 and increasing again after age 70.
The Linked sample included 9,772 women with both EHR and insurance data. The median follow-up was four years, and 32.7 % had at least five years of observation. Around 78.1 % of participants had a single follow-up HPV test, with a median interval of two years. The mean age was 45 years; 67.3 % were White, 80.0 % were non-Hispanic, and 67.9 % had commercial insurance.
In the Linked sample, the five-year cumulative incidence of HPV infection was 12.3 %. Age-specific trends mirrored those in the Dataworks group. Among subgroups, Black women had the highest incidence at 17.3 %, Medicaid enrollees at 21.6 %, and Hispanic women at 12.7 % compared to 10.4 % for non-Hispanic women.
High HPV incidence persists in older and minority women
As the current study revealed, newly detected HPV infections occur among women aged 27 and older throughout the lifespan, not just in younger adults. Incidence increased again after age 60, though it remained highest among women aged 27–29, as well as among Black women and Medicaid recipients.
The authors note that some incident detections, particularly in older women, may reflect reactivation of latent HPV infection rather than entirely new acquisition, and could also be influenced by changes in sexual behavior such as new partnerships later in life.
These findings highlight the importance of continued awareness and informed discussions about HPV vaccination among eligible adults aged 27–45 years under shared clinical decision-making. Ongoing efforts by patients, health care providers, and policy makers are essential to help reduce the burden of HPV-related cancers and diseases.
The study has several limitations, including reliance on EHR data, which may miss care received outside participating health systems, potential under-ascertainment of vaccination status, and limited ability to distinguish new infections from reactivation. The cohort, drawn largely from healthcare-seeking populations, may not fully represent the broader US population. The study was funded by Merck, with several authors affiliated with Merck or TriNetX, which should be considered when interpreting the findings.
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