New real-world data reveals that HPV risk does not end in early adulthood and provides important insights into lifelong infection patterns and what this means for older women’s vaccination decisions.
Study: Incidence of human papillomavirus infection in women aged 27 years and older in the United States: A federated data network study. Image credit: Orawan Pattarawimonchai/Shutterstock.com
recent international infectious disease journal The study looked at how often unvaccinated U.S. women aged 27 and older develop newly detected anogenital HPV infections. This information may assist in 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 and cancers such as cervical and oropharyngeal cancer. Most HPV infections are asymptomatic and resolve without intervention, but persistent infection can cause severe disease.
More than 42 million people in the United States are currently infected with HPV, and approximately 13 million people are newly infected each year. HPV is the most common sexually transmitted disease in Japan, and approximately 85% of people are expected to contract it during their lifetime. Each year, HPV is associated with approximately 45,000 cancer cases and 200,000 cervical precancers, resulting in significant healthcare costs.
Prophylactic HPV vaccination is an important prevention strategy against HPV infection and its associated diseases. The U.S. Centers for Disease Control and Prevention’s (CDC) Advisory Committee on Immunization Practices (ACIP) recommends routine vaccination with the 9-valent HPV vaccine. This vaccine targets HPV types that cause about 90% of cervical cancers and anogenital warts and is recommended for everyone between the ages of 11 and 12, with catch-up vaccination recommended up to age 26.
In 2018, the U.S. Food and Drug Administration (FDA) expanded approval of the HPV vaccine to adults ages 27 to 45. ACIP recommends shared clinical decision-making regarding vaccination for this elderly group, as they are more likely to have previously been exposed to HPV, which may reduce the overall benefit.
Due to the lack of large, nationally representative studies, the incidence of newly detected HPV infections among unvaccinated individuals aged 27 years and older in the United States remains incompletely understood, especially in large real-world datasets. Such evidence is critical to inform clinical decisions and vaccination policy for adults aged 26 years and older.
Assessment of HPV prevalence among older women in the United States
The current study used electronic health records (EHR) and linked claims data to assess the 5-year cumulative incidence of HPV infection in women aged 27 years and older. Two data sources were used. The TriNetX Dataworks-USA network, which provides de-identified electronic medical record data from U.S. healthcare providers, and the Linked EHR plus Closed Claims network, which combines EHR and claims data for commercial, Medicaid, and Medicare Advantage members.
Both sources include demographic and clinical information. Dataworks’ sample is larger but limited to in-network care. The linked sample is more comprehensive, but smaller. Dataworks samples were used for the primary analysis and linked samples were used for the secondary analysis.
Eligible women were 27 years or older who visited a healthcare facility between January 1, 2012 and January 6, 2024, had at least one year of 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, 5 years of observation, or disenrollment (linked samples only).
Risk of HPV infection varies by age, race, and region
The study included 305,974 women in the Dataworks-USA network with a median follow-up of 3.5 years. Most participants had a follow-up HPV test approximately 2.8 years after their initial test, and 29% had at least 5 years of follow-up.
Baseline characteristics of the Dataworks sample revealed that the average age of participants was 44 years. Approximately 69% of participants were white and more than 80% were non-Hispanic.
Over a 5-year period, HPV prevalence peaked at 21.1% in women aged 27 to 29 years, decreased to 13.4% in women aged 30 to 34 years, reached a low of 6.7% in women aged 55 to 59 years, and then increased again in older age. Black women and women living in the South had the highest rates. Hispanic women also had higher rates of morbidity than non-Hispanic women. The cumulative incidence increased from 1.4% after 1 year to 10.3% after 5 years, decreased until age 59, and increased again after age 70.
The linked sample included 9,772 women with both EHR and insurance data. Median follow-up was 4 years, and 32.7% had at least 5 years of observation. Approximately 78.1% of participants had one follow-up HPV test, with a median interval of 2 years. The average age was 45 years. 67.3% were white, 80.0% were non-Hispanic, and 67.9% had commercial insurance.
In the linked sample, the 5-year cumulative incidence of HPV infection was 12.3%. Trends by age mirrored those in the Dataworks group. Among subgroups, black women had the highest incidence at 17.3%, Medicaid participants at 21.6%, and Hispanic women at 12.7%, compared with 10.4% among non-Hispanic women.
HPV prevalence continues to be high among older adults and minority women
As revealed in this study, newly detected HPV infections occur throughout the lifespan, not only in young adults but also in women over 27 years of age. Incidence increased again after age 60, but was still highest among women ages 27 to 29, black women, and Medicaid recipients.
The authors note that some incident detections, especially in older women, may reflect reactivation of latent HPV infection rather than entirely new infections, and may also be influenced by changes in sexual behavior, such as new partnerships later in life.
These findings highlight the importance of continued awareness. Informed discussions about HPV vaccination among eligible adults aged 27 to 45 years under shared clinical decision making. Continued efforts by patients, healthcare providers, and policy makers are essential to reduce the burden of HPV-related cancers and diseases.
The study has several limitations, including its reliance on EHR data, which may miss care received outside the participating health system, vaccination status may not be fully captured, and limited ability to distinguish between new infections and reactivation. This cohort is drawn primarily from the health care-seeking population and may not be fully representative of the broader U.S. population. This study was sponsored by Merck, and several authors are affiliated with Merck or TriNetX, which should be considered when interpreting the findings.
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