Women in the United States continue to acquire new human papillomavirus (HPV) infections well into midlife and older age, with more than one in 10 unvaccinated women testing positive within five years, according to a study published last week in the International Journal of Infectious Diseases. HPV infection is a risk factor for cervical and other types of cancer in women.

For the large retrospective cohort study, researchers from software company TriNetX, vaccine maker Merck, and the Yale School of Public Health analyzed electronic health record (EHR) data from more than 305,000 unvaccinated women aged 27 years and older from 2012 to 2024. All participants had a negative HPV test at the start of the study and were followed up for up to five years to assess for new infections.

Over that period, 10.3% of women developed a new HPV infection. Incidence was highest among women ages 27 to 29, with a five-year cumulative rate of 21.1%, then declined steadily through midlife to 6.7% among women ages 55 to 59. Rates rose again in older age-groups, reaching 15.9% among women ages 70 years and older.

Infection rate falls, then rises again with age

Previous research has identified a U-shaped pattern in HPV incidence over the lifespan, with high rates observed in younger women, a dip in midlife, and an increase later in life. 

This pattern may reflect the presence of new exposures later in life due to changes in social behavior and sexual networks as a result of divorce or widowhood. It may also reflect the reactivation of infections acquired years earlier. Age-related changes in immune function may reduce the body’s ability to keep latent viruses in check.

The findings also showed disparities in infection rates by race and insurance status. Five-year incidence was higher among Black (13.3%) and Hispanic women (11.5%) than among White (9.7%) and non-Hispanic women (10.0%). 

Compared with those who had commercial insurance (8.5%), Medicare Advantage (13.0%), or unknown insurance status (14.1%), Medicaid enrollees had the highest incident rate, at 21.6%. This aligns with previous observations that lower socioeconomic status may be associated with lower rates of cervical cancer screening, allowing undetected infections to progress. 

Findings may inform HPV vaccination

The findings may have implications for HPV vaccination in adults. While routine vaccination is recommended through age 26, US guidelines call for shared clinical decision-making for adults ages 27 to 45. 

That recommendation has contributed to relatively low vaccine uptake in this group. “Despite proven efficacy and safety, the shared clinical decision-making recommendation has resulted in low uptake among women aged 27 years and older,” write the researchers. 

“This is really useful when you talk about shared clinical decision making,” Kevin Ault, MD, professor in the Division of Obstetrics and Gynecology at Western Michigan University, tells CIDRAP news, noting that the findings will allow doctors to talk with patients about their specific risk based on their age. “That is really good data to have to be able to tell patients.” Ault was not involved in the study.

This is really useful when you talk about shared clinical decision making.

The findings also have implications for screening. “We know that a quarter of cervical cancer diagnoses occur in women aged 65 years and older, so we need to make sure we are screening [the] older population appropriately and per the guidelines,” said Jessica DiSilvestro, MD, a gynecologic oncologist at Tufts Medical Center, who was not involved in the study. 

“Data has demonstrated that adherence with screening guidelines decreases with age,” she said. “Adherence to guidelines is going to be increasingly important as our aging population increases in volume and more women are aging with a cervix in place.”

While the study had some limitations, including potential misclassifications in the EHR and the inability to distinguish between new HPV cases and reactivation of latent infections, the findings suggest that HPV acquisition continues throughout adulthood, which may inform vaccine decisions.  

“Our findings suggest that HPV vaccination may be under-recognized for its potential clinical impact in this age group,” write the researchers, referring to women aged 27 and older. “With adequate vaccine supply and evidence of safety and efficacy, these results of ongoing acquisition of infections throughout the lifespan may be used by patients, providers, and policy makers to increase the population benefit of HPV vaccination.”