Widespread vaccination against human papillomavirus (HPV) has already reshaped the prevention landscape for cervical cancer. Now, a new modeling study from the University of Oslo suggests it may be time to rethink one of the most entrenched pillars of cancer prevention: how often vaccinated women need to be screened.
In a paper from Annals of Internal Medicine based on a large-scale decision analytic model, researchers show that women who received the HPV vaccine—especially at younger ages—could safely undergo cervical cancer screening far less frequently than current guidelines recommend, without sacrificing health benefits. In some cases, optimal screening may involve only two or three tests over a lifetime.
“What our study investigates is, given that you have received the HPV vaccine, how should you screen for cervical cancer,” said Kine Pedersen, PhD, the study’s lead author, in an interview. “And how should the screening program be designed if you tailor the guidelines by age of HPV vaccination receipt and individual vaccination status?”
Screening guidelines built for an unvaccinated era
Current cervical cancer screening recommendations in both the United States and Norway call for HPV-based screening every five years, beginning at age 25. Over a lifetime, that can amount to roughly nine screening tests per person.
“These guidelines were designed primarily for unvaccinated women,” Pedersen explained. “The majority of women who are currently in screening age were past the age of vaccination when the HPV vaccine was introduced.”
That reality is changing rapidly. In many countries, women vaccinated as adolescents—or even earlier—are now entering the age range when screening begins. Yet screening guidelines have largely remained unchanged, even as HPV vaccination has sharply reduced the risk of acquiring the infections that lead to cervical cancer.
“The HPV vaccine prevents new HPV infections,” Pedersen said. “So the earlier you receive the vaccine, the more of a preventive effect it has.”
Because HPV is sexually transmitted, vaccination before exposure offers the strongest protection. Vaccination later in adolescence or adulthood can still reduce risk by preventing infections acquired after vaccination, but it cannot eliminate infections already present. Importantly, HPV-related cervical cancer can take 15 to 20 years to develop, making it difficult to directly observe the long-term interaction between vaccination timing and cancer outcomes.
Modeling long-term outcomes
To address this challenge, the researchers turned to a mathematical simulation approach rather than waiting decades for empirical data. Using an individual-based state transition model—in this case the Harvard Cervical Cancer (Harvard CC) model developed at Harvard University and refined over more than 20 years—the team simulated lifetime outcomes for hypothetical cohorts of women vaccinated between ages 12 and 30.
“We use an established decision analytic framework where we develop a state transition model that reflects the underlying natural history of disease,” Pedersen said. “We try to reflect everything we know about the disease and everything we know about the intervention.”
The model draws on data from vaccine trials, clinical studies, systematic reviews, and real-world screening programs. It was extensively validated by comparing its projections against data not used to build the model, a critical step for ensuring credibility in policy modeling.
The researchers compared the current five-year screening interval with a wide range of alternatives, including screening every seven, ten, fifteen, twenty, or even twenty-five years, as well as strategies involving only two lifetime screening tests. Outcomes were evaluated in terms of health benefits, resource use, cost-effectiveness, and potential harms such as unnecessary follow-up procedures.
Fewer screens, same protection
Across all vaccination age groups and for both bivalent (e.g., Cervarix) and nonavalent (e.g., Gardasil 9) HPV vaccines, less frequent screening was consistently preferred under a standard cost-effectiveness threshold. However, the optimal strategy varied depending on the age at which vaccination occurred.
The researchers proposed that for women vaccinated at ages 25 to 30 years (with either vaccine type), the number of lifetime screening tests could be reduced from nine (current recommendation) to five, with screening at 10-year intervals starting at age 25 years. For women vaccinated between the ages of 12 and 24 years (either vaccine type), preferred strategies further reduced the number of lifetime screening tests to two or three by delaying the age at which screening begins and extending the screening intervals. Women vaccinated later still benefited from extended intervals, though not to the same degree.
The findings remained robust even when the researchers accounted for imperfect screening adherence and conservative assumptions about vaccine cross-protection. Importantly, fewer screenings were associated not only with cost savings but also with reduced harms, including fewer unnecessary colposcopy referrals.
A signal for change
Pedersen emphasized that the study is not a call for immediate changes to clinical guidelines, but rather a signal that the prevention landscape has fundamentally shifted.
“After having implemented HPV vaccines, that’s changing the landscape of cervical cancer prevention,” she said. “This paper signals that we need to start thinking about how we can adapt cervical cancer screening programs for individuals who have received the vaccine, given their individual vaccination status.”
She stressed that any move toward de-intensified screening must be paired with accumulating empirical evidence and implemented gradually.
“Of course, it needs to be paired with the empirical evidence,” Pedersen said. “But it’s time to start thinking about how to adapt the screening program, given that we have these effective vaccines.”
Implications for policy and prevention
Although the model was parameterized using data from Norway, the findings are highly relevant to other high-income countries, including the United States, where cervical cancer risk and vaccine uptake are similar. As vaccinated cohorts age into screening eligibility, policymakers will increasingly face questions about how to balance prevention, cost, and patient burden.
Taken together, the study suggests that HPV vaccination not only reduces cancer risk, but may also dramatically reduce the lifelong burden of screening—strengthening the public health case for vaccination while opening the door to more personalized prevention strategies.
As Pedersen put it, “It’s about adapting our prevention tools to the reality we now have.”
