Cervical cancer screening intensity can be substantially reduced among patients who received human papillomavirus vaccination, with the optimal strategy varying by age at vaccination and vaccine type, according to a modeling study published in Annals of Internal Medicine.
Successful implementation of human papillomavirus vaccination programs worldwide has led to substantial reductions in human papillomavirus infections, cervical precancer, and cervical cancer in vaccinated age cohorts. Although it will take decades for the entire cervical cancer screening population to be protected by vaccination, declining disease prevalence in younger cohorts has implications for screening efficiency and raises questions about how screening recommendations may be adapted to reduce unnecessary procedures, harms, and costs.
Human papillomavirus vaccines are highly effective at preventing cervical precancer and cervical cancer when administered prior to first exposure to the virus. Vaccine effectiveness decreases when vaccination occurs at older ages, as a greater proportion of patients have already been exposed to the virus. These differences in protection have implications for cervical cancer screening strategies.
In a modeling study published in Annals of Internal Medicine, researchers led by Kine Pedersen, PhD, of the University of Oslo, Norway, evaluated cervical cancer screening strategies among patients who received human papillomavirus vaccination at different ages. The researchers used an individual-based health state transition model, calibrated and validated using Norwegian data, to simulate lifetime outcomes. The model followed patients through human papillomavirus infection, cervical precancer, cervical cancer, and death and addressed uncertainty by averaging outcomes across 50 well-fitting natural history parameter sets.
Screening strategies evaluated in the model were based on Norwegian guidelines, which include primary human papillomavirus testing with extended genotyping and reflex cytology triage, along with risk-adapted referral to colposcopy. Analyses were conducted across seven vaccination age groups ranging from 12 to 30 years and were performed separately for the bivalent and nonavalent vaccines. In the modeled scenarios, age at first screening and screening intervals varied by age at vaccination. While the base-case analysis assumed full adherence to screening, additional scenarios incorporated imperfect adherence based on observed participation data in Norway.
Outcomes were assessed using cost-effectiveness and harm–benefit tradeoffs. Cost-effectiveness was evaluated using incremental cost-effectiveness ratios, defined as the additional cost per quality-adjusted life-year gained, with a willingness-to-pay threshold of $55,000. Harm–benefit tradeoffs were defined as the number of additional colposcopy referrals per cervical cancer case averted compared with current screening recommendations for unvaccinated patients. The two metrics produced similar rankings of screening strategies, although the most favorable strategies varied by age at vaccination and vaccine type.
Overall, the modeling results indicated that cervical cancer screening intensity could be reduced in vaccinated cohorts while maintaining effective cancer prevention. For patients vaccinated between ages 12 and 24 years, preferred strategies involved screening every 15 to 25 years, resulting in 2 or 3 lifetime screening tests. For those vaccinated between ages 25 and 30 years, screening every 10 years, for a total of 5 lifetime tests, was preferred. Reduced screening intensity was associated with fewer screening tests, diagnostic procedures, and treatments, demonstrating how screening strategies may be more closely aligned with individual cancer risk.
However, screening recommendations that account for age at human papillomavirus vaccination require reliable individual-level vaccination data and an organized screening infrastructure capable of implementing personalized screening invitations. While this approach is feasible in Norway, which has nationwide vaccination registries and an organized screening program, it presents challenges in other settings. In the US, vaccination registries are incomplete and organized screening does not exist, placing responsibility on patients to recall vaccination history and on physicians to apply screening recommendations modified by individual factors.
As a result, current US screening recommendations primarily consider population-level vaccination coverage and population prevalence of human papillomavirus, cervical precancer, and cervical cancer rather than individual vaccination status. Current American Cancer Society guidelines recommend initiating cervical cancer screening at age 25 years in response to declining disease prevalence in younger populations.
Extended human papillomavirus genotyping offers an alternative risk-adapted approach. Independent of vaccination status, detection of higher-risk types, such as human papillomavirus 16 and 18, warrants more aggressive management, whereas lower-risk types can be managed more conservatively. Vaccinated cohorts are more likely to have negative screening results and, if positive, to harbor lower-risk types. The Norwegian screening program similarly uses genotype-based management strategies that reduce colposcopy referrals among patients with lower-risk infections.
In this context, differences in harm–benefit ratios between 5-year and 10-year screening intervals were limited, whereas cost differences were driven primarily by population-level screening intensity. Over time, as vaccinated cohorts age further into the screening population and herd protection extends to older unvaccinated groups, screening strategies for vaccinated patients and the overall screening population may converge.
The study investigators reported no relevant financial conflicts of interest.
Source: Annals of Internal Medicine
