Pop Health Data Models Refine Chronic Disease Prevention, Screening

In a recent study, researchers used population health strategies to examine changes in human papillomavirus (HPV)-based cervical screening modalities as HPV vaccination becomes more widespread, promoting chronic disease prevention.

The goal of the study was to estimate outcomes of different screening methods to show how an increasing uptick in HPV vaccination rate could impact the interpretation of screening results. Since the development of high-quality national screening programs, there has been an estimated 80 percent reduction in mortality for women older than 25 years with squamous cell carcinoma.

“HPV DNA testing as a screening tool has superior sensitivity in detecting cervical intraepithelial neoplasia (CIN) grade 2 and 3.5,” the researchers stated in the JAMA Network report. “Less emphasis has been placed on the high prevalence of HPV infection, and suboptimal implementation of primary HPV screening may result in increased referrals to colposcopy. As national programs transition to HPV testing, this necessitates reeducating the screened population regarding the benefits and limitations of cervical screening.”

According to the report, false negatives have proven to have detrimental consequences for women who receive cervical screenings. For this reason, it is critical to determine what is an acceptable false negative rate is within programs. The acceptable false negative rate is further complicated by legal standards in the United Kingdom and Ireland requiring “absolute confidence” in negative tests.

Due to the HPV vaccine reducing the prevalence of CIN globally, the future of screening has become crucial. Recently, a Scottish cohort found an 88 percent reduction in cervical cancer disease due to vaccination, and a study in Australia suggests cervical cancer could be almost eliminated in the coming decades, the JAMA authors reported.

“As prevalence decreases, the proportion of positive results that will be false positives will increase relative to the true positives, with emerging evidence of this in younger women. Implications of increased vaccination uptake must also be considered for any viable screening modality, as these shape the interpretation of results and clinical judgement,” the study stated. 

The study used a population health method to simulate 1,000 women aged 25 years and older with an HPV prevalence of 2 percent. Within the population, the HPV-based modalities performed better than the liquid-based cytology (LBC)-based approaches, detecting 19 percent more true positives.

When the two models were cotested, the researchers discovered 29 percent more true positives than LBC alone. However, it also exponentially increases excess colposcopy referral by 94 percent. By contrast, using the triage testing approach with reflex screening substantially reduced false positives.

Examining the data, researchers found that “reflex approaches with appropriate test intervals maximized therapeutic efficacy; as HPV vaccination rates increased, HPV-based screening approaches resulted in fewer unnecessary colposcopies than LBC approaches (HPV testing, 80% vaccine coverage: 44.1 [95% CI, 40-45.9] excess colposcopies; LBC testing, 80% vaccine coverage: 96.9 [95% CI, 96.8-97.0] excess colposcopies),” the study stated.

The study concluded that the effectiveness of cervical cancer screenings changed with the prevalence of the population-level of HPV vaccination. Additionally, the effectiveness of the selected testing modality was impacted.

In order to reduce the cervical cancer mortality rate, the study states that screening is a vital undertaking. All strengths and limitations of the process must be examined in order to maximize the benefits.

“This analysis should prove useful in optimizing approaches and demonstrating complexities of different implementations so that informed decisions can be made. Moreover, the balance of benefits and harms from screening will inevitably decrease in parallel with the decrease in cervical lesion prevalence, which will necessarily lead to rethinking what we accept today as test characteristics, age at start, age to exit, and frequency of screening,” the study stated.