Modeling Cervical Cancer Screening Strategies with Varying Levels of Human Papillomavirus Vaccination

Abstract

Importance: Cervical cancer screening is a lifesaving intervention, with an array of approaches, including liquid-based cytology (LBC), molecular testing for human papillomavirus (HPV) infection, and combinations via parallel cotesting or sequential triage. Maximizing screening efficacy while minimizing overtreatment is vital, especially when considering how the HPV vaccine will affect the interpretation of results. Objectives: To estimate the likely outcomes of different screening modalities and to model how the increasing uptake of the HPV vaccine could affect the interpretation of screening results. Design, Setting, and Participants: This decision analytic model established a simple Markov model to compare the outcomes of different cervical cancer screening modalities on a simulated population of women (aged ≥25 years), considering different levels of HPV vaccination. Main Outcomes and Measures: The number of cases of cervical intraepithelial neoplasia (CIN) grade 2 and 3 detected and missed, the number of false positives, and the number of tests required to achieve a given level of accuracy. Positive and negative predictive values of different modalities were simulated under varying levels of HPV vaccination and therefore HPV prevalence. Results: In a simulated population of 1000 women aged 25 years and older with an HPV prevalence of 2%, HPV-based modalities outperformed LBC-based approaches, detecting 19% more true positives (HPV test sensitivity, 89.9% [95% CI, 88.6%-91.1%]; LBC test sensitivity, 75.5% [95% CI, 66.6%-82.7%]). While cotesting markedly reduced missed cases, detecting 29% more true positives than LBC alone (19.5 [95% CI, 19.3-19.7] per 1000 women screened vs 15.1 [95% CI, 13.3-16.5] per 1000 women screened), it unacceptably increased excess colposcopy referral by 94% (184.4 [95% CI, 181.8-188.0] false positives per 1000 women screened vs 95.1 [95% CI, 93.1-97.0] false positives per 1000 women screened). By contrast, triage testing with reflex screening substantially reduced false positives by a factor of approximately 10 (eg, HPV with LBC triage, 9.6 [95% CI, 9.3-10.0] per 1000 women screened). Over a lifetime of screening, 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). Conclusions and Relevance: In this decision analytic model, the effectiveness of cervical cancer screening was dependent on the prevalence of cervical dysplasia and/or HPV infection or vaccination in a population as well as the sensitivity and specificity of various modalities. Although screening is lifesaving, overtesting or modalities inappropriate to the target population may cause significant harm, including overtreatment.