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 Ն25 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 RELEVANCEIn 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.
Objective: To quantify the impact and accuracy of different screening approaches for cervical cancer, including liquid based cytology (LBC), molecular testing for human papillomavirus (HPV) infection, and their combinations via parallel co-testing and sequential triage. The secondary goal was to predict the effect of differing coverage rates of HPV vaccination on the performance of screening tests and in the interpretation of their results. Design: Modelling study. Main outcomes measured: Different screening modalities were compared in terms of number of cases of Cervical intra-epithelial neoplasia (CIN) grade 2 and 3 detected and missed, as well as the number of false positives leading to excess colposcopy, and number of tests required to achieve a given level of accuracy. The positive predictive value (PPV) and negative predictive value (NPV) of different modalities were simulated under varying levels of HPV vaccination. Results: The model predicted that in a typical population, primary LBC screening misses 4.9 (95% Confidence Interval (CI) 3.5-6.7) CIN 2 / 3 cases per 1000 women, and results in 95 (95% CI: 93-97%) false positives leading to excess colposcopy. For primary HPV testing, 2.0 (95% CI: 1.9-2.1) cases were missed per 1000 women, with 99 (95% CI: 98-101) excess colposcopies undertaken. Co-testing markedly reduced missed cases to 0.5 (95% CI: 0.3-0.7) per 1000 women, but at the cost of dramatically increasing excess colposcopy referral to 184 per 1000 women (95% CI : 182-188). Conversely, triage testing with reflex screening substantially reduced excess colposcopy to 9.6 cases per 1000 women (95% CI: 9.3 - 10) but at the cost of missing more cases (6.4 per 1000 women, 95% CI: 5.1 - 8.0). Over a life-time of screening, women who always attend annual and 3-year co-testing were predicted to have a virtually 100% chance of falsely detecting a CIN 2 / 3 case, while 5 year co-testing has a 93.8% chance of a false positive over screening life-time. For annual, 3 year, and 5 year triage testing (either LBC with HPV reflex or vice versa), lifetime risk of a false positive is 35.1%, 13.4%, and 8.3% respectively. HPV vaccination rates adversely impact the PPV, while increasing the NPV of various screening modalities. Results of this work indicate that as HPV vaccination rates increase, HPV based screening approaches result in fewer unnecessary colposcopies than LBC approaches. Conclusion: The clinical relevance of cervical cancer screening is crucially dependent upon the prevalence of cervical dysplasia and/or HPV infection or vaccination in a given population, as well as the sensitivity and specificity of various modalities. Although screening is life-saving, false negatives and positives will occur, and over-testing may cause significant harm, including potential over-treatment.
Background: Liquid-based cytology (LBC) molecular testing for human papillomavirus (HPV) infection andcombinations are practical modalities for cervical-screening. While life-saving, false positive and negative results are possible, leading to potential over or under treatment. Quantifying this is complicated by the increasing number of options available, including parallel co-testing and sequential triage. As HPV vaccination rates increase, it also has a potential impact onscreening test performance and interpretation of results. Methods:A modelling approach was used to compare different screening modalities in terms of Cervical intra-epithelial neoplasia (CIN) grade 2 and 3 detected and missed, false positives leading to excess colposcopy, and number of tests required to achieve a given accuracy. The positive predictive value (PPV) and negative predictive value (NPV) of different modalities were simulated under varying levels of HPV vaccination. Results:The model suggested that in a cohort of 1000 women, LBC screening typically misses 4.9 cases (95% Confidence Interval (CI) 3.5-6.7), with 95 (95% CI: 93-97%) excess colposcopies. With primary HPV testing, 2.0 (95% CI:1.9-2.1) were missed with 99 (95% CI:98-101) excess colposcopies. Co-testing reduced missed cases to 0.5 (95% CI:0.3-0.7) but dramatically increased excess colposcopy referral (184, 95% CI:182-188). Conversely, triage testing with reflex screening substantially reduced excess colposcopy to 9.6 (95% CI:9.3-10) at the cost of missing more cases (6.4, 95% CI:5.1-8.0). Over a life-time of screening, women who always attend co-testing hada 93.8-100% chance of a false positive over screening life-time. For annual, 3-year, and 5-year triage testing (either LBC with HPV reflex or vice-versa), lifetime risk of a false positive is 35.1%, 13.4%, and 8.3% respectively.Results of this work indicate that as HPV vaccination rates increase, HPV based screening approaches result in fewer unnecessary colposcopies than LBC approaches. Conclusion:Clinical relevance of cervical cancer screening is crucially dependent upon prevalence of cervical dysplasia and/or HPV infection or vaccination in a population, and the sensitivity and specificity of modalities employed. Although screening is life-saving, false negatives and positives inevitably occur, and over-testing runs risk of significant harm, including potential over-treatment. As HPV becomes less common, HPV-based modalities may have greater utility.
Highlights Virtual follow up is acceptable to gynecological oncology patients. Some patients may be reluctant to sit in waiting rooms post pandemic. Lack of physical examination did not affect most patients’ appointments.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.