HPV=human papillomavirus. Impact and effectiveness of the quadrivalent human papillomavirus vaccine: a systematic review of 10 years of real-world experience. The comparator was the current National Cervical Screening Program in Australia (every 2 years, conventional cytology, in women aged 18–69 years, no HPV triage testing). Overall, 89% of women in the intervention and control groups completed the baseline survey (Table 1). Incidence at 18, 42, and 72 months is marked by a point and the confidence intervals around it are shown as the point range. Randomization occurred at the central laboratory. The cumulative incidence of CIN2+ was a secondary outcome. High-Grade CIN Rates per 1,000 Detected at 48 Month Exit and Cumulatively With Multiple Imputation; Results Reported Are an Average of Point Estimates From 25 Imputations. Methods An individual-based model of HPV acquisition, natural history, and cervical cancer screening was used to compare … Adding a high‐risk HPV test to cytology for primary cervical screening led to earlier detection of clinically significant preinvasive lesions, resulting in a reduced detection of CIN2+ lesions in subsequent rounds and an increased rate of colposcopy. The first component of this evaluation was funded by the Medical Services Advisory Committee Australia (MSAC application 1122). This article reports the 48-month exit round results of the Human Papillomavirus For Cervical Cancer screening trial (HPV FOCAL), a publicly funded Canadian trial designed to compare the effect of primary HPV testing alone with liquid-based cytology (LBC) screening for the prevention of cervical intraepithelial neoplasia (CIN) grade 3 or worse (CIN3+) in the context of an organized screening program. After 2010, women completed an abbreviated survey that included questions regarding marital status, race/ethnicity, smoking, and lifetime sexual history. Medical Services Advisory Committee (MSAC). Women in the intervention group received HPV testing; those whose results were negative returned at 48 months. Cumulative Cervical Intraepithelial Neoplasia Grade 3 or Greater (CIN3+) and Grade 2 or Greater (CIN2+) Incidence for All Intervention and Control Group Participants Attending 48-Month Exit, Figure 3.  M, Rozendaal  VA; US Preventive Services Task Force. KC oversaw all aspects of study design and conduct. All strategies were associated with further reductions in screening tests, follow-up tests, and precancer treatments compared with current practice (, Some other strategy variations affected results. The Australian Government's MSAC's Protocol Advisory Subcommittee (on which KC sits)—developed the Decision Analytic Protocol for the original analysis. The CIN2+ risk ratio for the intervention compared with the control group was 0.36 (95% CI, 0.24-0.54). Ogilvie GS, van Niekerk D, Krajden M, et al.  AV, Franco Corresponding Author: Gina Suzanne Ogilvie, MD, FCFP, DrPH, BC Women’s Hospital and Health Centre, 4500 Oak St, Room H203G (Box 42), Vancouver, BC V6H 3N1, Canada (gina.ogilvie@cw.bc.ca). Alternative assumptions were also assessed for the effect of call-and-recall on screening adherence for each primary screening approach (, The estimated cost of the existing National Cervical Screening Program in 2015 was $215 million. Conclusions and relevance: Among women undergoing cervical cancer screening, the use of primary HPV testing compared with cytology testing resulted in a significantly lower likelihood of CIN3+ at 48 months. Multiple imputation was based on logistic regression with the total number of imputations set to 25.  M, van Niekerk Schematic diagram of primary screening approach, Predicted age-specific cancer incidence and mortality for selected strategies, Cost-effectiveness of screening strategies compared with current practice with screening ending at age 64 years, Annual number of colposcopies for each primary screening approach with screening ending at age 64 years, Predicted incidence of cervical cancer and mortality, number of colposcopies and treatments for cervical intraepithelial neoplasia grades 2 and 3, and annual and discounted costs of the programme.  JM, Jacobs The denominator for the rate per 1000 is all women randomized into the intervention or control groups who also had valid baseline results. Design, Setting, and Participants  CC=conventional cytology. However, in the safety group, HPV-negative women were recalled for exit screening with LBC at 24 months. Cumulative disease incidence was plotted using 1 minus Kaplan-Meier estimates of disease-free probability. Australia is, thus, expected to be one of the first countries in the world to transition to primary HPV screening within a national organised screening programme.  D, Randomized clinical trial conducted in an organized Cervical Cancer Screening Program in Canada.  et al. Further research is needed to understand long-term clinical outcomes as well as cost-effectiveness. Findings  to download free article PDFs, R: A Language and Environment for Statistical Computing. Detailed trial methods and results have been previously described.11-14 As outlined in Figure 1, round 1 refers to the baseline screen and any 12-month follow-up results in both the intervention and control groups. Furthermore, extensive one-way and probabilistic sensitivity analyses of a range of assumptions were done; findings of the sensitivity analysis indicated that strategies entailing partial genotyping, which were more effective than current practice, remained more effective. Cumulative incidence curves show that women who were HPV negative at baseline had a significantly lower risk of CIN3+ at 48 months compared with cytology-negative women (Figure 3A). Abnormal cytology test results were referred to a cytopathologist for final interpretation and reporting. Women who were HPV negative at baseline were significantly less likely to have CIN3+ and CIN2+ at 48 months compared with women who were cytology negative at baseline. Race/ethnicity was captured based on fixed categories, self-reported, and collected as part of the sociodemographics to ensure randomization was true.  RL, Bentley Among 19 009 women who were randomized (mean age, 45 years [10th-90th percentile, 30-59]), 16 374 (8296 [86.9%] in the intervention group and 8078 [85.4%] in the control group) completed the study. Hence, the number at risk is the same across partitions within primary groups. HPV testing in primary cervical screening: a systematic review and meta-analysis. The baseline colposcopy referral rate reflects what happens when HPV-based screening is first implemented, when both prevalent and incident infections will be detected. The HART trial15 found that the rate of CIN3+ detection in women screened by combined HPV and cytology who had previously been screened by cytology was 8.1 per 1000. Kulasingam One of the concerns for adopting HPV-based screening is the lower CIN2+ specificity of HPV testing compared with cytology, leading to higher screen positive rates and the resulting need for more colposcopies and biopsies. J-BL, KTS, MH, and XMX ran the modelled analyses. This trial, which compares primary HPV testing vs LBC with standardized triage and colposcopy follow-up, found primary HPV testing detected significantly more CIN3+ and CIN2+ cases in the first round and significantly reduced CIN3+ and CIN2+ rates 48 months later. Effects predicted from the initial evaluation model and the final guidelines model (differences compared with current practice shown in parentheses). A comparison of HPV DNA testing and liquid based cytology over three rounds of primary cervical screening: extended follow up in the ARTISTIC trial. Primary HPV screening every 5 years with partial genotyping is predicted to be substantially more effective and potentially cost-saving compared with the current cytology-based screening programme undertaken every 2 years. It was assumed that at least 80% of those randomized would be eligible and return for screening at 48 months.  J, Rozendaal Baseline HPV-negative women had a significantly lower cumulative incidence of CIN3+ at 48 months than cytology-negative women (CIN3+ incidence rate, 1.4/1000 [95% CI, 0.8-2.4]; CIN3+ risk ratio, 0.25 [95% CI, 0.13-0.48]). First, as with every modelled evaluation, our findings are sensitive to specific assumptions—eg, unknown future adherence to screening behaviours, and test characteristics.  et al. We did the evaluation from a health services perspective.  et al; Canadian Cervical Cancer Screening Trial Study Group. Participants underwent a pelvic examination, and cervical specimens were placed in a ThinPrep vial (Hologic Inc). Efficacy of human papillomavirus testing for the detection of invasive cervical cancers and cervical intraepithelial neoplasia: a randomised controlled trial. The CIN3+ risk ratio was 0.42 (95% CI, 0.25-0.69). Among 19 009 women who were randomized (mean age, 45 years [10th-90th percentile, 30-59]), 16 374 (8296 [86.9%] in the intervention group and 8078 [85.4%] in the control group) completed the study.  E, Rodrigues All intervention and control group women who did not have a CIN2+ lesion detected during the trial or otherwise became ineligible (eg, hysterectomy, moved out of province) were invited for the 48-month exit screening. Women who were negative on both LBC and HPV co-testing at 48 months were deemed negative for CIN2+. In our evaluation of the cost-effectiveness of cervical screening in cohorts offered next-generation vaccine in four high-income countries (Australia, the USA, New Zealand, and England). eTable 1. 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