Plots were truncated at 24 months after their 48-month screening and based on all women randomized regardless of attendance at all trial recommended screening. Previous studies found the benefit of HPV and cytology co-testing was based primarily on the contribution of HPV,21 which this trial now prospectively validates. Results for four developed countries. We report a comprehensive modelled assessment of the effectiveness, resource utilisation, and cost-effectiveness of several cervical screening approaches in the context of the National HPV Vaccination Program in Australia. Although some evidence shows that HPV vaccines provide a degree of cross-protection against HPV types 31, 33, 45, and 58, their quantitative effect has yet to be defined, and the long-term duration of cross-protection has not been determined. The CIN3+ risk ratio for the intervention group compared with the control group was 0.25 (95% CI, 0.13-0.48). We found that the renewed Australian National Cervical Screening Program will reduce cervical cancer incidence and mortality and is cost-saving when compared with the current programme. Therefore, results may underestimate the effect of the trial findings by underrepresentation of underscreened women who may face the highest risk of cervical cancer. After incorporating the new clinical management guidelines, a 31–36% long-term reduction in incidence and mortality compared with current practice was predicted in unvaccinated cohorts, corresponding to 265 fewer cases of cancer and 82 fewer deaths if steady-state rates are applied to the projected female Australian population in 2017 (. We used an extensively calibrated modelling platform to assess cervical screening strategies in both vaccinated and unvaccinated cohorts, did an analysis of many screening strategies, and undertook an extensive sensitivity analysis. Incidence at 18, 42, and 72 months is marked by a point and the confidence intervals around it are shown as the point range. However, the outcomes presented here represent long-term predictions. Unnecessary colposcopies potentially cause unintended harm for women and increased costs to health care systems.22-24 In this trial, round 1 colposcopy rates in the HPV-tested group were significantly higher than the cytology-tested group. The number of colposcopies per year was calculated by applying the steady-state rates to the projected female Australian population in 2015. Almost all screening strategies were less costly than current practice and many were also more effective, in both unvaccinated and vaccinated cohorts (. 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. Ethics approval was obtained from the University of British Columbia Clinical Research Ethics Board (H06-04032) and written consent was obtained from all participants.  WK, Ault LSV and KC wrote the report, with input from J-BL, MAS, and KTS. We did each cost and effectiveness calculation for each possible variation within each of the six primary screening approaches. Between January 1, 2008, and December 31, 2010, 6104, 6214, and 6204 women were recruited to the control, safety, and intervention groups, respectively.14 After January 1, 2011, a further 3353 and 3348 women were recruited to the control and intervention groups, respectively. A total of 19 009 women were randomized to the intervention (n = 9552) and control (n = 9457) groups. J-BL, KTS, MH, and XMX ran the modelled analyses. Huh This trial also confirmed that women who were HPV negative at baseline have lower rates of CIN2+ at 48 months than cytology-negative women at baseline. Customize your JAMA Network experience by selecting one or more topics from the list below. Concept and design: Ogilvie, van Niekerk, Krajden, Smith, Martin, Peacock, Stuart, Franco, Coldman. Dr Franco reported receiving grants, personal fees, and/or nonfinancial support from Merck, GlaxoSmithKline, and Roche outside the submitted work. However, with the advent of the ability to test for HPV, cervical cancer screening now includes three approaches: HPV testing, which looks for the presence of high-risk HPV types in cervical cells; Pap testing; and HPV/Pap cotesting, which checks the same cell sample for both high-risk HPV types and cervical cell changes. Inclusion criteria were women in British Columbia, Canada, with a personal health number, aged 25 to 65 years who had not had a Papanicolaou test in the previous 12 months, were not pregnant, were not HIV positive or receiving immunosuppressive therapy, and had no history of CIN2+ in the past 5 years; did not have invasive cervical cancer; or did not have total hysterectomy. • HPV testing, similar to traditional cytology testing (Pap smear), requires an organized program in which high screening coverage, follow-up care and quality control are achieved. The primary objective of this study was to evaluate primary HPV testing for cervical cancer screening in an organized program setting. The cumulative incidence of CIN2+ was a secondary outcome. Histopathological assessment was blinded to HPV and cytology results. Quiz Ref IDOne 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. Get free access to newly published articles. The cohort was highly educated and primarily from 2 geographic regions in the province with limited representation from rural and remote populations. For our evaluation, we assumed that no screening occurs in women younger than 25 years. Recruitment occurred from January 2008 through May 2012. Our website uses cookies to enhance your experience. Nevertheless limitations remain and new screening methods are emerging. In this trial, by 48 months, among women screened for cervical cancer with HPV testing without cytology, there were significantly fewer CIN3+ and CIN2+ cases compared with women who were screened with cytology alone at baseline. © 2021 American Medical Association. Those in which an invitation was sent at age 25 years further reduced overall mortality by an additional 1–3% relative to the same strategy without an active invitation at age 25 years (, Further analyses were done to assess the effect of retaining a screening end-age of 69 years, for all strategies (, Extending the screening interval to 6 years for HPV screening strategies is predicted to increase incidence by 3–4% for both unvaccinated and vaccinated cohorts, relative to the same strategy with screening every 5 years. The second limitation is that we did not account for cross-protection against non-vaccine targeted HPV types. A total of 19 009 women were randomized to the intervention (n = 9552) and control (n = 9457) groups. We then did additional analyses for all screening strategies to ascertain the effect of retaining an end-age of 69 years and of extending HPV testing intervals from every 5 years to every 6 years. The round 1 risk ratio for CIN2+ in the intervention vs control group was 1.61 (95% CI, 1.24-2.09) and the absolute difference in the incidence rates was 5.84/1000 (95% CI, 2.70-9.07) for CIN2+ (eTable 1 in Supplement 2). Efficacy of HPV-based screening for prevention of invasive cervical cancer: follow-up of four European randomised controlled trials. Creative Commons Attribution – NonCommercial – NoDerivs (CC BY-NC-ND 4.0), https://doi.org/10.1016/S2468-2667(17)30007-5, Primary HPV testing versus cytology-based cervical screening in women in Australia vaccinated for HPV and unvaccinated: effectiveness and economic assessment for the National Cervical Screening Program, http://www.hpvregister.org.au/research/coverage-data/HPV-Vaccination-Coverage-by-Dose-20132, http://www.cancerscreening.gov.au/internet/screening/publishing.nsf/Content/MSAC-recommendations, http://www.cancerscreening.gov.au/internet/screening/publishing.nsf/Content/E6A211A6FFC29E2CCA257CED007FB678/$File/Renewal%20Economic%20Evaluation.pdf, http://www.msac.gov.au/internet/msac/publishing.nsf/Content/1276-public, View Large Cost-effectiveness analysis on primary screening including clinical follow-up. Women aged 25 to 65 years with no history of CIN2+ in the past 5 years, no history of invasive cervical cancer, or no history of hysterectomy; who have not received a Papanicolaou test within the past 12 months; and who were not receiving immunosuppressive therapy were eligible. Dillner CR=set of screening adherence assumptions assuming a call-and-recall programme (proactive invitation).  et al. The safety group was closed December 31, 2010, when the planned sample size for this group was achieved.11. 2016.  SK, Muñoz Participants randomized to LBC testing (control group) with negative test results were asked to return at 24 months for repeat testing with LBC in accordance with the cervical cancer screening guidelines in British Columbia. For imputation, enrollment screen results were dichotomized to be either negative (HPV or cytology negative) or positive (HPV or cytology positive [≥ASCUS]). Accessibility Statement, Visual Abstract.  EB, Dunn Cervical cancer remains one of the most common cancers among Thai women.  L, Fall in genital warts diagnoses in the general and indigenous Australian population following implementation of a national human papillomavirus vaccination program: analysis of routinely collected national hospital data. 6,7 Meta-analyses have shown that inclusion of HPV testing alone or combined with cytology (co-testing) for screening, compared with cytology alone, is associated with increased detection of precancerous lesions in the first screening round, followed by a subsequent reduction in precancerous lesions. HPV testing was performed with the Hybrid Capture 2 High Risk HPV DNA test (Qiagen), which detects high-risk HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68.  ER. This Exit screening for both the intervention and control groups occurred 48 months after baseline screening and consisted of HPV testing and LBC (exit co-testing). 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). Specifically, our initial findings indicated that primary HPV screening with partial genotyping for women aged 25–69 years, with an exit HPV test at age 70–74 years, would result in a 13–22% reduction in cervical cancer mortality compared with current practice.  A.  HPV testing with cytology triage for cervical cancer screening in routine practice. Colposcopy procedures were standardized for all participants. Among baseline HPV or LBC-negative women, rates of CIN2+ at 48 months were significantly higher across all age groups in the control group compared with the intervention group (Table 2). Sociodemographic and Lifestyle Characteristics of the Intervention and Control Participants, Table 2. Cohorts offered vaccination, all results, eTable 2 responsibility for the rate per (. 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