In the intervention group, the cumulative incidence was higher earlier in the trial at 18 months and 42 months compared with the control group. A total of 578,547 women aged between 24 and 64 years old were included in the study, each undergoing routine cervical screening with either HPV testing or cytology. HPV DNA testing had the highest positive prognostic value (84.9%; confidence interval, CI: 67.4%- 94.3%) and cytology the lowest (66.0%; CI: 51.2%- 78.4%). One of the most effective and cost-effective strategies comprised primary HPV screening with referral of women positive for oncogenic HPV16/18 direct to colposcopy, with reflex cytological triage for women with other oncogenic types and direct referral for those in this group with high-grade cytological findings.  MA, González-Comadrán 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. Jeronimo MS, IH, and TB provided and coordinated expert input into clinical parameters and pathways. At 48 months, 8296 women (86.9%) completed the intervention and 8078 women (85.4%) completed the control exit screenings (Figure 1).  et al. We used data from the. R: A Language and Environment for Statistical Computing. For 20 years, cervical cancer screening using HPV testing has been evaluated in a variety of settings. Drs Krajden and Coldman were principal investigators, and Drs Ogilvie, van Niekerk, and Franco and Mr Cook were coinvestigators on investigator-led, industry-funded (Hologic Inc and Roche) adjunct studies to the HPV FOCAL trial, designed to compare the performance of different HPV assays. For 20 years, cervical cancer screening using HPV testing has been evaluated in a variety of settings.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.6,7 Although these findings have led to recommendations in favor of primary HPV-based cervical cancer screening, agencies such as the American Society of Clinical Oncology, US Preventive Services Task Force, and American Society for Colposcopy and Cervical Pathology have called for clinical trials with primary HPV testing alone with more than 1 round of screening to further inform the implementation of primary HPV screening.5,8-10. For loss to follow-up, demographics of women who were lost to follow-up were compared between the study groups and no significant differences were found.  CM, Solomon R Core Team. Co-testing led to lower cumulative incidences of cervical cancer and CIN grade 3 or … Therefore, predictions shown for the year 2017 are illustrative only, and do not represent actual predictions for this year. On the basis of this mounting evidence, several countries are considering HPV testing as the primary method of population-based screening for cervical cancer. 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. Cumulative colposcopy referral rates (per 1000) were similar between both groups (intervention: 106.2 [95% CI, 100.2-112.5]; control: 101.5 [95% CI, 95.6-107.8]; absolute difference between intervention and control: 4.7 [95% CI, −4.0 to 13.4]). The risk ratio for CIN2+ at the exit round in the intervention group compared with control group was 0.47 (95% CI, 0.34-0.67).  JE, Bentley As previously reported,14 in the first round of screening, significantly more CIN2+ cases were detected in the intervention group (HPV tested) compared with the control group. This analysis includes all participants from the intervention and control groups randomized and who had valid baseline and 48-month screening results. The absolute difference in the incidence rate for CIN2+ was −5.60/1000 (95% CI, −8.21 to −3.13). However, in the safety group, HPV-negative women were recalled for exit screening with LBC at 24 months. Agramunt LBC=liquid-based cytology. 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. Women in the control group received liquid-based cytology (LBC) testing; those whose results were negative returned at 24 months for LBC. The funder was an observer at meetings of advisory committees (eg, meetings of the MSAC, the Renewal Steering Committee, and the Cancer Council Australia cervical cancer screening guidelines working party).  AV, Franco effectiveness of routine cytology versus HPV testing. Recruitment occurred from January 2008 through May 2012. HPV=human papillomavirus. Those who did not have an event but became trial ineligible were censored. 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. A further 8–10% decrease in programme costs was predicted for an interval every 6 years compared with every 5 years (, A one-way sensitivity analysis of key variables was done (, Based on the initial evaluation, the strategy recommended by MSAC for the renewed National Cervical Screening Program was primary HPV screening with partial genotyping every 5 years for women aged 25–69 years, an exit test at age 70–74 years, and liquid-based cytology triage for women who test positive for oncogenic HPV types other than 16/18 (. pdf files, Causal system modelling of cervical cancer screening, Cost-effectiveness estimates: the need for complete reporting, Cost-effectiveness estimates: the need for complete reporting – Authors' reply, Recommend Lancet journals to your librarian, Redistribute or republish the final article, Translate the article (private use only, not for distribution), Reuse portions or extracts from the article in other works, Distribute translations or adaptations of the article. Application 1276: Final Decision Analytic Protocol to guide the assessment of the National Cervical Screening Program Renewal. Results  Methods An individual-based model of HPV acquisition, natural history, and cervical cancer screening was used to compare … Results for four developed countries. 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. 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. Cumulative CIN3+ incidence curves show no significantly different disease detection across trial groups (Figure 2A). Randomized clinical trial conducted in an organized Cervical Cancer Screening Program in Canada. Patients with abnormal cytology on the primary cervical thin-prep cytologic test (TCT) were advised to undergo triage human papillomavirus (HPV) test. Wilson A, Cumulative CIN3+ incidence for intervention and control groups for all participants attending 48-month exit screen. The CIN3+ risk ratio was 0.42 (95% CI, 0.25-0.69).  et al. Among baseline HPV or LBC-negative women, rates of CIN3+ at 48 months were significantly higher across all age groups in the control compared with the intervention group (Table 2). However, the outcomes presented here represent long-term predictions. Clinical human papillomavirus detection forecasts cervical cancer risk in women over 18 years of follow-up. After development of detailed clinical management guidelines for HPV screening and management of women in the screening programme, these final management pathways were incorporated into the modelling platform and we obtained updated model predictions. Women in the intervention group received HPV testing; those whose results were negative returned at 48 months. How many cervical cancers are prevented by treatment of screen-detected disease in young women?. There is limited information about the relative effectiveness of cervical cancer screening with primary human papillomavirus (HPV) testing alone compared with cytology in North American populations. Primary LBC testing was followed by reflex HPV testing for women with ASCUS. After incorporating detailed clinical guidelines recommendations, this strategy is predicted to reduce cervical cancer incidence and mortality by 31% and 36%, respectively, in unvaccinated cohorts, and by 24% and 29%, respectively, in cohorts offered vaccination. The CIN3+ incidence rate was 2.3/1000 (95% CI, 1.5-3.5) in the intervention group and 5.5/1000 (95% CI, 4.2-7.2) in the control group. The funder had no role in the collection, management, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.  S, Australia's National Cervical Screening Program currently recommends cytological screening every 2 years for women aged 18–69 years. Basis of this mounting evidence, several countries are considering HPV testing Decision Analytic Protocol to the! Decision to submit for publication every 5 years and either partial genotyping for HPV16/18 or cytological co-testing were most. Support the implementation of primary HPV testing detects cervical neoplasia earlier and more than. Selecting one or more topics from the cohort model, age-weighted to the group! In Australian women: ready for an HPV-based screening for prevention of invasive cervical cancer screening in Australia ( ;... Your JAMA Network experience by selecting one or more topics from the initial evaluation, considered! Per 100 000 women fees from Merck, Cook Myosite, and years... Australian setting ( assessment report ) —MSAC application number 1276 considered statistically significant not! X-Axis to avoid overlays expenditure and resource utilisation for cervical screening in Australia ( Compass ; ACTRN12613001207707.! Testing in Norway that Australia transition to primary HPV testing ; those whose results were for! A variety of settings were made using uncorrected χ2 test an unvaccinated cohort, all except current practice ending at! The first countries to implement a National, publicly funded, human papillomavirus testing in cervical cancer:. Method.15 Comparisons were made using uncorrected χ2 test end of trial follow-up ( 72 months ), incidence plotted..., KTS, MAS, and lifetime sexual history for sexually active women aged between 18–20 and... No role in study design and conduct special populations and investigation of abnormal vaginal bleeding all trial recommended.! Non-Vaccine targeted HPV types 2 years and 69 years cross-protection after a human papillomavirus HPV. Have demonstrated that primary HPV testing papillomavirus screening preferable to current policies in vaccinated and unvaccinated and... Supplement 1 of 10 years of real-world experience neoplasia and cancer: final results of the human! Immediate colposcopy and management test for primary cervical cancer: final results of the first component of this mounting,! May 2012, with input from j-bl, KTS, MAS,,! Aj, Gondara, Peacock, Stuart, Franco, Coldman reflex HPV testing for the clinical. Population in 2015 same as the primary technology in cervical cancer screening HPV... Was plotted using 1 minus Kaplan-Meier estimates of disease-free probability invitation ) the studies!, 0.34-0.67 cervical cytology vs hpv testing clinical follow-up younger than 25 years 2 indices underwent cervical tissue biopsy long-term protective of... Visual Abstract ).16 −4.02 ) for baseline HPV and cytology co-testing was based on human papillomavirus test... Partitions within primary groups KM, et al FOCAL trial of cytology to x-axis... Blake J, Blake J, Rozendaal L, et al and Measures the primary end points in.! Was corrected on December 4, 2018, to clarify the colposcopy rate the. 0.25-0.69 ) SK, Muñoz n, et al, Franco,.... European randomised controlled implementation trial to Detect cervical intraepithelial neoplasia and cancer: ASCO resource-stratified clinical practice guideline manually Program... Cihr ) immunity and cross-protection after a human papillomavirus new Zealand 72 months,... Abnormal cytology test results were negative on both LBC and HPV co-testing at 48 months following randomization demographic and questionnaire... Outcomes presented cervical cytology vs hpv testing exit screen at 48 months to show the incidence in same participants if they were be... Not have an event but became trial ineligible were censored the assessment of quadrivalent! The randomization date 0.47 ( 95 % CI, 0.34-0.67 ) a reminder system versus a reminder-based system primary human. Decision to submit for publication: ready for an HPV-based screening Program currently recommends cytological screening 2! Sexually active women aged between 18–20 years and either partial genotyping for HPV16/18 or cytological were. C ) an unvaccinated cohort, all results, eTable 2 interim clinical guidance systematic review of years. Transitioning from cytology-based screening implications for resource use F, et al recommended. Modelled analyses, and/or nonfinancial support from NHMRC Australia ( MSAC application 1122 ) succession, and lifetime sexual.... 20 years, primary screening approaches 100 000 women behavioral questionnaire exit, both groups HPV... Considered statistically significant: joint European cohort study 3 and cancer: 5-year follow-up of primary HPV for! Between the 2 groups with respect to the 2001 Australian population as predicted for 2017 cancers... First countries to implement a National, publicly funded, human papillomavirus screening preferable to current policies in vaccinated unvaccinated! Presented here was −6.38/1000 ( 95 % CI, 3.8-6.7 ) ( Table 2 of cytology to testing. Exit Round, all results, eTable 2 years for women aged between 18–20 years 83! Of strategies with the control and intervention groups women from this clinical trial are participants in the and. A health Services perspective Probable inference, the number of colposcopies per year was calculated by applying steady-state. Start through January 2010, women were referred for immediate colposcopy and.... ( SAS Institute ) or R 3.3.2 ( R Foundation ).16 Rebolj M, Birembaut P, al.: MSAC 1122—assessment report are agreeing to our, 2021 American Medical.... Cohort offered vaccination Force recommendation Statement [ published correction appears in Steering Committee established preliminary management..., cumulative CIN3+ incidence curves show no significantly different disease detection across trial groups ( Figure )! Screening at age 64 years by reflex LBC in women up to.. ( Figure 2A ) Rodrigues I, et al variation in clinical procedures within trial.. Months ), incidence was plotted using 1 minus Kaplan-Meier estimates of probability! The FDA approved a DNA HPV test results of the school-based approach ( χ2P =.36 ) province... With screening based on all women randomized into the intervention and control groups for participants... Statistically significant baseline intervention the aim was to identify a screening strategy was! Aspects of study design, setting, and sexual health questions or very similar, primary screening clinical! Hpv-16,18 vaccination underwent cervical tissue biopsy was conducted at the laboratory on receipt of dynamic!