Triaging of women positive for high‐risk human papillomavirus (hrHPV) on self‐collected samples requires a molecular reflex test to avoid recall for cytology or visual tests. We assessed triage performance and predictive value of human gene methylation panel (ZNF671/ASTN1/ITGA4/RXFP3/SOX17/DLX1) alone and with combination of HPV16/18 genotyping in a longitudinal screening study. Out of 9526 women at baseline, 1758 women positive for hrHPV on self‐collected samples followed up yearly were included in the current analysis. Satisfactory risk stratification to detect cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was demonstrated by the methylation panel with an odds ratio (OR) of 11.3 among methylation‐positive women compared to methylation‐negative counterparts. Triaging with methylation panel reduced colposcopy referral rate by 67.2% with sensitivity and specificity of 83.0% and 69.9% to detect CIN2+. The corresponding values for the combining methylation and HPV 16/18 were 96.6% and 58.3%. The cumulative 3‐year incident CIN2+ risk was 6.8% (95% CI: 4.9%‐8.6%) for hrHPV positive women, which was reduced to 4.5% (95% CI: 2.7%‐6.3%) and 2.9% (95% CI: 1.2%‐4.5%) for women negative on methylation triaging alone and negative on the combined strategy. The corresponding risk for women positive for both methylation and HPV 16/18 reached 33.7% (95% CI: 19.0%‐45.8%). Our study demonstrated the satisfactory triage performance and predictive value of the methylation panel, especially in combination with HPV 16/18 genotyping. The substantially lower risk of CIN2+ among the triage negative women over the next 3 years suggests that the interval for repeat HPV test can be safely extended to at least 2 years.

Background High variability in the definition and interpretation of organized cancer screening needs to be addressed systematically. Moreover, the relevance of the current practice of categorizing screening programmes dichotomously into organized or non-organized needs to be revisited in the context of considerable heterogeneity that exists in the delivery of cancer screening in the real world. We aimed to identify the essential and desirable criteria for organized cancer screening that serve as a charter of best practices in cancer screening. Methods We first did a systematic review of literature to arrive at an exhaustive list of criteria used by various publications to describe or define organized cancer screening, based on which, a consolidated list of criteria was generated. Next, we used a Delphi process comprising of two rounds of online surveys to seek agreement of experts to categorize each criterion into essential, desirable, or neither. Consensus was considered to have been achieved based on a predetermined criterion of agreement from at least 80% of the experts. The outcomes were presented before the experts in a virtual meeting for feedbacks and clarifications. Results A total of 32 consolidated criteria for an organized screening programme were identified and presented to 24 experts from 20 countries to select the essential criteria in the Delphi first round. Total 16 criteria were selected as essential with the topmost criteria (based on the agreement of 96% of experts) being the availability of a protocol/guideline describing at least the target population, screening intervals, screening tests, referral pathway, management of positive cases and a system being in place to identify the eligible populations. In the second round of Delphi, the experts selected eight desirable criteria out of the rest 16. The most agreed upon desirable criterion was existence of a specified organization or a team responsible for programme implementation and/or coordination. Conclusions We established an international consensus on essential and desirable criteria, which screening programmes would aspire to fulfil to be better-organized. The harmonized criteria are a ready-to-use guide for programme managers and policymakers to prioritize interventions and resources rather than supporting the dichotomous and simplistic approach of categorizing programmes as organized or non-organized.

The CanScreen5 project is a global cancer screening data repository that aims to report the status and performance of breast, cervical and colorectal cancer screening programs using a harmonized set of criteria and indicators. Data collected mainly from the Ministry of Health in each country underwent quality validation and ultimately became publicly available through a Web-based portal. Until September 2022, 84 participating countries reported data for breast (n = 57), cervical (n = 75) or colorectal (n = 51) cancer screening programs in the repository. Substantial heterogeneity was observed regarding program organization and performance. Reported screening coverage ranged from 1.7% (Bangladesh) to 85.5% (England, United Kingdom) for breast cancer, from 2.1% (Côte d’Ivoire) to 86.3% (Sweden) for cervical cancer, and from 0.6% (Hungary) to 64.5% (the Netherlands) for colorectal cancer screening programs. Large variability was observed regarding compliance to further assessment of screening programs and detection rates reported for precancers and cancers. A concern is lack of data to estimate performance indicators across the screening continuum. This underscores the need for programs to incorporate quality assurance protocols supported by robust information systems. Program organization requires improvement in resource-limited settings, where screening is likely to be resource-stratified and tailored to country-specific situations.

Objectives: We aims to assess the efficacy and safety of therapeutic HPV vaccines to treat cervical intraepithelial neoplasia of grade 2 or 3 (CIN2/3). Design: This study is a systematic review and meta-regression that follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations. Data sources: PubMed, Embase, Web of Science, Global Index Medicus and CENTRAL Cochrane were searched up January 31, 2022. Eligibility criteria: Phase II/III studies reporting the efficacy of therapeutic vaccines to achieve regression of CIN2/3 lesions were included. Data extraction and synthesis: Two independent reviewers extracted data, evaluated study quality. A random-effect model was used to pool the proportions of regression and/or HPV clearance. Results: 12 trials met the inclusion criteria. Out of the total 734 women receiving therapeutic HPV vaccine for CIN 2/3, 414 regressed to normal/CIN1 with the overall proportion of regression of 0.54 (95%CI: 0.39, 0.69) for vaccinated group. Correspondingly, 166 women receiving placebo only achieving the pooled normal/CIN1 regression of 0.27 (95%CI: 0.20, 0.34). When only including two-arm studies, the regression proportion of the vaccine group was higher than that of control group (relative risk (RR): 1.52, 95%CI: 1.14, 2.04). Six studies reported the efficacy of the therapeutic vaccines to clear high-risk human papillomavirus (hrHPV) with the pooled proportion of hrHPV clearance of 0.42 (95%CI: 0.32, 0.52) for the vaccine group and 0.17 (95%CI: 0.11, 0.26) for the control group and the RR of 2.03 (95%CI: 1.30, 3.16). Similar results were found regarding HPV16/18 clearance. No significant unsolicited adverse events have been consistently reported. Conclusions: The efficacy of the therapeutic vaccines in the treatment of CIN2/3 was modest. Besides, the implementation issues like feasibility, acceptability, adoption, and cost-effectiveness need to be further studied. PROSPERO registration number: CRD42020189617