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Objective: WHO recommends human papillomavirus (HPV) testing for cervical screening, with triage of high-risk HPV (hrHPV) positive women. However, there are limitations to effective triage for low-resource, high-burden settings, such as Papua New Guinea. In this exploratory study, we assessed the performance of host methylation as triage tools for predicting high-grade squamous intraepithelial lesions (HSIL) in self-collected and clinician-collected samples., Design: Exploratory observational study., Setting: Provincial hospital, same-day cervical screen-and-treat trial, Papua New Guinea., Participants: 44 hrHPV+women, with paired self/clinician-collected samples (4 squamous cell carcinomas (SCC), 19 HSIL, 4 low-grade squamous intraepithelial lesions, 17 normal)., Primary and Secondary Outcome Measures: Methylation levels of CADM1, MAL and miR124-2 analysed by methylation-specific PCRs against the clinical endpoint of HSIL or SCC (HSIL+) measured using liquid-based-cytology/p16-Ki67 stain., Results: In clinician-collected samples, MAL and miR124-2 methylation levels were significantly higher with increasing grade of disease (p=0.0046 and p<0.0015, respectively). miR124-2 was the best predictor of HSIL (area under the curve, AUC 0.819) while MAL of SCC (AUC 0.856). In self-collected samples, MAL best predicted HSIL (AUC 0.595) while miR124-2 SCC (AUC 0.812). Combined miR124-2/MAL methylation yielded sensitivity and specificity for HSIL+ of 90.5% (95% CI 69.6% to 98.8%) and 70% (95% CI 45.7% to 88.1%), respectively, in clinician-collected samples, and 81.8% (95% CI 59.7% to 94.8%) and 47.6% (95% CI 25.7% to 70.2%), respectively, in self-collected samples. miR124-2/MAL plus HPV16/HPV18 improved sensitivity for HSIL+ (95.2%, 95% CI 76.2% to 99.9%) but decreased specificity (55.0%, 95% CI 31.5% to 76.9%)., Conclusion: miR124-2/MAL methylation is a potential triage strategy for the detection of HSIL/SCC in low-income and middle-income country., Competing Interests: Competing interests: AJV, JG, JBo, GM, PJT, SGB and JK have received subsidised test kits for research from Cepheid. MS, JBr, GT and DH have received donated test kits for research from Abbott, BD, Cepheid, Hologic, Qiagen, Roche and Seegene. AJV and MS jointly lead the Elimination of Cervical Cancer in the Western Pacific (ECCWP) programme with philanthropic funding support from the Minderoo Foundation and the Frazer Family Foundation; and equipment, tests and consumables donated by Cepheid for HPV-based cervical screening in Papua New Guinea and Vanuatu. SG is a member of the Global Advisory Board for HPV vaccines Merck and has led investigator-initiated grants from Merck on HPV in young women. MM, DAM, SP, PB, GH, ZK and GLM declare no conflicting interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Introduction: WHO has launched updated cervical screening guidelines, including provisions for primary HPV screen-and-treat. Papua New Guinea (PNG) has a high burden of cervical cancer, but no national cervical screening programme. We recently completed the first field trials of a screen-and-treat algorithm using point-of-care self-collected HPV and same-day treatment (hereafter self-collected HPV S&T) and showed this had superior clinical performance and acceptability to visual inspection of the cervix with acetic acid (VIA). We, therefore, evaluated the effectiveness, cost-effectiveness and resource implications of a national cervical screening programme using self-collected HPV S&T compared with VIA in PNG., Methods: An extensively validated platform ('Policy1-Cervix') was calibrated to PNG. A total of 38 strategies were selected for investigation, and these incorporated variations in age ranges and screening frequencies and allowed for the identification of the optimal strategy across a wide range of possibilities. A selection of strategies that were identified as being the most effective and cost-effective were then selected for further investigation for longer-term outcomes and budget impact estimation. In the base case, we assumed primary HPV testing has a sensitivity to cervical intraepithelial neoplasia 2 (CIN2+) + of 91.8% and primary VIA of 51.5% based on our earlier field evaluation combined with evidence from the literature. We conservatively assumed HPV sampling and testing would cost US$18. Costs were estimated from a service provider perspective based on data from local field trials and local consultation., Results: Self-collected HPV S&T was more effective and more cost-effective than VIA. Either twice or thrice lifetime self-collected HPV S&T would be cost-effective at 0.5× gross domestic product (GDP) per capita (incremental cost-effectiveness ratio: US$460-US$656/life-years saved; 1GDPper-capita: US$2829 or PGK9446 (year 2019)) and could prevent 33 000-42 000 cases and 23 000-29 000 deaths in PNG over the next 50 years, if scale-up reached 70% coverage from 2023., Conclusion: Self-collected HPV S&T was effective and cost-effective in the high-burden, low-resource setting of PNG, and, if scaled-up rapidly, could prevent over 20 000 deaths over the next 50 years. VIA screening was not effective or cost-effective. These findings support, at a country level, WHO updated cervical screening guidelines and indicate that similar approaches could be appropriate for other low-resource settings., Competing Interests: Competing interests: MS is Executive Director at VCS Foundation which has developed the canSCREEN digital health platform used in Project ROSE, which is a partnership between the University of Malaya and VCS Foundation. VCS Foundation is a not-for-profit organisation that offers services to implement, support, monitor and manage population health programs. KC and MS are co-PIs of an investigator-initiated trial of cytology and primary HPV screening (Compass; ACTRN12613001207707 and NCT02328872), which is conducted and funded by the VCS Foundation (VCS), a government-funded health promotion charity. KC is also an investigator of Compass New Zealand (ACTRN12614000714684), which was conducted and funded by Diagnostic Medlab (DML), now Auckland District Health Board. The VCS Foundation received equipment and a funding contribution from Roche Molecular Systems and Ventana USA and DML received equipment and a funding contribution for Compass from Roche Molecular Systems. However, neither KC nor her institution on her behalf (Daffodil Centre) receives direct funding from industry for this trial or any other project., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Left untreated, sexually transmitted and genital infections (henceforth STIs) in pregnancy can lead to serious adverse outcomes for mother and child. Papua New Guinea (PNG) has among the highest prevalence of curable STIs including syphilis, chlamydia, gonorrhoea, trichomoniasis and bacterial vaginosis, and high neonatal mortality rates. Diagnosis and treatment of these STIs in PNG rely on syndromic management. Advances in STI diagnostics through point-of-care (PoC) testing using GeneXpert technology hold promise for resource-constrained countries such as PNG. This paper describes the planned economic evaluation of a cluster-randomised cross-over trial comparing antenatal PoC testing and immediate treatment of curable STIs with standard antenatal care in two provinces in PNG., Methods and Analysis: Cost-effectiveness of the PoC intervention compared with standard antenatal care will be assessed prospectively over the trial period (2017-2021) from societal and provider perspectives. Incremental cost-effectiveness ratios will be calculated for the primary health outcome, a composite measure of the proportion of either preterm birth and/or low birth weight; for life years saved; for disability-adjusted life years averted; and for non-health benefits (financial risk protection and improved health equity). Scenario analyses will be conducted to identify scale-up options, and budget impact analysis will be undertaken to understand short-term financial impacts of intervention adoption on the national budget. Deterministic and probabilistic sensitivity analysis will be conducted to account for uncertainty in key model inputs., Ethics and Dissemination: This study has ethical approval from the Institutional Review Board of the PNG Institute of Medical Research; the Medical Research Advisory Committee of the PNG National Department of Health; the Human Research Ethics Committee of the University of New South Wales; and the Research Ethics Committee of the London School of Hygiene and Tropical Medicine. Findings will be disseminated through national stakeholder meetings, conferences, peer-reviewed publications and policy briefs., Trial Registration Number: ISRCTN37134032., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)