Marion Saville

Clinical validation of the Roche cobas HPV test on the Roche cobas 5800 system for the purpose of cervical screening

ABSTRACT This study assessed the relative clinical sensitivity and specificity, as well as reproducibility, for high-risk HPV types of the Roche cobas HPV test when processed using the Roche cobas 5800 system. The results from this study demonstrate that the cobas HPV test using the cobas 5800 system fulfils the Meijer criteria for use in population-based cervical screening. This clinical validation study also examines the clinical sensitivity and specificity based on partial genotyping, with separate detection of HPV16 and HPV18, compared with the Roche cobas 4800 HPV test, a second-generation standard comparator assay. The cobas HPV test has a relative clinical sensitivity of 1.000, when compared with the cobas 4800 HPV test to detect histologically confirmed CIN2+ lesions in woman aged 30 years or older, with a relative clinical specificity of 0.995. The general intra- and inter-laboratory agreement for the cobas HPV test on the cobas 5800 system for finding a HPV positive result were 99.1% and 99.6%, respectively. IMPORTANCE This study demonstrates, for the first time, the clinical performance of the Roche cobas HPV test when processed using the new cobas 5800 system [cobas (5800)]. This study shows that the cobas (5800) demonstrates relative clinical sensitivity and specificity, when compared with a standard comparator HPV test, which meets the international HPV test validation requirements. Intra- and inter-laboratory reproducibility also fulfills these criteria. The current study demonstrates that the cobas (5800) can be used for primary HPV-based cervical screening on cervical specimens.

Reasons for rejection of self‐collected samples for cervical screening

Participation in the National Cervical Screening Program Among Women Who Gave Birth in New South Wales, Australia by Place of Maternal Birth: A Data Linkage Analysis

ABSTRACT Objective High participation rates in the National Cervical Screening Program (NCSP) by all groups of women are required to ensure the equitable elimination of cervical cancer in Australia. In this study, we examine screening participation of overseas‐born women compared to Australian‐born women who gave birth. Design Population‐based retrospective cohort study using linked health datasets. Setting and Participants Women who gave birth in New South Wales between January 1, 2000 and June 30, 2017. Main Outcome Measures Participation in the NCSP (≥ 1 cytology test) in the 3‐ and 5‐year periods prior to delivery by place of maternal birth, adjusted for multiple socio‐demographic and health characteristics. Results Among the 1 332 669 mothers who gave birth over the study period, overall cervical screening participation in the 3‐ and 5‐year periods prior to delivery was 67.0% and 75.7%, respectively. Participation was lower for overseas‐born mothers compared to Australian‐born mothers for both the 3‐year (57.8% vs. 71.7%; adjusted odds ratio [aOR]: 0.51, 95% confidence interval [CI]: 0.50–0.51) and 5‐year (64.9% vs. 81.2%; aOR: 0.40, 95% CI: 0.40–0.40) participation periods. All groups of overseas‐born women had substantially lower screening participation compared to Australian‐born women, with the lowest relative 3‐year participation in mothers born in Southern/Central Asia (aOR: 0.30, 95% CI: 0.30–0.31), Oceania (aOR: 0.31, 95% CI: 0.30–0.32), North‐East Asia (aOR: 0.49, 95% CI: 0.48–0.50), and New Zealand (aOR: 0.49, 95% CI: 0.48–0.51). Conclusions Overseas‐born women had around half the cervical screening participation in the period prior to birth compared to Australian‐born women. It is likely that opportunities to screen these under‐screened groups during the antenatal period, typically a time of repeated health services contact, are missed.

Protocol for a cervical screening implementation trial comparing two approaches for delivering HPV self-collection in low-resource settings in India: a type 3 hybrid cluster randomised controlled trial (SHE-CAN)

Background Although multiple studies have offered self-collection for human papillomavirus (HPV)-based cervical screening in community settings, there are no randomised controlled trials (RCTs) that have compared implementation outcomes of programme approaches for self-collection. This trial will compare two such approaches in low-resource settings in the states of Tamil Nadu and Mizoram, India. Methods A cluster RCT will be conducted over a year, offering self-collection to 3000 women aged 30–49 from 28 clusters (average size 101) in selected districts. Clusters in tribal, rural and urban low-income settings will be randomised to two arms. The intervention arm, co-designed with multiple stakeholders, will involve campaigns to offer self-collection in the community. The comparison arm will be offered self-collection at the nearest health facilities. HPV-based cervical screening will be performed at central laboratories using clinically validated screening assays that can identify the highest risk carcinogenic HPV types (Group 1a–c - HPV16/18/31/33/45/52/58, ±35). Ablative treatment will be based on positivity with this extended genotyping triage, while those with any of the lower carcinogenic HPV types (Group 1d - 39, 51, 56, 59, ±35, Groups 2a/b - 66, 68) will undergo further assessment with visual inspection with acetic acid. Outcomes will be evaluated quantitatively and qualitatively using RE-AIM and the Theoretical Framework of Acceptability. Analysis The primary outcome will be percentage of women well-managed (screened and appropriately treated) in both arms, with secondary outcomes including proportion screened, proportion treated, acceptability (willingness to screen, rescreen, and/or recommend to others) to women, community and healthcare providers, adoption (by providers), implementation fidelity, costs, sustainability assessment and systematically identified implementation barriers and facilitators. The reach, effectiveness and acceptability of community-based self-collection and the use of extended genotyping for triage in resource-constrained, hard-to-reach populations will be assessed, with lessons that can inform future statewide and national programmes. Ethics and dissemination Ethics approval has been obtained from the Institutional Review Board (IRB) and Ethics Committee of the Christian Medical College Vellore, Tamil Nadu, India (IRB Min. No 14314; INTERVEN), the Alfred Hospital Ethics Committee (HREC Ref 80134, Local Reference: project 601/21), Melbourne, Australia, the IARC Ethics Committee (IEC 21-32), Lyon, France, the Salem Polyclinic Institutional Ethics Committee (SPCIEC/2022/June/01/02), Tamil Nadu, India and the Institutional Ethics Committee, Civil Hospital, Aizawl, Mizoram, India (No.B.12018/1/13-CHA(A)/IEC/115). The study is also approved by the State Scientific Advisory Committee, Directorate of Public Health and Preventive Medicine, Chennai, Tamil Nadu (R. No. 011575/HEB/A2/2023). The Alfred Hospital Approval, as an authorised Australian ethics committee for national mutual recognition, is recognised and registered with the University of Melbourne Human Research Ethics Committee (2024-25255-57650-1). Written informed consent will be obtained from participants. The results of the trial will be disseminated through a peer-reviewed medical journal, and also through workshops, reports and conferences. Trial registration number The trial has been registered with the Clinical Trials Registry - India: CTRI/2022/04/042327.

Cervical Cancer Elimination in Australia and the Asia Pacific: Progress and Barriers

ABSTRACT Australia has been at the forefront of innovation and implementation of cervical cancer control and is predicted to eliminate cervical cancer by 2035, the first country to achieve elimination using active measures. This is a result of Australia being an early adopter of universal human papillomavirus (HPV) vaccination and early transition to a primary HPV‐based cervical screening program. However, to ensure timely and equitable elimination, disparities in coverage among underserved populations must be addressed, and recent declines in vaccination and screening uptake must be reversed. Improved routine data linkages are required to ensure gaps in participation in subpopulations can be identified. Primary health providers have an important role in checking vaccination and screening status and offering vaccination catch‐up or screening as appropriate. A universal option of self‐collection of an HPV sample for all screen‐eligible people has increased acceptability overall, but further innovative and flexible models of service delivery are required to ensure equitable access for all. Australia has also played an important role in cervical cancer control globally and was a co‐sponsor of the 2020 World Health Assembly resolution to accelerate the global elimination of cervical cancer as a public health problem. In the Indo‐Pacific region, regional frameworks have been developed to advance strategic actions to progress implementation of the global strategy. The Elimination Partnership in the Indo‐Pacific for Cervical Cancer (EPICC), a major initiative supported by the Australian Government and the Minderoo Foundation, provides tailored support to countries, considering local needs and priorities.