Reengenharia do rastreio do cancro do colo do útero para o século XXI: ação conjunta para um programa de rastreio novo, atual e sustentável

Despite the large potential of cervical cancer screening (CCS) to reduce the burden of cancer, its implementation has been suboptimal in many settings, and the usefulness and sustainability of screening programs are going to be challenged by the expectedly dramatic reduction in the frequency of cervical precancerous lesions, as the coverage of vaccination against human papillomavirus (HPV) increases. In this context, a change in the paradigm for CCS programs, towards a substantial improvement of efficiency, and ability to reach those more in need of screening, is essential to maintain their cost-effectiveness. The rationale for this investigation relies on the potential for self-sampling (collection of one’s own cervical-vaginal exudate using a kit with a single-use cervical brush) to gradually replace CCS based on samples collected by a health professional, with reduction of human and material resources, along with deoxyribonucleic acid (DNA) methylation testing for risk stratification and streamlining CCS. This project aims to develop and test the implementation of a state-of-the-art approach to population-based screening for cervical cancer (CC), at an expectedly lower cost and improved efficiency, through the use of self-sampling and triage based on DNA methylation biomarkers. The primary objectives are: 1) To compare the adherence to CCS based on self-sampling (for HrHPV testing) with screening based on sampling for liquid-based cytology (LBC)-based HPV testing performed by a health professional (the current standard of care), in a non-inferiority framework of analysis; 2) To compare the adherence to CCS based on self-sampling, followed by LBC-based HPV testing for the non-adherent to self-sampling, with the current standard of care, in a superiority framework of analysis; 3) To compare the adherence to CCS based on self-sampling, followed by LBC-based HPV testing for the non-adherent to self-sampling, with the current standard of care followed by self-sampling for the non-adherent to the standard of care, in a non-inferiority framework of analysis; 4) To assess biomarker performance of DNA methylation markers for high-grade squamous intraepithelial lesions or worse (HSIL+) detection, in different contexts of population-based CCS, involving self-sampling and LBC HPV testing performed by a health professional, used alone or sequentially. Secondary objectives include stratified analyses in sub-groups of the population defined according to age, deprivation index of the place of residence, CCS history and organization model of the primary healthcare units. This study uses a randomized design for assessing the effect of using self-sampling instead of the standard of care, but also the effect of two alternative options for the sequential incorporation of self-sampling in the screening process, namely self-sampling as the primary option, complemented (among women non-adherent to self-sampling) by collection of the sample by a health professional, versus the standard of care, complemented (among women non-adherent) by self-sampling. Furthermore, the assessment of performance of methylation markers will determine whether a full molecular flow may be feasible, enabling the exclusive use of self-collected samples and precluding the need for a subsequent LBC collection in HrHPV positive cases identified in self-collected samples.