Background
Despite cervical cancer is high on the global women health agenda, implementing screening programs remains challenging in LMIC.  WHO recommends HPV-based screening requiring complex health system capacity insufficiently available in LMIC. The high prevalence of HPV in the Global South, in particular among WLHIV, poses unsolved problems of too many HPV-positive tested women requiring follow up. , Overburdened capacity and loss-to-follow-up is frequent. There is an urgent need for innovative testing systems. Molecular triage assays are high-throughput, objective, with high clinical specificity and potentially reducing false positive results by transient HPV infection.
Objectives
(i) to assess key problems in HPV-based screening in SSH Africa, (ii) to design and field-testing of a molecular-based triage algorithms with high clinical specificity for dysplasia (CIN2+) in need for treatment and (iii) to assess by implementation studies their feasibility, efficacy and cost-efficacy. 
Methods
We assessed specific obstacles in molecular HPV testing program implementation by visits to Morocco, Ghana, Ethiopia, Tanzania, Botswana, South Africa, Cameroon.
We developed a test format which addresses (i) the high prevalence of HPV in the general screening population and high-risk populations like WLHIV (ii) the need for point-of-care testing and for short time period to-result (matching WHO new  TPP) (iii) self-sampling in combination with mobile community outreach screening using robust devices at point-of-care. We aimed at delivering high accuracy results in HPV genotype identification, identification of active infection and quantification of cellular biomarker expression which enables the evaluation of the severity of dysplasia and adequate treatment. The test algorithm includes HPV oncogene and cellular biomarker expression by mRNA-quantification with two potential platforms (Luminex suspension-array and RTqPCR) resulting in prototype assays (QuantiGene-Molecular-Profiling-Histology, QG-MPH). The tests were piloted in real-life implementation trials in different settings (Ethiopia, Tanzania, Botswana, Cameroon).
Results
Main problems identified were (1) low health-literacy in the target population concerning cervical cancer prevention, (2) difficulties to reach healthcare facilities, (3) low healthcare capacity and technical infrastructure, (4) fragmented screening/triage/treatment services, and (5) delays of HPV test and diagnostic results (scarce pathology and molecular diagnostic services).  Consequently, a low uptake of population-based screening and high proportion of loss to follow-up of women testing positive was documented.
The innovative mRNA-based HPV oncogene and cellular biomarker assay allowed a risk score development reporting cervical dysplasia severity with >80% accuracy, reducing time to definitive result and false-positive results for CIN2+ detection, and is robust to be implemented in low resource settings and by mobile units.
By implementation studies (Ethiopia, Tanzania, Cameroon, Botswana) feasibility of self-sampled cervicovaginal smear testing in outreach settings was shown. The modular robust assay format allows adaptation of approaches to the given circumstances,  e.g. comprehensive single-day outreach to villages (Tanzania)  by smear self-sampling, rapid molecular testing, triaging and treatment of women testing positive..
Outlook
Piloting of field-adapted cervical cancer screening and same day treatment strategies with innovative tests delivers data for informed decisions by stakeholders to adopt locally adequate programs. These should help countries with limited resources achieving target two of the WHO elimination strategy.