Project Title: “Cervical cancer screening in rural African countries as a benchmark for cancer prevention in the developing world”

Main laboratory: Prof. Gian-Paolo Dotto, University of Lausanne

Partners in Cameroon

Prof. Lazare Kaptue & Dr. Adamo Bongoe, Université des Montagnes

Dr. Zacharie Sando, Université de Yaoundé

Dr. Kenfack Bruno, Dschang District Hospital

Partners in Kenya

Dr. Nelly Yatich, Research Care and Training Program, Nairobi

Dr. Dr. Bhavna Chohan, Kenya Medical Research Institute, Nairobi

Cervical cancer (CC) is amongst the most lethal (and most easily preventable) forms of cancer, where 85% of all CC-related deaths occur in low- and middle income countries (LMICs), like sub-Saharan African countries. While in developed countries, cervical cancer screening is performed by cytological analysis
(Papanicolau Test), this is not feasible in LMICs, due to the prohibitive infrastructure requirements, and to the lack of trained pathologists and the high volume of women that would require testing. The onset of CC is tightly linked to a single etiopathological agent: high-risk human papillomaviruses (hrHPV). There are 14 types of high risk HPVs, also known as IARC class I for which screening methods are already established and practical to apply in LMICs. HPV vaccination has been shown to be highly effective in high-income countries. By contrast, in LMICs it has only been introduced in pilot projects, without broad population coverage. Importantly, this approach does not eliminate the need for cervical cancer screening, and will only impact future generations rather than the presently HPV-infected female population. The lifetime risk of hrHPV infection in the global female population is around 80%. However, only a minority of infected women develop an aggressive cancer, meaning that basic HPV detection has low specificity and positive predictive value.
The lack of specificity leads to unacceptable rates of overtreatment and burden on the referral system. Biomarkers which detect virus that has undergone oncogenic transformation, such as E6/E7, would be able to stratify cases into degrees of risk. More specific biomarkers have not been introduced in LMICs due to costs, infrastructure needs and availability as durable point-of-care test.

We plan to:
• Implement precision cervical cancer screening in rural outposts of Africa
• Identify of novel diagnostic markers and druggable targets for detection and prevention of HPV-driven malignancy
• Joint analysis of data to produce clinical and epidemiological results that inform clinical and public health planning

The participants enrolling in the study will be direct beneficiaries, obtaining accurate, high-quality risk-assessment for CC as well as meaningful advice and medical referral. At the same time, any markers of malignant transformation found in this study will serve as an entry point for improving diagnostics, triage and chemoprevention for CC worldwide. Moreover, given the underlying common basis of SCCs at various body sites, the findings of this study will establish a new paradigm for early detection and prevention of other malignancies of this type, specifically Head/Neck and Oesophageal SCCs that are also of great relevance in LMICs. Prof. Dotto has set up a network of collaborators in two African countries, Cameroon and Kenya, who will be responsible for the community-based outreach program and samples collection and hrHPV E6/E7 screening in local Universities and Hospital facilities. Selected samples will be sent to Switzerland (UNIL and CHUV), where we have all necessary tools and expertise to identify new biomarkers and develop probes and simplified procedures to then be used in the African countries (as depicted in the flow diagram below). At the same time, we will make a concerted effort for cost and sustainability projections and outreach/educational programs including raising awareness of local policymakers and political leaders for health care improvements that could be implemented in their settings.