Enhancing Cervical Cancer Prevention in South African Women: Primary HPV mRNA Screening with Different Genotype Combinations

Sveinung Wergeland Sørbye; Bente Marie Falang; Matthys H Botha; Leon Cornelius Snyman; Haynes van der Merwe; Cathy Visser; Karin Richter; Greta Dreyer

doi:10.3390/cancers15225453

Enhancing Cervical Cancer Prevention in South African Women: Primary HPV mRNA Screening with Different Genotype Combinations

Cancers (Basel). 2023 Nov 17;15(22):5453. doi: 10.3390/cancers15225453.

Authors

Sveinung Wergeland Sørbye¹, Bente Marie Falang², Matthys H Botha³, Leon Cornelius Snyman⁴, Haynes van der Merwe³, Cathy Visser⁴, Karin Richter⁵, Greta Dreyer⁴

Affiliations

¹ Department of Clinical Pathology, University Hospital of North Norway, 9038 Tromsø, Norway.
² PreTect AS, 3490 Klokkarstua, Norway.
³ Department of Obstetrics and Gynaecology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town 7505, South Africa.
⁴ Gynaecological Oncology Unit, Department of Obstetrics and Gynaecology, Faculty of Health Sciences, University of Pretoria, Pretoria 0028, South Africa.
⁵ Department of Medical Virology, Faculty of Health Sciences, University of Pretoria, Pretoria 0028, South Africa.

Abstract

Background: Cervical cancer prevention in regions with limited access to screening and HPV vaccination necessitates innovative approaches. This study explored the potential of a test-and-treat strategy using mRNA HPV tests to impact cervical cancer prevention in a high-prevalence HIV population.

Methods: A cervical screening study was conducted at three South African hospitals involving 710 under-screened, non-pregnant women (25 to 65 years) without known cervical diseases. Cytology, HPV testing, colposcopy, and biopsies were performed concurrently. Histopathologists determined final histological diagnoses based on biopsy and LLETZ histology. mRNA-HPV-genotyping for 3 (16, 18, 45) to 8 (16, 18, 31, 33, 35, 45, 52, 58) high-risk types was performed on leftover liquid-based cytology material. The preventive potential of the test-and-treat approach was estimated based on published data, reporting the causative HPV types in cervical cancer tissue from South African women. Treatment was provided as needed.

Results: The HPV positivity rate more than doubled from 3-type (15.2%; 95% CI: 12.6-17.8) to 8-type mRNA (31.5%; 95% CI: 28.8-34.9) combinations, significantly higher among HIV-positive women. CIN3+ prevalence among HIV-positive women (26.4%) was double that of HIV-negative women (12.9%) (p < 0.01). The 6-type combination showed the best balance of sensitivity, specificity and treatment group size, and effectiveness to prevent cervical cancer. A 4-type combination (16, 18, 35, 45) could potentially prevent 77.6% (95% CI: 71.2-84.0) of cervical cancer burden by treating 20% and detecting 41.1% of CIN3 cases in the study group. Similarly, a 6-type combination (16, 18, 31, 33, 35, 45), treating 25% and including 62% of CIN3 cases, might prevent 85% of cervical cancer cases (95% CI: 79.6-90.6) among HIV-positive and negative women.

Conclusion: Employing mRNA HPV tests within a test-and-treat approach holds huge promise for targeted cervical cancer prevention in under-screened populations. Testing for mRNA of the 6 highest-risk HPV types in this population and treating them all is projected to effectively prevent progression from CIN3 to invasive cervical cancer while reducing overtreatment in resource-constrained settings.

Keywords: HIV interaction; HPV screening; cervical cancer; global health challenges; human papillomavirus; negative predictive value; number needed to treat; positive predictive value; prevention strategies; risk management; “Test and Treat” approach.

Grants and funding

For this specific sub-study, the South African study group covered specimen preparation and storage, while PreTect AS, Klokkarstua, Norway, provided HPV mRNA reagents and performed all testing free of charge.