Comprehensive Human Papillomavirus Genotyping in Cervical Squamous Cell Carcinomas and Its Relevance to Cervical Cancer Prevention in Malawian Women

Abstract

Purpose: Cervical squamous cell carcinoma (SCC) continues to be a significant cause of cancer morbidity and is the third leading cause of cancer-related death in women worldwide. In sub-Saharan Africa, cervical cancer is not only the most common female cancer but also the leading cause of cancer-related deaths in women. Malawi, in particular, has the highest burden of cervical cancer. With the increasing use of human papillomavirus (HPV) vaccination, documenting the prevalent HPV types in those high-risk populations is necessary to both manage expectations of HPV vaccination and guide future vaccine development.

Materials and methods: In this study, we performed HPV typing on 474 cervical SCC samples and analyzed the potential impact of HPV vaccination in this population.

Results: Ninety-seven percent of tumors were positive for at least one HPV type, and 54% harbored more than one HPV type. HPV 16 was the most common type (82%), followed by HPV 18 (34%), HPV 35 (24%), and HPV 31 (12%). A vaccine against HPV 16 and 18 would ideally prevent 53% of cervical SCC, and the nonavalent HPV vaccine (covering HPV 16, 18, 31, 33, 45, 52, and 58) would prevent 71% of cervical SCC in Malawi (assuming 100% vaccine efficacy). The main reason for a lack of coverage was high prevalence of HPV 35, which was also present as a single infection in a small subset of patients.

Conclusion: Although any HPV vaccination in this population would likely prevent a significant proportion of cervical cancer, the nonavalent vaccine would provide better coverage. Furthermore, investigation of the role of HPV 35 in this population, including possible cross-protection with other HPV types, should be pursued.

Fig 1

Prevalence and types of human papillomavirus (HPV) across all cervical squamous cell carcinomas. The HPV types identified across all samples, presented as percentage (green bars; vertical axis) of total samples and absolute number (displayed above green bar) against HPV type (horizontal axis), regardless of single or multiple infections.

Fig 2

Summary of prevalence of human papillomavirus (HPV) single and multiple infections in 407 high-risk HPV cervical squamous cell carcinomas. More than half of the patients demonstrated more than one HPV type, whereas 46% had one HPV type (green). In patients with more than one HPV type identified, the majority harbored two HPV types (blue); however a significant subset (red, orange, purple) harbored three or more HPV types.