Cervical Cancer Stages, Human Papillomavirus Integration, and Malignant Genetic Mutations: Integrative Analysis of Datasets from Four Different Cohorts

Foziya Ahmed Mohammed; Kula Kekeba Tune; Marti Jett; Seid Muhie

doi:10.3390/cancers15235595

Cervical Cancer Stages, Human Papillomavirus Integration, and Malignant Genetic Mutations: Integrative Analysis of Datasets from Four Different Cohorts

Cancers (Basel). 2023 Nov 26;15(23):5595. doi: 10.3390/cancers15235595.

Authors

Foziya Ahmed Mohammed^{1

2

3}, Kula Kekeba Tune^{1

2}, Marti Jett⁴, Seid Muhie^{5

6}

Affiliations

¹ Department of Software Engineering, College of Engineering, Addis Ababa Science and Technology University, Addis Ababa 16417, Ethiopia.
² Center of Excellence for HPC and Big Data Analytics, Addis Ababa Science and Technology University, Addis Ababa 16417, Ethiopia.
³ Department of Information Technology, College of Computing and Health Informatics, Wolkite University, Wolkite P.O. Box 07, Ethiopia.
⁴ US Army Medical Research and Development Command, Head Quarter, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
⁵ Medical Readiness Systems Biology, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
⁶ The Geneva Foundation, Silver Spring, MD 20910, USA.

Abstract

Cervical cancer represents a significant global health concern, stemming from persistent infections with high-risk types of human papillomavirus (HPV). The understanding of cervical cancer's clinical correlates, risk factors, molecular mechanisms, stages, and associated genetic mutations is important for early detection and improved treatment strategies. Through integrated analysis of clinical and molecular datasets, this study aims to identify key factors that are overlapping and distinct across four cohorts of different races and regions. Here, datasets from four distinct cohorts of patients from Uganda (N = 212), the United States of America (USA) (N = 228), China (N = 106), and Venezuela (N = 858) were examined to comprehensively explore the relationships between cervical cancer stages, HPV types (clades), productive HPV integration, and malignant genetic mutations. Cohort-specific findings included the occurrence frequencies of cervical cancer stages and grades. The majority of patients from the USA and China were diagnosed with stages I and II, while those from Uganda were diagnosed with stages II and III, reflecting levels of awareness and the availability of HPV vaccines and screening services. Conversely, cervical cancer and its stages were positively correlated with HPV types (clades), HPV integration, and risk-factor habits across the cohorts. Our findings indicate that the more common squamous cervical cancer can be potentially due to productive HPV16 (clade 9) integration. At the molecular level, pathways related to HPV infection, cancer-related conditions, and viral carcinogenesis were among the most significant pathways associated with mutated genes in cervical cancer (across cohorts). These findings collectively corroborate the prominent role of HPV infection and integration leading to genetic mutation and hence to the development of cervical cancer and its stages across patients of distinct races and regions.

Keywords: cervical cancer; human papillomavirus (HPV); molecular pathways; mutation; productive integration; protein networks; stages of cervical cancer.

Grants and funding

F.A.M. was financially and logistically supported by Wolkite University, Wolkite, Ethiopia, and the Addis Ababa Science and Technology University, Addis Ababa, Ethiopia.