Abstract
BackgroundThe variation of human papillomavirus (HPV) genotypes shapes the risks of cervical cancer and these variations are not well defined in Africa. Nucleotide changes within the L1 gene, nucleotide variability, and phylogeny were explored in relation to HIV in samples from Botswana and Kenya.MethodsA total of 98 HPV-positive cervical samples were sequenced to identify different HPV variants. Phylogenetic inferences were used to determine HPV genotypes and investigate the clustering of sequences between women living with HIV (WLWHIV) and -women not living with HIV (WNLWHIV).ResultsOut of 98 generated sequences, 83.7% (82/98) participants had high-risk (HR) HPV genotypes while 16.3% (16/98) had low-risk (LR) HPV genotypes. Among participants with HR-HPV genotypes, 47.6% (39/82) were coinfected with HIV. The prevalence of HR-HPV genotypes was statistically higher in the Botswana population compared to Kenya (p-value < 0.001). Multiple amino acid mutations were identified in both countries. Genetic diversity differed considerably among WLWHIV and WNLWHIV. The mean pairwise distances between HPV-16 between HIV and HIV/HPV as well as for HPV-18 were statistically significant. Six (6) new deleterious mutations were identified in the HPV genotypes based on the sequencing of the L1 region, HPV-16 (L441P, S343P), HPV-18 (S424P), HPV-45 (Q366H, Y365F), and HPV-84 (F458L). The majority of the patients with these mutations were co-infected with HIV.ConclusionsGenomic diversity and different genomic variants of HPV sequences were demonstrated. Candidate novel mutations within the L1 gene were identified in both countries which can be further investigated using functional assays.
Highlights
The variation of human papillomavirus (HPV) genotypes shapes the risks of cervical cancer and these variations are not well defined in Africa
Study design and population Formalin-fixed paraffin-embedded (FFPE) tissue specimens from women living with human immunodeficiency virus (HIV) (WLWHIV) and -women not living with HIV (WNLWHIV), diagnosed with invasive cervical cancer previously typed using the Abbot Real-Time polymerase chain reaction (PCR) and Linear Array HPV Genotyping Test, Linear array HPV genotyping test (LA-HPV) (Roche Applied Sciences, Indianapolis, IN) from prior retrospective cross-sectional studies [19, 21] from Botswana and Kenya were utilized
We proposed to describe the sequence variation of samples with single HPV infections for the two high risk (HR)-HPV genotypes (HPV-16 and -18) which are responsible for the majority of cervical cancer cases reported in both countries within the ~ 450 base pairs region amplified by these HPV genotyping systems
Summary
The variation of human papillomavirus (HPV) genotypes shapes the risks of cervical cancer and these variations are not well defined in Africa. Tawe et al BMC Infectious Diseases (2022) 22:95 cancer is the most common cancer and its accounts for 22.2% of all the cancers in women and it is the the most common cause of cancer death among women [2] It is one of the most common cancers in women living with human immunodeficiency virus (HIV) and presents a significant public health threat to women especially on the African continent. In sub-Saharan Africa, human papillomavirus (HPV)-associated cervical cancer is an important cause of morbidity and mortality [3]. Despite having the highest burden of risk factors associated with HPV infection, persistence, and progression to cervical cancer [8], comprehensive data on HPV genotypes and profiles of HPV mutations associated with different cervical cancer risk groups such as HIV/HPV co-infected in Africa are lacking
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