TY - JOUR
T1 - Genetic diversity in L1 ORF of human papillomavirus in women with cervical cancer with and without human immunodeficiency virus in Botswana and Kenya
AU - Tawe, Leabaneng
AU - Choga, Wonderful T.
AU - Paganotti, Giacomo M.
AU - Bareng, Ontlametse T.
AU - Ntereke, Tlhalefo D.
AU - Ramatlho, Pleasure
AU - Ditshwanelo, Doreen
AU - Gaseitsiwe, Simani
AU - Kasvosve, Ishmael
AU - Ramogola-Masire, Doreen
AU - Orang’o, Omenge E.
AU - Robertson, Erle
AU - Zetola, Nicola
AU - Moyo, Sikhulile
AU - Grover, Surbhi
AU - Ermel, Aaron C.
N1 - Funding Information:
This work was supported by the Sub-Saharan African Collaborative HIV and Cancer Consortia-U54 [Grant # 1U54 CA190158-01], the American Cancer Society International Fellowships for Beginning Investigators (ACSBI), Conquer Cancer Foundation Young Investigator Award, Mentored Patient-Oriented Career Research Development Award (1-K08CA230170-01A1) and Penn Center for AIDS Research [Grant # 5-P30-AI-045008-17]. This work was also supported by the Sub-Saharan African Network for TB/HIV Research Excellence (SANTHE), a DELTAS Africa Initiative [Grant # DEL-15-006]. The DELTAS Africa Initiative is an independent funding scheme of the African Academy of Sciences (AAS)’s Alliance for Accelerating Excellence in Science in Africa (AESA) and supported by the New Partnership for Africa’s Development Planning and Coordinating Agency (NEPAD Agency) with funding from the Wellcome Trust [Grant # 107752/Z/15/Z]. The funding bodies had no role in the design of the study, in the collection, analysis, and interpretation of data, or in writing the manuscript.
Funding Information:
We would like to acknowledge the contributions of Ms Dorcas Maruapula, and Mr Patrick Mokgethi from Botswana Harvard AIDS Institute, who provided insight and expertise that greatly assisted the completion of the study.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - Background: The 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. Methods: A 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). Results: Out 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. Conclusions: Genomic 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.
AB - Background: The 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. Methods: A 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). Results: Out 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. Conclusions: Genomic 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.
KW - Botswana
KW - Cervical cancer
KW - HIV
KW - HIV co-infection
KW - HPV variants phylogenetic analysis
KW - Human papillomavirus
KW - Kenya
KW - L1 gene
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U2 - 10.1186/s12879-022-07081-3
DO - 10.1186/s12879-022-07081-3
M3 - Article
C2 - 35086475
AN - SCOPUS:85123765908
VL - 22
JO - BMC Infectious Diseases
JF - BMC Infectious Diseases
SN - 1471-2334
IS - 1
M1 - 95
ER -