The association between smoking and cervical human papillomavirus infection among women from indigenous communities in western Botswana.

INTRODUCTION: Cervical cancer, a malignancy caused by infection with oncogenic human papillomavirus, disproportionally affects women from low resource settings. Persistence of human papillomavirus infection may mediate an association between tobacco use and cervical cancer. In limited resource settings, women from indigenous communities are often marginalized and do not benefit from evidence-based interventions to prevent tobacco use or cervical cancer due to the limited reach of mainstream healthcare services to these communities. This study determined the association between smoking and high-risk human papillomavirus infection among women from indigenous communities in western Botswana. METHODS: A cross-sectional study of women in indigenous communities was conducted between June and October 2022. Demographic, clinical and self-reported smoking data were collected. Cervical cytology and HPV DNA testing for high-risk human papillomavirus genotypes were performed. Multilevel multivariable logistic regression models were fit to evaluate the association between smoking and high-risk human papillomavirus infection while adjusting for potential confounders. RESULTS: A total of 171 participants with a median (interquartile range) age of 40 (31-50) years from three settlements and two villages were recruited for the study. Of these, 17% were current smokers, 32.8% were living with HIV and high-risk human papillomavirus DNA was detected in 32.8% of the cervical specimens. Women who were current smokers, were nearly twice as likely to have cervical high-risk human papillomavirus infection compared to non-smokers (Adjusted Odds Ratio (95% CI); 1.74(1.09, 2.79)) after controlling for confounders. CONCLUSION: These data underscore the need for effective tobacco control to help mitigate cervical cancer risk in this setting. These findings can help inform decisions about targeted cervical cancer prevention and tobacco cessation interventions for women from indigenous communities.

No woman left behind: achieving cervical cancer elimination among women living with HIV.

Cervical cancer is the fourth most common malignancy in women of reproductive age globally. The burden of this disease is highest in low-income and middle-income countries, especially among women living with HIV. In 2018, WHO launched a global strategy to accelerate cervical cancer elimination through rapid scale-up of prophylactic vaccination, cervical screening, and treatment of precancers and cancers. This initiative was key in raising a call for action to address the stark global disparities in cervical cancer burden. However, achieving elimination of cervical cancer among women with HIV requires consideration of biological and social issues affecting this population. This Position Paper shows specific challenges and uncertainties on the way to cervical cancer elimination for women living with HIV and highlights the scarcity of evidence for the effect of interventions in this population. We argue that reaching equity of outcomes for women with HIV will require substantial advances in approaches to HPV vaccination and improved understanding of the long-term effectiveness of HPV vaccines in settings with high HIV burden cervical cancer, just as HIV, is affected by social and structural factors such as poverty, stigma, and gender discrimination, that place the elimination strategy at risk. Global efforts must, therefore, be galvanised to ensure women living with HIV have optimised interventions, given their substantial risk of this preventable malignancy.

Bibliometric analysis of cancer research outputs in Botswana between 2009 and 2021.

INTRODUCTION: Cancer research is critical for cancer control policies; however, the state of cancer research activities in Botswana is largely unknown. The goal of this review was to describe trends and patterns of cancer research outputs in Botswana. METHODS: PubMed, Web of Science, EBSCOhost, African Journals Online, and African Index Medicus databases were systematically searched for peer-reviewed, primary cancer-related research articles published on the Botswana population or by Botswana institutions between January 2009 and June 2021. RESULTS: Of the 86 publications included, 39 (45 %) were about cervical cancer, followed by breast cancer (10 %) and Kaposi sarcoma (7 %). The remainder (27 %) were not focused on any specific cancer type. The research activities were skewed towards three main areas of scientific interest: early detection, diagnosis, and prognosis; cancer control, survivorship, and outcomes; and treatment. Botswana was represented by authors in the first (54 %), last (53 %), and any authorship (53 %) positions. The United States of America had the strongest collaborative partnerships with Botswana, followed by the United Kingdom and South Africa. The majority of funding institutions were American (76 %) and the National Institutes of Health was the most mentioned funding organization, accounting for 33 % of all financial acknowledgments. Only 9 % of the funding acknowledgments came from Botswana. CONCLUSION AND POLICY SUMMARY: Although cancer research in Botswana is expanding because of substantial foreign assistance, it is also hampered by a lack of local funding, minimal participation by Botswana-affiliated researchers, and research that is not aligned with disease burden. Our study highlights the need to strengthen local research capacity in Botswana.

Pharmacogenetics of Breast Cancer Treatments: A Sub-Saharan Africa Perspective.

Breast cancer is the most frequent cause of cancer death in low- and middle-income countries, in particular among sub-Saharan African women, where response to available anticancer treatment therapy is often limited by the recurrent breast tumours and metastasis, ultimately resulting in decreased overall survival rate. This can also be attributed to African genomes that contain more variation than those from other parts of the world. The purpose of this review is to summarize published evidence on pharmacogenetic and pharmacokinetic aspects related to specific available treatments and the known genetic variabilities associated with metabolism and/or transport of breast cancer drugs, and treatment outcomes when possible. The emphasis is on the African genetic variation and focuses on the genes with the highest strength of evidence, with a close look on CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4/5, CYP19A1, UGT1A4, UGT2B7, UGT2B15, SLC22A16, SLC38A7, FcγR, DPYD, ABCB1, and SULT1A1, which are the genes known to play major roles in the metabolism and/or elimination of the respective anti-breast cancer drugs given to the patients. The genetic variability of their metabolism could be associated with different metabolic phenotypes that may cause reduced patients' adherence because of toxicity or sub-therapeutic doses. Finally, this knowledge enhances possible personalized treatment approaches, with the possibility of improving survival outcomes in patients with breast cancer.

Prevalence of high-risk human papilloma virus in women with high-grade squamous cell intraepithelial lesions in Botswana using Abbott RealTime HPV assay.

BACKGROUND: High-risk human papillomavirus (HR-HPV) has been demonstrated to be the necessary cause of cervical carcinoma. High-risk HPV detection has a prognostic significance for the women who are at increased risk of disease progression. HPV genotyping in cervical cancer precursor lesions is crucial for prevention and management of cervical cancer. This study was designed to investigate the distribution of HR-HPV genotypes among a group of patients with high-grade squamous intraepithelial lesions and higher, of the cervix, in Botswana. MATERIALS AND METHODS: 185-archived residual formalin-fixed paraffin-embedded cervical biopsies collected between the years, 2006 and 2008 were studied. These tissues were diagnosed with HSIL (n = 146) and squamous cell carcinoma (n = 39). DNA was extracted using the Abbott m2000 analyser (Abbott Laboratories, Illinois) using reagents provided by the manufacturer. HPV genotyping was done using the Abbott RealTime HR-HPV PCR, which qualitatively detects 14 HR-HPV (reported as HPV 16, 18 & Other HR-HPV). RESULTS: DNA was successfully extracted from 162/185 (87.6%) tissues as indicated by a positive ß-globin test. 132/162 (82%) tested positive for HR-HPV The HPV 16 prevalence was 50% (66/132), HPV 18 at 15.2% (20/132) and other Group 1 HR-HPV plus HPV 66 and 68 had a prevalence of 56.1% (74/132). Other HR-HPV types were common in HSIL than in carcinoma, while HPV 16 was more prevalent in carcinomas than other HR-HPV genotypes. CONCLUSION: In this study, HPV 16 and other HR-HPV genotypes were commonly associated with HSIL but HPV 18 was uncommon among Botswana women. Our data highlights the need for multivalent HPV vaccines with cross coverage for other high risk HPV other than HPV 16 and 18.

Prevalence of oncogenic human papillomavirus genotypes in patients diagnosed with anogenital malignancies in Botswana.

BACKGROUND: Human papillomavirus (HPV) associated malignancies are the leading cause of cancer death in Botswana. We sought to determine causative HPV types in patients with anogenital malignancies in Botswana to inform vaccine strategy. METHODS: We used formalin-fixed and paraffin-embedded (FFPE) tissue blocks from patients diagnosed with anal, penile and vulvar squamous cell carcinomas between the years, 2014 and 2016. Presence of HPV 16, 18, or other high-risk (HR) types was detected using Abbott m2000 real-time PCR platform. Tissues with other high-risk types were subsequently analysed using a multiplex qPCR assay that includes 15 validated fluorophore probes. RESULTS: A total of 126 tissue specimens, comprising of 21 anal (9 males, 12 females), 31 penile and 74 vulvar were studied. Ninety-three (73.8%) patients had their HIV status documented in the records while the rest did not. Eighty-three (83) out of 93 were HIV positive, a prevalence of 89.4% (95% CI: 81-94). HPV was detected in 68/126 (54%) tissues, of which 69% (95% CI: 54-79) had HPV 16 only, 28% (95% CI: 19-40) had other hr.-HPV types and 2.9% (95% CI, 3.5-10.1) were co-infected with HPV 16 and other hr.-types. Other high-risk types detected included HPV 26, 31, 33, 35, 39, 45, 51, 52, 66 and 68. HPV 18 was not detected. Multiple-type HPV infection was detected in 44 of 47 (93.6%) HIV positive participants co-infected with HPV. In HIV-negative individuals, only HPV 16 was detected. CONCLUSION: In our study, anogenital carcinomas were associated with HPV 16 and other hr.-HPV types besides HPV 16 and 18. HIV co-infected patients had multiple hr.-HPV types detected whereas in HIV-negative patients only HPV 16 was detected. Our study suggests that multivalent vaccines may be more suitable in this setting, especially for HIV-infected individuals.