4. Electronic Theses and Dissertations (ETDs) - Faculties submissions

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    Characterising the Role of Cholesterol in Hypoxia-induced Epithelial- Mesenchymal Transition in Breast Cancer
    (University of the Witwatersrand, Johannesburg, 2022) Abdulla, Naaziyah; Kaur, Mandeep
    The cellular epithelial-mesenchymal transition (EMT) process is a complex labyrinth dependent on subversion of critical cellular signalling pathways, which crosstalk extensively to confer cancer cells with characteristics that mediate metastasis. Based on the pleotropic role of cholesterol in the cell, it is not surprising that cancer cells have evolved several mechanisms to facilitate cholesterol dyshomeostasis. In addition to meeting the increased metabolic demands of cancer cells, deregulated cholesterol metabolism also facilitates increased cellular cholesterol availability which is crucial to regulating the activity of protein intermediates in EMT-related signalling pathways. Despite evidence indicating that cholesterol directly regulates signalling pathways related to EMT, no publication to date has attempted to address the effect of EMT induction on cellular cholesterol levels in cancer. To shed light on the dynamics of cholesterol in the relationship between hypoxia and EMT, cholesterol content in MCF-7 cells pre- and post-hypoxia induced EMT was assessed. This dissertation presents findings indicating increased levels of free cholesterol, cholesteryl esters as well as lipid raft cholesterol in MCF-7 cells following hypoxia-induced EMT. Interestingly, MCF-7 cells post- EMT induction displayed increased sensitivity to treatment with cholesterol targeting agents and presented with reversion to an epithelial state as evidenced by the increased expression of epithelial markers, decreased expression of mesenchymal markers and also reduced invasive potential. Importantly, treatment with cholesterol targeting agents is also seen to abrogate the drug resistant potential following hypoxia-induced EMT. Based on these observations, it is proposed that targeting cellular cholesterol could be a promising area to invest in the search for novel therapeutics effective in combatting cancer metastasis
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    An evaluation of the integration of oral pre-exposure prophylaxis (prep) as standard of care for HIV prevention in clinical trials in South Africa
    (University of the Witwatersrand, Johannesburg, 2023) Beesham, Ivana; Mansoor, Leila E; Beksinska,Mags
    Background: Oral tenofovir-based pre-exposure prophylaxis (PrEP) is an effective biomedical HIV prevention option. In 2015, the World Health Organization (WHO) recommended oral PrEP for those at substantial risk of HIV infection, and several countries have since adopted oral PrEP into their national guidelines. In the context of trials, HIV endpoint-driven trials frequently enrol individuals who are at elevated risk of acquiring HIV. Ethical guidelines recommend that study sponsors and investigators should provide access to a package of HIV prevention methods to trial participants, as recommended by WHO, including adding new prevention methods as these are validated. In 2017, the South African Medical Research Council recommended that oral PrEP be provided in HIV prevention trials. The Evidence for Contraceptive Options and HIV Outcomes (ECHO) Trial was ongoing at the time and incorporated oral PrEP into the trial’s HIV prevention package, including the onsite provision of oral PrEP at the South African trial sites during the last eight months of the trial. The ECHO Trial, conducted from 2015 to 2018, enrolled women aged 16-35 years, from 12 research sites in four African countries, and assessed the effect of three contraceptives on HIV incidence. In 2019, when this PhD project was conceptualised, there was a lack of data on the integration of oral PrEP as part of the HIV prevention package in HIV endpoint-driven trials. To address this gap, I evaluated the integration of oral PrEP as standard of care for HIV prevention in clinical trials in South Africa. Objectives: 1. To describe the process of implementing oral PrEP provision, the uptake of oral PrEP and the characteristics of women who initiated (versus those who did not initiate) oral PrEP during the ECHO Trial. 2. To evaluate oral PrEP adherence and factors associated with adherence by conducting plasma tenofovir (TFV) drug level testing using stored blood samples among a subset of women from South Africa who reported current oral PrEP use at the final ECHO Trial visit. 3. To describe the experiences of women who initiated oral PrEP at the Durban, South Africa, ECHO Trial site. 4. To explore post-trial access to oral PrEP, and barriers and enablers to post-trial oral PrEP access, among a subset of women from the Durban, South Africa, ECHO Trial site. 5. To review the current status of oral PrEP as standard of care for HIV prevention in clinical trials in South Africa. Methods: This was a mixed methodology study, conducted from 2019 to 2022, and both qualitative and quantitative methods were utilized. I describe the process undertaken by the ECHO Trial team to incorporate oral PrEP delivery into the trial’s HIV prevention package, including the onsite provision of oral PrEP by ECHO Trial staff at the South African trial sites. Characteristics between women who ever initiated oral PrEP versus those who had access to but did not initiate oral PrEP, were assessed using Chi-squared/Fisher’s exact tests for categorical variables and t-tests for continuous variables. HIV seroincidence comparisons between participants who never versus ever initiated oral PrEP were modelled using exact Poisson regression. To objectively measure adherence to oral PrEP, plasma samples collected at the final ECHO Trial visit, from a subset of women enrolled at the South African ECHO Trial sites, who reported ongoing PrEP use, were tested for TFV. Bivariate logistical regression was used to evaluate participant characteristics associated with quantifiable TFV at the final ECHO Trial visit. 10 | P a g e To understand experiences of women who used oral PrEP and patterns of oral PrEP use, we conducted questionnaires with women who initiated oral PrEP onsite at the Durban, South Africa, ECHO Trial site. Face-to-face questionnaires were conducted approximately three months following oral PrEP initiation, and explored reasons for using and discontinuing oral PrEP, side effects experienced, oral PrEP adherence and disclosure of oral PrEP use. I also evaluated factors associated with oral PrEP continuation at the final ECHO Trial visit using univariate and multivariate logistical regression. Among women continuing oral PrEP at ECHO Trial exit, telephonic follow-up was conducted 4-6 months later, to briefly explore oral PrEP access and ongoing use following study exit. Additional face-to-face, participant in-depth interviews were conducted in 2021 with a subset of women from the Durban, South Africa, ECHO Trial site, who reported ongoing oral PrEP use at ECHO Trial exit and who were given a 3-month PrEP supply at study exit. The interviews explored barriers and enablers to post-trial oral PrEP access. Finally, telephonic in-depth interviews were held with key stakeholders from research sites across South Africa known to conduct HIV endpoint-driven clinical trials to explore their perspectives on providing oral PrEP as HIV prevention standard of care in clinical trials in South Africa. Participant and stakeholder interviews were audio-recorded and transcribed, and thematic analysis was facilitated using NVivo. Results: Our key findings indicate that it was feasible to integrate oral PrEP as standard of care for HIV prevention in the ECHO Trial. PrEP uptake was 17.2% (622/3626) among those eligible for oral PrEP when it became available. Women who initiated oral PrEP were more likely to be unmarried, not living with their partner, having multiple partners; and less likely to be earning their own income and receiving financial support from partners (all p<0.05). There were 37 HIV seroconversions among women who had access to oral PrEP but did not initiate oral PrEP, and 2 seroconversions among women who initiated oral PrEP (HIV incidence 2.4 versus 1.0 per 100 person-years; Incidence Risk Ratio = 0.35; 95% confidence interval (CI) = 0.04 to 1.38). Among the 260 plasma samples from the eight South African ECHO Trial sites that were available for TFV testing, plasma TFV was quantified in 36% of samples (94/260). Women >24 years old had twice the odds of having TFV quantified compared to younger women (Odds Ratio (OR) = 2.12; 95% CI = 1.27 to 3.56). Women who reported inconsistent/no use of condoms had lower odds of TFV quantification (age-adjusted OR = 0.47; 95% CI = 0.26 to 0.83). The ancillary study conducted at the Durban, South Africa ECHO Trial site found that onsite oral PrEP uptake was high (43%, 138/324). Almost all women who initiated oral PrEP at the trial site agreed to participate in the ancillary study (96%, 132/138). Of these, 88% reported feeling at risk of acquiring HIV. Most women (>90%) heard of oral PrEP for the first time from trial staff. Oral PrEP continuation via self- report was 87% at month-1, 80% at month-3, and 75% elected to continue using oral PrEP at trial exit and were referred to off-site facilities for ongoing access. Disclosure of oral PrEP use was associated with five-fold increased odds of continuing oral PrEP at trial exit (adjusted OR = 4.98; 95% CI = 1.45 to 17.13; p=0.01). At telephonic follow-up 4-6 months after women exited the ECHO Trial, >50% reported discontinuing PrEP. Qualitative interviews conducted with a subset of women from the Durban, South Africa ECHO Trial site identified several barriers to post-trial oral PrEP access at facilities such as long queues, facilities being located far from women’s homes, unsuitable clinic operating hours, negative attitudes from providers, and oral PrEP being unavailable at some clinics. Interviews with key stakeholders from research sites in South Africa found that most stakeholders reported incorporating oral PrEP provision as part of the HIV prevention package offered to participants in HIV endpoint-driven trials. Stakeholders identified barriers to oral PrEP 11 | P a g e uptake, adherence, persistence, and post-trial access. Demand creation, and education and counselling about oral PrEP were reported as factors that facilitated uptake. Conclusion: The ECHO Trial provides evidence that it was feasible to successfully integrate oral PrEP provision as part of the trial’s HIV prevention package offered to study participants. Other HIV endpoint-driven trials can utilize our findings as a model to integrate oral PrEP provision into the HIV prevention package offered in a trial. The ancillary study findings on PrEP uptake, adherence and persistence can be utilized to guide oral PrEP trials and implementation programs. While post-trial oral PrEP access was concerning and several barriers were identified, it is possible that with the scale-up of oral PrEP in the public sector in South Africa after the ECHO Trial was completed, participants exiting trials and desiring to continue oral PrEP could have better access
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    The effects of COVID 19 on consumer mobile and online purchase behaviour
    (University of the Witwatersrand, Johannesburg, 2023) Chanetsa, Edphan Peter; Saini, Yvonne K.
    There obtains an acute paucity of research on the how Covid-19 impacted consumer online and mobile application purchase behaviour in South Africa. Much of the work done on the impact of the pandemic on consumer behaviour has primarily focused on one aspect: online purchase behaviour. This study sought to assess the effects of the restrictions of the novel Covid-19 virus on consumer mobile and online purchase behaviour. The main objective was to understand the impact of Covid-19 related restrictions on mobile application purchase intention in grocery shopping. Similarly, the study also sought to understand the impact of Covid-19 related restrictions on online (desktop/laptop) purchase intention in grocery shopping. An online survey was conducted wherein 345 responses were obtained. The study employed a mixed methodology approach with the primary analysis being done quantitatively employing path analysis to establish the existence of causal links between Covid-19 restrictions and consumer behaviour in terms of both direction and magnitude. Regression analysis was further carried out to corroborate the findings of the path analysis. The qualitative aspect of the analysis was primarily employed to buttress the results of the quantitative analysis. The results showed that Covid-19 had a significant and positive impact on mobile and online consumer behaviour in South Africa. The advent of the pandemic caused an increase in the uptake of alternative means of making grocery purchases. Specifically, the institution of Covid-19 restrictions produced a substitution effect wherein digital purchase platforms were preferred to in-store purchases of groceries. Consequently, all the hypotheses developed by the study proved to be robust as they were confirmed by the results
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    Retrospective audit of the appropriate use criteria for ventilation/perfusion imaging in pulmonary embolism in a South African population cohort
    (University of the Witwatersrand, Johannesburg, 2023-09) Sibindlana, Amanda Patiswa; Vangu, Mboyo-Di-Tamba; Malan, Nico; Momodu, Jaleelat
    Background: Venous thromboembolism (VTE) is blood clot formation comprising deep vein thrombosis (DVT) and pulmonary embolism (PE). Stasis, endothelial dysfunction and hypercoagulability place an individual at increased risk for developing DVT. VQ scans are crucial to determine the appropriate treatment in patients. The use of VQ scans is addressed in several clinical scenarios, including pregnancy, renal failure, contrast allergy, haemodynamic instability and abnormal chest X-ray findings. Aim: This study assessed the appropriateness of VQ scan requests received by the nuclear medicine departments at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) and Chris Hani Baragwanath Academic Hospital (CHBAH). Methods: The appropriateness of referrals and VQ scintigraphy in patients with suspected PE at CMJAH and CHBAH nuclear medicine clinical departments was determined. A retrospective audit was done on the request forms of patients referred for VQ scintigraphy to a diagnose pulmonary embolism over five years from 01 January 2015 to 31 December 2019. The clinical information in the request forms was compared to the appropriate use criteria (AUC) to determine the level of appropriateness and categorised as appropriate, maybe appropriate and rarely appropriate. Statistical software (STATA) was used for data analysis. T-tests were used for continuous variables, and Pearson’s chi-squared tests were used for dichotomous data. A p-value of <0.05 was considered statistically significant. Results: A total of 1167 records were reviewed, and fewer than 50% of the referrals were found to be appropriate overall. There were 440 records that fitted the relevant criteria, 580 were rarely appropriate, and 149 maybe appropriate. The median age of individuals referred was 45 years. Most records were for females, with 321 (73%) falling into the appropriate category. There were 72 (13%) confirmed pregnancies and 17 (24%) were appropriate for a VQ scan. The average D-dimer concentration for these patients was 2.15 mg/L. The average D-dimer concentration was the highest in patients where referrals for VQ scans were considered as maybe appropriate (2.6 mg/L; 1.18 – 6.7) compared to an average D-dimer concentration of 2.5 mg/L (1.35 – 6.78) in patients appropriately referred for VQ scans and 0.68 mg/L (0.41 – 1.51) for patients inappropriately referred for VQ scans. Some patients were still referred for VQ scans to exclude the possibility of PE. Conclusion: The criteria used for referrals in our clinical setting were found insufficient due to the inefficient system and criteria used to refer patients in our clinical setting. This may result from a lack of required information and standardisation of the assessments with which clinicians judge the patient’s risk for PE/VTE. This was the case even in a largely female cohort with many concurrent risk factors.
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    The incidence of pathological findings in contralateral reduction mammoplasty specimens in patients with breast cancer
    (University of the Witwatersrand, Johannesburg, 2023-11) Diakakis, Alexander; Sofianos, Chrysis; Mabe, Neo; Nel, Carolina; Phiri, Sibusiso
    Objectives: Occult invasive contralateral breast carcinoma negatively affects survival in breast cancer patients. The objective of this study is to measure the incidence of abnormal pathological specimens in reduction mammoplasty specimens in patients known to have contralateral breast cancer in a specialist breast unit in South Africa and to interpret the pathological findings and stratify them according to cancer stage and immunohistochemistry. Methods: A retrospective record review of the pathological findings in the contralateral breast of patients known with breast cancer who underwent either oncoplastic bilateral breast reduction or unilateral mastectomy and contralateral reduction between January 2017 and December 2022. Data was obtained from the breast cancer database used at our institution (OncoDB) and histology reports were obtained from the National Health Laboratory Services. The association between cancer stage, axillary findings and immunohistochemistry when compared to contralateral histology findings was done using the Chi-squared test. Results: A total of 112 patients were included with a mean (SD) age of 50.6 (10.8). Within the cohort of patients, 69 underwent mastectomy and contralateral reduction and 43 patients had bilateral oncoplastic breast reductions performed. 91 (81.3%) were 14 found to have no pathology, 12 (10.7%) had benign lesions, 8 (7.1%) were found to have proliferative lesions and 1 patient (0.8%) had a lobular carcinoma in situ (LCIS). Conclusion: There was an increased prevalence of contralateral breast pathology in ER positive patients and as cancer stage increased, however these findings were not statistically significant. Findings were similar with regards to PR, HER2 and nodal status.
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    The usefulness of monocyte fluorescence as a biomarker of Tuberculosis infection at Chris Hani Baragwanath Academic Hospital
    (University of the Witwatersrand, Johannesburg, 2023-11) Moosa, Aamina Yunus; Vaughan, Jenifer; Hodkinson, Katherine
    Introduction: South Africa has the 5th highest burden of Tuberculosis (TB) as well as coinfection with Human immunodeficiency virus (HIV) worldwide. Routine laboratory methods have varying sensitivity and specificity. The Xpert MTB/RIF (GXPU) (Cepheid, Sunnyvale, CA), has lower sensitivity in sputum smear negative cases and poor quality sputum samples. A robust, non-sputum based, inexpensive biomarker of TB would be of value in such cases. Monocytes are the major leucocyte involved in the immune response to TB. The Sysmex haematology analysers (Sysmex, Kobe, Japan) measure monocyte activation via monocyte fluorescence (MO-Y). This study aimed to evaluate the MO-Y and other Sysmex extended differential parameters (EDPs) as biomarkers of TB infection in the local setting. Methods: The MO-Y and EDPs were retrieved from the analyser for 121 adult cases (56 with TB, 65 controls). Further information was obtained from the laboratory information system, including patient demographics and other laboratory results; TB culture, SARS-CoV-2 results, C-reactive protein level, HIV status, bone marrow biopsies and the cycle threshold (CT) values on positive GXPU analysis. The MO-Y, EDPs and full blood count (FBC) values were compared among patients with and without TB (HIV positive and negative). Statistical significance was assessed (P-value of <0.05). Results: The MO-Y did not show utility in identifying patients with TB. A sub-population of patients living with HIV (PLWH) with a CD4 <100 cells/ul showed significantly higher MO-Y levels, due to other opportunistic infections affecting monocytes. Neutrophil surface fluorescence (a marker of neutrophil activation), was significantly higher in PLWH and with concomitant TB infection, possibly due to immune activation, worse illness, or increased bacterial infection. Among the PLWH, those with TB had significantly lower CD4 counts, absolute lymphocyte counts and mean cell volume (MCV) values. The MCV (cut-off value 87 fL) showed the strongest diagnostic utility for discriminating PLWH with and without TB (AUC 0.79). Conclusion: The MO-Y is not a useful biomarker of TB, but is significantly elevated in PLWH with low CD4 counts. The MCV showed adequate discriminatory power for differentiating patients with and without TB, at a cut-off level of 87fL.
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    Caregiver's oral health knowledge, attitudes and practices towards children with special health care needs in Harare Province, Zimbabwe
    (University of the Witwatersrand, Johannesburg, 2023-11) Mashanda, Vimbai; Tootla, Saidah; Malauy, Cathrine
    Background: Children with Special Health Care Needs (CSHCN) are prone to oral diseases such as dental caries and periodontal disease. This is due to limitations in oral hygiene practices because of their debilitating conditions. Therefore, caregivers play a major role in the maintenance of CSHCN’s oral health. As a result, caregiver’s oral health knowledge and attitudes are important to ensure that the oral health of CSHCN is maintained. Aim and Objectives: The aim of this study was to describe the caregiver’s oral health knowledge, attitudes, and practices (KAP) towards CSHCN. The objectives of the study were to determine the caregiver’s demographic profile, to assess the caregiver’s oral health KAP towards CSHCN and to assess whether there is a relationship between the caregiver’s level of education, demographic characteristics, and oral health KAP and factors related to oral health practices. Methods: A quantitative cross-sectional study design and convenience sampling method was utilised. Caregivers above 18 years of CSHCN who attended support group meetings in Harare Province, Zimbabwe and were willing to participate, took part in the study. A modified self-administered questionnaire (SAQ) was used for data collection. The SAQ comprised of a demographics section for the caregiver, child’s disability type and oral health KAP questions. Two sample t-tests and Analysis of Variance (ANOVA) was used to compare the means of caregivers KAP. Multiple linear regression model was used to assess the association between caregivers’ KAP and demographic characteristics. Only the variables with p<0.15 in the univariate model were included in the multiple linear and multivariate logistic regression models. Multivariable logistic regression was used to assess the association between caregivers’ oral health practice and demographic characteristics. Apriori variables such as age, level of education, knowledge and attitude were selected for all multivariable logistic models. All variables with p<0.05 were considered to be statistically significant and statistical analysis were performed using Stata. Results: The response rate was 76.8% n=295). Almost 90% (89.2%, n=263) of the caregivers were females and nearly three quarters (72.5%, n=214) were mothers. A third (33.6%, n=99) of the caregivers were aged between 31-40 years. Fifty-three percent (n=157) of the caregivers were unemployed and 61.7% (n=182) were educated up to high school level. Forty-six percent (n=135) of the CSHCN had cerebral palsy. Out of the 295 caregivers, 45.4% (n=134) had fair oral health knowledge, 79.7% (n=235) had a good attitude towards oral health and 62% (n=183) had fair oral health practices. Conclusions: Most of the caregivers had good oral health attitude, however their knowledge and practices were fair. Factors associated with caregivers’ attitude were their knowledge and level of education, and the caregivers’ practices were associated with knowledge and attitude.
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    Factors associated with delayed presentation among patients with oral cancer in Malawi central hospitals
    (University of the Witwatersrand, Johannesburg, 2023-10) Lungu, Nathan; Sekhoto, M.G.; Turton, M.
    Background: Oral cancer patients are prone to delays in visiting healthcare facilities resulting in delayed diagnosis, poor prognosis, disfigurement of patients, and increase in management costs. Objective: The aim was to assess factors related to health-seeking delay among patients with oral cancer in Malawi's central hospitals. Methodology: This research was a descriptive cross-sectional study of patients with oral cancer. The study was conducted in all Malawi referral hospitals' dental clinics from April to June 2023 using a closed-ended, structured questionnaire. Results: Thirty-six (52.94%) patients visited the hospital when in pain, and 66.18% (n=45) were not aware of oral cancer. A significant, statistical relationship (p=0.042) was identified between the delay and reporting to the nearest health care facility. Conclusion: Lack of awareness, pain and distance to the nearest health care facility were associated with delays. Education and awareness in primary health care can help prevent treatment delays.
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    The contribution of common genetic variants to breast cancer risk in South African black populations
    (University of the Witwatersrand, Johannesburg, 2023-08) Hayat, Mahtaab; Brandenburg, Jean-Tristan; Ramsay, Michèle; Mathew, Christopher
    Breast cancer is the second most common cancer in South African black women. The contribution of common genetic variants to breast cancer risk is well studied in non-African populations, but little is known about their role in resident African populations, and there are no published genome-wide association studies (GWAS) on breast cancer in Africa. This PhD thesis aimed to determine the contribution of common genetic variants to breast cancer in a South African black population. A GWAS was carried out in 2,573 black female breast cancer patients from the Johannesburg Cancer Study and 744 population-matched, female controls from the AWI-Gen study. All participants were from Soweto, Johannesburg, South Africa. Samples were genotyped on the H3Africa SNP array. Replication testing was done of existing loci from European and African American (AA) populations in the resident African data, and loci from the resident African data in European and AA populations. A meta-analysis was carried out with an AA population. Finally, existing polygenic risk scores (PRSs) were tested in the resident African dataset. Three variants at two loci were strongly associated with breast cancer in this study. Two variants (rs77422433, p-value=2.89x10-08, odds ratio (OR):0.46, 95% confidence interval (95%CI): 0.40-0.52 and rs112410019, p-value=3.01x10-08, OR: 0.47, 95%CI: 0.41-0.53) were located within the DNA repair gene XRCC5. These variants were not previously associated with breast cancer, suggesting that it may be an African specific risk locus. The second locus is on chromosome 16 in CES5A (rs3859109, p-value=4.54x10-08, OR=0.70, 95%CI: 0.68-0.73), and had not previously been associated with breast cancer. None of these SNPs were replicated in European and AA populations. The meta-analysis with AA data revealed strong association of an intergenic SNP with breast cancer (rs139299680, pmeta=7.25x10-08) on chromosome 3. A polygenic risk score (PRS) developed in European populations demonstrated poor transferability to this African dataset. This GWAS is the first to be conducted in a resident black African population. This study suggests that there may be African-specific genetic risk factors for African breast cancer, and that large genome-wide studies in African populations are essential to develop a comprehensive understanding of the genetics of breast cancer in Africa.
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    A retrospective study of histologically diagnosed intra-oral lesions within Ugu district, KZN, South Africa
    (University of the Witwatersrand, Johannesburg, 2023-10) Reddy, Larisha Yashoda; Premviyasa, Vinayagie
    Introduction: The oral cavity is exposed to a magnitude of physical and chemical trauma, carcinogenic agents and microbial pathogens that may cause a wide spectrum of oral lesions. These oral lesions may appear as benign, potentially malignant, or malignant thereby requiring biopsies to determine histopathological features to confirm a diagnosis. Oral lesions have the potential to hinder the quality of life for the afflicted patient. The patients’ speech, mastication, swallowing may be affected with the occurrence of oral dysesthesia. With the confirmation of a positive malignant biopsy, the afflicted individual will have to endure the possible side effects of chemotherapy and radiation. In global studies, the prevalence of oral lesions may vary amongst different countries, geographical areas, ethnicities, cultural practices, and social habits. Aim: To identify the different types of intra-oral lesions and the prevalence of malignant oral lesions within UGU district, Kwa- Zulu Natal (KZN). Objectives: 1. To identify the different types of intra oral lesions and characterise by demographics. 2. To determine the prevalence of malignant oral lesions within UGU district, KZN. 3. To determine the association between patients’ social habits and the development of the most common intra oral lesions, with the differentiation of malignant vs non-malignant oral lesions. 4. To assess the concordance of a clinical differential diagnosis and histopathological diagnosis. Study design and Methodology: A quantitative, retrospective case review of dental patient files and histopathological reports of the four selected hospitals in UGU were analysed from January 2016 to August 2022. One hundred and thirty-four patient records were reviewed. Data collected included patients’ age, gender, comorbidities, social habits, differential diagnosis, and histological diagnosis. The data was analysed using a free open-source statistical software program called “R”. Study results: One hundred and thirty-four patients met the criteria of this study. The age of patients ranged between seven and eighty-seven (M= 46.37; SD= 20.77). There were 81 females (60.4%) and 53 males (39.6%). Benign lesions had represented 67.2% (N: 90) of the intra oral biopsies, with the remaining 32.8 %, (N:44), representing malignant lesions. The most common lesions presenting in UGU district were fibrous epulis (N: 15, 11.2%), pyogenic granuloma (N:36, 26.9%) and squamous cell carcinoma (N:37, 27.6%). No statistical relation was proven between ethnicity, sex, and social habits with the benign lesions of fibrous epulis and pyogenic granuloma. Statistical relation was proven between squamous cell carcinoma and ethnicity, gender, and social habits. A substantial level of concordance (agreement) was proven with the Kappa Statistic of 0.7437, hereby indicating a good general knowledge of intra-oral lesions amongst the dentist performing the intra oral biopsies within UGU district. Conclusion: Fibrous epulis, pyogenic granuloma and oral squamous cell carcinoma had been identified as the three most common lesions in UGU, KZN, representing 65.7% of the confirmed biopsy results. Fibrous epulis and pyogenic granuloma had shown no statistical association to ethnicity, gender, alcohol consumption and smoking. In this study, oral squamous cell carcinoma had shown statistical association to white males and consumption of alcohol and smoking. This study has demonstrated the diversity and prevalence of intra-oral lesions within the rural district of UGU, KZN, South Africa as compared to global studies.