Browsing by Author "Hoffman, Margaret"

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    The allelic distribution of -308 Tumor Necrosis Factor-alpha gene polymorphism in South African women with cervical cancer and control women
    (BioMed Central Ltd, 2006) Govan, Vandana; Constant, Debbie; Hoffman, Margaret; Williamson, Anna-Lise
    BACKGROUND:Cervical cancer is due to infection with specific high-risk types of human papillomavirus (HPV). Although the incidence of genital HPV infection in various population groups is high, most of these regress without intervention. Investigating genetic host factors and cellular immune responses, particularly cytokines, could help to understand the association between genital HPV infection and carcinogenesis. The tumor necrosis factor alpha (TNF-alpha) cytokine plays an important role in all stages of cervical cancer and has the ability to induce the regression of human tumors. Therefore the aim of the study was to investigate the allelic distribution of -308 TNF-alpha gene polymorphism in South African women with cervical cancer compared to control women. METHODS: Included in our study were women with histologically proven cancer of the cervix (n = 244) and hospital-based controls (n = 228). All patients and controls were from mixed race and black population groups in South Africa. The detection of a bi-allelic -308 (A/G) polymorphism in the promoter region of TNF-alpha was investigated using the amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) technique. The distributions of the allelic frequencies were stratified in both patients and controls into two South African ethnic population groups. RESULTS: In this study we observed no association between the distribution of -308 TNF-alpha polymorphism and the risk of developing cervical cancer even after combining the data from the two ethnic populations (X2 = 2.26). In addition, using the chi-squared test we found no significant association between the known risk factors for cervical cancer and the allele distribution of -308 TNF-alpha. However, the frequency of the rare high-producing allele -308A of TNF-alpha was significantly lower in the South African population when compared to Caucasians and Chinese population groups. CONCLUSION: We demonstrated no association between -308 TNF-alpha polymorphism and the risk of cervical cancer among two South African ethnic population groups. However, as the distribution of the -308A TNF-alpha was notably different between the control groups of South Africa and other population groups this result suggests that ethnic disparity may influence the levels of TNF-alpha produced.
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    An assessment of the factors that influence the infant feeding practices of HIV-positive mothers in The Mothers' Programmes : a qualitative study
    (2005) Mackowski, Amy M; Orner, Phyllis; Hoffman, Margaret
    Many researchers consider breastfeeding as the best way to feed an infant, as it provides numerous benefits both physical and psychological for mother and child (Baumslag & Michels, 1995; Preble & Piwoz, 1998; Smith & Kuhn, 2000; World Health Organization (WHO), 2000; WHO, 2003). However, breast milk is a body fluid, like blood or semen, which can transmit the Human Immunodeficiency Virus (HIV) from mother to baby (White, 1999). A woman infected with HIV may pass the virus on to her child via pregnancy, labour or delivery or through breastfeeding (WHO, 2003). In developing countries where the prevalence of HIV/AIDS is high, particularly among women of reproductive age, protecting children from HIV infection is a critical public health concern.
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    CCR2-V64I polymorphism is associated with increased risk of cervical cancer but not with HPV infection or pre-cancerous lesions in African women
    (BioMed Central Ltd, 2010) Chatterjee, Koushik; Dandara, Collet; Hoffman, Margaret; Williamson, Anna-Lise
    BACKGROUND: Cervical cancer, caused by specific oncogenic types of human papillomavirus (HPV), is the second most common cancer in women worldwide. A large number of young sexually active women get infected by HPV but only a small fraction of them have persistent infection and develop cervical cancer pointing to co- factors including host genetics that might play a role in outcome of the HPV infection. This study investigated the role of CCR2-V64I polymorphism in cervical cancer, pre-cancers and HPV infection in South African women resident in Western Cape. CCR2-V64I polymorphism has been previously reported to influence the progression to cervical cancer in some populations and has also been associated with decreased progression from HIV infection to AIDS. METHODS: Genotyping for CCR2-V64I was done by PCR-SSP in a case-control study of 446 women (106 black African and 340 mixed-ancestry) with histologically confirmed invasive cervical cancer and 1432 controls (322 black African and 1110 mixed-ancestry) group-matched (1:3) by age, ethnicity and domicile status. In the control women HPV was detected using the Digene Hybrid Capture II test and cervical disease was detected by cervical cytology. RESULTS: The CCR2-64I variant was significantly associated with cervical cancer when cases were compared to the control group (P = 0.001). Further analysis comparing selected groups within the controls showed that individuals with abnormal cytology and high grade squamous intraepitleial neoplasia (HSIL) did not have this association when compared to women with normal cytology. HPV infection also showed no association with CCR2-64I variant. Comparing SIL positive controls with the cases showed a significant association of CCR2-64I variant (P = 0.001) with cervical cancer. CONCLUSIONS: This is the first study of the role of CCR2-V64I polymorphism in cervical cancer in an African population. Our results show that CCR2-64I variant is associated with the risk of cervical cancer but does not affect the susceptibility to HPV infection or HSIL in South African women of black and mixed-ancestry origin. This result implies that the role of CCR2 is important in invasive cancer of the cervix but not in HPV infection or in the development of pre-cancers.
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    Depot medroxyprogesterone acetate versus norethisterone oenanthate for long-acting progestogenic contraception : a systematic review
    (2006) Draper, Beverly; Hoffman, Margaret
    [Background] Two injectable progestogen-only contraceptives (IPCs) depot medroxyprogesterone acetate (DMPA) and norethisterone oenanthate (NET-EN) continue to be extensively used in some countries, forming a large proportion of the health system's expenditure on contraception. Both these highly effective contraceptives receive wide acceptance amongst women in their fertile years. They differ in cost and frequently of administration. A systematic comparison was undertaken to investiage their rational use. [Objectives] To determine if there are differences between depot medroxyprogesterone acetate given at a dose of 150mg IM every three months and norethisterone oenathate given at a dose of 200mg IM every two months, in terms of contraceptive effectiveness, reversibility and discontinuation patterns, and adverse clinical effects. [Study Design] A Cochrane systematic review was used to answer the question posed in the research objective. This included a systematic search for all available literature comapring DMPA and NET-EN, followed by appraisal of all studies for inclusion in the review. Meta-analysis was then applied to the included study.
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    Determinants of sexual activity and its relation to cervical cancer risk among South African Women
    (BioMed Central Ltd, 2007) Cooper, Diane; Hoffman, Margaret; Carrara, Henri; Rosenberg, Lynn; Kelly, Judy; Stander, Ilse; Denny, Lynnette; Williamson, Anna-Lise; Shapiro, Samuel
    BACKGROUND:Invasive cervical cancer is the commonest cause of cancer morbidity and mortality in South African women. This study provides information on adult women's sexual activity and cervical cancer risk in South Africa. METHODS: The data were derived from a case-control study of hormonal contraceptives and cervical cancer risk. Information on age of sexual debut and number of lifetime sexual partners was collected from 524 incident cases and 1541 hospital controls. Prevalence ratios and adjusted prevalence ratios were utilised to estimate risk in exposures considered common. Crude and adjusted relative risks were estimated where the outcome was uncommon, using multiple logistic regression analysis. RESULTS: The median age of sexual debut and number of sexual partners was 17 years and 2 respectively. Early sexual debut was associated with lower education, increased number of life time partners and alcohol use. Having a greater number of sexual partners was associated with younger sexual debut, being black, single, higher educational levels and alcohol use. The adjusted odds ratio for sexual debut < 16 years and [greater than or equal to] 4 life-time sexual partners and cervical cancer risk were 1.6 (95% CI 1.2 - 2.2) and 1.7 (95% CI 1.2 - 2.2), respectively. CONCLUSION: Lower socio-economic status, alcohol intake, and being single or black, appear to be determinants of increased sexual activity in South African women. Education had an ambiguous effect. As expected, cervical cancer risk is associated with increased sexual activity. Initiatives to encourage later commencement of sex, and limiting the number of sexual partners would have a favourable impact on risk of cancer of the cervix and other sexually transmitted infections
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    Fas and FasL gene polymorphisms are not associated with cervical cancer but differ among Black and Mixed-ancestry South Africans
    (BioMed Central Ltd, 2009) Chatterjee, Koushik; Engelmark, Malin; Gyllensten, Ulf; Dandara, Collet; Merwe, Lize; Galal, Ushma; Hoffman, Margaret; Williamson, Anna-Lise
    BACKGROUND:Cervical cancer is one of the most important cancers in African women. Polymorphisms in the Fas (FasR) and Fas ligand (FasL) genes have been reported to be associated with cervical cancer in certain populations. This study investigated whether these polymorphisms are associated with cervical cancer or human papillomavirus (HPV) infection in South African women.FINDINGS:Participants were 447 women with invasive cervical cancer (106 black African and 341 women of mixed-ancestry) and 424 healthy women controls, matched by age, (101 black African and 323 women of mixed-ancestry) and domicile (rural or urban). Two polymorphisms in Fas gene (FasR-1377G/A, FasR-670A/G) and one in FasL gene (FasL844T/C) were genotyped by TaqMan. None of the polymorphisms, or the Fas haplotypes, showed a significant association with cervical cancer. There was also no association with HPV infection in the control group. However, on analysis of the control group, highly significant allele, genotype and haplotype differences were found between the two ethnic groups. There were generally low frequencies of FasR-1377A alleles, FasR-670A alleles and FasL-844C alleles in black women compared to the women of mixed-ancestry. CONCLUSION: This is the first study on the role of Fas and FasL polymorphisms in cervical cancer in African populations. Our results suggest that these SNPs are not associated with cervical cancer in these populations. The allele frequencies of the three SNPs differed markedly between the indigenous African black and mixed-ancestry populations.
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    HIV and pre-neoplastic and neoplastic lesions of the cervix in South Africa: a case-control study
    (BioMed Central Ltd, 2006) Moodley, Jennifer; Hoffman, Margaret; Carrara, Henri; Allan, Bruce; Cooper, Diane; Rosenberg, Lynn; Denny, Lynette; Shapiro, Samuel; Williamson, Anna-Lise
    BACKGROUND:Cervical cancer and infection with human immunodeficiency virus (HIV) are both major public health problems in South Africa. The aim of this study was to determine the risk of cervical pre-cancer and cancer among HIV positive women in South Africa. METHODS: Data were derived from a case-control study that examined the association between hormonal contraceptives and invasive cervical cancer. The study was conducted in the Western Cape (South Africa), from January 1998 to December 2001. There were 486 women with invasive cervical cancer, 103 control women with atypical squamous cells of undetermined significance (ASCUS), 53 with low-grade squamous intraepithelial lesions (LSIL), 50 with high-grade squamous intraepithelial lesions (HSIL) and 1159 with normal cytology. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multiple logistic regression. RESULTS: The adjusted odds ratios associated with HIV infection were: 4.4 [95% CI (2.3 - 8.4) for ASCUS, 7.4 (3.5 - 15.7) for LSIL, 5.8 (2.4 - 13.6) for HSIL and 1.17 (0.75 - 1.85) for invasive cervical cancer. HIV positive women were nearly 5 times more likely to have high-risk human papillomavirus infection (HR-HPV) present compared to HIV negative women [OR 4.6 (95 % CI 2.8 - 7.5)]. Women infected with both HIV and high-risk HPV had a more than 40 fold higher risk of SIL than women infected with neither of these viruses. CONCLUSION: HIV positive women were at an increased risk of cervical pre-cancer, but did not demonstrate an excess risk of invasive cervical cancer. An interaction between HIV and HR-HPV infection was demonstrated. Our findings underscore the importance of developing locally relevant screening and management guidelines for HIV positive women in South Africa.
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    Human papillomavirus prevalence, viral load and pre-cancerous lesions of the cervix in women initiating highly active antiretroviral therapy in South Africa: a cross-sectional study
    (BioMed Central Ltd, 2009) Moodley, Jennifer; Constant, Deborah; Hoffman, Margaret; Salimo, Anna; Allan, Bruce; Rybicki, Ed; Hitzeroth, Inga; Williamson, Anna Lise
    BACKGROUND:Cervical cancer and infection with human immunodeficiency virus (HIV) are both important public health problems in South Africa (SA). The aim of this study was to determine the prevalence of cervical squamous intraepithelial lesions (SILs), high-risk human papillomavirus (HR-HPV), HPV viral load and HPV genotypes in HIV positive women initiating anti-retroviral (ARV) therapy. METHODS: A cross-sectional survey was conducted at an anti-retroviral (ARV) treatment clinic in Cape Town, SA in 2007. Cervical specimens were taken for cytological analysis and HPV testing. The Digene Hybrid Capture 2 (HC2) test was used to detect HR-HPV. Relative light units (RLU) were used as a measure of HPV viral load. HPV types were determined using the Roche Linear Array HPV Genotyping test. Crude associations with abnormal cytology were tested and multiple logistic regression was used to determine independent risk factors for abnormal cytology. RESULTS: The median age of the 109 participants was 31 years, the median CD4 count was 125/mm3, 66.3% had an abnormal Pap smear, the HR-HPV prevalence was 78.9% (Digene), the median HPV viral load was 181.1 RLU (HC2 positive samples only) and 78.4% had multiple genotypes. Among women with abnormal smears the most prevalent HR-HPV types were HPV types 16, 58 and 51, all with a prevalence of 28.5%. On univariate analysis HR-HPV, multiple HPV types and HPV viral load were significantly associated with the presence of low and high-grade SILs (LSIL/HSIL). The multivariate logistic regression showed that HPV viral load was associated with an increased odds of LSIL/HSIL, odds ratio of 10.7 (95% CI 2.0 - 57.7) for those that were HC2 positive and had a viral load of [less than or equal to] 181.1 RLU (the median HPV viral load), and 33.8 (95% CI 6.4 - 178.9) for those that were HC2 positive with a HPV viral load > 181.1 RLU. CONCLUSION: Women initiating ARVs have a high prevalence of abnormal Pap smears and HR-HPV. Our results underscore the need for locally relevant, rigorous screening protocols for the increasing numbers of women accessing ARV therapy so that the benefits of ARVs are not partially offset by an excess risk in cervical cancer.
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    Papanicolaou smears and cervical inflammatory cytokine responses
    (BioMed Central Ltd, 2007) Passmore, Jo-Ann; Morroni, Chelsea; Shapiro, Samual; Williamson, Anna-Lise; Hoffman, Margaret
    In a case-control study among 2064 South African women to investigate the risk of clinically invasive cancer of the cervix, we found a marked reduction in the risk of cervical cancer among women who gave a history of ever having undergone even a single Pap smear, and a statistically significant decline in the HPV positivity rate correlated with the lifetime number of Pap smears received. HPV infections and their associated low-grade lesions commonly regress, indicating that most often there is an effective host immune response against HPV infection. We hypothesized that act of performing a Pap smear is associated with inflammatory responses at the site of trauma, the cervix, and that this inflammatory signalling may be an immunological factor initiating these productive anti-HPV responses. In the present study, a randomized controlled trial, we enrolled 80 healthy young women to investigate the impact of performing a Pap smear on cervical inflammation. Forty one women, in the intervention group, received a Pap smear at enrollment and cervicovaginal lavages (CVLs) were collected at baseline and 2 weeks later. Thirty nine women received no intervention at enrollment (control group) but CVLs were collected at enrolment and 2 weeks later. We assessed various markers of inflammation including IL-12 p70, TNF-alpha, IL-8, IL-6, IL-10, and IL-1beta in CVL specimens. While CVL levels of IL-8, IL-1beta and IL-6 remained unchanged following a Pap smear, markers of cell mediated immunity (IL-12 p70 and TNF-alpha) and T cell regulation (IL-10) were significantly elevated.
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    Prevention of cervical cancer in South Africa : opportunities and challenges
    (2011) Moodley, Jennifer Rose; Myers, Jonny; Hoffman, Margaret
    This thesis examines the challenges to and opportunities for comprehensive (primary and secondary) prevention of cervical cancer in South Africa (SA), a middle-income country.
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    The agreement between cervical abnormalities identified by cytology and detection of high-risk types of human papillomavirus
    (2006) Allan, Bruce R; Marais, Dianne J; Denny, Lynette; Hoffman, Margaret; Shapiro, Samuel; Williamson, Anna-Lise
    Objectives and design. Human papillomavirus (HPV) is causally associated with cervical cancer. Using the Digene Hybrid Capture 2 high-risk HPV test (HC2), we investigated the prevalence of high-risk HPV in cervical specimens, and compared results with those of Papanicolaou (Pap) smears taken concurrently Subjects and setting. Cervical specimens were obtained from women attending hospitals/community health centres in the Western Cape province of South Africa. They were participating in a case-control study of the association of hormonal contraceptives and invasive cervical cancer. Results. Of 1 491 women tested, 254 (17%) were HPV DNA positive. The age-specific prevalence of HPV was 36/97 (37.1%) in those aged < 30 years, 78/369 (21.1%) in those aged 30 - 39 years, 78/603 (12.9%) in those aged 40 - 49 years and 62/422 (14.7%) in those aged 50 - 59 years. In women with normal cytology the prevalence of HPV was 10.9% (138/1 264); in those with abnormal squamous cells of unknown significance (AS-CUS) it was 30.8% (36/117); in those with low-grade squamous intraepithelial lesions (LSIL) it was 63.2% (36/57), and in those with high-grade squamous intraepithelial lesions (HSIL) it was 83% (44/53). The odds ratio between HPV and HSIL in women aged 40 - 59 years was 57.1 (confidence interval 22.4 - 170.7). Conclusions. HC2 detected a high prevalence of HPV (17%) in this population. Most women with HSIL (83%) were positive, indicating that HPV testing of AS-CUS women may aid in management. When costs decrease, HC2 could be introduced as an adjunct to Pap smears in identifying women at risk for high-grade cervical disease and could be useful in the maintenance of cervical health in those who remain Pap smear negative.
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    Using quantitative ultrasound for epidemiological research : associations with risk factors for low bone mineral density in South African premenopausal women
    (2008) Constant, Deborah; Hoffman, Margaret
    Quantitative Ultrasound (QUS) measurement at the calcaneum is a convenient, cost effective and noninvasive method of determining bone strength well suited to community-based research in countries with limited resources. Although only moderately correlated with dual X-ray absorptiometry (DEXA) measurement of bone mineral density (BMD) at the hip and spine, quantitative ultrasound has shown to be a reliable predictor of osteoporotic fracture. This study aims to evaluate the use of QUS in epidemiological studies in South African settings. To this end, this report determines whether characteristics associated with QUS measures of bone strength in a large sample of premenopausal South African women are similar to those known to be associated with the BMD as measured by DEXA, and compares these associations with those in other populations. This cross-sectional study included 3493 black and mixed race women aged 18 - 44 living in Cape Town. Trained study nurses administered structured interviews on reproductive history and lifestyle factors. In addition they took height, weight and calcaneal QUS measurements using the Sahara device. Adjusted means of QUS measures according to categories of risk factors were obtained using multivariable regression analysis. In both groups associations between QUS measures and age, Body Mass Index (BMI), age at menarche, parity and primary school physical activity were similar to those known to be associated with BMD as measured by DEXA. There were no clear associations between QUS and educational level, alcohol use, cigarette smoking, and current calcium intake. The data give support to the use of QUS as an epidemiological tool in large studies of bone strength in premenopausal women.