Masters Degrees (Anatomical Pathology)

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Browsing Masters Degrees (Anatomical Pathology) by Subject "Cervix uteri -- Cancer -- Genetics apsects"

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    Correlating p16INK4a /Ki-67 co-expression and gene methylation with HIV infection and high-risk HPV in abnormal cervical squamous intraepithelial cells
    (Stellenbosch : Stellenbosch University, 2023-03) Louw, Meagan; Sanderson-November, Micheline; Neethling, Greta; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Pathology: Anatomical Pathology.
    ENGLISH SUMMARY: Globally, cervical cancer is the fourth most common cancer amongst women. Persistent infection with high-risk human papillomavirus (HPV) is shown as the causal factor in cervical cancer development. Women living with HIV is six times more prone to cervical cancer development. The aim of this study was to identify the HR-HPV types, investigate the simultaneous expression of p16INK4a and Ki-67 and evaluate the methylation status of CADM1, MAL and miR124-2 genes in cytology samples from HIV-positive and HIV-negative women with LSIL, HSIL, ASC-US, and ASC-H Pap smear results. Study participants were women between the ages of 21 years to 60 years referred to the Colposcopy clinic at Tygerberg Academic Hospital. Exfoliated cervical intraepithelial cells were collected in Surepath medium and HR-HPV types were determined using the Hybrispot HPV direct flow chip kit, whereas the co- expression of p16INK4a/Ki-67 proteins was evaluated with the CINtec® Plus cytology immunocytochemistry kit. For methylation assays, DNA was isolated from the left-over exfoliated cells followed by the assessment of quantity and purity of isolated DNA using fluorometry and spectrophotometry, respectively. Isolated DNA was bisulfite converted and the methylation assays for the CADM 1, MAL and miR-124-2 genes were done using the respective EpiMelt assays. HPV DNA detection results were associated with cytological diagnosis as well as HIV status. In our study group 74 % (51/69; 95% CI: 62,1%-83%) of woman tested positive for HPV of which 70.6% (36/51) were of WLWH and 29.4% (15/51) of HIV negative women. Our results showed that p16INK4a /Ki-67 dual-staining was detected in 43.8% (25/57) of the samples with the HSIL cytology showing the highest p16INK4a /Ki-67 co-expression rate of 64% (16/25) compared to the other cytology groups. The proportion of the LSIL group with p16INK4a /Ki- 67 dual staining was 33,3% (4/12), whereas that of the ASC-US and ASC-H groups were 25% (2/8) and 23% (3/13) ASC-H, respectively. CADM1 methylation was detected in 12.3% (7/57) of samples, while MAL and the miR-124-2 genes showed methylation in 14% (8/57) and 12.3% (7/57)of the samples, respectively. HPV infection was detected in 28.1% (16/57) of the samples with methylated CADM1, MAL and miR-124-2 genes. A significant relationship was found between HR-HPV and miR-124-2 methylation. The logistic regression model analysis employing predictors such HR-HPV, p16INK4a and Ki- 67 co-expression, as well as the methylation status of the CADM1, MAL, and miR-124-2 genes, for LSIL cytology showed low sensitivity and high specificity, contrasting to that of the HSIL model with high sensitivity and low specificity. Therefore, we conclude that a larger study is warranted, with removing or adding predictors for model improvement.