Immunohistochemical study of p16 INK4A and survivin expressions in cervical squamous neoplasm.

Introduction:Cervical cancer is the second most common cancer affecting Malaysian women. Despite the implementation of pap smear screening, many women are still diagnosed only in the advanced stage of cervical cancer. This could partly be due to failure of detection of its precursor lesions; hence the need to search for novel biomarkers to assist in the screening and diagnosis of cervical neoplasia. This study aims to determine the expression of p16INK4A and survivin as possible predictive biomarkers in cervical squamous neoplasm. Material and Methods: This is a retrospective study on 201 cases of cervical neoplasm comprising of 129 cervical intraepithelial neoplasia (CIN) and 72 squamous cell carcinoma (SCC). All samples were evaluated by two independent observers using p16INK4A and survivin monoclonal antibodies. The p16 INK4A expression was graded as negative, focal and diffuse positivity. The intensity for survivin expression was graded as weak, moderate and intense. Results: It is seen that p16 INK4A expression in CIN 1, CIN 2 and CIN 3 were 25.4%, 42.9% and 95.9% respectively. Majority of SCC (98.6%) showed p16 INK4A expression. Survivin expressions in CIN 1, CIN 2, CIN 3 and SCC were 56.7%, 33.4%, 87.5% and 98.6%. There was a linear relationship between increasing grade of CIN and p16 INK4A expressions. Conclusion: Our study showed that p16 INK4A expressions correlate well with the increasing grade of CIN. Although survivin does not correlate well to the increasing grade of CIN, it could be useful in differentiating CIN 3 from SCC.

Quality of Life Among Preinvasive & Invasive Cervical Cancer In Malaysia

Objective: This study aims to determine the quality of life (QOL) of Malaysian women based on their physical and mental scores and correlates with age and cervical disease severity. Methods: This is a cross-sectional study from Nov 2006 till Dec 2007 from participating Gynecology-Oncology outpatient and in patient’s wards. QOL interviews used the SF-36 questionnaires. Main domains were the Physical Composite Scores (PCS) and the Mental Composite Scores (MCS). Results: A total of 396 participated in the study. Mean respondents age were 53.31 ± 11.21 years, educated till secondary level (39.4%), Malays (44.2%) with mean marriage duration of 27.73 ± 12.12 years. Among pre-invasive diseases, the cervical intra epithelial neoplasia (CIN) 1 was the highest in percentage of cases (8.1%). Among invasive cancer, stage 1 cancer was highest (31.1%), followed with stage 2 (28.3%), stage 3 (7.3%) and stage 4 cancers (5.8%). PCS scores are highest among the pre-invasive and stage 1 cancer (F=4.357; p<0.0001) and influenced by age and income. MCS were not significantly influenced by age or stage of cervical diseases (F= 1.393; p=0.206) but the regression model showed that amount spent on health care was a significant factor. Conclusion: Cervical diseases posed a substantial cause in reducing QOL with increasing age and disease severity. This disability can be reduced with early screening and intervention to prevent disease progression. Reducing disease burden play a role to improve QOL among at risk women before developing late stages of disease.

Economic burden of cervical cancer in Malaysia.

Cervical cancers form the second highest number of female cancers in Malaysia, imposing a substantial amount of cost burden on its management. However, an estimation of cost burden of abnormal smears, cervical pre-invasive and invasive diseases needs to be done to show how much spending has been allocated to the problem. An expert panel committee came up with the clinical pathway and management algorithm of cervical pre invasive and invasive diseases from July-December 2006 Malaysia. An activity based costing for each clinical pathway was done. Results were converted to USD. The cost of managing pre-invasive cervical cancers stage is USD 420,150 (Range: USD 197,158-879,679). Management of invasive cancer (new cases) costs USD 51,533,233.44 (Range: USD 32,405,399.69 - USD 129,014,768.40). The cost of managing existing cases is USD 17,005,966.87 (Range: USD 10,693,781.90 - USD 28,901,587.12). The total cost of managing cervical cancers by health care providers in a public setting is around USD 75,888,329.45 (Range: USD 48,083,804.60 - USD 48,083,804.60). The outcome of this study has shown that preventive modalities such as screening have only contributed to 10.3 % of the total management cost of cervical cancer. The major cost contribution (67%) came from treatment of invasive cancer especially at more advanced stages of cancer, followed by treatment of existing cases (22%) and lastly on pre-invasive disease (0.6%). This study revealed that proportion of preventive modality in this country was still low, and the major cost came from actual treatment cost of cervical cancer. Therefore, heightened public cervical cancer screening in the country is needed.

Utility of Ki-67 and p53 in distinguishing cervical intraepithelial neoplasia 3 from squamous cell carcinoma of the cervix.

The differentiation between cervical intraepithelial neoplasia 3 (CIN 3) and early squamous cell carcinoma (SCC) of the cervix may be difficult in certain situations. Identification of invasion beyond the basement membrane is the gold standard for the diagnosis of the latter. The objective of this study was to determine whether the use of Ki-67 and p53 could help in solving the above dilemma. This was a retrospective study on 61 cases of cervical neoplasms comprising of 25 cases of CIN 3 and 36 SCC. All cases were evaluated by immunohistochemistry using Ki-67 and p53 monoclonal antibodies. Results showed that the differences of Ki-67 and p53 expression between CIN 3 and SCC were statistically significant. In conclusion, Ki-67 and p53 may serve as helpful adjuncts to routinely-stained histological sections in differentiating between CIN 3 and SCC.