Budiningsih Siregar

Human papillomavirus type 18 variants: histopathology and E6/E7 polymorphisms in three countries.

In cervical cancer, human papillomavirus type 18 (HPV 18) and HPV 16 are predominantly related to adenocarcinomas (ADCs) and squamous cell carcinomas (SCCs), respectively. Here, we studied whether the geographically distributed HPV intratypic variants are also associated with histologically different tumors. A total of 44 HPV 18‐positive and 91 HPV 16‐positive cervical carcinomas from Indonesian, Surinamese and Dutch patients were histologically classified using hematoxilin and eosin, periodic acid Schiff plus and Alcian Blue staining. Samples were sequenced and intratypic variants were classified into the known phylogenetic branches. The Asian Amerindian HPV 18 variant was observed in 56% of ADCs compared to 15% of SCCs (p < 0.006). The African HPV 18 variant was exclusively found in SCCs. By sequencing the HPV 18 E6 and E7 open reading frames, we found predicted amino acid changes only in 8 samples. Two amino acid changes were consistent throughout the African branch. In HPV 16‐positive tumors, we did not find a specific linkage between intratypic variants and histopathology. We conclude that HPV 18 intratypic variants are differentially associated with adenocarcinoma and squamous cell carcinoma of the cervix. The findings described here stress the biologic significance of intratypic HPV variants and might help explaining differences in the pathogenesis of cervical ADCs and SCCs.

Prevalence of human papillomavirus in Indonesia: a population-based study in three regions

Cervical cancer is the most common cancer among women in the Indonesian population, yet little is known about the prevalence of human papillomavirus (HPV). We investigated age-specific prevalence of HPV types and possible risk factors of HPV positivity in a population-based sample of 2686 women, aged 15–70 years, in Jakarta, Tasikmalaya, and Bali, Indonesia. The overall HPV prevalence was 11.4%, age-standardized to the world standard population 11.6%. The most prevalent types found were HPV 52, HPV 16, HPV 18, and HPV 39, respectively, 23.2, 18.0, 16.1, and 11.8% of the high-risk HPV types. In 20.7% of infections, multiple types were involved. Different age-specific prevalence patterns were seen: overall high in Jakarta, and in Tasikmalaya, and declining with age in Bali. The number of marriages was most associated with HPV positivity (OR 1.81 95% CI 1.31–2.51)). Remarkably, in Indonesia HPV 16 and HPV 18 are equally common in the general population, as they are in cervical cancer. HPV 52 was the most prevalent type in the general population, suggesting that this type should be included when prophylactic HPV vaccination is introduced in Indonesia.

Cervical cancer prevention program in Jakarta, Indonesia: See and Treat model in developing country.

Objective The purpose of this study was to describe the implementation of single visit approach or See-visual inspection of the cervix with acetic acid (VIA)-and Treat-immediate cryotherapy in the VIA positive cases-model for the cervical cancer prevention in Jakarta, Indonesia. Methods An observational study in community setting for See and Treat program was conducted in Jakarta from 2007 until 2010. The program used a proactive and coordinative with VIA and cryotherapy (Proactive-VO) model with comprehensive approach that consists of five pillars 1) area preparation, 2) training, 3) awareness, 4) VIA and cryotherapy, and 5) referral. Results There were 2,216 people trained, consist of 641 general practitioners, 678 midwives, 610 public health cadres and 287 key people from the society. They were trained for five days followed by refreshing and evaluation program to ensure the quality of the test providers. In total, 22,989 women had been screened. The VIA test-positive rate was 4.21% (970/22,989). In this positive group, immediate cryotherapy was performed in 654 women (67.4%). Conclusion See and Treat program was successfully implemented in Jakarta area. The Proactive-VO model is a promising way to screen and treat precancerous lesions in low resource setting.

Overexpression and amplification of Murine double minute 2 as a diagnostic tool in large lipomatous tumor and its correlation with Ki67 proliferation index: an institutional experience.

CONTEXT Well-differentiated liposarcoma (WDLPS) is the most common type of liposarcoma and sometimes can be difficult to distinguish from large lipoma due to the similar morphology. AIMS This study proposed to evaluate the expression and amplification of Murine double minute 2 (MDM2) gene and determine its correlation with Ki67 proliferation index. SETTINGS AND DESIGN This study used cross-sectional design. MATERIALS AND METHODS This study enrolled 37 cases of lipomatous tumors with >5 cm in size. Eighteen cases of WDLPS and 19 cases of lipoma were stained for MDM2 and Ki67 immunohistochemistry, followed by MDM2 in situ hybridization in 12 selected cases. STATISTICAL ANALYSIS USED MDM2 overexpression and amplification status for both groups were compared using Chi-square test, with the alternative of Fishers exact test. Correlation test between MDM2 overexpression and clinical characteristics with the Ki67 proliferation index were performed using Pearsons test with the alternative of Spearmans rho test. RESULTS MDM2 overexpression was detected in all WDLPS cases and in 3 (16%) of lipoma cases with significance difference (P = 0.000), whereas MDM2 amplification was found in all WDLPS and in 1 of lipoma cases (P = 0.200). There was a strong correlation between MDM2 overexpression and higher Ki67 proliferation index (r = 0.645, P = 0.000). CONCLUSION Evaluation of MDM2 overexpression can be used as a useful adjunct to differentiate WDLPS from large lipoma and seems to be related with Ki67 proliferation index.

Cytomorphological Analysis of Uterine Cervical Pap Smears in Relation to Human Papillomavirus Infection in Indonesian Women

Objective: Cervical cancer is the number one cause of cancer-associated death in Indonesian women (30/100,000 annually), where no screening program is present. The Papanicolaou test is widely accepted as an effective screening method for cervical neoplasia detection and often shows certain cytological features associated with human papillomavirus (HPV) infection. Especially in developing countries, cytological investigation is still the method of choice as compared to the frequent use of HPV DNA testing in western countries. Study Design: In the present study, we investigated the validity of the use of cytomorphological changes as a marker for HPV infection. A total of 140 smears collected in three different areas in Indonesia (Jakarta, Tasikmalaya and Bali) were analyzed. HPV DNA testing was performed using INNO-LiPA assays. Results and Conclusions: We found a highly significant association of classical koilocytosis, multinucleated cells, dyskeratosis-parakeratosis, nuclear membrane, enlarged nuclei, moderate/strong hyperchromasia and chromatin pattern with HPV positivity. Using classical and nonclassical cytomorphological parameters we found an overall sensitivity of 42% and a specificity of 90%. The combination of classical and nonclassical parameters led to a higher sensitivity of HPV positivity prediction. These results are of importance for cytologists in developing countries as molecular HPV testing still poses a major financial, logistic and expertise problem.