Gatot Purwoto

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.

Differences in genetic variation in antigen-processing machinery components and association with cervical carcinoma risk in two Indonesian populations

Genetic variation of antigen-processing machinery (APM) components has been shown to be associated with cervical carcinoma risk and outcome in a genetically homogeneous Dutch population. However, the role of APM component single nucleotide polymorphisms (SNPs) in genetically heterogeneous populations with different distributions of human papillomavirus (HPV) subtypes remains unclear. Eleven non-synonymous, coding SNPs in the TAP1, TAP2, LMP2, LMP7 and ERAP1 genes were genotyped in cervical carcinoma patients and healthy controls from two distinct Indonesian populations (Balinese and Javanese). Individual genotype and allele distributions were investigated using single-marker analysis, and combined SNP effects were assessed by haplotype construction and haplotype interaction analysis. Allele distribution patterns in Bali and Java differed in relation to cervical carcinoma risk, with four ERAP1 SNPs and one TAP2 SNP in the Javanese population showing significant association with cervical carcinoma risk, while in the Balinese population, only one TAP2 SNP showed this association. Multimarker analysis demonstrated that in the Javanese patients, one specific haplotype, consisting of the ERAP1-575 locus on chromosome 5 and the TAP2-379 and TAP2-651 loci on chromosome 6, was significantly associated with cervical carcinoma risk (global P = 0.008); no significant haplotype associations were found in the Balinese population. These data indicate not only that genetic variation in APM component genes is associated with cervical carcinoma risk in Indonesia but also that the patterns of association differ depending on background genetic composition and possibly on differences in HPV type distribution.

The Need for Laparoscopic Ovarian Transposition in Young Patients with Cervical Cancer Undergoing Radiotherapy

Maintaining the quality of life by preserving ovarian function in premenopausal patients with cervical cancer undergoing radiation is crucial. This can be accomplished with a simple and safe laparoscopic ovarian transposition procedure. This procedure aims to move the ovary out of the irradiation field, protecting it from direct radiation and irreversible damage and preserving its function. However, this procedure is often forgotten and seldom offered to patients. This review aims to lay stress on and reconsider the importance of laparoscopic ovarian transposition as a simple, safe, and extremely useful procedure. The biological effects of radiation are described briefly and several studies are evaluated, which reveal that this procedure has more benefits than risks.

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.

The landscape of somatic mutations in Indonesian cervical cancer is predominated by the PI3K pathway

OBJECTIVE To investigate the prevalence of somatic mutations in Indonesian cervical carcinoma patients in the context of histology and human papillomavirus (HPV) type. METHODS In total 174 somatic hot-spot mutations in 13 genes were analyzed by mass spectrometry in 137 Indonesian cervical carcinomas. RESULTS In 66/137 tumors (48%) 95 mutations were identified. PIK3CA was most frequently mutated (24%), followed by FBXW7 (7%), CTNNB1 (6%), and PTEN (6%). In squamous cell carcinomas more often multiple mutations per sample (p=0.040), and more PIK3CA (p=0.039) and CTNNB1 (p=0.038) mutations were detected compared to adenocarcinomas. PIK3CA mutations were associated with HPV 16 positivity, CDKN2A mutations with HPV 52 positivity, and, interestingly, PTEN mutations with HPV negativity. Balinese tumor samples more often carried multiple mutations (p=0.019), and more CTNNB1, CDKN2A, and NRAS mutations compared to Javanese tumor samples. CONCLUSIONS Potentially targetable somatic mutations occurred in 48% of Indonesian cervical carcinomas. The landscape of mutations is predominated by mutations concerning the PI3K pathway, and we prompt for more research on developing therapies targeting this pathway, explicitly for the more advanced stage cervical carcinoma patients.

Modified Cervicography and Visual Inspection With Acetic Acid as an Alternative Screening Method for Cervical Precancerous Lesions

Background We compared the diagnostic accuracy between visual inspection with acetic acid (VIA) and modified cervicography as an alternative screening method for cervical precancerous lesions. Methods A diagnostic cross-sectional study was performed at the outpatient clinic at an Indonesian national referral hospital from February until April 2015. We collected samples from patients who sequentially underwent VIA examination, modified cervicography, and colposcopy. Results A total of 185 patients were included in this study. Modified cervicography showed positive results in 7.6% of patients, while 7.0% of patients had a VIA positive result. This is compared to 5.4% of patients showing abnormal colposcopy results. From those results, we obtained that sensitivity and specificity of VIA were 96.0% and 90.9%. Meanwhile, sensitivity and specificity of modified cervicography were 97.7% and 90.9%, respectively, compared to colposcopy as a gold standard. Conclusions Modified cervicography and VIA are reliable tools for cervical cancer screening, with comparable sensitivity and specificity. Modified cervicography can be used as a supplementary tool to improve the documentation of VIA and as an alternative to VIA alone.

Prevalence, Age Distribution, and Risk Factors of Visual Inspection With Acetic Acid-Positive From 2007 to 2011 in Jakarta

Background Cervical cancer is still the second most frequent cancer among Indonesian women, thus screening program is still critically important to prevent it. Visual inspection with acetic acid (VIA) was introduced as a method which is most suitable with Indonesia’s condition compared with the other screening methods. The Female Cancer Program from Jakarta Regional collaborated with Leiden University in 2007 to 2011 has done cervical cancer screening using VIA method, involving 25,406 women spreading across several primary health centers in Jakarta. By using these data, we found out the prevalence, age distribution, and risk factor of VIA positive in Jakarta as a basis to predict the budget and logistics for the next cervical cancer screening and to do an advocating to the Jakarta’s government. Methods A secondary data analysis was conducted from several areas in Jakarta from 2007 to 2011. VIA test was used as the screening method, and performed by doctors and midwives with technical supervision by gynecologists. Results From 25,406 women, there were 1,192 cases (4.7%) of VIA test positive. The risk factors that can significantly influence the result of VIA positive were number of marriage, parity, smoking habits, and the use of hormonal contraception with OR 1.51, 1.85, 1.95, and 0.68, respectively. Conclusions Prevalence of VIA test-positive is 4.7% in Jakarta population. The findings of precancerous lesions and cervical cancers are not only between thirty and fifty years old, but also below the thirty years old and after fifty years old. We suggest that VIA test should be performed to all reproductive age and elder women who are not screened yet.