Single and multiple high-risk and low-risk Human Papillomavirus association with cervical lesions of 11,224 women in Jakarta.

PURPOSE: We sought to evaluate prevalence, age-adjusted distribution, and impact of single and multiple high- and low-risk human papillomavirus (HPV) subtypes and their associations with cervical lesions. METHODS: Data were extracted from 11,224 women who underwent routine screening of HPV genotyping and liquid-based cytology co-testing. Fifteen high-risk (HR) and six low-risk (LR) HPV types were genotyped. RESULTS: Overall HPV prevalence was 10.7 %, and young women (under 21 years old) harbored highest HPV infection rate (40.38 %). The rate declined in old women 9.49 % (age 30-49) and 6.89 % (age 50 and above). Normal cytology had lowest HPV (5.66 %) compared to low-grade (60.49 %), high-grade (71.96 %) squamous intraepithelial lesions (LSIL and HSIL) and squamous cell carcinoma SCC (86.9 %). LR HPV subtypes were absent in SCC and were consistently lower than HR HPV in LSIL (6.74 vs. 33.54 %) and HSIL (2.12 vs. 51.32 %). Multiple HPV infection was more frequent in young women under 30 years old (10 %) than older women (2 %) and in LSIL (20.2 %), HSIL (18.5 %) than SCC (4.4 %). HR HPV 52, 16, 18, and 58 were the most frequent subtypes in normal, LSIL, and HSIL. Greater or equal proportion of HPV 16, 18, 45, and 52 was found in SCC compared to normal cytology (SCC/normal ratios 4.8, 1.2, 1.6, and 1.7). While important in LSIL and HSIL, HPV58 was not detected in SCC. CONCLUSION: Taken together, identification of these HPV types, especially HPV 16, 18, 45, and 52, and their associated cervical lesions may improve cervical cancer preventive strategies 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.

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.

Cancer epidemiology and control in peninsular and island South-East Asia - past, present and future.

Malaysia, Brunei, Singapore, Indonesia, East Timor and the Philippines constitute peninsular and island South-East Asia. For reasons of largely shared ethnicity, with Chinese elements added to the basic Austromalaysian populations, as well as geographical contiguity, they can be usefully grouped together for studies of chronic disease prevalence and underlying risk factors. The fact of problems are shared in common, particularly regarding increasing cancer rates, underlines the necessity for a coordinated approach to research and development of control measures. To provide a knowledge base, the present review of available data for cancer registration, epidemiology and control was conducted. The most prevalent cancer site in males is the lung, followed by the liver, colon or the prostate in the majority of cases, while breast and cervical cancers predominate in most female populations. However, there are interesting differences among the racial groups, particularly regarding the stomach. General tendencies for increase in adenocarcinomas but decrease in squamous cell carcinomas and gastric cancer, point to change in environmental influence over time. Variation in risk factors depends to some extent on the level of economic development but overall the countries of the region face similar challenges in achieving effective cancer control. A major task is persuading the general populace of the efficacy of early detection and clinical treatment.

Variations and trends of biologically effective doses of solar ultraviolet radiation in Asia, Europe and South America from 1999 to 2007.

Biological monitoring of solar UV radiation using spore dosimeters has been undertaken since the year 1999 at more than 20 sites in Asia, Europe and South America. The monthly-cumulative data to the end of the year 2004 have been presented before. In this paper, successive data to the end of the year 2007 are compiled and the trends and correlation analyses with yearly and monthly average amounts of columnar ozone are presented. Mean yearly doses at 10 northern and 6 southern hemisphere sites exhibited exponential latitudinal gradients with similar slopes indicating a doubling of the dose with the decline of about 14 degrees. Among 12 sites where continual data for more than 6 years were available, increasing trends in yearly UV doses were observed at 11 sites. At one European (Brussels), two tropical Asian (Padang and Denpasar), and two South American (São Martinho and Punta Arenas) sites, decreasing trends of ozone amounts were noted, whereas at the remaining 6 sites (five sites in Japan and Thessaloniki), increasing trends of the UV doses were observed without notable changes, or with an increase at one site (Kiyotake), of the average ozone amounts. At one site (Taipei), the UV doses and the ozone amounts stayed constant. In the monsoon areas, climatic variations and changes, particularly in the extent of cloudiness and frequency of rainfall in summer months, might have been largely responsible for the trends of the UV doses. However, even at these sites, the decreases in the ozone amounts in summer months were frequently observed and might have contributed to the increasing trends of the UV doses. Since each region and locality is unique in climatic and atmospheric conditions, it is not easy to generalize the global trends. However, at many sites involved in this monitoring project, the increases in the biological UV doses during this period seemed to be linked to the decreases in the ozone amounts.

Biological monitoring of solar UV radiation at 17 sites in Asia, Europe and South America from 1999 to 2004.

A small and robust dosimeter for determining the biologically effective dose of ambient UV radiation has been developed using UV-sensitive mutant spores of Bacillus subtilis strain TKJ6312. A membrane filter with four spots of the spores was snapped to a slide mount. The slide was wrapped and covered with two or more layers of polyethylene sheet to protect the sample from rain and snow and to reduce monthly-cumulative doses within the measurable range. From 1999, monthly data were collected at 17 sites for more than 1 year, and data for 4 to 6 consecutive years were obtained from 12 sites. Yearly total values of the spore inactivation dose (SID) ranged from 3200 at subarctic Oulu to 96 000 at tropical Denpasar, and the mean yearly values of SID exhibited an exponential dependence on latitude in both hemispheres with a doubling for about every 14 degrees of change. During the observation period, increasing trends of UV doses have been observed at all sites with more than 5 years of data available. Year-to-year variations at high and middle latitude sites are considered due mostly to climatic variation. At three tropical sites, negative correlations between the yearly doses and the column ozone amounts were observed. The results verified the applicability of spore dosimetry for global and long-time monitoring of solar UV radiation, in particular at tropical sites where no monitoring is taking place.

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.

Human papillomavirus type 16 E6, E7, and L1 variants in cervical cancer in Indonesia, Suriname, and The Netherlands.

OBJECTIVE: Human papillomavirus type 16 (HPV 16) has several intratypic variants, and some are associated with enhanced oncogenic potential. For risk determination as well as for future vaccine development, knowledge about variants is important. Regarding the geographical distribution of HPV variants and the lack of data from Indonesia and Suriname, we studied the prevalence of HPV 16 variants in cervical cancer in these high incidence countries. Data were compared with The Netherlands, a low-risk country. METHODS: DNA samples from 74 formalin-fixed paraffin-embedded HPV 16-positive cervical carcinomas from Indonesia (Java, N = 22), Suriname (N = 25), and The Netherlands (N = 27) were amplified using primers specific for the E6, E7, and part of the L1 regions. Products were sequenced and analyzed. RESULTS: A specific Javanese variant, with mutations 666A in E7 and 6826T in L1, was found in 73% of the Indonesian samples, 56% having an additional mutation in the E6 open reading frame (ORF; 276G), giving the predicted amino acid change N58S. This Javanese variant was also found in three Surinamese samples, which reflects what could be expected from migration of Javanese people to Surinam. Other non-European variants were identified in Indonesian, Surinamese, and Dutch samples in 14%, 28%, and 19%, respectively. CONCLUSION: The majority of the HPV 16-positive cervical cancers in Indonesia are caused by a specific intratypic variant that was rarely found before in other countries.

Prevalence of single and multiple HPV types in cervical carcinomas in Jakarta, Indonesia.

OBJECTIVES: Cervical cancer is the second most frequently occurring type of cancer in women worldwide. A persistent infection with high-risk human papillomavirus (HPV) is a necessary causal factor in cervical carcinogenesis. The distribution of HPV types in populations has been studied worldwide. In Indonesia, however, few data are available describing the prevalence of HPV. Cervical carcinoma is the most common female cancer in Indonesia and causes high morbidity and mortality figures. With HPV vaccination studies in progress, it is important to map the HPV status of a population that would benefit greatly from future prevention programs. METHODS: We tested 74 cervical cancer specimens from consecutive, newly diagnosed cervical cancer patients in the outpatient clinic of the Dr. Cipto Mangunkusumo Hospital, Jakarta. After additional staining, the formalin-fixed, paraffin-embedded tissue samples were histologically classified. HPV presence and genotype distribution were determined by SPF10 polymerase chain reaction and line probe assay. RESULTS: HPV DNA of 12 different HPV types was detected in 96% of the specimens. The three most common types were 16 (44%), 18 (39%) and 52 (14%). In 14% of the specimens, multiple HPV types were present. The multiple HPV types were significantly more prevalent among adenosquamous carcinomas in comparison with squamous cell carcinoma or adenocarcinoma (P = 0.014). CONCLUSIONS: Distribution of HPV types in Indonesia with a more prominent role for HPV 18 is slightly different from that in other parts of the world. The high amount of multiple HPV infections found in adenosquamous carcinomas may prompt further research on the pathogenesis of this type of cervical tumours.

Suppression of in vivo tumorigenicity of rat hepatoma cell line KDH-8 cells by soluble TGF-beta receptor type II.

We have previously reported that transforming growth factor beta (TGF-beta) produced by rat hepatoma cell line KDH-8 cells suppressed the interleukin-2 (IL-2) production of T cells and the tumoricidal activity of macrophages in KDH-8 tumor-bearing rats and that the inhibition of TGF-beta production by low-dose bleomycin restored these activities significantly. In this study, we established three transfectant clones with stable expression of soluble TGF-beta receptor type II (sTRII), namely KT1, KT2 and KT3, and one with an empty vector used as control vector (KV), and then investigated the effects of sTRII on the tumorigenicity of KDH-8 cells and immune responses in syngeneic Wistar King Aptekman/Hok (WKAH) rats. We found that sTRII expressed in sTRII transfectants could abolish growth inhibition of Mv1Lu cells by TGF-beta1 produced by the cells themselves, and that tumor growth of KT2 and KT3 clones in vivo was suppressed significantly compared with that of parent, KV and KT1 clones. Furthermore, we demonstrated that IL-2 production of splenocytes and IL12p40 mRNA expression in tumor tissues were restored in rats inoculated with KT2 and KT3 clones, whereas such restoration was not observed in rats inoculated with parent, KV and KT1 clones. Combined with a low expression of sTRII in KT1 tumor tissues, these results suggest that sTRII may to some extent be able to abolish the tumor-promoting activity of TGF-beta, and imply that sTRII might have a therapeutic effect on TGF-beta-producing tumors.