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.

Endometrial epithelial integrity and subepithelial reticular fibre expression in progestin contraceptive acceptors.

Long-acting progestin contraceptives have been available in many countries for a number of years with a large number of women now using them. Although some improvements in delivery systems have been made, the major problem with progestin-only contraceptives remains unpredictable endometrial breakthrough bleeding (BTB), which is responsible for more than 50% of drop-outs from this form of contraception. Using hysteroscopy, endometrial petechiae and ecchymoses are a common finding among Norplant users, although these features do not always correlate with BTB. It has been postulated that epithelial and subepithelial tissues may provide a barrier to BTB, as long as epithelial integrity is maintained. The aim of this pilot study is to explore structural changes in the endometrial surface epithelium, and subepithelial collagen III fibres. Endometrial biopsies from noresthisterone-enanthate (NetEn) users (n = 6) and controls (n = 6) were assessed using routine haematoxylin and eosin staining and immunohistochemical staining for cytokeratins 8, 18 and 19, and collagen III. A conventional silver impregnation method was also used to identify subepithelial collagen III fibres. Most of the Net-En tissues showed reduced surface epithelial cell height compared controls (P = 0.002). Cytokeratin staining as weaker (P = 0.04) and distributed evenly between basal and apical parts of the cell in Net-En tissue, compared to more apically in controls. Both immunohistochemical and conventional silver staining methods revealed that the subepithelial collagen III meshwork remained unchanged in Net-En compared to control endometrium. Both staining methods identified collagen fibres with equal sensitivity. In conclusion, atrophic changes remain the dominant appearance for progestin-exposed endometrium, with reduced cytokeratin staining, but apparently there is little change in subepithelial collagen III expression.

Decreased CD4+/CD8+ ratio in major type of recurrent aphthous ulcers: comparing major to minor types of ulcers.

The etiology of recurrent aphthous ulcers (RAU) has not been clearly defined. However, the results of several studies indicated the evidence of the role of immunological factors. The association between the regulator and effector component of the immune system in RAU needs clarifying by comparing major and minor type of RAU patients. The proportion of peripheral blood lymphocyte subsets were enumerated during active ulcer phase and analyzed in relation to ulcer types. Nineteen patients with RAU (12 minor type and 7 major type) and 8 healthy volunteers, of both sexes, aged 24-54 years old were tested. CD3+ (T cell), CD4+ (helper T cell), CD8+ (suppressor/cytotoxic T cell), CD19+ (B cell), and CD16+/CD56+ (NK cell) were determined by using appropriate monoclonal antibodies in double colored flow cytometry. The results showed that CD4+ was lower in RAU than control (P < 0.01). Comparing both types of RAU, it appeared that CD8+ was higher in the major type than the minor type (p < 0.01); CD4+/CD8+ ratio in the major type was lower than the minor type (P < 0.01). There was no difference in CD19+ and CD16+/CD56+ between any groups compared. The finding indicated that RAU was associated with abnormal proportions of CD4+ and CD8+ cells which was dependent on the severity of the lesion.

Cytokeratin 8, 18 and 19 in endometrial epithelium of Norplant and norethisterone enanthate injectable progestogen contraceptive users.

Cytokeratins 8, 18 and 19 are members of the cytoskeletal intermediate filament family found in all simple epithelia. Intermediate filaments are dynamic intracytoplasmic structures that can be influenced by a number of external factors. Norethisterone enanthate (NET-EN) is a long-acting progestogen contraceptive that has been found to arrest endometrial growth in the rat. Both Norplant and NET-EN cause bleeding problems among users which are responsible for > 50% of withdrawals with these methods. The aim of this study was to explore changes in the expression and distribution of cytokeratins 8, 18 and 19 in NET-EN- and Norplant-exposed endometrial epithelium which could be related to bleeding disturbances. Seven NET-EN and 37 Norplant endometrial biopsies were paraffin-embedded and stained immunohistochemically to evaluate cytokeratin expression and distribution. The results showed that women who had received NET-EN for 3-4 months had a cytokeratin distribution similar to that seen in the normal menstrual cycle. This is in contrast to endometrium from Norplant users in which cytokeratin expression was reduced and the epithelial cells were more rounded. No relationship between cytokeratin expression and breakthrough bleeding pattern was found. NET-EN and Norplant may act differently on endometrial epithelial cytokeratin.

PIP: All endometrial epithelium contain the cytoskeletal intermediate filaments cytokeratins 8, 18, and 19. The aim of this study was to observe changes in the expressions of these cytokeratins in endometrial epithelial cells from Indonesian women receiving norethindrone enanthate and to compare them with the patterns of expression reported for Norplant users. Study subjects received 2 norethindrone enanthate injections (150 mg) spaced 8 weeks apart. Regardless of bleeding pattern or histopathologic finding, epithelial tissues from these 7 women stained either strongly or intensely for cytokeratin, including isolated epithelial fragments from unclassified biopsies. Surface and glandular epithelia from norethindrone enanthate users consisted of a single layer of high columnar cells, with no obvious differences between proliferative-like and secretory-like endometria. In contrast, surface epithelial tissue from 37 Norplant users showed weaker immunostaining and epithelial cells were rounded and stratified. No relationship between cytokeratin expression and breakthrough bleeding pattern was detected. These findings suggest that norethindrone enanthate and Norplant act differently on endometrial epithelial cytokeratin, with women receiving the former contraceptive agent showing a cytokeratin distribution similar to that seen in the normal menstrual cycle. The capability of norethindrone enanthate to preserve epithelial integrity may have implications for reducing the incidence of progestogen-related breakthrough bleeding.

Reduced endothelial cell migratory signal production by endometrial explants from women using Norplant contraception.

Bleeding problems can be one of the major reasons for women to discontinue the use of hormonal contraceptives. Causes of endometrial bleeding can include disturbances in endometrial regeneration and angiogenesis. Endothelial cells migrate and proliferate rapidly as part of the angiogenic process under the influence of appropriate stimuli. The aim of this study is to investigate the production of endothelial cell migratory signals by endometrial explants from women receiving Norplant and to compare it to that of those with a normal menstrual cycle. The subjects were selected from Norplant users with an exposure of 3-9 months. The endothelial cell migratory signal production was assayed using the Folkman method (1989), modified by Rogers (1992). Blood serum concentrations of oestradiol, progesterone and sex hormone binding globulin were monitored for 2 weeks prior to endometrial biopsy. Endothelial cell migration toward endometrial explants of 30 women as control and 46 Norplant acceptors was assayed. The results showed that endothelial cell migratory activity toward endometrial explants from the control group was significantly higher than toward those from Norplant acceptors (z = 3.89, P < 0.001). There were no differences between endometrial endothelial cell migratory activities in Norplant acceptors with bleeding or without bleeding problems.

PIP: Researchers examined the production of endothelial cell migratory signals by endometrial explants from 46 Norplant acceptors aged 18-40 and compared it with endothelial cell migratory signals produced by endometrial explants from women using no hormonal contraception or an IUD and having a normal menstrual cycle. The results will provide insight into the role of endothelial cell migration in endometrial bleeding among Norplant acceptors. Both cases and controls attended the Raden Saleh Clinic in Jakarta, Indonesia. Health providers took peripheral blood samples 6 times at 2-3 day intervals before the endometrial biopsy to monitor serum levels of estradiol, progesterone, and sex hormone-binding globulin (SHBG). Laboratory researchers used a three-dimensional collagen matrix culture medium containing dispersed human umbilical vein endothelial cells as modified by Rogers (1992) to conduct the endothelial cell migration assay. Endothelial cell migration toward endometrial explants of the control group was much higher than toward those of the Norplant group (p 0.001). For example, 30 of 46 of the Norplant endometrial explants had a median endothelial cell migratory score of zero compared to 8 of the 30 control biopsies. In fact, only 1 of the control biopsies of the individual 500-cubic-micrometer explants did not respond, while 19 of the like Norplant explants did. In controls, endothelial cell migration was greater in the proliferative phase than in the secretory phases. Endothelial cell migration toward endometrial biopsies of Norplant acceptors with bleeding problems was the same as that toward Norplant acceptors with no bleeding problems. Serum levels of estradiol, progesterone, and SHBG were not associated with endothelial cell migration. These findings do not support the belief that increased angiogenesis in the endometrium of Norplant acceptors is responsible for endometrial bleeding.