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BackgroundMen who have sex with men (MSM) are at elevated risk of having anal cancer. However, the prevalence and incidence among MSM of high-grade anal intraepithelial neoplasia (HGAIN), the putative precursor of anal cancer, is understudied, particularly in Asians.MethodsA total of 123 HIV-positive and 123 HIV-negative MSM were enrolled at the Thai Red Cross AIDS Research Centre in Bangkok, Thailand, and followed for 12 months. Anal sample collection for human papillomavirus (HPV) genotyping and high-resolution anoscopy (HRA) with biopsies were performed at every visit.ResultsMean age at enrollment was 28.9 years. HIV-positive MSM were more commonly infected with high-risk HPV types in the anus than HIV-negative MSM (57.5 vs. 36.6%; P  =  0.001). The prevalence of HGAIN was 18.9% in HIV-positive and 11.4% in HIV-negative MSM (P  = 0.1). The incidence of HGAIN at 12 months was 29% in HIV-positive and 8% in HIV-negative MSM (P  =  0.001). The hazard ratios for incident HGAIN in multivariate models were 5.16 [95% confidence interval (CI) 1.89-14.08, P  < 0.001] in MSM with persistent HPV 16 and/or 18 infection and 2.62 (95% CI 1.04-6.61, P  =  0.042) in HIV-positive MSM.ConclusionsApproximately one-third of HIV-positive MSM developed incident HGAIN within 12 months. Given the relative increased prevalence of HIV among MSM worldwide, local HGAIN data are needed to guide practitioners, policy makers, and communities in planning for strategies to screen for and treat HGAIN in this population.

Persistent infection with high-risk human papillomaviruses (HR-HPVs), particularly HPV16 and 18, has long been known to induce cervical cancer progression. However, given that a minority of HPV-infected women develop cancer, analysis of HR-HPV-infected women could help to predict who is at risk of acquiring cervical cancer. Therefore, to improve HR-HPVs detection, we used the FDA-approved cobas® 4800 HPV and REBA HPV-ID® HPV assays to detect HR-HPVs in colposcopy-derived cervical cells from 303 patients, detecting 72.28% (219) and 71.62% (217) of HR-HPVs positive cases, with HPV16 detection rates of 35.64% (108) and 30.69% (93), respectively. Of the HPV16-positive cases, cobas® 4800 and REBA HPV-ID® identified 28.81% (51) and 25.42% (45) of the CIN1 cases, and 55% (33) and 50% (30) of the 60 CIN2/3 cases, respectively. HPV-diagnostic concordance was 82.17% overall (kappa = 0.488), 87.45% for HR-HPVs (kappa = 0.689), and 88.33% for CIN2/3 (kappa = 0.51). The HR-HPVs detection rates of these assays were comparable. Our findings reveal that the FDA-approved HR-HPVs detection assay is appropriate for screening women with HR-HPVs infection, and for predicting increased risk of cervical cancer progression. REBA HPV-ID® can be used to detect low risk-HPV types in high-grade cervical lesions that are HR-HPV negative as well as in the distribution of HPV types. [ABSTRACT FROM AUTHOR]

Objective: Post-menopausal vaginal pain and burning sensation are not solely relieved by improving vaginal dryness. Stimulation of pain receptor (nociceptor) may be a part of the post-menopausal vaginal pain mechanism. The authors primarily evaluated the level of substance P receptor in pre- and post-menopausal women and secondarily studied the level of calcitonin gene-related peptide (CGRP) receptor and nociceptor-activating substances in pre- and post-menopausal women. The association between vaginal pain score and the change in nociceptor and nociceptoractivating substances was analyzed. Materials and Methods: A cross-sectional study was conducted in 122 pre- and post-menopausal women that underwent total abdominal hysterectomy. Vaginal specimens were obtained and stained for substance P receptor, substance P, CGRP receptor and CGRP, which were used as nociceptive parameters in the present study. Vaginal stromal cells were counted for pain-related protein expressions. Mean pain-related protein expressions in vaginal stromal cells were compared between pre- and post-menopausal women. Results: Fifty-eight pre-menopausal women and 33 post-menopausal women were included for analysis. Mean substance P receptor, substance P, CGRP receptor and CGRP in post-menopausal women were higher than in pre-menopausal women (47.69, 42.32, 71.31 and 60.73 cells, respectively for post-menopausal women, and 22.03, 21.54, 41.45 and 35.80 cells, respectively for pre-menopausal women). These differences were under the major influence of hormonal status rather than age. The changes in mean pain-related protein expression in vaginal stromal cell after menopause were highest in the first two years. No difference in mean pain-related protein expression in vaginal stromal cell was observed between pain and no pain groups. Conclusion: In the present study, post-menopausal women were found to have higher mean pain-related protein expressions in vaginal stromal cells than pre-menopausal women. [ABSTRACT FROM AUTHOR]

Abstract Background The aim of this study was to evaluate epigenetic status of cyclin A1 in human papillomavirus-associated cervical cancer. Y. Tokumaru et al., Cancer Res 64, 5982-7 (Sep 1, 2004)demonstrated in head and neck squamous-cell cancer an inverse correlation between cyclin A1 promoter hypermethylation and TP53 mutation. Human papillomavirus-associated cervical cancer, however, is deprived of TP53 function by a different mechanism. Therefore, it was of interest to investigate the epigenetic alterations during multistep cervical cancer development. Methods In this study, we performed duplex methylation-specific PCR and reverse transcriptase PCR on several cervical cancer cell lines and microdissected cervical cancers. Furthermore, the incidence of cyclin A1 methylation was studied in 43 samples of white blood cells, 25 normal cervices, and 24, 5 and 30 human papillomavirus-associated premalignant, microinvasive and invasive cervical lesions, respectively. Results We demonstrated cyclin A1 methylation to be commonly found in cervical cancer, both in vitro and in vivo, with its physiological role being to decrease gene expression. More important, this study demonstrated that not only is cyclin A1 promoter hypermethylation strikingly common in cervical cancer, but is also specific to the invasive phenotype in comparison with other histopathological stages during multistep carcinogenesis. None of the normal cells and low-grade squamous intraepithelial lesions exhibited methylation. In contrast, 36.6%, 60% and 93.3% of high-grade squamous intraepithelial lesions, microinvasive and invasive cancers, respectively, showed methylation. Conclusion This methylation study indicated that cyclin A1 is a potential tumor marker for early diagnosis of invasive cervical cancer.

The most common side-effect and reason for discontinuation with Norplant use is bleeding disturbance. The aim of this study was to investigate whether the 6 week application of a patch which released 100 μg/day oestradiol would reduce the number of abnormal bleeding days or eliminate the problem. Another objective was to find out the correlation between the bleeding pattern and endometrial concentrations of oestrogen receptor (ER) and progesterone receptor (PR). Of 98 Norplant users, 34 patients had normal bleeding patterns and 64 patients had abnormal bleeding patterns. An oestradiol patch or a placebo patch were randomly used to treat 33 and 31 women with abnormal bleeding respectively. There was a clinical improvement in the oestradiol group compared with the placebo group, although this was not statistically significant There were no correlations between PR and ER concentration and the serum oestradiol, progesterone, levonorgestrel and sex hormone-binding globulin concentrations. Significantly increased mean immunostaining scores of stromal PR were observed in those Norplant users whose endometrium had an atrophic histological appearance. The serum oestradiol concentration did not show a significant change after treatment with the oestradiol patch compared with the placebo patch. [ABSTRACT FROM PUBLISHER]

Pyomyoma (suppurative leiomyoma) is a rare disease, which is considered to be a serious complication of uterine leiomyoma. Since 1945, only 18 patients have been reported and ours is the 19th. Although it is frequently reported in pregnant women or postmenopausal women who have vascular disease, our case is a 42-year-old woman in the perimenopausal period who presented with fever and a tender lower abdominal mass. She used the intrauterine device as a contraceptive method but leiomyoma had never been found before. Ultrasonographic findings suggested an ovarian tumor. She was diagnosed as having infected malignant ovarian cancer with an elevated CA 125 level that was initially treated with broad spectrum antibiotics; then she underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy. Pathological findings showed acute and chronic inflammation of the endometrium with abscess formation in an intramural leiomyoma. The intrauterine device might be the origin of pyomyoma due to a direct spread of the infection from the uterine cavity. Pyomyoma may be difficult to diagnose especially in those with a nonspecific clinical presentation without any history of leiomyoma. Delayed diagnosis may result in serious complications, whereas adequate surgery and broad spectrum antibiotics may decrease serious morbidity and mortality. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: Assess the occurrence of endometrial hyperplasia and endometrial cancer among PCOS patients having abnormal menstrual pattern. Endometrial thickness and other clinical characteristics associated with endometrial hyperplasia and endometrial cancer were also evaluated, Material and Method: Women with PCOS and abnormal menstrual pattern were enrolled into this cross-sectional study. Endometrial thicknesses were evaluated using transvaginal sonography. Endometrial aspiration was performed with endometrial aspirator and sent for pathology., Results: Out of 52 PCOS patients with abnormal menstrual pattern, nine (17.3%) and one (1.9%) had endometrial hyperplasia and endometrial cancer, respectively. There was no significant difference in mean endometrial thickness between those who had abnormal and normal endometrium (8.19 +/- 2.58 mm and 7.76 +/- 4.03 mm, respectively). However BMI and age of patients with abnormal endometrium were significantly higher and older than those with normal endometrium (p = 0.031 and p = 0.009, respectively)., Conclusion: Nineteen point two percent (19.2%) of patients with PCOS and abnormal menstrual pattern had endometrial hyperplasia or endometrial cancer Endometrial thickness was not different between those with abnormal and normal endometrium.

Background: Anal cytology has increasingly been used to screen for anal intraepithelial neoplasia (AIN) among men who have sex with men (MSM) at increased risk for anal cancer. Use of liquid-based cytology has been reported to reduce fecal and bacterial contamination and air-drying artifact compared with conventional cytology. Costs associated with liquid-based cytology, however, may limit its use in resource-limited settings., Methods: Anal swab samples were collected from MSM participants and used to prepare conventional and liquid-based cytology slides. Abnormal conventional cytology results triggered referral for high-resolution anoscopy and biopsy. Agreement between the 2 cytology techniques and the positive predictive value ratios of histology confirmed AIN were calculated., Results: Among 173 MSM, abnormal anal cytology was identified in 46.2% of conventional and 32.4% of liquid-based slides. The results agreed in 62.4% of cases with a κ value of 0.49 (P < 0.001). HIV-infected MSM had a 3.6-fold increased odds of having discordant anal cytology results (95% confidence interval: 1.6 to 7.8; P = 0.001) compared with HIV-uninfected MSM. Histological AIN 2 and 3 were identified in 20 MSM. The positive predictive value ratios and 95% confidence interval indicated no difference between the 2 techniques., Conclusions: Conventional anal cytology may be a preferred option for resource-limited settings given comparable performances to liquid-based cytology for the detection of AIN, although the agreement between the 2 techniques was lower among HIV-infected MSM. Due to high prevalence of abnormal anal cytology and AIN, health systems should prepare adequate infrastructure for high-resolution anoscopy services and AIN treatment.

Objective(s): To compare HOXA10 protein expression in the endometrium between natural control cycles and GnRH antagonist-treated cycles obtained during the window of implantation of normally menstruating women., Study Design: This study was conducted at the Department of Obstetrics and Gynecology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. Thirty-five volunteers were recruited into this prospective, self-controlled study, which was divided into two cycles, the first a natural control cycle and the second a GnRH antagonist-treated cycle. The two cycles were separated by one resting cycle. In the GnRH antagonist-treated cycle, when the leading follicle was 15 mm, ganirelix (Orgalutran®) 0.25mg was administered daily. In both cycles, ovulation was induced when the largest follicle reached 18 mm in diameter. Finally, endometrial biopsy was performed on day 6 after documented ovulation, which corresponds to the window of implantation. Endometrial HOXA10 protein expression, a marker of endometrial receptivity, was analyzed by immunohistochemistry. The protein expression was compared between the two cycles regarding their percentage of immunostained cells and IHC-scores (percentage of stained cells×intensity of nuclear staining)., Results: HOXA10 protein was exclusively localized in the stromal compartment of the endometrium. The percentage of HOXA10 nuclear staining in the endometrium collected from GnRH antagonist-treated cycles was higher than that of the natural cycles, whereas the IHC-scores showed no difference between the two cycles., Conclusion(s): GnRH antagonists may have no effect on HOXA10 protein expression in the endometrium obtained during the implantation window of normally menstruating women., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: The pattern of infection in cervical lesions with respect to HPV subtype has not been systematically studied in Thai women. The aim here was to determine HPV prevalence, genotype, and infection pattern in cervical lesions and to estimate the potential efficacy of an HPV prophylactic vaccine., Design: Formalin-fixed paraffin-embedded cervical tissue blocks of 410 Thai patients from 8 institutes in 4 regions of Thailand (northern, southern, north-eastern, and central) were studied. The samples included 169 low grade squamous intraepithelial lesions (LSILs), 121 high grade squamous intraepithelial lesions (HSILs), and 120 squamous cell carcinomas (SCCs). HPV-DNA was amplified by PCR using consensus primers GP5+ and GP6+. The HPV genotype was then determined by reverse linear blot assay that included 37 HPV-specific 5'-amino-linked oligonucleotide probes. Patterns of infection were classified as single infection (one HPV type), double infection (two HPV types), and multiple infection (three or more HPV types)., Results: The mean age of the subjects was 42 years. The prevalence of HPV infection was 88.8%. The highest HPV prevalence was found in the southern region (97.1%) and the lowest in the central region (78.6%). HPV-DNA was detected in 84.6% of LSILs, 90.1% of HSILs, and 93.3% of SCCs. A total of 20 HPV genotypes were identified. The five most common high risk HPV were HPV16 (83.2%), HPV18 (59.3%), HPV58 (9.3%), HPV52 (4.1%), and HPV45 (3.8%). In double and multiple infection patterns, the most common genotypes were HPV16/18 (27.8%) and HPV11/16/18 (54.9%). HPV6 was found only in LSIL and never in combination with other subtypes. HPV11 was most common in LSIL., Conclusion: There is no difference of HPV type distribution in women from 4 regions of Thailand with prominent HPV16 and HPV18 in all cases. The bivalent and quadrivalent vaccines have the potential to prevent 48.6 % and 74.5% of cervical cancers in Thai women. The potential of cancer prevention would rise to 87.6% if other frequent HR-HPV types (HPV58, 52, and 45) were also targeted by an HPV vaccine.

Objective: To investigate the expression of human telomerase reverse transcriptase (hTERT) in epithelial borderline ovarian tumor (BOT) by immunohistochemistry with correlation to clinicopathologic variables., Material and Method: Paraffin-embedded tissue sections of 62 borderline ovarian tumors (47 mucinous, 14 serous, and 1 clear cell) and 12 epthelial ovarian carcinomas were immunostained with antibodies to hTERT. The intensity and quantity of the immunostaining was determined and analyzed with clinicopathological characteristics., Results: hTERT expression was detected in 48.4% of BOT and all cases of epithelial ovarian carcinoma. In immunoreactive BOT 50% of cases were scored as high expression. Serous BOT had the highest rate of hTERT expression. There was no significant statistical difference of hTERT immunoreactivity between histologic types of BOT. No hTERT immunoreactivity was observed in the benign parts of the same slides of each immunoreactive case. hTERT immunoreactivity was positively correlated with FIGO stage (p = 0.04), but not with other variables. The mean follow-up time of BOT cases was 81.63 months and no recurrence or death was noted., Conclusion: hTERT expression was found in half of BOT and all of epithelial ovarian carcinoma. High hTERT expression was associated with FIGO stage.

Objectives: To evaluate interobserver reproducibility of a combined scoring method for immunohistochemical interpretation of p16 overexpression in cervical lesions., Materials and Methods: p16 immunostaining was performed in cervical samples from 183 patients, including 69 normal, 42 low grade squamous intraepithelial lesions(LSIL), 36 high grade SIL (HSIL), and 36 squamous cell carcinomas(SCCAs). Each case was evaluated by a combined scoring method based on the percentage of positive cells (score 0-3), the intensity of staining (score 0-3), and the distribution pattern (score 0-2). Immunoexpression for p16 was considered as positive when the combined score was 4-8 and negative with a score of 0-3. Ten pathologists with varied experience in interpretating p16 immunostains evaluated each slide independently., Results: All normal cervical squamous epithelia (69/69) were uniformly negative for p16. All HSILs (36/36), all SCCAs (100/100), and all but one of the LSILs (40/41, 97.6%) showed positive expression. In 172 of 183 cases (93.9%), p16 interpretation was concordant with all pathologists. Eleven cases with discordant results included 10 LSILs and 1 normal mucosa sample. Percentage of agreement of each pathologist pair ranged from 96.7-100% (mean 98.1%) with mean kappa value of 0.96 (range 0.93-1.000)., Conclusion: The proposed combined scoring method shows good reproducibility among the participating pathologists and good correlation with the histologic diagnosis. This method may be a useful guide in the interpretation of p16 expression in cervical epithelial lesions.

Objective: To evaluate the hysterectomy specimen findings in the patients who underwent fractional curettage (F&C) with presence of adenocarcinoma in both endocervical and endometrial specimens., Material and Method: Forty-one patients who had adenocarcinoma in both endocervical and endometrial specimens from F&C and underwent subsequent hysterectomy for surgical staging without pre-operative radiotherapy or chemotherapy at King Chulalongkorn Memorial Hospital between 1999 and 2007 were evaluated Histologic slides from both F&C and hysterectomy specimens were reviewed and assessed All cases of endometrial adenocarcinoma with cervical involvement (stage 2) in hysterectomy specimens were also assessed and compared to the results in F&C specimens., Results: Fifteen patients (36.6%) with both positive endocervical and endometrial specimens from F&C were diagnosed as endometrial adenocarcinoma within uterine cavity with lower uterine segment involvement. Only 34.1% of cases were endometrial carcinomas with cervical involvement. In the 35 cases with endometrial carcinoma stage 2, 60% had adenocarcinoma in both endocervical and endometrial specimens from F&C., Conclusion: In the patients who had adenocarcinoma in both endocervical and endometrial specimens from fractional curettage, the most common final pathological diagnosis from hysterectomy specimens was endometrial adenocarcinoma within uterine cavity with lower uterine segment involvement. Therefore, only 60% of endometrial carcinoma stage 2 revealed positive adenocarcinoma in both endocervical and endometrial specimens from fractional curettage.