Molecular-based classification of endometrial carcinoma in Northern Thailand: impact on prognosis and potential for implementation in resource-limited settings.

BACKGROUND: Endometrial carcinoma is molecularly categorized into four subgroups: polymerase-E exonuclease domain-mutant (POLE-mut), mismatch repair-deficient (MMR-d), p53-abnormal (p53-abn), and no specific molecular profile (NSMP). This classification scheme has been included into clinical recommendation for post-operative risk-based management, although there have been few Asian studies on this topic. The present study aimed to evaluate the prevalence and clinical outcomes of endometrial carcinoma using this classification in Northern Thailand and the feasibility of implementation in resource-limited settings. METHODS: Endometrial carcinomas from hysterectomy specimens were classified using immunohistochemistry for MMR proteins and p53, as well as POLE mutation testing. Clinicopathological variables and outcomes were analyzed. The costs of the molecular information-based approach were compared to those incurred by the conventional approach (without molecular classification). RESULTS: Of 138 patients, 52.9% in the NSMP subgroup, 28.2% were in the MMR-d, 13.8% in the p53-abn, and 5.1% in the POLE-mut. After adjusting for other variables, patients with POLE-mut showed the most favorable outcomes, while those with p53-abn had the poorest survival. When estimating the costs for post-operative management, the use of molecular classification resulted in a 10% increase over the conventional approach. However, the cost increased only by 1% if only POLE testing was used to identify patients for treatment omission. CONCLUSION: In Northern Thailand, endometrial carcinoma had comparable subgroup distribution and prognostic implications to previous reports, supporting the implementation of management guidelines that incorporate molecular information. In resource-limited settings, at least POLE mutation testing in early-stage patients should be considered.

Depot medroxyprogesterone acetate and endometrial cancer: A multicenter case-control study.

OBJECTIVE: To assess the associations between depot medroxyprogesterone acetate (DMPA) and endometrial cancer. METHODS: This multicenter case-control study was conducted among tertiary hospitals in Thailand. Patients were women with endometrial cancer. Controls were women admitted for other conditions, matched for age within 5 years of the patients' age. The controls had to have no abnormal vaginal bleeding, history of hysterectomy, or cancers of the other organs. A standardized questionnaire was used to gather information. Conditional logistic regression was applied to calculate adjusted odds ratio (aORs) and 95% confidence intervals (CIs). RESULTS: During 2015 to 2021, 378 patients and 1134 controls were included. Ever use of DMPA was associated with a 70% decreased overall risk of endometrial cancer (aOR, 0.30 [95% CI, 0.21-0.42]). Endometrial cancer risk declined by 3% (aOR, 0.97 [95% CI, 0.96-0.98]) for every 3 months of DMPA use. The magnitude of the decline in endometrial cancer risk did not vary appreciably by cancer subtypes (aOR, 0.26 [95% CI, 0.17-0.41] and 0.38 [95% CI, 0.22-0.65] for low-grade and high-grade tumors, respectively). CONCLUSIONS: Depot medroxyprogesterone acetate use was inversely associated with endometrial cancer risk in a duration-dependent manner. This association was independent of cancer subtype.

Clear-Cell Mesothelioma of Uterine Corpus: Diagnostic Challenges in Intraoperative Frozen Sections.

The clear-cell variant of epithelioid mesothelioma is an extremely rare neoplasm of the peritoneum. It shares histomorphologic features overlapping with a wide variety of tumors including carcinomas and other non-epithelial neoplasms. The diagnosis of peritoneal clear-cell mesothelioma is not always straightforward, despite known immunohistochemistry (IHC) markers. Due to its rarity, this entity may be diagnostically confused with other clear-cell neoplasms, particularly in intraoperative frozen sections. Here, we present a case of clear-cell mesothelioma originating in the uterine serosa that was initially misdiagnosed as clear-cell adenocarcinoma in the intraoperative frozen section. Microscopically, the tumor showed diffuse tubulocystic spaces of variable size lined by clear cells with moderate nuclear atypia. Immunohistochemical staining confirmed the diagnosis of clear-cell mesothelioma. Recognition of this entity, albeit rare, is important as the diagnosis may significantly affect the management considerations. The judicious use of an IHC panel helps to distinguish this tumor from other mimickers.

Popcorn Appearance of Severely Calcified Uterine Leiomyoma: Image-Pathological Correlation.

Calcified subserous leiomyoma is a rare benign tumor commonly seen in the postmenopausal age group. Cases with severely calcified degeneration all over the mass are extremely rare. It causes diagnostic confusion with the solid calcified adnexal mass and the large bladder calculi in the pelvis. We hereby present a case of heavily calcified subserous uterine leiomyoma in a 66-year-old postmenopausal woman. An X-ray of the abdomen and pelvis and CT scan showed a pelvic mass with scattered popcorn appearance in the pelvis, representing severely calcified discrete spots all over the mass. Sonographically, different from typical uterine leiomyomas which exhibit recurrent refractory shadowing patterns, our case showed heavy homogeneous acoustic shadow obscuring all structures beneath the mass surface, resulting in a suboptimal ultrasound examination. Accordingly, CT scans, which are usually not a primary tool for the diagnosis of uterine leiomyomas, are helpful to characterize the mass and identify their organ of origin. The case presented here was treated with a hysterectomy with bilateral oophorectomy and was post-operatively confirmed for severely calcified subserous leiomyomas.

Profiling the Expression and Prognostic Values of FYN, A Non-Receptor Tyrosine Kinase, in Different Histological Types of Epithelial Ovarian Cancer.

OBJECTIVE: This study was aimed at evaluating FYN expression among different histologic types of epithelial ovarian cancer (EOC) and its associated prognostics. METHODS: The FYN expression levels using quantitative real-time PCR method were evaluated in 98 primary EOC. Receiver operating characteristic curve were used to select an optimal cut-off value for determining the presence or absence of a disease progression. RESULT: The median level of FYN expression varied among different EOC types, being the highest in high-grade serous carcinomas and the lowest in clear cell carcinomas (CCC). Using the cutoff FYN value to predict disease progression, the FYN-positive group had a poorer progression-free survival (PFS) compared to the FYN-negative group (p = 0.001). In multivariate Cox regression analysis, FYN expression was an independent predictor for disease progression (Hazard ratio = 2.30; 95% CI: 1.21- 4.38; p = 0.011). In subgroup analysis, FYN expression was significantly associated with lower PFS in early stage CCC patients (p = 0.009). CONCLUSION: FYN expression is variable among different types of EOC while impacting on the prognostic values in patients with early stage CCC.

Microcystic Stromal Tumor with Predominant Bizarre Nuclei of Ovary in a Pregnant Woman.

Microcystic stromal tumor (MST) is a rare type of pure stromal tumor in the category of ovarian sex cord-stromal tumors. It is characterized by a distinctive microcystic appearance with bland tumor cells. Although the pathological diagnosis can be straightforward based on the typical histomorphology in most MSTs, the cases with morphologic variation can pose a diagnostic challenge due to unfamiliarity of pathologists with the histologic spectrum of MST and its negativity for inhibin and calretinin, the commonly used sex cord-stromal markers. The coexistence between MST and mucinous epithelial tumor is extremely rare. We present the first case, to our knowledge, of ovarian MST with predominant bizarre nuclei coexisting with mucinous cystadenoma in a pregnant woman. The histomorphology in this case presents a diagnostic challenge and raises differential diagnosis for a wide variety of ovarian malignant neoplasms including nonneoplastic lesions.

An Evaluation of Phosphate Buffer Saline as an Alternative Liquid-Based Medium for HPV DNA Detection.

OBJECTIVE: HPV detection has been proposed as part of the co-testing which improves the sensitivity of cervical screening. However, the commercially liquid-based medium adds cost in low-resource areas. This study aimed to evaluate the performance of ice-cold phosphate buffer saline (PBS) for HPV detection. METHODS: HPV DNA from SiHa cells (with 1-2 copies of HPV16 per cell) preserved in ice-cold PBS or PreserveCyt solution at different time points (24, 36, 48, 72, 120 and 168 h) was tested in triplicate using Cobas 4800. The threshold cycle (Ct) values of both solutions were compared. An estimated false negative rate of PBS was also assessed by using the difference in Ct values between both solutions (∆Ct) and Ct values of HPV16-positive PreserveCyt clinical samples (Ctsample) at corresponding time points. Samples with a (Ctsample+∆Ct) value > 40.5 (the cutoff of HPV16 DNA by Cobas 4800) were considered as false negativity. RESULTS: The Ct values of HPV16 DNA of SiHa cells collected in PBS were higher than PreserveCyt ranging from 0.43 to 2.36 cycles depending on incubation times. There was no significant difference at 24, 72, 120, and 168 h.  However, the Ct values were statistically significantly higher for PBS than PreserveCyt at 36 h (31.00 vs 29.26), and 48 h (31.06 vs 28.70). A retrospective analysis in 47 clinical PreserveCyt collected samples that were positive for HPV16 DNA found that 1 case (2%) would become negative if collected in ice-cold PBS. CONCLUSIONS: The PBS might be an alternative collecting medium for HPV detection in the low-resource areas. Further evaluations are warranted.

Clinicopathological Prognostic Factors Influencing Survival Outcomes of Vulvar Cancer.

BACKGROUND: The prognostic factors for survival in squamous cell carcinoma (SCCA) of vulva cancer such as groin node involvement, postmenopausal status, tumor size, margin status, tumor grade, lymph vascular space invasion (LVSI) were reported in the past. However, with limited data from Southeast - Asian population, the present study was conducted to evaluate the clinicopathological prognostic factors for survival outcomes of this disease after treatment with surgery. METHODS: All SCCA vulva cancer patients who underwent surgery between January 2006 and December 2017 were reviewed. The clinicopathological factors were analyzed to identify the prognostic factors for the progression-free survival (PFS) and overall survival (OS) using the Kaplan- Meier method and Cox-Proportional Hazard model. RESULTS: One hundred twenty-five patients were recruited. The independent poor prognostic factors for PFS were groin node-positive and  pathologic tumor diameter of more than 25 mm. Whereas postmenopausal status and groin node positive were independent poor prognostic factors for OS. CONCLUSION: Groin node-positive was the only one independent poor prognostic factor for both PFS and OS. In addition, the tumor diameter longer than 25 mm. was independent poor prognostic factors for PFS while postmenopausal status was independent poor prognostic factors for OS. Special adjuvant treatment for patients with these factors should be further investigated. 
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Platinum-based chemotherapy and bevacizumab instigate the destruction of human ovarian cancers via different signaling pathways.

The standard chemotherapy regimens of ovarian cancer are platinum-based chemotherapy (carboplatin and paclitaxel) and bevacizumab (BEV). However, the effects of BEV alone or combined with carboplatin and paclitaxel on mitochondrial dynamics, mitochondrial function, mitophagy, apoptosis, inflammation and vascular endothelial growth factor (VEGF) in human ovarian cancer mitochondria and cells have not yet been investigated. Therefore, we aimed to test the hypothesis that 1) platinum-based chemotherapy and BEV equally damage isolated mitochondria from human ovarian cancers, and ovarian cancer cells through inducing mitochondrial dynamics dysregulation, mitochondrial dysfunction, increased mitophagy and apoptosis, as well as altered inflammation and VEGF; and 2) combined therapies exert greater damage than monotherapy. Each isolated human ovarian cancer mitochondria (n = 16) or CaOV3 cells (n = 6) were treated with either platinum-based chemotherapy (carboplatin 10 µM and paclitaxel 5 µM), BEV (2 mg/mL) or combined platinum-based chemotherapy and BEV for 60 min or 24 h, respectively. Following the treatment, mitochondrial dynamics, mitochondrial function, mitophagy, apoptosis, cytotoxicity, inflammation and VEGF were determined. Platinum-based chemotherapy caused ovarian cancer mitochondria and cell damage through mitochondrial dysfunction, increased cell death with impairment of membrane integrity, and enhanced VEGF reduction, while BEV did not. BEV caused deterioration of ovarian cancer mitochondria and cells through mitochondrial-dependent apoptosis, but it had no effect on cell viability. Interestingly, combined platinum-based chemotherapy and BEV treatments had no addictive effects on all parameters except mitochondrial maximal respiration, when compared to monotherapy. Collectively, these findings suggest that platinum-based chemotherapy and BEV caused human ovarian cancer mitochondrial and cell damage through different mechanisms.

Prevalence of Tissue BRCA Gene Mutation in Ovarian, Fallopian Tube, and Primary Peritoneal Cancers: A Multi-Institutional Study.

BACKGROUND AND OBJECTIVE: Ovarian, fallopian tube, or primary peritoneal cancer patients with BRCA gene mutation have enhanced sensitivity to platinum-based regimens and PARP inhibitors. However, the knowledge regarding BRCA mutation in Thai patients is limited. This study aimed at identifying the prevalence and characteristics of somatic and germline BRCA 1 and 2 mutations in Thai patients with these cancers. MATERIALS AND METHODS: The paraffin blocks of tumors with histology of high grade serous, high grade endometrioid, or clear cell carcinoma obtained between June 2016 and December 2017 were analyzedto evaluate BRCA mutation using next-generation sequencing system. Blood or normal tissue paraffin blocks of positive patients were further tested for germline BRCA mutation. RESULTS: Tissue paraffin blocks of 178 patients were collected but only 139 were analyzed. Positive BRCA mutation was identified in 24 patients (17.3%): BRCA1 in 13 cases, BRCA2 in 10 cases, and BRCA1 and 2 in the rest one. Germline mutation study in blood or normal tissue in 23 positive patients revealed BRCA mutation in 14 cases, BRCA1 in 8 cases and BRCA 2  in 6 cases. Overall, the prevalence of somatic and germline mutation was 6.5% (9 out of 138 patients) and 8.7% (14 out of 138 patients), respectively. The most common histology associated with BRCA mutation was high grade serous cancer (27.3%). No significant difference was found between patients with or without BRCA mutation in terms of stage, outcome, platinum status, and survival outcome. CONCLUSION: BRCA mutation was demonstrated in less than 10% of Thai ovarian cancer patients. Higher rate of mutation was found in high grade serous cancer.
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Primary signet ring cell carcinoma with neuroendocrine differentiation arising in mucinous borderline tumor of the ovary.

•Primary signet ring cell carcinoma in ovarian mucinous tumor is rare.•The most important differential diagnosis is metastatic carcinoma.•We report a case of primary ovarian signet ring cell carcinoma in mucinous tumor.•Clinicopathological correlation is essential to establish the correct diagnosis.

Role of genomic DNA methylation in detection of cytologic and histologic abnormalities in high risk HPV-infected women.

Cervical cancer is the fourth most common malignancy affecting women worldwide. The development of disease is related to high-risk human papillomavirus (hrHPV) infection. Cytology has been the most recommended triage for primary cervical (pre)cancer screening despite relatively low sensitivity. Recently, genomic DNA methylation has been proposed as an additional marker to increase sensitivity for detecting cervical precancerous lesion. This study aimed to evaluate the performance of methylation status of three tumor suppressor genes (CADM1, FAM19A4, and MAL) and HPV genotyping in detection of cytologic and histologic abnormalities in cervical cancer screening. Two hundred and sixty samples with available frozen cell pellets including 70 randomly selected cases of negative for intraepithelial lesion or malignancy (NILM)&HPV-negative, 70 randomly selected cases of NILM&HPV-positive, and 120 cytologic abnormalities & HPV-positive from a population-based cervical cancer screening program (n = 7,604) were investigated for the DNA methylation pattern of CADM1, FAM19A4, and MAL. Of 120 cytologic abnormalities & HPV-positive cases, there were 115 available histologic results. HPV52 and HPV58 were most commonly found in histologic HSIL+. The methylation levels of CADM1, FAM19A4, and MAL were elevated with the severity of cytologic abnormality which significantly increased by 3.37, 6.65 and 2 folds, respectively, in cytologic HSIL comparing with NILM. A significant increase in methylation levels of these three genes was also observed in histologic HSIL+ compared with negative histology but only CADM1 showed a significant higher methylation level than histologic LSIL. Using the ROC curve analysis, DNA methylation levels of FAM19A4 performed best in differentiating high-grade cytology (ASC-H+ from NILM/ASC-US/LSIL), followed by CADM1 and MAL. Whilst the CADM1 methylation performed best in distinguishing histologic HSIL+ from negative/LSIL with an area under the ROC curve of 0.684, followed by MAL (0.663) and FAM19A4 (0.642). Interestingly, after combining high DNA methylation levels to HPV16/18 genotypes, rates of histologic HSIL+ detection were substantially increased from 25% to 79.55% for CADM1, 77.27% for FAM19A4, and 72.73% for MAL, respectively. The rate further increased up to 95.45% when at least one of three genes had a high methylation level. This suggests a possible role of genomic DNA methylation, especially CADM1, in detecting histologic HSIL+ lesions in combination with hrHPV testing.

Prognostic Value of Tumor Budding in Early-Stage Cervical Adenocarcinomas

Background: Tumor budding has recently been reported as an independent adverse prognostic factor for colorectal adenocarcinomas and other types of carcinoma in the digestive tract. This study aimed to evaluate the prognostic value of tumor budding in patients with early-stage cervical adenocarcinomas and any associations with other clinical and pathological features. Methods: Histological slides of patients with early-stage (IB-IIA) usual-type endocervical adenocarcinoma who underwent radical hysterectomy and pelvic lymph node dissection, without preoperative chemotherapy, between January 2006 and December 2012 were reviewed. Tumor budding was evaluated in routinely-stained sections and defined as detached single cells or clusters of fewer than 5 cells in a tumor invasive front and was stratified based on the number of bud counts in 10-high-power fields as low (<15 buds) and high (≥15 buds). Correlations between tumor bud count and other clinical and pathological variables including follow-up outcomes were assessed. Results: Of 129 patients, a high tumor bud count was observed in 15 (11.6%), positively associated with histologic grade 3 (p<0.001), invasive pattern C (Silva System) (p=0.004), lymph node metastasis (p=0.008), stage IB2-IIA (p=0.016), and tumor size >2 cm (p=0.036). Kaplan-Meyer analysis showed a significant decrease in both disease-free survival and cancer-specific survival for patients with a high tumor bud count (p=0.027 and 0.031, respectively). On multivariate analysis, histologic grade 3 was the only independent predictor for decreased disease-free survival (p=0.004) and cancer-specific survival (p=0.003). Conclusions: A high tumor budding count based on assessment of routinely-stained sections was found to be associated with decreased disease-free and cancer-specific survival in patients with early-stage cervical adenocarcinomas. However, it was not found to be an independent prognostic predictor in this study.

Leiomyosarcoma and Squamous Cell Carcinoma Arising in Mature Cystic Teratoma of the Ovary.

The occurrence of malignant transformation in mature cystic teratoma of the ovary is rare, with squamous cell carcinoma being the most common histologic type. Sarcomatous transformation has been rarely described in the literature. We present a case of leiomyosarcoma with a minor component of squamous cell carcinoma arising in mature cystic teratoma of ovary in a 65-year-old woman. The malignant tumor showed two distinct components of sarcomatous and invasive epithelial elements, which were confirmed by immunostaining. To our knowledge, only four cases of leiomyosarcoma in ovarian mature cystic teratoma have been reported and this is a unique case report of leiomyosarcoma and squamous cell carcinoma arising in a mature cystic teratoma of ovary.

Angiosarcoma Arising in Ovarian Mucinous Tumor: A Challenge in Intraoperative Frozen Section Diagnosis.

Angiosarcoma of the ovary is rare but represents an aggressive type of malignant ovarian neoplasms. The purpose of this report is to describe the features of angiosarcoma arising in mucinous tumor that was misinterpreted as a benign vascular proliferation during the intraoperative consultation. A 45-year-old woman presented with an abdominal mass for 1 month. Exploratory laparotomy was performed. A 35 cm right ovarian mass submitted for intraoperative consultation was a multicystic mucinous tumor with an 8 cm area of hemorrhagic lesion between cystic locules. The frozen section diagnosis was at least mucinous borderline tumor. The hemorrhagic area, which was intraoperatively interpreted as organizing vessels associated with previous hemorrhage, represented angiosarcoma in permanent sections. Angiosarcoma may present a challenge in intraoperative frozen section diagnosis of an ovarian mass. The presence of ectatic anastomosing vessels with dissecting growth appears to be the clue to a suspicion of angiosarcoma. The presence of endothelial atypia provides further support for the diagnosis. A macroscopic hemorrhagic area in an ovarian mucinous tumor should be evaluated with care, and the possibility of angiosarcoma should be borne in mind.

Ovarian Carcinosarcoma and Its Association with Mature Cystic Teratoma and Primary Tubal Carcinoma.

Introduction. Carcinosarcoma is an uncommon form of ovarian cancers, classified as being part of the group of mixed epithelial and mesenchymal tumors. The occurrence of carcinosarcoma in association with a mature cystic teratoma and synchronous tubal carcinoma is very rare. Case Report. A 69-year-old woman presented with a pelvic mass. An abdominal computerized tomographic scan detected a 15 cm right pelvic mass which was suggestive of malignant transformation of a dermoid cyst. Intraoperative, bilateral ovarian masses (left 10 cm and right 12 cm) with diffuse peritoneal metastatic nodules were identified. Histologically, the left ovarian mass was composed of 2 components including carcinosarcoma and mature cystic teratoma, whereas the right ovarian mass represented a mature cystic teratoma with serosal surface involvement of high-grade serous adenocarcinoma. The left fallopian tube was macroscopically unremarkable but contained a 5.0 mm focus of high-grade serous adenocarcinoma in the distal part, with adjacent serous tubal intraepithelial carcinoma. Conclusion. As the fallopian tube has recently been proposed to be an origin for a majority of pelvic or ovarian high-grade serous adenocarcinomas, tubal carcinoma may be the origin for ovarian carcinosarcomas through an epithelial-mesenchymal transition. The coexistence of ovarian carcinosarcoma and teratoma in the present case should represent a collision tumor.

Genotyping for Human Papillomavirus (HPV) 16/18/52/58 Has a Higher Performance than HPV16/18 Genotyping in Triaging Women with Positive High-risk HPV Test in Northern Thailand.

BACKGROUND: Testing for high-risk human papillomavirus DNA (HPV test) has gained increasing acceptance as an alternative method to cytology in cervical cancer screening. Compared to cytology, HPV test has a higher sensitivity for the detection of histologic high-grade squamous intraepithelial lesion or worse (HSIL+), but this could lead to a large colposcopy burden. Genotyping for HPV16/18 has been recommended in triaging HPV-positive women. This study was aimed to evaluate the screening performance of HPV testing and the role of genotyping triage in Northern Thailand. METHODS: A population-based cervical screening program was performed in Chiang Mai (Northern Thailand) using cytology (conventional Pap test) and HPV test (Hybrid Capture 2). Women who had abnormal cytology or were HPV-positive were referred for colposcopy. Cervical samples from these women were genotyped using the Linear Array assay. RESULTS: Of 5,456 women, 2.0% had abnormal Pap test results and 6.5% tested positive with Hybrid Capture 2. Of 5,433 women eligible for analysis, 355 with any positive test had histologic confirmation and 57 of these had histologic HSIL+. The sensitivity for histologic HSIL+ detection was 64.9% for Pap test and 100% for Hybrid Capture 2, but the ratio of colposcopy per detection of each HSIL+ was more than two-fold higher with Hybrid Capture 2 than Pap test (5.9 versus 2.8). Genotyping results were available in 316 samples. HPV52, HPV16, and HPV58 were the three most common genotypes among women with histologic HSIL+. Performance of genotyping triage using HPV16/18/52/58 was superior to that of HPV16/18, with a higher sensitivity (85.7% versus 28.6%) and negative predictive value (94.2% versus 83.9%). CONCLUSIONS: In Northern Thailand, HPV testing with genotyping triage shows better screening performance than cervical cytology alone. In this region, the addition of genotyping for HPV52/58 to HPV16/18 is deemed necessary in triaging women with positive HPV test.

Comparison of Human Papillomavirus Detection in Urine and Cervical Samples Using High-Risk HPV DNA Testing in Northern Thailand.

Objective. To evaluate the performance of high-risk human papillomavirus (HPV) DNA testing in urine samples compared to that of cervical sample testing in Northern Thailand. Methods. Paired urine and cervical samples were collected during the follow-up of women with a previous positive HPV test. HPV testing was performed using the Cobas 4800 HPV Test. Linear Array assay was used for genotyping in selected cases. Results. Paired urine and cervical samples were obtained from 168 women. Of 123 paired samples with valid results, agreement in the detection of high-risk HPV DNA was present in 106 cases (86.2%), with a kappa statistic of 0.65 (substantial agreement). Using the cervical HPV results as a reference, the sensitivity of urine HPV testing was 68.6% (24/35) and the specificity 93.2% (82/88). For the detection of histologic high-grade squamous intraepithelial lesion or worse (HSIL+), the sensitivity of urine HPV testing was 80.0% (4/5) and the specificity 78.0% (92/118). Conclusion. Although urine HPV testing had a rather low sensitivity for HPV detection, its sensitivity for histologic HSIL+ detection was high. For clinical use of urine HPV testing, standardization of specimen collection and processing techniques or application of a more sensitive test, especially in the detection of HPV52 and HPV58, is necessary.

High performance of combined HPV testing and genotyping for HPV16/18/52/58 in triaging women with minor cervical cytological abnormalities in northern Thailand.

Human papillomavirus (HPV) infection is an important cause of cervical cancer. Screening with cytology or combined cytology and HPV testing helps to detect early cervical cancers and precancerous lesions (high-grade squamous intraepithelial lesion or worse [HSIL+]). Minor cytological abnormalities (atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesion) account for the majority of abnormal cervical cytology results, but only 10-20% of women with minor cytological abnormalities have histologic HSIL+. Triage tests are useful to identify the high-risk patients and reduce the colposcopy burden. This study was aimed to evaluate the triage performance of combined HPV DNA testing and genotyping. Cervical samples from women with minor cytological abnormalities, who underwent colposcopy at Chiang Mai University Hospital in northern Thailand between October 2010 and February 2014, were tested for HPV DNA using Hybrid Capture 2 (HC2). Genotyping was performed using Linear Array assay. Of 223 women with cervical histology confirmation, histologic HSIL+ was detected in 25 women (11.2%). The sensitivity, specificity, positive predictive value, and negative predictive value of 3 triage methods for histologic HSIL+ were; 100%, 47.5%, 19.4%, and 100% by HC2 only; 40.0%, 88.4%, 30.3%, and 92.1% by combined HC2 and genotypes HPV16/18; and 96.0%, 75.8%, 33.3%, and 99.3% by combined HC2 and genotypes HPV16/18/52/58. Triage using combined HC2 and genotypes HPV16/18/52/58 showed significantly greater area under the receiver operating curve than the other 2 methods (P < 0.001). Combined HPV DNA testing and genotyping for HPV16/18/52/58 is useful for triaging women with minor cervical cytological abnormalities in northern Thailand.

Short-Term Isoflavone Intervention in the Treatment of Severe Vasomotor Symptoms after Surgical Menopause: A Case Report and Literature Review.

Isoflavones are soy phytoestrogens that potentially exert various favorable effects in postmenopausal women, for example, alleviating vasomotor episodes, attenuating bone loss, and stimulating vaginal epithelial maturation. There has, however, been lack of consensus regarding those therapeutic effects. Most clinical studies of isoflavones have been conducted with women who had undergone natural menopause, but not those who had undergone surgical menopause. This study reports on a 51-year-old woman who presented with severe vasomotor episodes after undergoing a hysterectomy and a bilateral oophorectomy due to hypermenorrhea secondary to myoma uteri. She refused hormone therapy due to fear of adverse drug reactions so was treated with oral soy isoflavones (two capsules twice daily, equivalent to at least 100 mg daily dose) for 8 weeks. The number and severity of hot flushes and her menopause-specific quality of life dramatically improved from baseline values. The serum bone resorption marker (beta C-telopeptide) decreased markedly, while vaginal epithelial maturation improved slightly, suggesting the potential of isoflavones in attenuating bone loss and stimulating vaginal maturation. The intervention did not adversely affect the hormonal profile (FSH, LH, and estradiol) and liver or renal functions. Thus, isoflavones could be an option for women experiencing severe vasomotor episodes after surgical menopause.