Liquid biopsy of PIK3CA mutations in cervical cancer in Hong Kong Chinese women.

INTRODUCTION: Cervical cancer is the fourth most common female cancer worldwide. The prognosis for women with advanced-stage or recurrent cervical cancer remains poor and response to treatment is variable. Standardized management protocols leave little room for individualization. We report on a novel blood-based liquid biopsy for specific PIK3CA mutations as a clinically useful biomarker in patients with invasive cervical cancer. METHODS: One hundred seventeen Hong Kong Chinese women with primary invasive cervical cancer and their pre-treatment plasma samples were investigated. Two PIK3CA mutations, p.E542K and p.E545K were measured in cell free DNA (cfDNA) extracted from plasma using droplet digital PCR. This liquid biopsy of PIK3CA in cervical cancer was correlated to clinico-pathological features to verify the potential of PIK3CA as a clinically useful molecular biomarker for predicting disease prognosis and monitoring for progression. RESULTS: PIK3CA mutations, either p.E542K or p.E545K, were detected in plasma cfDNA from 22.2% of the patients. PIK3CA mutation status was significantly correlated to median tumor size (p<0.01). PIK3CA mutations detected in the plasma were significantly associated with decreased disease-free survival and overall survival (p<0.05). CONCLUSIONS: As a liquid molecular biopsy, analysis of circulating PIK3CA mutations shows promise as a way to refine risk stratification of individual patients with cervical cancer, and provides a platform for further research to offer individualized therapy with the purpose of improving outcomes.

Genomic aberrations in cervical adenocarcinomas in Hong Kong Chinese women.

Although the rates of cervical squamous cell carcinoma have been declining, the rates of cervical adenocarcinoma are increasing in some countries. Outcomes for advanced cervical adenocarcinoma remain poor. Precision mapping of genetic alterations in cervical adenocarcinoma may enable better selection of therapies and deliver improved outcomes when combined with new sequencing diagnostics. We present whole-exome sequencing results from 15 cervical adenocarcinomas and paired normal samples from Hong Kong Chinese women. These data revealed a heterogeneous mutation spectrum and identified several frequently altered genes including FAT1, ARID1A, ERBB2 and PIK3CA. Exome sequencing identified human papillomavirus (HPV) sequences in 13 tumors in which the HPV genome might have integrated into and hence disrupted the functions of certain exons, raising the possibility that HPV integration can alter pathways other than p53 and pRb. Together, these provisionary data suggest the potential for individualized therapies for cervical adenocarcinoma based on genomic information.

Efficacy and outcomes of transobturator tension-free vaginal tape with or without concomitant pelvic floor repair surgery for urinary stress incontinence: five-year follow-up.

OBJECTIVES: To compare the 5-year subjective and objective outcomes of transobturator tension-free vaginal tape alone versus the same procedure with concomitant pelvic floor repair surgery for pelvic organ prolapse in women with urinary stress incontinence. DESIGN: Prospective cohort study. SETTING: Urogynaecology unit at a university hospital in Hong Kong. PATIENTS: Of 218 women, 96 (44%) received transobturator tension-free vaginal tape alone and 122 (56%) received transobturator tension-free vaginal tape with concomitant pelvic floor repair surgery from September 2004 to December 2009. The women were followed up annually for up to 5 years after the operation. MAIN OUTCOME MEASURES: The 5-year subjective and objective cure rates were assessed. Subjective cure was defined as no urine loss during physical activity and objective cure was defined as no urine leakage on coughing during urodynamic study. RESULTS: Overall, 88 women receiving transobturator tension-free vaginal tape alone and 101 women receiving transobturator tension-free vaginal tape with concomitant pelvic floor repair surgery were followed up for 5 years after operation. The subjective and objective cure rates of the two groups were 70.5% versus 94.1% (P<0.01) and 80.3% versus 85.7% (P=0.58), respectively. CONCLUSIONS: Transobturator tension-free vaginal tape is an effective treatment for urinary stress incontinence in women who received it alone or with concomitant pelvic floor repair surgery for pelvic organ prolapse, providing high subjective and objective efficacy for up to 5 years after operation. Transobturator tension-free vaginal tape with concomitant pelvic floor repair surgery achieved similar, if not better, long-term outcome compared with transobturator tension-free vaginal tape alone.

Effect of levator ani muscle injury on primiparous women during the first year after childbirth.

INTRODUCTION AND HYPOTHESIS: To evaluate the effect of levator ani muscle (LAM) injury on pelvic floor disorders and health-related quality of life in Chinese primiparous women during the first year after delivery. METHODS: At 8 weeks and 12 months after delivery, 328 women were assessed for symptoms of pelvic floor disorders and quality of life using the standardised questionnaire, POP-Q; and translabial ultrasound to detect LAM injury. Descriptive analysis, independent sample t test, non-parametric testing, Chi-squared test and two-sided Fisher's exact test were used. RESULTS: At 8 weeks after delivery, 48 (19.0% [95% CI, 14.2-23.8%]) women with vaginal delivery had LAM injury; 38 women (79.2%) had persistent LAM injury at 12 months. At 8 weeks, LAM injury was associated with prolapse symptoms, descent at Pelvic Organ Prolapse Quantification (POP-Q) Aa and Ba points and a higher Pelvic Organ Prolapse Distress Inventory (POPDI) general and Urinary Distress Inventory (UDI) Obstructive subscale score. At 12 months, it was not associated with prolapse symptoms, Pelvic Floor Distress Inventory (PFDI) or Pelvic Floor Impact Questionnaire (PFIQ). There was also no association between stress urinary incontinence (SUI), urge urinary incontinence (UUI), mixed urinary incontinence (UI), faecal incontinence (FI) with LAM injury at both time points. CONCLUSIONS: Seventy-nine per cent of women who had LAM injury at 8 weeks after vaginal delivery had persistent LAM injury at 12 months. LAM injury was associated with prolapse symptoms, lower POP-Q Aa and Ba points at 8 weeks after delivery and a higher POPDI general and UDI Obstructive subscale scoring. However, we are not able to confirm the association between LAM injury and SUI, UUI, mixed UI, FI at 8 weeks or 12 months after delivery; or prolapse symptoms, PFDI or PFIQ scores at 12 months after delivery.

Prevalence of urinary and fecal incontinence in Chinese women during and after their first pregnancy.

INTRODUCTION AND HYPOTHESIS: This study evaluated factors and their prevalence associated with urinary (UI) and fecal (FI) incontinence during and after a woman's first pregnancy. METHODS: Nulliparous Chinese women with no UI or FI before pregnancy were studied with a standardized questionnaire for UI and FI from early pregnancy until 12 months after childbirth. Maternal characteristics and obstetric data were analyzed using descriptive analysis, independent sample t test, chi-square test, and logistic regression. RESULTS: Three hundred and twenty-eight (74.2 %) women completed the study. The prevalence of antenatal UI increased with gestation. Overall, 192 (58.5 %), 60 (18.3 %), and 76 (23.1 %) had normal vaginal delivery, instrumental delivery, and cesarean section, respectively. Twelve months after delivery, prevalence of stress urinary incontinence (SUI) and urge urinary incontinence (UUI) was 25.9 % [95 % confidence interval (CI) 21.5-30.6] and 8.2 % (95 % CI 5.2-11.2), respectively. In those who delivered vaginally, the prevalence was 29.7 % and 9.1 %, respectively. Prevalence of FI was 4.0 % (95 % CI 1.9-6.1). On logistic regression, vaginal delivery [odds ratio (OR) 3.6], antenatal SUI (OR 2.8), and UUI (OR 2.4) were associated with SUI. Antenatal UUI (OR 6.4) and increasing maternal body mass index (BMI) at the first trimester (OR 1.2) were associated with UUI. Antenatal FI was associated with FI (OR 6.1). CONCLUSIONS: The prevalence of SUI, UUI, and FI were 25.9 %, 8.2 %, and 4.0 %, respectively, 12 months after delivery. Vaginal delivery, antenatal SUI, and UUI were associated with SUI; antenatal UUI and increasing maternal BMI at the first trimester were associated with UUI. Antenatal FI was associated with FI. Pregnancy, regardless of route of delivery and obstetric practice, had an effect on UI and FI.

Risk of malignancy in women who underwent hysterectomy for uterine prolapse.

AIMS: To evaluate the risk of missing a malignancy in surgical specimens following hysterectomy for uterine prolapse if routine pathological examination is not performed. Additionally, information on the risk of missing an hitherto unsuspected malignancy if uterine preservation is the preferred management option will be provided. MATERIALS AND METHODS: A retrospective study was performed on all cases of surgery performed for uterine prolapse in a tertiary referral institution from 2003 to 2011. Those with confirmed malignancy before operation were excluded. The study subjects had their clinical history, investigations, the type of operations and histopathology report analysed. They were classified into symptomatic or asymptomatic, depending on whether they reported symptoms that were suggestive of uterine malignancy. RESULTS: A total of 640 women were studied. Three cases of hitherto unsuspected uterine malignancy were found, giving an incidence of 0.47%. Among the 456 asymptomatic women, both pre- and postmenopausal, the risk of incidental malignancy was 0.22%. Within the postmenopausal group, risk of incidental malignancy was 0.26%. Another 3 cases of uterine premalignant conditions were identified, giving an overall risk of premalignant and malignant uterine condition of 0.94%. Five cases of cervical intra-epithelial neoplasia were found, contributing to a risk of 0.78%. CONCLUSIONS: The risk of missing an uterine malignancy in patients with uterine prolapse is low if appropriate investigations are carried out prior to surgery. If hysterectomy is to be performed, we recommend that all surgical specimens be subjected to histopathological examination.

Tension-free vaginal mesh for the treatment of pelvic organ prolapse in Chinese women.

OBJECTIVE: To assess perioperative and short-term outcomes after tension-free vaginal mesh repair of pelvic organ prolapse in local Chinese women. DESIGN: Case series. SETTING: The urogynaecology unit of a university teaching hospital in Hong Kong. PATIENTS: All women with stage III or more pelvic organ prolapse who underwent tension-free vaginal mesh repair with or without vaginal hysterectomy from May 2007 to June 2011. MAIN OUTCOME MEASURES: Perioperative and short-term outcomes. RESULTS: In all, 47 women underwent the procedure during the study period. The mean operating time was 94 minutes, the mean estimated blood loss was 163 mL, and the mean hospital stay was 4 days. Four patients had visceral injuries, all of which were identified and repaired during the operation; all four patients recovered uneventfully. The mean duration of follow-up was 25 (standard deviation, 13) months. Pelvic organ prolapse quantification improved significantly; nine (19%) of the patients had recurrent stage II prolapse but only one was symptomatic, six (13%) had postoperative mesh exposure, three of whom underwent mesh excision. There were five (11%) who had de-novo urodynamic stress incontinence, which was mostly mild and managed conservatively. Overall 91% (43/47) were satisfied with their operative outcome. CONCLUSIONS: The success rate of tension-free vaginal mesh repair for the treatment of pelvic organ prolapse in local Chinese women was comparable to rates reported internationally. There was a high degree of subjective satisfaction with the procedure. There were low rates of mesh exposure and de-novo stress incontinence that was mostly asymptomatic or mild.

Quality of life in women with urinary incontinence is impaired and comparable to women with chronic diseases.

OBJECTIVES: To evaluate the quality of life in women with urinary incontinence (categorised by urodynamic findings). DESIGN: Prospective cohort study on patients. SETTING: Urogynaecology unit of a university teaching hospital in Hong Kong. PATIENTS. Female patients presenting to our clinic from July 2008 to December 2009 and having their urinary incontinence categorised by urodynamic study. MAIN OUTCOME MEASURES: Patient's quality of life was assessed using the Medical Outcomes Study Short Form, Urogenital Distress Inventory Short Form, and Incontinence Impact Questionnaire Short Form. Their quality of life was compared according to their urodynamic category and a subgroup analysis was performed on patients having continence surgery for urodynamic stress incontinence. RESULTS: Among the 223 women studied, 46% had urodynamic stress incontinence, 18% had detrusor overactivity, 2% had both urodynamic stress incontinence and detrusor overactivity, and 34% had no urodynamic abnormality. In all, the Medical Outcomes Study Short Form scoring was lower than normal local population. The Medical Outcomes Study Short Form score in detrusor overactivity group was significantly lower than urodynamic stress incontinence group in vitality and mental health domains. Detrusor overactivity group also had higher scores in Incontinence Impact Questionnaire Short Form in travel, social and emotional health subscales and total score (46.3 vs 29.1; P<0.01). Women with urodynamic stress incontinence and required continence surgery had higher scores in Incontinence Impact Questionnaire Short Form. CONCLUSION: Women with urinary incontinence had impaired quality of life and it was comparable to other chronic medical diseases. Women with detrusor overactivity have more impaired quality of life than women with urodynamic stress incontinence. Severity of urodynamic stress incontinence did not correlate with quality of life. Women who opted for continence surgery had poorer quality of life.

CHD5 Downregulation Associated with Poor Prognosis in Epithelial Ovarian Cancer.

BACKGROUND: The CHD5 gene located on 1p36 encodes a protein-chromodomain helicase DNA-binding protein 5. CHD5 has been shown to be a tumor suppressor gene candidate. This study investigated the involvement of CHD5 in ovarian cancer and its clinicopathological significance. METHODS: CHD5 expression in ovarian cancer and its counterpart were determined by quantitative RT-PCR. The correlation of CHD5 expression to clinicopathological features of the tumor was analyzed. RESULTS: CHD5 expression was downregulated by at least twofold in 32 of 72 (41%) invasive epithelial ovarian carcinomas when compared to 12 controls in Hong Kong Chinese women. CHD5 downregulation was correlated to clinical status (p < 0.05), but not to patient age, tumor type and grade, recurrence and clinical stage (p > 0.05). Survival analysis showed that patients with CHD5 downregulation in their tumors were associated with shorter disease-free and total survival times compared to those without CHD5 downregulation (p < 0.05). Cox proportional-hazards regression analysis indicated that downregulation of CHD5 is an independent adverse prognostic factor in ovarian cancer. CONCLUSION: This study shows that CHD5 is downregulated in a certain number of ovarian cancers and appears to be an adverse predictor candidate of ovarian cancer disease-free and total survival.

Menstrual disorders in a Paediatric and Adolescent Gynaecology Clinic: patient presentations and longitudinal outcomes.

OBJECTIVE. To study the presentations, diagnoses, and outcomes in adolescents with menstrual disorders. DESIGN. Prospective cohort study. SETTING. Paediatric and Adolescent Gynaecology Clinic, Hong Kong. PARTICIPANTS. A total of 577 adolescents aged 14 to 19 years. MAIN OUTCOME MEASURES. The presentations and diagnoses of adolescents with menstrual disorders were reviewed and their menstrual outcomes determined by a telephone survey. RESULTS. In all, 47% presented with menorrhagia, prolonged menstruation, and short menstrual cycles; 27% had secondary amenorrhoea, 12% had dysmenorrhoea, 11% had oligomenorrhoea, and 3% had primary amenorrhoea. Significant diagnoses included congenital genital tract anomalies, premature ovarian failure, anorexia nervosa, and polycystic ovarian syndrome. Polycystic ovarian syndrome was diagnosed in 16% of the cohort. In all, 24% of these 577 patients had abnormal menstrual cycles 4 years later. Direct logistic regression analysis indicated a cycle length of more than 35 days at presentation (adjusted odds ratio=2.8; 95% confidence interval, 1.8-4.5), previous diagnosis of polycystic ovarian syndrome (adjusted odds ratio=2.0; 95% confidence interval, 1.1-3.4), and current body mass index of 23 kg/m(2) or higher (adjusted odds ratio=1.8; 95% confidence interval, 1.0-3.0) were risk factors for persistently long menstrual cycle exceeding 35 days. Adolescents who were screened out with a definitive diagnosis after initial assessment were at low risk of persistently long menstrual cycles at follow-up (adjusted odds ratio=0.3; 95% confidence interval, 0.1-0.8). CONCLUSIONS. Adolescent menstrual disorders should not be ignored. Long cycle, diagnosis of polycystic ovarian syndrome at first consultation, and a current body mass index of 23 kg/m(2) or higher were statistically associated with persistent problems.

Dissection of PIK3CA Aberration for Cervical Adenocarcinoma Outcomes.

Personalized treatment of genetically stratified subgroups has the potential to improve outcomes in many malignant tumors. This study distills clinically meaningful prognostic/predictive genomic marker for cervical adenocarcinoma using signature genomic aberrations and single-point nonsynonymous mutation-specific droplet digital PCR (ddPCR). Mutations in PIK3CA E542K, E545K, or H1047R were detected in 41.7% of tumors. PIK3CA mutation detected in the patient's circulating DNA collected before treatment or during follow-up was significantly associated with decreased progression-free survival or overall survival. PIK3CA mutation in the circulating DNA during follow-up after treatment predicted recurrence with 100% sensitivity and 64.29% specificity. It is the first indication of the predictive power of PIK3CA mutations in cervical adenocarcinoma. The work contributes to the development of liquid biopsies for follow up surveillance and a possibility of tailoring management of this particular women's cancer.

Detecting postnatal depression in Chinese men: a comparison of three instruments.

Postnatal depression affects both men and women. The detection of postnatal depression is important, yet there are few validated screening tools on Chinese men. The goals of the present study were to compare the psychometric properties of the Edinburgh Postnatal Depression Scale (EPDS), the Beck Depression Inventory (BDI), and the Patient Health Questionnaire - Depression Module (PHQ-9) in screening for postnatal depression among Chinese fathers in Hong Kong. The prevalence of depression at 8 weeks postpartum was also estimated. A prospective cohort of 551 men completed the EPDS, BDI, and PHQ-9 at 8 weeks postpartum. Clinical diagnosis of depression was established with the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV), non-patient version (SCID-NP). The criterion validity of the instruments was evaluated against this clinical diagnosis. The EPDS was significantly more accurate than the BDI and PHQ-9 in detecting postnatal depression among Chinese men. With a cut-off score of 10 or more, the EPDS has a sensitivity of 91%, specificity of 97%, positive predictive value of 57%, and negative predictive value of 99%. Approximately 3.1% men met the DSM-IV criteria for depression at 8 weeks postpartum. The prevalence rate of postnatal depression in Chinese men is comparable to their Western counterparts. The Chinese EPDS is a valid instrument for detecting postnatal depression in men. It could be applied as a supplementary assessment tool in Chinese fathers who may be reluctant to disclose their depressive symptoms in face-to-face interviews.

Influences of mastery, spousal support, and adaptive coping on sexual drive and satisfaction among chinese gynecologic cancer survivors.

This study investigated sexual drive and satisfaction of Chinese gynecologic cancer survivors. It also examined the extent to which personal mastery, adaptive coping, and perceived spousal support would exert direct and/or indirect influences on sexual outcomes. The cancer survivor group included 134 Chinese women who had received treatment for gynecologic cancer, while the healthy control group included 105 Chinese women who did not have a known history or current diagnosis of cancer. Compared to healthy women, cancer survivors reported lower levels of sexual drive and sexual satisfaction. Among sexually active participants, cancer survivors relative to healthy women engaged in less masturbation, less kissing and caressing, and less sexual fantasy in the past month. Hierarchical multiple regression analyses showed that mastery and spousal support, but not adaptive coping, had a direct influence on sexual outcomes in cancer survivors. Contrary to moderation hypotheses, the three psychological factors did not interact with each other to influence sexual drive and satisfaction. Mediation analyses showed that spousal support fully mediated the influence of mastery on sexual satisfaction. Routine assessment of sexual functioning prior to and following treatment of gynecologic cancer is suggested. Sexual rehabilitation should also aim to enhance personal mastery and spousal support.

A prospective longitudinal study investigating neuroticism and mastery as predictors of quality of life among Chinese gynecologic cancer survivors.

PURPOSE: The aim of the study was to examine the role of neuroticism and mastery in predicting the quality of life (QOL) among Chinese gynecologic cancer survivors. METHODS: A total of 184 women participated in this prospective longitudinal study. Participants were to rate their quality of life at baseline (T1) and one year later (T2). Neuroticism as a predictor of QOL was examined by controlling for baseline QOL, sociodemographic, and disease variables using hierarchical linear regression modeling. Mastery as a mediator between the relationship of neuroticism and QOL was also examined. RESULTS: Bivariate correlations showed that the cancer site, time since diagnosis, neuroticism, and mastery at T1 were related to various aspects of QOL at T1 and T2. After controlling for cancer site, time since diagnosis, QOL at T1, high levels of neuroticism at T1 predicted poor physical and emotional QOL at T2, but mastery at T1 did not mediate the relationship between neuroticism at T1 and QOL at T2. CONCLUSIONS: Neuroticism is a salient personality variable that predicts poor emotional and physical well-being over time. Gynecologic cancer survivors high on neuroticism should be the target for intervention to reduce negative effects during the course of recovery.

Chinese validation of Urogenital Distress Inventory and Incontinence Impact Questionnaire short form.

INTRODUCTION AND HYPOTHESIS: UDI-6 and IIQ-7 are useful disease-specific questionnaires evaluating the impact of urinary incontinence on the QOL of women. We aim at validating them in Chinese language. METHODS: Both instruments were translated; 207 urinary incontinent women completed UDI-6 and IIQ-7, SF-36, bladder diary and urodynamic evaluation. The reliability and validity were assessed. RESULTS: There were high internal consistency (Cronbach's alpha for UDI-6 and IIQ-7 was 0.80 and 0.93) and test-retest reliability (Intraclass correlation coefficient was 0.72 and 0.75, P < 0.001). Scoring of UDI-6 and IIQ-7 was negatively correlated with SF-36 (P < 0.001); positively correlated with daytime urinary frequency and incontinent episodes (P < 0.001), and women's VAS (P < 0.001). Subscales of UDI-6 and IIQ-7 could discriminate women with different urodynamic diagnoses. CONCLUSIONS: The Chinese UDI-6 and IIQ-7 is reliable and valid. Study on the responsiveness to treatment is in progress. They are useful in assessing impact of the urinary incontinence in Chinese women.

Conflicting perceptions between health care professionals and patients on the psychological morbidity following miscarriage.

BACKGROUND: Miscarriage is common and may result in significant psychological morbidity for women. Recent research has revealed that health care professionals often tend to neglect this factor. This negligence may lead to delayed diagnosis and appropriate care. AIMS: To assess health care professionals' and patients' attitudes towards the psychological impact of miscarriage. METHODS: A prospective, cross-sectional survey of nearly 3000 subjects was conducted. Of these, 1269 were health care professionals and 1519 were pregnant women or their spouses. Their perceptions of the psychological impact of miscarriage, in comparison with postnatal depression were studied. RESULTS Health care professionals were less aware of the psychological impact of miscarriage compared with postnatal depression (91.9 vs 98.4%, P = 0.02). Furthermore, they believed that the psychological impact of miscarriage was less than that of postnatal depression (79.9 vs 88.9%, P < 0.001). However, more patients believed that psychological impact after miscarriage can seriously affect women (59.0 vs for health care professionals 38.3%, P < 0.001). A higher proportion of patients compared with health care professionals (85.2 vs 74.3%, P < 0.001) believed that routine psychological support should be provided after miscarriage, but few agreed that primary health professionals were the most suitable people to provide this care although most health care professionals thought this to be appropriate (9.1 vs 59.7%, P < 0.001). CONCLUSION: Health care professionals should be more aware of the psychological morbidity associated with miscarriage and also be sensitive to a currently unmet need for psychological care.

Dysregulated microRNAs and their predicted targets associated with endometrioid endometrial adenocarcinoma in Hong Kong women.

The objective of this study, a parallel study to global gene expression profiling, was to identify dysregulated microRNAs (miRNAs) associated with endometrioid endometrial adenocarcinoma (EEC), examine their correlation with clinico-pathological characteristics and identify predicted target genes of the dysregulated miRNAs. Using real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR), profiling of miRNA expression was performed in 30 EECs and 22 normal counterparts in which genome-wide gene expression had been previously profiled and reported. Clustering analysis identified 30 miRNAs which were significantly dysregulated in EEC. The expression of a sub-group of miRNAs was significantly correlated with clinico-pathological characteristics including stage, myometrial invasion, recurrence and lymph node involvement. By searching for predicted miRNA targets that were linked to the dysregulated genes previously identified, 68 genes were predicted as candidate targets of these 30 dysregulated miRNAs. miR-205 was significantly overexpressed in EECs compared with normal controls. After transfection of a miR-205 inhibitor, the expression of miR-205 in endometrial cancer cell line RL95-2 cells decreased whereas its predicted target gene, JPH4, showed increased protein expression. JPH4 seems to be a real miR-205 target in vitro and in vivo, and a candidate tumor suppressor gene in EEC. Based on this study in EEC, miRNAs predicted to be involved in tumorigenesis and tumor progression have been identified and placed in the context of the transcriptome of EEC. This work provides a framework on which further research into novel diagnosis and treatment of EEC can be focused.

Menstrual problems and health-seeking behaviour in Hong Kong Chinese girls.

OBJECTIVE: To ascertain the prevalence of menstrual problems in adolescent girls and their health-seeking behaviour. DESIGN: Questionnaire survey on menstruation, menstrual problems, medical consultation, and factors influencing girls seeking medical care. SETTING: Secondary schools in the catchment area of a tertiary teaching hospital in Hong Kong. PARTICIPANTS: A total of 5609 girls from 10 secondary schools. MAIN OUTCOME MEASURES: Prevalence of menstrual problems and health-seeking behaviour of adolescent girls. RESULTS: The mean age of the girls and their mean age at menarche were 15.1 (standard deviation, 2.0) years and 12.3 (1.1) years, respectively. The prevalence of menorrhagia, dysmenorrhoea, and menstrual symptoms were 17.9% (95% confidence interval, 16.9-19.1%), 68.7% (67.7-70.3%), and 37.7% (36.7-39.3%), respectively. The prevalence of menstrual symptoms (P<0.001) and dysmenorrhoea (P<0.001) increased with gynaecological age (calendar age minus age at menarche), whilst the proportion having short or long cycles decreased (P=0.002 and P=0.009). One in eight girls reported having been absent from school, whilst only 6.4% had sought medical care because of menses. Multivariate analysis indicated that seeking medical care for menorrhagia was dependent on the opinion of a family member (P=0.005), and for dysmenorrhoea on its severity (P=0.046) and anxiety about embarrassing questions (P=0.039). CONCLUSIONS: The prevalence of menstrual problems in Hong Kong Chinese girls is high and causes significant disruption to their school and daily activities. However, only a minority seek medical advice.

Liquid biopsy of HPV DNA in cervical cancer.

BACKGROUND: A blood test to serve as a tumor marker for cervical cancer would be useful to clinicians to guide treatment and provide an early signal for recurrence. The development of droplet digital PCR has enabled the detection of HPV DNA in patient serum, providing a potential marker for cervical cancer. OBJECTIVES: To report on a blood-based test for HPV-specific E7 and L1 genes, which may serve as a tumor marker to guide treatment and detect early recurrence in cervical cancer. STUDY DESIGN: Pre-treatment plasma samples were investigated from 138 Hong Kong Chinese women with primary invasive squamous cell carcinoma and adenocarcinoma of the cervix with tumor samples expressing HPV16 or HPV18. Two genes specific to the human papillomavirus, E7 and L1, were measured in cell free DNA (cfDNA) extracted from plasma using droplet digital PCR. Analysis of detectable E7 and L1 levels was performed to investigate the potential of liquid biopsy of E7 and L1 as a clinically useful molecular biomarker. RESULTS: The majority of patients had HPV16 (71.7%), squamous cell carcinoma (78.3%) and stage IB-II disease (82.6%). HPV E7 and L1 sequences were detected in plasma cfDNA from 61.6% (85/138) of patients. Patients with high viral load (defined as ≥20 E7 or L1 copies per 20 µL reaction volume) had increased risk of recurrence and death at 5 years on univariate analysis but not multivariate analysis. CONCLUSIONS: HPV DNA can be quantitatively detected with the use of cfDNA. This has the potential to provide a clinically useful tumor marker for patients with cervical cancer that can aid in post-treatment surveillance and estimating the risk of disease relapse.

Predictors for dislodgment of vaginal pessary within one year in women with pelvic organ prolapse.

OBJECTIVES: To identify clinical risk factors for dislodgment of vaginal pessary within one year in women with symptomatic pelvic organ prolapse. STUDY DESIGN: This was a prospective observational study which recruited consecutive women with symptomatic pelvic organ prolapse in a tertiary urogynecology center. Basic demographics, clinical symptoms and staging of pelvic organ prolapse were assessed. A vaginal pessary was offered where appropriate. MAIN OUTCOME MEASURES: Demographics and clinical parameters were compared between women who were able to use a vaginal pessary for one year and those whose pessaries were dislodged within one year. RESULTS: A total of 779 women were recruited and had a vaginal pessary inserted. Of them, 528 women, with a mean age of 64.7 (SD 10.1) years, returned for one-year follow-up; 177 (33.5%) had their pessary dislodged within one year and 351 (66.5%) had been able to retain the pessary. Stage III or IV prolapse (OR 1.76), prolapse predominant at the apical compartment (OR 2.14) and larger genital hiatus (OR 1.63) were factors associated with dislodgment of the vaginal pessary. Age, body mass index, previous hysterectomy and short vagina were not associated with dislodgment. Nevertheless, 47.6% of women with stage III/IV prolapse could still keep the pessary for one year. CONCLUSION: Higher staging of prolapse, larger genital hiatus and apical compartment prolapse are clinical predictors for dislodgment of a vaginal pessary. Despite this, nearly half of women with stage III/IV prolapse were able to use a vaginal pessary for one year. Therefore, a vaginal pessary should be offered despite their staging of prolapse.