Awareness, perceptions, and acceptance of human papillomavirus vaccination among parents in Hong Kong.

INTRODUCTION: This study investigated the awareness, perceptions, and acceptance of human papillomavirus (HPV) vaccination for children among parents in Hong Kong. It also explored factors associated with, and differences in, vaccine acceptance and hesitancy between parents of girls and boys. METHODS: Parents of boys or girls in Primary 5 to 6 were invited to participate in an online survey through an established health and lifestyle e-platform. RESULTS: Overall, 851 parents completed the survey: 419 (49.2%) had daughters, 348 (40.9%) had sons, and 84 (9.9%) had children of both genders. Parents who enrolled their children into the Childhood Immunisation Programme were more likely to accept HPV vaccination (79.7% vs 33.7%, odds ratio [OR]=7.70; 95% confidence interval [CI]=5.39-11.01; P<0.001); parents of girls were more likely to accept than parents of boys (86.0% vs 71.8%, OR=2.40; 95% CI=1.67-3.46; P<0.001). Among parents of girls and boys, the main reasons for HPV vaccination acceptance were prevention of cancers (girls: 68.8% and boys: 68.7%), prevention of sexually transmitted diseases (girls: 67.3% and boys: 68.3%), and optimal timing before initiation of sexual activity (girls: 62.8% and boys: 59.8%). Vaccine hesitancy was mainly associated with concerns about serious side-effects (girls: 66.7% and boys: 68.0%) and the belief that their children were too young (girls: 60.0% and boys: 54.0%). CONCLUSION: Parents in Hong Kong are hesitant about HPV vaccination for their sons. This barrier could be removed by providing information to correct vaccine safety misconceptions and offering a gender-neutral vaccination programme through the school-based Childhood Immunisation Programme.

Efficacy, Immunogenicity, and Safety of a 9-Valent Human Papillomavirus Vaccine: Subgroup Analysis of Participants From Asian Countries.

Background: A 9-valent human papillomavirus-6/11/16/18/31/33/45/52/58 (9vHPV) vaccine extends coverage to 5 next most common oncogenic types (31/33/45/52/58) in cervical cancer versus quadrivalent HPV (qHPV) vaccine. We describe efficacy, immunogenicity, and safety in Asian participants (India, Hong Kong, South Korea, Japan, Taiwan, and Thailand) from 2 international studies: a randomized, double-blinded, qHPV vaccine-controlled efficacy study (young women aged 16-26 years; NCT00543543; Study 001); and an immunogenicity study (girls and boys aged 9-15 years; NCT00943722; Study 002). Methods: Participants (N = 2519) were vaccinated at day 1 and months 2 and 6. Gynecological samples (Study 001 only) and serum were collected for HPV DNA and antibody assessments, respectively. Injection-site and systemic adverse events (AEs) were monitored. Data were analyzed by country and vaccination group. Results: 9vHPV vaccine prevented HPV-31/33/45/52/58-related persistent infection with 90.4%-100% efficacy across included countries. At month 7, ≥97.9% of participants seroconverted for each HPV type. Injection-site AEs occurred in 77.7%-83.1% and 81.9%-87.5% of qHPV and 9vHPV vaccine recipients in Study 001, respectively, and 62.4%-85.7% of girls/boys in Study 002; most were mild to moderate. Conclusions: The 9vHPV vaccine is efficacious, immunogenic, and well tolerated in Asian participants. Data support 9vHPV vaccination programs in Asia. Clinical Trials Registration: NCT00543543; NCT00943722.

The interaction between C35 and ΔNp73 promotes chemo-resistance in ovarian cancer cells.

BACKGROUND: The purpose of this study was to characterise the oncogenic roles of C35, a novel protein binding partner of ΔNp73, in ovarian cancer and to investigate the functional significance of C35-ΔNp73 interaction in the regulation of chemo-resistance. METHODS: C35 expression was evaluated by quantitative real-time PCR in human ovarian cancer tissues and cell lines. The aggressiveness of ovarian cancer cells overexpressing C35 was examined by cell proliferation, migration, soft agar and nude mouse xenograft. The significance of C35-ΔNp73 interaction in chemo-resistance was evaluated by apoptosis assays and cell viability after cisplatin treatment. RESULTS: The expression of C35 was significantly enhanced in human ovarian cancer tissues. Overexpression of C35 augmented proliferation, migration and tumourigenicity in ovarian cancer cell lines. C35 knockdown inhibited cell motility and cell growth. The co-expression of C35 and ΔNp73 by transient or stable transfection in ovarian cancer cells induced greater resistance to cisplatin treatment than did transfection with C35 or ΔNp73 alone. The cisplatin resistance was demonstrated to be caused by increased AKT and NFκB activity induced by C35-ΔNp73. CONCLUSION: Our results suggest that ΔNp73 might cooperate with C35 to promote tumour progression and contribute to cisplatin resistance in ovarian cancer cells. Future studies of the functional roles of ΔNp73 and C35 will provide insight that will aid in the establishment of new strategies and more effective therapies.

The use of Chinese herbal medicine to improve quality of life in women undergoing chemotherapy for ovarian cancer: a double-blind placebo-controlled randomized trial with immunological monitoring.

BACKGROUND: This study aimed to evaluate traditional Chinese medicine (TCM) in improving quality of life (QOL), reducing chemotoxicity and modulating immune function in patients undergoing chemotherapy. PATIENTS AND METHODS: Patients with ovarian cancer were randomized to receive either TCM or placebo in addition to standard chemotherapy. The primary outcome was global health status (GHS) score, assessed by European Organization for Research and Treatment of Cancer questionnaire, while the secondary outcomes were other QOL items, chemotoxicity according to World Health Organization criteria and alterations in immune function as measured by immune cells count and the numbers of cytokines-secreting cells. RESULTS: There was no significant difference in the GHS between the two groups. With adjustment for stage, chemotherapy type, disease status, age and baseline value, emotional function, cognitive function and nausea and vomiting were found to be worse or less improved in the TCM group compared with placebo group after six cycles of chemotherapy. The TCM group had less neutropenia after three cycles (0% grade 4 neutropenia versus 28.6%). There were no other significant differences in terms of chemotoxicity. Lymphocyte counts and cytokine activities decreased less in the TCM group. CONCLUSIONS: TCM did not improve QOL but did have some effects in terms of maintaining immune function.

Functional polymorphisms in the BRCA1 promoter influence transcription and are associated with decreased risk for breast cancer in Chinese women.

BACKGROUND: The BRCA1 gene is an important breast-cancer susceptibility gene. Promoter polymorphisms can alter the binding affinity of transcription factors, changing transcriptional activity and may affect susceptibility to disease. METHODS AND RESULTS: Using direct sequencing of the BRCA1 promoter region, we identified four polymorphisms c.-2804T-->C (rs799908:T-->C), c.-2265C-->T (rs11655505:C-->T), c.-2004A-->G (rs799906:A-->G) and c.-1896(ACA)(1)-->(ACA)(2) (rs8176071:(ACA)(1)-->(ACA)(2)) present in Hong Kong Chinese. Each polymorphism was studied independently and in combination by functional assays. Although all four variants significantly altered promoter activity, the c.-2265T allele had stronger binding than the C allele, and the most common mutant haplotype, which contains the c.-2265T allele, increased promoter activity by 70%. Risk association first tested in Hong Kong Chinese women with breast cancer and age-matched controls and replicated in a large population-based study of Shanghai Chinese, together totalling >3000 participants, showed that carriers of the c.-2265T allele had a reduced risk for breast cancer (combined odd ratio (OR) = 0.80, 95% CI 0.69 to 0.93; p = 0.003) which was more evident among women aged >or=45 years at first diagnosis of breast cancer and without a family history of breast cancer (combined OR = 0.75, 95% CI 0.61 to 0.91; p = 0.004). The most common haplotype containing the c.-2265T allele also showed significant risk association for women aged >or=45 years without a family history of breast cancer (OR = 0.64, 95% CI 0.46 to 0.89; p = 0.008). CONCLUSION: This comprehensive study of BRCA1 promoter polymorphisms found four variants that altered promoter activity and with the most significant contribution from c.-2265C-->T, which could affect susceptibility to breast cancer in the Chinese population. Its significance in other populations remains to be investigated.

Overexpression of FOXG1 contributes to TGF-beta resistance through inhibition of p21WAF1/CIP1 expression in ovarian cancer.

BACKGROUND: Loss of growth inhibitory response to transforming growth factor-beta (TGF-beta) is a common feature of epithelial cancers. Recent studies have reported that genetic lesions and overexpression of oncoproteins in TGF-beta/Smads signalling cascade contribute to the TGF-beta resistance. Here, we showed that the overexpressed FOXG1 was involved in attenuating the anti-proliferative control of TGF-beta/Smads signalling in ovarian cancer. METHODS: FOXG1 and p21(WAF1/CIP1) expressions were evaluated by real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR), western blot and immunohistochemical analyses. The effect of FOXG1 on p21(WAF1/CIP1) transcriptional activity was examined by luciferase reporter assays. Cell lines stably expressing or short hairpin RNA interference-mediated knockdown FOXG1 were established for studying the gain-or-loss functional effects of FOXG1. XTT cell proliferation assay was used to measure cell growth of ovarian cancer cells. RESULTS: Quantitative RT-PCR and western blot analyses showed that FOXG1 was upregulated and inversely associated with the expression levels of p21(WAF1/CIP1) in ovarian cancer. The overexpression of FOXG1 was significantly correlated with high-grade ovarian cancer (P=0.025). Immunohistochemical analysis on ovarian cancer tissue array was further evidenced that FOXG1 was highly expressed and significantly correlated with high-grade ovarian cancer (P=0.048). Functionally, enforced expression of FOXG1 selectively blocked the TGF-beta-induced p21(WAF1/CIP1) expressions and increased cell proliferation in ovarian cancer cells. Conversely, FOXG1 knockdown resulted in a 20-26% decrease in cell proliferation together with 16-33% increase in p21(WAF1/CIP1) expression. Notably, FOXG1 was able to inhibit the p21(WAF1/CIP1) promoter activity in a p53-independent manner by transient reporter assays. CONCLUSION: Our results suggest that FOXG1 acts as an oncoprotein inhibiting TGF-beta-mediated anti-proliferative responses in ovarian cancer cells through suppressing p21(WAF1/CIP1) transcription.

Acceptability of human papillomavirus vaccination among Chinese women: concerns and implications.

OBJECTIVE: To explore Chinese women's perceptions of human papillomavirus (HPV) vaccination and their intention to be vaccinated. DESIGN: A cross-sectional community-based survey study. SETTING: Thirteen community women's health centres of The Family Planning Association of Hong Kong. SAMPLE: A total of 1450 ethnic Chinese women aged 18 or above who attended the health centres. METHODS: Participants completed a written consent and an anonymous questionnaire onsite. MAIN OUTCOME MEASURES: Knowledge and beliefs about HPV and HPV vaccination against cervical cancer and participants' own intention to be vaccinated. RESULTS: About 38% of the participants (n = 527) had heard of HPV and 50% (n = 697) had heard of vaccination against cervical cancer. HPV infection was perceived to be stigmatising and detrimental to intimate, family and social relationships. Despite misconceptions and a grossly inadequate knowledge about HPV and HPV vaccination, 88% of the participants (n = 1219) indicated that they would likely be vaccinated. Majority of the participants believed that sexually experienced women should be vaccinated, while 27% opposed vaccinating sexually naive women. Younger age women who perceived a disruptive impact of HPV infection on intimate relationship and their partners' approval were significantly associated with a positive intention to be HPV vaccinated. CONCLUSIONS: The easy acceptability of HPV vaccination among the mostly sexually experienced Chinese participants and their knowledge deficit on the subject may implicate potential misuse of the vaccines and a false sense of security against cervical cancer. There is a dire need for culturally sensitive and tailored education for the public, women of different ages and their partners about HPV and HPV vaccination. Emphasis must be placed on the prophylactic nature of the current vaccines, the uncertain effects when given to sexually experienced women, the importance of adolescent vaccination and the need for continued cervical screening whether vaccinated or not.

Oct4 is epigenetically regulated by methylation in normal placenta and gestational trophoblastic disease.

Oct4 is a transcription factor that plays a crucial role in maintaining pluripotency of embryonic stem cells. Down-regulation of Oct4 is associated with the differentiation of trophectoderm cell lineage, from which the normal placenta derives. We investigated the methylation and expression status of Oct4 in normal placenta and gestational trophoblastic disease (GTD) as attempts to investigate the role of Oct4 in the pathogenesis of GTD. By methylation-specific PCR, we observed both methylated and unmethylated Oct4 alleles in all 25 first trimester and 10 term placentas while 33% (18/54) of hydatidiform moles, and two choriocarcinoma cell line (JEG3 and JAR), only displayed methylated Oct4 allele. By quantitative TaqMan real-time PCR, Oct4 mRNA was significantly reduced in hydatidiform moles (P=0.04), JEG3 and JAR (P=0.024) when compared with normal placentas. Oct4 methylation was significantly correlated with Oct4 mRNA expression in placenta and GTD (P=0.012). Hypermethylation in minimal promoter and exon 1 region of Oct4 were confirmed in JEG3 and JAR by bisulfite genomic sequencing. The Oct4 mRNA expression in JEG3 and JAR increased after treatment with 5-aza-2'-deoxycytidine and/or trichostatin A. Our findings suggest that Oct4 is down-regulated by hypermethylation in normal placenta and GTD and such process is important in pathogenesis of GTD.

Overexpression of prostate stem cell antigen is associated with gestational trophoblastic neoplasia.

AIMS: Hydatidiform mole (HM) is the most common type of gestational trophoblastic disease. A proportion of patients with HM develop gestational trophoblastic neoplasia (GTN) requiring chemotherapy. The aim was to identify differentially expressed genes that are associated with development of GTN. METHODS AND RESULTS: Using cDNA microarray, differential expression of prostate stem cell antigen (PSCA) was identified in HMs that developed GTN compared with those that spontaneously regressed. Significant overexpression of PSCA RNA (P = 0.037) and protein (P < 0.05) in aggressive HM was verified by real-time polymerase chain reaction (PCR) and immunohistochemical analysis in 10 first-trimester placentas, 36 HM that subsequently regressed and 11 HM that developed GTN. A high level of PSCA expression was also found in three choriocarcinomas and three placental site trophoblastic tumours. A positive correlation was observed between PSCA expression and proliferation and apoptotic indices as assessed by Ki67 (P = 0.01), mcm7 (P = 0.001) and M30 (P = 0.016), as well as p53 (P < 0.01), p21(WAF1/CIP1) (P < 0.01) and mdm2 (P = 0.002) expression. CONCLUSIONS: Overexpression of PSCA is associated with development of GTN in HM. PSCA probably plays a role in the regulation of cell growth through p53-related signaling pathways.

Activated Stat3 expression in gestational trophoblastic disease: correlation with clinicopathological parameters and apoptotic indices.

AIMS: To assess the expression profile of the activated form of signal transducer and activator of transcription (Stat)3 in gestational trophoblastic disease (GTD) and correlate the findings with clinicopathological parameters. METHODS AND RESULTS: By immunohistochemistry, both cytoplasmic and nuclear expression of p-Stat3-Ser(727) was demonstrated in 88 trophoblastic tissues, including placentas and GTD. Nuclear immunoreactivity of p-Stat3-Ser(727) was significantly higher in hydatidiform mole (HM) (P < 0.001) and choriocarcinoma (P = 0.009) when compared with normal placentas. Placental site trophoblastic tumours (PSTT) and epithelioid trophoblastic tumours (ETT) also demonstrated higher nuclear p-Stat3-Ser(727) expression than their normal trophoblast counterparts. Higher p-Stat3-Ser(727) expression was confirmed in choriocarcinoma cell lines, JEG-3 and JAR, than in a normal trophoblast cell line, with both nuclear and cytoplasmic fractions demonstrated by immunoblotting. Spontaneously regressed HM showed significantly increased nuclear and cytoplasmic p-Stat3-Ser(727) immunoreactivity over those that developed gestational trophoblastic neoplasia (GTN) (P = 0.013, P = 0.039). There was a significant positive and inverse correlation between nuclear p-Stat3-Ser(727) immunoreactivity and apoptotic indices [terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick end labelling and M30 CytoDeath antibody] (P = 0.001, P < 0.001, Spearman's rho test) and Bcl-2 expression (P = 0.034), respectively. CONCLUSIONS: p-Stat3-Ser(727) plays a role in the pathogenesis of GTD, probably through the regulation of apoptosis. p-Stat3-Ser(727) immunoreactivity is a potential marker in predicting GTN in HM.

Barriers and facilitators to human papillomavirus vaccination among Chinese adolescent girls in Hong Kong: a qualitative-quantitative study.

OBJECTIVES: To explore perceptions towards cervical cancer, human papillomavirus (HPV) infection and HPV vaccination and to identify factors affecting the acceptability of HPV vaccination among Chinese adolescent girls in Hong Kong. METHODS: Six focus groups were conducted with Chinese adolescent girls (median age 16 years, age range 13-20, n = 64) in Hong Kong in April 2007. Thematic analysis was employed to identify major themes related to cervical cancer and HPV vaccination. A supplementary questionnaire was administered to all participants before and after group discussion to assess their knowledge, attitudes and intention to be vaccinated and to collect demographic information. RESULTS: Participants' knowledge on cervical cancer was limited and HPV was largely unheard of. They had difficulty understanding the mechanism linking cervical cancer with HPV infection. Participants held a favourable attitude towards HPV vaccination but the perceived timing of vaccination varied. Barriers to vaccination include high monetary cost, uncertain length of vaccine effectiveness, low perceived risk of HPV infection, no immediate perceived need of vaccination, anticipated family disapproval and fear of the pain of injection. Factors conducive to vaccination include perceived family and peer support and medical reassurance on safety and efficacy of vaccine. The differences on knowledge, attitudes, intention to be vaccinated now and willingness to conform to significant others before and after the discussion were statistically significant, with an increased tendency towards favouring vaccination after the focus group. CONCLUSIONS: Participants favoured HPV vaccination despite not feeling an immediate need to be vaccinated. Interventions could focus on providing professional information on HPV vaccination and raising adolescents' perceived need to take preventive measures against HPV infection.

The role of regular physical examination in the detection of ovarian cancer recurrence.

OBJECTIVE: To evaluate how ovarian recurrences were first detected and the relative role of Ca 125, symptom enquiry and physical examination in recurrence detection. METHODS: In this retrospective study, records from women with ovarian cancer recurrences diagnosed between 1999 and 2004 were reviewed to determine how the recurrences were first detected. Women were routinely followed up by a combination of symptom enquiry, physical examination and Ca 125. When recurrence was suspected, further investigations such as imaging and biopsy of the suspected recurrence would be arranged to confirm the diagnosis. The patients were followed up for a median of 53.5 months. RESULTS: Eighty patients were identified to have ovarian cancer recurrences, with median time to recurrence of 12 months. Although 41 (51%) had abnormal physical findings, only three (3.8%) first presented with physical findings and none had positive physical findings alone. Ca 125 taken at the clinic visits in these 3 patients when the signs were detected turned out to be raised. For the remaining 77 patients, 49 (61%) and 28 (35%) first presented with raised Ca 125 level and symptoms respectively. The median survival from the time of recurrence for those first presented with Ca 125, symptoms and physical findings were 25 months, 17 months and 11 months respectively. CONCLUSION: Routine physical examination had a very limited additional role and could be possibly omitted as part of the routine follow up strategy.

Natural history of pelvic lymphocysts as observed by ultrasonography after bilateral pelvic lymphadenectomy.

OBJECTIVES: To determine, in patients who have undergone bilateral pelvic lymphadenectomy for gynecological cancer, the incidence of lymphocyst formation, their change in size with time, risk factors and correlation with symptoms. METHODS: This was a prospective observational study of 108 patients undergoing bilateral pelvic lymphadenectomy for gynecological cancer in our unit. We performed serial three-dimensional (3D) ultrasound assessment at 2 and 6 weeks and 3, 6, 9 and 12 months after surgery. Before each ultrasound assessment, symptoms were recorded and a physical examination was performed. RESULTS: Forty-eight (44.4%) patients had unilateral or bilateral lymphocysts detected during the follow-up period; 26 were on the left side, 16 were on the right side and six were bilateral. In 39 (81.2%) of the patients, the lymphocysts were first noted 2 weeks after the operation. In nine (18.8%) the lymphocysts persisted until 12 months after surgery. There was no association between lymphocyst formation and diagnosis, type of operation performed, surgeon, operative blood loss, adjuvant radiotherapy and number of lymph nodes removed. Four lymphocysts were detected by physical examination before the ultrasound diagnosis. There was no association between lymphocyst and symptoms, including pain over the abdomen, pelvis, thigh, legs or back, lymphedema, fever or symptoms of cystitis. Only one patient developed an infection of the lymphocyst, which required surgical intervention. CONCLUSION: Lymphocyst formation is common following bilateral pelvic lymphadenectomy. Most patients with lymphocysts are asymptomatic and the development of major complications is rare.