Establishment of a New Ovarian Cancer Cell Line CA5171.

A new cell line, CA5171, derived from a chemotherapy-naive, high-grade undifferentiated ovarian carcinoma was established and characterized. The CA5171 cells presented with cobblestone morphology and a doubling time of 24 hours. Gene mutation analysis showed that the cells belonged to the type II ovarian cancer pathway with mutations of PIK3CA, PTEN, and TP53. Single-nucleotide polymorphism array analysis showed no homozygous gene deletion; however, several loci of gene copy number gains were noted in chromosome 1, 2, 5, 9, 10, 12, 15, 16, 20, and X. The in vitro and in vivo experiments showed that the cells were sensitive to paclitaxel and doxorubicin, but resistant to cisplatin. The cells also presented epithelial-mesenchymal transition properties that may have been related to their invasion and migration potential. The CA5171 cells show the potential as a new cell line for studies on epithelial ovarian carcinoma.

High-risk human papillomavirus, other than type 16/18, in predominantly older Taiwanese women with high-grade cervical preinvasive lesions.

OBJECTIVE: To investigate the various genotypes of human papillomavirus (HPV) in Taiwanese women patients with abnormal cervical cytology and analyze the associations between HPV types, cervical preinvasive lesions, and the medical characteristics of these patients. MATERIALS AND METHODS: We performed HPV genotyping GeneChip procedures and colposcopies for 784 women with abnormal Papanicolaou smears. The characteristics of the patients and the status of the HPV infection were correlated. RESULTS: A total of 706 (90.1%) of the 784 women were positive for HPV infection, including 641 patients with high-risk HPV (HR-HPV). Among the patients with high-grade squamous intraepithelial lesions (HSILs), the average age of the 273 patients with other HR-HPV types (48.6 ± 13.8 years) was significantly older than the 222 patients infected with HPV 16/18 (39.8 ± 11.8 years) (p < 0.001). The proportion of patients with HSILs who were older than 40 years and infected with other HR-HPV types (76.6%) was also significantly higher than those with HPV 16/18 (20.3%) (p < 0.001). CONCLUSION: Women older than 40 years and having abnormal Pap smears and HR-HPV infections other than type 16/18 should be managed carefully because of the risk for HSILs.

Intratypic variants of human papillomavirus type 16 and risk of cervical neoplasia in Taiwan.

The associations between variants of human papillomavirus (HPV) 16 and risk of cervical neoplasia have been reported, but nucleotide variations of HPV 16 in Asian populations and their association with cervical neoplasia have not been evaluated extensively. During 1991-1992, 11,923 women from seven townships in Taiwan were enrolled. The HPV DNA in cervical cells was detected and genotyped using EasyChip HPV blot. Nucleotide variations in the long control region (LCR), E6, and E7 genes were determined using DNA sequencing for 170 HPV 16-positive cervical samples. The Asian variant was the most prevalent variant (81.8%) of HPV 16 in Taiwan, and was also associated with increased prevalence of histologically confirmed cervical intraepithelial neoplasia grade 3 or worse, showing an age-adjusted odds ratio (exact confidence limits) of 10.70 (1.62-451.05; P = 0.0049) compared to the HPV 16 European variant. Similar significant associations with cervical intraepithelial neoplasia grade 3 or worse were also observed for distinct nucleotide substitutions, including T178A/G, A647G, A7730C/G, T7781C, G7842A, and C24T/G. These results demonstrate that non-European variants (non-E) of HPV 16, predominantly Asian variants, are associated with increased risk for severe cervical neoplasia, compared with European variants. Molecular mechanisms accounting for varied cervical neoplasia risk among different HPV 16 variants warrant further investigation.

Epigenetic silencing of BLU through interfering apoptosis results in chemoresistance and poor prognosis of ovarian serous carcinoma patients.

Epithelial ovarian carcinoma is usually present at the advanced stage, during which the patients generally have poor prognosis. Our study aimed to evaluate the correlation of gene methylation and the clinical outcome of patients with advanced-stage, high-grade ovarian serous carcinoma. The methylation status of eight candidate genes was first evaluated by methylation-specific PCR and capillary electrophoresis to select three potential genes including DAPK, CDH1, and BLU (ZMYND10) from the exercise group of 40 patients. The methylation status of these three genes was further investigated in the validation group consisting of 136 patients. Patients with methylated BLU had significantly shorter progression-free survival (PFS; hazard ratio (HR) 1.48, 95% CI 1.01-2.56, P=0.013) and overall survival (OS; HR 1.83, 95% CI 1.07-3.11, P=0.027) in the multivariate analysis. Methylation of BLU was also an independent risk factor for 58 patients undergoing optimal debulking surgery for PFS (HR 2.37, 95% CI 1.03-5.42, P=0.043) and OS (HR 3.96, 95% CI 1.45-10.81, P=0.007) in the multivariate analysis. A possible mechanism of BLU in chemoresistance was investigated in ovarian cancer cell lines by in vitro apoptotic assays. In vitro studies have shown that BLU could upregulate the expression of BAX and enhance the effect of paclitaxel-induced apoptosis in ovarian cancer cells. Our study suggested that methylation of BLU could be a potential prognostic biomarker for advanced ovarian serous carcinoma.

Serous ovarian carcinoma patients with high alpha-folate receptor had reducing survival and cytotoxic chemo-response.

The alpha-folate receptor (α-FR) is highly-expressed in various non-mucinous tumors of epithelial origin, including ovarian carcinoma. The aim of this study was to investigate the relationship between alpha-folate receptor (α-FR) and the clinico-pathologic features and outcomes of serous ovarian carcinoma patients and the possible mechanism of α-FR to chemo-resistance. Therefore, semi-quantitative reverse-transcription polymerase chain reactions for α-FR expression were performed in the 91 specimens of serous ovarian carcinomas. The expression of α-FR in each ovarian cancer tissue specimen was defined as the ratio of density of α-FR to density of glyceraldehyde-3-phosphate dehydrogenase (GAPDH). In vitro apoptotic experiments were tested in the original OVCAR-3 tumor cells and various OVCAR-3 α-FR-transfectants. Patients with an increased α-FR expression level had poorer responses to chemotherapy (per α-FR expression level increase: odds ratio (OR): 8.97 (95% confidence interval (CI): 1.40-57.36), p = 0.021). An increased α-FR expression level was an independently poor prognostic factor for disease free interval (DFI) (per α-FR expression level increase: hazard ratio (HR): 2.45 (95% CI: 1.16-5.18), p = 0.02) and had a negative impact on overall survival (OS) of these serous ovarian cancer patients (per α-FR expression level increase: HR: 3.6 (95% CI: 0.93-13.29), p = 0.03) by multivariate analyses. α-FR inhibited cytotoxic drug-induced apoptosis in our in vitro apoptotic assays. α-FR could induce chemo-resistance via regulating the expression of apoptosis-related molecules, Bcl-2 and Bax. Therefore, α-FR can be a potential biomarker for the prediction of chemotherapeutic responses and clinical prognosis. It also could be the target of ovarian cancer treatment.

Associations of human leukocyte antigen class II genotypes with human papillomavirus 18 infection and cervical intraepithelial neoplasia risk.

BACKGROUND: Only a small proportion of women infected with human papillomavirus type 18 (HPV18) may progress to persistent infection and cervical neoplasia. This community-based cohort study aimed to assess associations with human leukocyte antigen (HLA) class II genotypes for natural infection of HPV18 and subsequent risk of cervical neoplasia. METHODS: Among 10,190 cytologically normal participants, 125 with HPV18 infection were identified by HPV blot kit. HPV18 viral load at study entry was examined by real-time polymerase chain reaction; persistent infection was defined as HPV18 infection at 2 consecutive examinations. RESULTS: There was a significant association between HLA-DRB1*0403 allele and high HPV18 viral load (>1000 copies in 50 ng of total DNA) at study entry (odds ratio [OR], 7.2; 95% confidence interval [CI], 2.0-25.2). After adjustment for age and viral load at study entry, haplotype HLA-DRB1*0405-DQA1*0301-DQB1*0302 was significantly associated with persistent HPV18 infection (OR, 13.3; 95% CI, 1.7-105.9). HLA-DRB1*0403 allele was also associated with a significantly increased risk of high-grade squamous intraepithelial lesion or cancer, showing a multivariate-adjusted hazard ratio (95% CI) of 18.1 (2.6-128.5). CONCLUSIONS: HLA-DRB1*0403 allele and HLA-DRB1*0405-DQA1*0301-DQB1*0302 haplotype may play important roles in determination of high viral load and persistent infection of HPV18 and subsequent cervical neoplasia risk.

Persistence of type-specific human papillomavirus infection and increased long-term risk of cervical cancer.

BACKGROUND: Human papillomavirus (HPV) persistence is the pivotal event in cervical carcinogenesis. We followed a large-scale community-based cohort for 16 years to investigate the role of genotype-specific HPV persistence in predicting cervical cancer including invasive and in situ carcinoma. METHODS: At the baseline examination in 1991-1992, 11,923 participants (aged 30-65 years) consented to HPV testing and cytology; 6923 participants were reexamined in 1993-1995. For HPV testing, we used a polymerase chain reaction-based assay that detected 39 HPV types. Women who developed cervical cancer were identified from cancer and death registries. Cumulative risks for developing cervical cancer among infected and persistently infected women were calculated by the Kaplan-Meier method. RESULTS: Of 10,123 women who were initially cytologically normal, 68 developed cervical cancer. The 16-year cumulative risks of subsequent cervical cancer for women with HPV16, HPV58 (without HPV16), or other carcinogenic HPV types (without HPV16 or HPV58) were 13.5%, 10.3%, and 4.0%, respectively, compared with 0.26% for HPV-negative women. Women with type-specific persistence of any carcinogenic HPV had greatly increased risk compared with women who were HPV-negative at both visits (hazard ratio = 75.4, 95% confidence interval = 31.8 to 178.9). The cumulative cervical cancer risks following persistent carcinogenic HPV infections increased with age: The risks were 5.5%, 14.4%, and 18.1% for women aged 30-44 years, 45-54 years, and 55 years and older, respectively. However, newly acquired infections were associated with a low risk of cervical cancer regardless of age. CONCLUSIONS: HPV negativity was associated with a very low long-term risk of cervical cancer. Persistent detection of HPV among cytologically normal women greatly increased risk. Thus, it is useful to perform repeated HPV testing following an initial positive test.

Incidence of cervical cancer and age-specific survival of small cell cervical carcinoma in Taiwan.

OBJECTIVE: To determine the incidence of cervical cancer and the age-specific survival from small cell cervical carcinoma in Taiwan. DESIGN: Retrospective study. Setting. Taiwan. POPULATION: Women diagnosed with cervical cancer from 1991 to 2005. METHODS: Analysis of data from the National Cancer Registration System and National Death Certification System. MAIN OUTCOME MEASURES: Incidence and age at diagnosis of cervical carcinoma and age-specific and overall survival from small cell cervical carcinoma. RESULTS: During the study period, 36 122 women were diagnosed with cervical cancer, and 81.8% had squamous cell carcinoma (SCC). For the periods 1991-1995, 1996-2000 and 2001-2005, the mean age at diagnosis increased from 53.9 ± 13.3 to 55.0 ± 14.9 and then to 56.7 ± 14.7 years, respectively. The incidence of SCC decreased from 1991 to 2005. During the same period, non-significant increases of adenocarcinoma and small cell carcinoma were noted. For SCC, occurrence peaked in 1991-1995 in patients 50-59 years of age. From 1996 to 2005, it peaked in patients 40-49 years of age. For cervical adenocarcinoma, occurrence peaked in patients 40-49 years of age, with a steady increase in this age group from 1991 to 2005. Occurrence of small cell cervical carcinoma peaked in the period 1991-1995 in patients 30-39 years of age. During the 15 years of the study, the overall mortality rate of the 198 patients with small cell cervical carcinoma was 65.7%. CONCLUSIONS: In Taiwan, the incidence of small cell cervical carcinoma and adenocarcinoma tended to increase, but the incidence of squamous cell cervical carcinoma significantly decreased during the period 1991-2005.

Impact of various treatment modalities on the outcome of stage IB1-IIA cervical adenocarcinoma.

OBJECTIVE: To evaluate the outcomes of patients with stage IB1-IIA cervical adenocarcinoma treated by various modalities in order to formulate a better treatment strategy. METHODS: The impact of various treatment modalities on the prognosis of 258 patients with stage IB1-IIA cervical adenocarcinoma was investigated. The therapeutic modalities included radical surgery (n=174); radical surgery followed by adjuvant radiation therapy (RT), such as RT alone or concurrent chemo-radiotherapy (CCRT) (n=46); or primary RT or CCRT (n=38). RESULTS: As compared with patients in the surgery-only group, patients with 1 postoperative major risk who underwent surgery followed by RT or CCRT had a significantly higher likelihood of disease relapse (2.3-fold, P=0.041) and disease-related death (2.9-fold, P=0.014). The likelihood of recurrence (P=0.32) and death (P=0.58) did not differ between patients who underwent adjuvant RT or CCRT for 1 major risk factor and those who underwent primary RT or CCRT. By contrast, patients with more than 1 major risk factor had a higher likelihood of disease recurrence (2.9-fold, P=0.037) and disease-related death (3.4-fold, P=0.051) than those who underwent primary RT or CCRT. CONCLUSION: Radical surgery is recommended for patients with stage IB1-IIA cervical adenocarcinomas without contraindications. Those with more than 1 postoperative pathologic risk factor had the worst prognosis despite adjuvant RT or CCRT.

Post-coital vaginal douching is risky for non-regression of low-grade squamous intraepithelial lesion of the cervix.

BACKGROUND: Vaginal douching is a common practice worldwide. Its effect on the natural history of the early lesion of human papillomavirus (HPV) infection, low-grade squamous intraepithelial lesion (LSIL), is unknown. METHODS: In a prospective nation-wide cohort (n=1332), epidemiological variables including habit of vaginal douching after intercourse and outcomes of LSIL were studied. Colposcopy-confirmed LSIL women (n=295) were followed every 3 months. Parameters of HPV infection, sexual behavior, personal hygiene and environmental exposures were compared with the follow-up outcomes. RESULTS: There was a 15% chance of HSIL co-existing with the LSIL cytology result. Eight percent of colposcopy-confirmed LSIL were found with HSIL in 1 year. With a follow-up of up to 36 months, 83% LSIL regressed, 11% progressed and 6% persisted. The mean time (95% CIs) to regression and progression were 5.2 (4.7-5.8) and 8.0 (5.8-10.3) months, respectively. Risk factors of the non-regression of LSIL included HPV prevalence on enrollment, habit of vaginal douching after intercourse with a hygiene product and non-regular Pap screening, with odd ratio of 4.4 (1.9-10.3), 3.14 (1.04-9.49) and 2.12 (1.24-3.62), respectively. HPV prevalence and vaginal douching also conferred a slower regression of LSIL (8.0 vs. 4.1 months, P<.001 and 8.0 vs. 5.6 months, P=0.02, respectively). CONCLUSION: The study disclosed a transient but warning nature of cytological LSIL. Practicing of vaginal douching after intercourse, especially with hygiene products, is associated with non-regression of LSIL.

Testing for methylated PCDH10 or WT1 is superior to the HPV test in detecting severe neoplasms (CIN3 or greater) in the triage of ASC-US smear results.

OBJECTIVE: Management of equivocal Papanicolaou smear result remains to be challenging even with the aid of human papillomavirus test. Recently, 3 novel methylation-silenced genes, PAX1, WT1, and PCDH10, have been found to be specifically associated with cervical cancer. We compared the performances of methylation test of these genes with human papillomavirus tests in triage of equivocal Papanicolaou smear result. STUDY DESIGN: Two hundred twenty-two women with Papanicolaou smear results of atypical cells of undetermined significance nested to a multicenter, nation-wide cohort (the T1899 cohort) were studied. Status of cervical neoplasm was diagnosed with colposcopic biopsy. Status of gene methylation was determined by methylation-specific polymerase chain reaction. High-risk human papillomavirus DNA was detected by polymerase chain reaction-reverse line blot hybridization and Hybrid Capture 2. RESULTS: Cervical intraepithelial neoplasm 1, cervical intraepithelial neoplasm 2, cervical intraepithelial neoplasm 3, carcinoma in situ, carcinoma, and normal cervix were diagnosed in 58, 17, 14, 10, 1, and 120 women, respectively. Methylation of PCDH10, WT1, and PAX1 was highly associated with the severity of cervical neoplasm (P < 10⁻9, < 10⁻7, and < 10⁻5, respectively). In comparison with a negative test result, the odds ratio (95% confidence intervals) for cervical intraepithelial neoplasm 3 or more severe neoplasms for women tested positive for methylation of these 3 genes were 26.4 (9.0-77.3), 18.1 (6.9-47.2), and 10.3 (4.1-25.9), respectively; whereas those positive for human papillomavirus polymerase chain reaction and Hybrid Capture 2 were 10.5 (3.5-31.9) and 5.6 (2.3-21.4). In triage for atypical cells of undetermined significance, each methylation test had less colposcopy referral and false-positive rates, but higher false-negative rate than the human papillomavirus tests. With a combination test of PCDH10 or WT1 methylation, a comparable false-negative rate (P = .62) but much less false-positive rate (P = .002) and colposcopy referral rate (P < 10⁻6) were achieved. CONCLUSION: In triage of atypical cells of undetermined significance Papanicolaou smear results, methylation test of WT1 and PCDH10 is superior to human papillomavirus test in this multicenter cohort. Comparing to current human papillomavirus triage, the new test has only one third of false positivity and half of colposcopy referral, with no compromise of the sensitivity in diagnosis of cervical intraepithelial neoplasm 3 or more severe neoplasms.

Prevalence of genotype-specific human papillomavirus infection and cervical neoplasia in Taiwan: a community-based survey of 10,602 women.

Human papillomavirus (HPV) causes cervical neoplasia; but limited data are available from Asia. We conducted a large-scale community-based cohort study in Taiwan to estimate prevalence of genotype-specific HPV infection and cervical neoplasia. Following written informed consent, cervical cells for cytology and HPV testing were collected from 11,923 participants (aged 30-65 years old, mean 46.3) in 1991-1992. Genotyping was performed using MY11/GP6+ PCR-based HPV Blot (EasyChip) for 39 HPV types. The overall HPV prevalence was 16.2% for 10,602 eligible participants, and 13.8% for 10,190 cytologically normal participants. The most common carcinogenic types were HPV52 (2.5%), HPV16 (2.0%), HPV56 (1.8%), HPV18 (1.6%), HPV33 (1.2%), HPV58 (1.3%) and HPV39 (1.0%). Among the 56 prevalent invasive and in situ cases, HPV16 (48.2%) was most common, followed by HPV58 (25.0%), HPV52 (19.6%), HPV31 (8.9%), HPV33 (8.9%) and HPV18 (3.6%). HPV16 and HPV58 caused cytological HSIL+ at younger ages than HPV52. Approximately half of the cervical cancer cases and high-grade precursors in Taiwan could be prevented by prophylactic vaccines against HPV16 and HPV18 infection. Up to 40% more could be prevented by targeting HPV58, HPV52, HPV33 and HPV31, arguing for the introduction of vaccines including more types.

Unique variants of human papillomavirus genotypes 52 and 58 and risk of cervical neoplasia.

Human papillomavirus (HPV) 52 and 58 are oncogenic HPV types prevalent in Asia. Our study aims to explore intratypic variants of HPV 52 and 58 in Taiwan. A total of 11,923 women were enrolled from seven townships in 1991-1992. HPV DNA in their cervical cells was detected and typed by EasyChip® HPV blot. Among 424 participants infected with HPV 52 and/or 58, nucleotide variations were determined in cervical cell samples of 406 participants by the polymerase chain reaction sequencing of the long control region, E6 and E7 genes. Nonprototype-like variants including lineages B and C were detected in 278 (99.3%) of 280 HPV 52 samples. The prototype and prototype-like group (lineage A) of HPV58 was found in 132 (98.5%) of 134 HPV 58 samples, with sublineage A1, A2 and A3 variant in 14.2, 27.6 and 56.7%, respectively. Among women infected with single HPV 52 type, the C variant (vs. B variant) was associated with an increased prevalence of cytologically diagnosed high-grade squamous intraepithelial lesion or worse lesions showing an age-adjusted odds ratio (95% confidence interval, CI) of 5.2 (1.0-27.6) and an increased prevalence of histologically confirmed high-grade cervical intraepithelial neoplasia or more severe lesions with an age-adjusted odds ratio (95% CI) of 7.6 (1.3-43.8). It was concluded that frequency distributions of HPV 52 and 58 variants in Taiwan were different from those in European and American populations. The association between C variant of HPV 52 and prevalence of cervical neoplasia needs further validation.

Prognostic and predictive values of E-cadherin for patients of ovarian clear cell adenocarcinoma.

OBJECTIVES: The purpose of the study was to analyze negative versus positive immunoexpression of epithelial cadherin (E-cadherin) and p53 in patients with primary advanced ovarian clear cell adenocarcinoma (OCCA) and its significance in relation to clinical features, progression-free survival and overall survival (OS). METHODS AND MATERIALS: Protein expression of E-cadherin and p53 was immunohistochemically evaluated in 61 OCCA patients with stages IIC to IV. The clinical factors studied included stage, age, CA-125, residual tumors, and chemotherapy regimens. RESULTS: Positive p53 immunoexpression was 44.8% (26/58) of OCCAs; in contrast, E-cadherin immunoexpression was observed in 75.9% (44/58) of OCCAs. The expected 5-year OS rate of OCCA treated with paclitaxel-based chemotherapy was significantly better than non-paclitaxel-based chemotherapy (40% vs 0%, P = 0.001). The expected 5-year OS rate of OCCA patients with positive E-cadherin immunoexpression (>10%) was also significantly better than patients with negative E-cadherin immunoexpression (≤10%) (35% vs 0%, P = 0.02). The expected 5-year OS rate of those receiving paclitaxel-platinum chemotherapy was not significantly different from platinum-based chemotherapy for those with negative E-cadherin immunoexpression (P = 0.11). The expected 5-year OS rate of those receiving paclitaxel-based chemotherapy was better than non-paclitaxel-based chemotherapy for those with positive E-cadherin immunoexpression (43% vs 0%, P = 0.01). Paclitaxel-based chemotherapy and positive E-cadherin immunoexpression were 2 independent prognostic factors in OS of patients with OCCA (P = 0.01 and 0.04, respectively). CONCLUSIONS: E-cadherin is a useful prognostic marker for OCCA patients, and paclitaxel-based chemotherapy can improve survival among patients with positive E-cadherin immunoreactivity.

Association between human papillomavirus and adenocarcinoma of rectum and recto-sigmoid junction: a cohort study of 10,612 women in Taiwan.

This study aimed at assessing the association between the type-specific human papillomavirus (HPV) infection and the risk of adenocarcinoma of the rectum and recto-sigmoid junction. A total of 10,612 women aged 30-65 years old were enrolled from seven townships in Taiwan. Cervical cells collected at study entry were tested for 39 types of HPV infection by polymerase chain reactions and HPV blot kit. Newly developed adenocarcinomas of rectum and recto-sigmoid junction were ascertained through computerized linkage with national cancer registry profiles. An increased risk of adenocarcinomas of the rectum and recto-sigmoid junction was observed with HPV infection, showing a hazard ratio [HR] (95% confidence interval [CI]) of 1.99 (0.98-4.04) after adjustment for age and body mass index. The adjusted HR (95% CI) for the infection of HPV types other than 6 and 11 was 2.18 (1.04-4.60). Women with cervical infection of HPV types other than 6 and 11 at study entry may have an increased risk of adenocarcinomas of the rectum and recto-sigmoid junction, which deserves further validation by large-scale studies.

Phase II study of capecitabine (Ro 09-1978) in patients who have failed first line treatment for locally advanced and/or metastatic cervical cancer.

PURPOSE: The objective of this study is to evaluate the efficacy and safety of capecitabine in cervical cancer patients who have locoregional failure and/or distant metastasis and failed first line therapy. The efficacy of capecitabine is determined by the overall response rate (ORR) according to WHO criteria for response and the safety by adverse event (AE) and tolerability profiles according to NCI CTC version 2.0. PATIENTS AND METHODS: Patients with loco-regional failure and/or metastatic cervical cancer who have failed first line therapy were enrolled into the study. The patient received capecitabine 1, 250 mg/m2 twice daily for 14 consecutive days with 7 days rest (21-day cycle). The treatment was continued for up to six cycles. RESULTS: Forty-five patients previously treated by single or combination of surgery, or chemotherapy or radiotherapy were enrolled for study. Thirty-seven of 45 patients (82%) received at least 2 cycles of treatment and they were evaluated for response. The intention to treat analyses revealed 6/45(13%) ORR, 1/45 (2%) CR and 5/45 (11%) PR. Twenty-four patients (53%) had stable disease and 20% had progression of the disease. The median time to progression was 4. 1 months and the median overall survival was 9.3 months. CONCLUSION: Capecitabine as a monotherapy has a modest response in locoregional failure and/or metastatic cervical cancer who have failed first line therapy.

Metronomic chemotherapy enhances antitumor effects of cancer vaccine by depleting regulatory T lymphocytes and inhibiting tumor angiogenesis.

Although cancer vaccines are emerging as innovative methods for cancer treatment, these alone have limited potential for treating measurable tumor burden. Thus, the importance of identifying anticancer strategies with greater potency is necessary. The chimeric DNA vaccine CTGF/E7 (connective tissue growth factor linked to the tumor antigen human papillomavirus 16 E7) generates potent E7-specific immunity and antitumor effects. We tested immune-modulating doses of chemotherapy in combination with the CTGF/E7 DNA vaccine to treat existing tumors in mice. Metronomic low doses of paclitaxel, not the maximal tolerable dose, are synergistic with the antigen-specific DNA vaccine. Paclitaxel, given in metronomic sequence with the CTGF/E7 DNA vaccine enhanced the vaccine's potential to delay tumor growth and decreased metastatic tumors in vivo better than the CTGF/E7 DNA vaccine alone. The two possible mechanisms of metronomic paclitaxel chemotherapy are the depletion of regulatory T cells and the inhibition of tumor angiogenesis rather than direct cancer cell cytolytic effects. Results indicate that combination treatment of metronomic chemotherapy and antigen-specific DNA vaccine can induce more potent antigen-specific immune responses and antitumor effects. This provides an immunologic basis for further testing in cancer patients.

The psychological impact of illness among women experiencing human papillomavirus-related illness or screening interventions.

The present study describes the psychological impact of human papillomavirus (HPV)-related conditions or preventive interventions on Taiwanese women. Women with an HPV-related diagnosis or intervention within the past 3 months were invited to participate in a cross-sectional survey before the receipt of HPV-related diagnostic results. Participants completed a 29-item HPV impact profile (HIP), which was a questionnaire designed to represent the full spectrum of potential HPV-related impacts. The HIP assesses worries and concerns; emotional impact; sexual impact; self-image; partner issues and transmission; interactions with doctors; and control/life impact. The final sample size was 249 women from three hospitals. The mean HIP score (0-100) was normal Pap: 28.2; abnormal Pap: 44.3; CIN: 47.5; genital warts: 62.5; abnormal Pap with high-risk HPV positive: 48.8. This study indicates that significant psychological impact is found in women diagnosed with abnormal Pap, CIN, high-risk HPV test positive and genital wart compared to women with a normal Pap. Women with genital warts had the highest psychological impact scores. This is the first quantitative data that can lay the ground work for future studies that enable the comparison of the effectiveness of different interventions in alleviating the psychological burden of HPV-associated infection and preventive interventions in Taiwan.