ABSTRACT
Subject(s)
Adult , Female , Humans , Atypical Squamous Cells of the Cervix , Education , Genotype , Immunization Programs , Korea , Papanicolaou Test , Prevalence , Retrospective Studies , Single Person , Squamous Intraepithelial Lesions of the Cervix , Uterine Cervical Neoplasms , Vaccination , VaccinesABSTRACT
Objectives@#Since 2007, human papillomavirus (HPV) vaccines have been administered for the prevention of cervical cancer in Korea. We investigated the status of HPV vaccination among HPV-infected adult women with abnormal cervical cytology before the introduction of National Immunization Program. @*Methods@#From 2010 to 2016, HPV-positive women (age, 20–60 years) with atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion (LSIL) were enrolled from five hospitals across Korea. Their HPV genotype, epidemiologic, and clinical data, including HPV vaccination history, were obtained. We compared the epidemiological characteristics and prevalence of HPV-16/18 genotypes between vaccinated and unvaccinated women. @*Results@#Among the 1,300 women, approximately 26% had a history of vaccination. Vaccinated patients were significantly younger, unmarried, and had a higher education level than unvaccinated women. For HPV-vaccinated individuals by vaccine dose, there was a significant younger age at vaccination initiation (p=0.025), longer duration from HPV vaccination to Pap test date (p=0.001), and lower proportion of HPV-16/18 (p=0.028) in the women with three doses. There was a significantly lower prevalence of HPV-16/18 genotypes in women who were vaccinated at least 12 months prior than in unvaccinated women(adjusted prevalence ratio [aPR]=0.51; 95% confidence interval [CI]=0.29–0.88). For women with LSIL, the prevalence of the HPV-16/18 genotypes was significantly lower in women who were vaccinated more than 12 months prior than in unvaccinated women (aPR=0.35; 95% CI=0.13–0.96). @*Conclusion@#This study highlighted the status of HPV vaccination and the prevalence of HPV-16/18 genotypes among HPV-infected women with abnormal cervical cytology according to HPV vaccination. It provides preliminary information regarding the status of HPV vaccination among Korean adult women.
ABSTRACT
OBJECTIVE: Persistent infection of HPV increases the chance of carcinoma in situ of cervix through stages of cervical intraepithelial neoplasia (CIN) 1, 2, and 3, and finally progresses into cervical cancer. We aimed to explore the safety and efficacy of BLS-M07 which is orally administered agent expressing human papillomavirus (HPV) 16 E7 antigen on the surface of Lactobacillus casei in patients with CIN 3. METHODS: Patients with CIN 3 were recruited in our clinical trial. Reid Colposcopic Index (RCI) grading and serum HPV16 E7 specific antibody production were used to evaluate efficacy of BLS-M07. In phase 1, BLS-M07 was administered orally, 5 times a week, on weeks 1, 2, 4, and 8 with dosages of 500 mg, 1,000 mg, and 1,500 mg. In phase 2a, patients were treated with 1,000 mg. The primary endpoints were the safety and the pathologic regression on colposcopic biopsy. RESULTS: Nineteen patients were enrolled in the CIN 3 cohort. In phase 1, no patients experienced dose limiting toxicity. No grade 3 or 4 treatment-related adverse events or deaths were observed. At 16 weeks after treatment, RCI grading was improved and serum HPV16 E7 specific antibody production increased (p<0.05). Six of 8 (75%) patients with CIN 3 were cured in phase 2a. CONCLUSIONS: Oral immunization with BLS-M07 increases production of serum HPV16 E7 specific antibody which induces protective humoral immunity. The safety of this oral vaccine was proved and could be a competitive non-surgical therapeutic agent of CIN 3. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02195089
Subject(s)
Female , Humans , Antibody Formation , Biopsy , Carcinoma in Situ , Uterine Cervical Dysplasia , Cervix Uteri , Cohort Studies , Immunity, Humoral , Immunization , Lacticaseibacillus casei , Papillomavirus E7 Proteins , Papillomavirus Vaccines , Uterine Cervical NeoplasmsABSTRACT
OBJECTIVE: This study was to identify the risk factors for cytological progression in women with atypical squamous cells of undetermined significance (ASC-US) or low-grade squamous intraepithelial lesions (LSIL). METHODS: We analyzed data from women infected with the human papillomavirus (HPV) who participated in the Korean HPV cohort study. The cohort recruited women aged 20–60 years with abnormal cervical cytology (ASC-US or LSIL) from April 2010. All women were followed-up at every 6-month intervals with cervical cytology and HPV DNA testing. RESULTS: Of the 1,158 women included, 654 (56.5%) and 504 (43.5%) women showed ASC-US and LSIL, respectively. At the time of enrollment, 143 women tested positive for HPV 16 (85 single and 58 multiple infections). Cervical cytology performed in the HPV 16-positive women showed progression in 27%, no change in 23%, and regression in 50% of the women at the six-month follow-up. The progression rate associated with HPV 16 infection was higher than that with infection caused by other HPV types (relative risk [RR], 1.75; 95% confidence interval [CI], 1.08–2.84; P=0.028). The cytological progression rate in women with persistent HPV 16 infection was higher than that in women with incidental or cleared infections (P < 0.001). Logistic regression analysis showed a significant relationship between cigarette smoking and cytological progression (RR, 4.15; 95% CI, 1.01–17.00). CONCLUSION: The cytological progression rate in HPV 16-positive women with ASC-US or LSIL is higher than that in women infected with other HPV types. Additionally, cigarette smoking may play a role in cytological progression.
Subject(s)
Female , Humans , Atypical Squamous Cells of the Cervix , Cohort Studies , Epidemiology , Follow-Up Studies , Human papillomavirus 16 , Human Papillomavirus DNA Tests , Logistic Models , Papillomaviridae , Risk Factors , Smoking , Squamous Intraepithelial Lesions of the CervixABSTRACT
PURPOSE: This study aimed to evaluate the performance of the PANArray human papilloma virus (HPV) test, a PCR-based DNA microarray assay, in detecting HPV from patient samples and its concordance with the cobas 4800 HPV and Hybrid Capture 2 (HC2) tests. MATERIALS AND METHODS: The PANArray HPV, cobas 4800 HPV, and HC2 tests were performed on 504 cervical swab samples from patients with atypical cells of undetermined significance at five hospitals. The samples that were interpreted as ‘HPV-other’ type positive in the PANArray HPV test were confirmed by direct sequencing. RESULTS: The concordance rates were 80.8% between the cobas 4800 HPV and PANArray HPV tests [κ=0.59, 95% confidence interval (CI) 0.52–0.66] and 80.2% (κ=0.6, 95% CI 0.55–0.68) between the HC2 and PANArray HPV tests. Among the 62 patients negative on PANArray HPV (defined as the absence of high risk HPV), but positive on both cobas 4800 HPV and HC2 tests, 42 (67.7%) tested positive for ‘HPV-other’ types on the PANArray HPV test, and 31 (50.0%) had gray zone results [relative light unit/control (RLU/CO), 1.4–9.25] in the HC2 test. Of the patients deemed positive by the PANArray HPV test, 43 tested positive for high-risk (HR) HPV in cobas 4800 HPV and HC 2 tests. Among them, 58.2% showed HR HPV, including HPV 16, by direct sequencing, of which 25% had gray results. CONCLUSION: Results classified as ‘HPV-other’ type by the PANArray HPV test, or gray zone results by HC2 (RLU/CO ratio level 1–10) should be carefully interpreted using comprehensive clinical information.
Subject(s)
Female , Humans , Atypical Squamous Cells of the Cervix , Human papillomavirus 16 , Oligonucleotide Array Sequence Analysis , PapillomaviridaeABSTRACT
OBJECTIVE: Human papillomavirus (HPV) 16 is the most carcinogenic HPV genotype. We investigated if HPV16 L1 capsid protein and E2/E6 ratio, evaluated by cervical cytology, may be used as biomarkers of ≥cervical intraepithelial neoplasia (CIN) 2 lesions. METHODS: Cervical specimens were obtained from 226 patients with HPV16 single infection. Using cytology specimen, L1 capsid protein and E2/E6 ratio were detected and the results were compared with those of the conventional histologic analysis of cervical tissues (CIN1–3 and squamous cell carcinoma [SCC]) to evaluate the association. RESULTS: The L1 positivity of CIN2/3 was significantly lower than that of normal cervical tissue (p < 0.001) and SCC demonstrated significantly lower L1 positivity than CIN1 (p < 0.001). The mean E2/E6 ratios of specimens graded as SCC (0.356) and CIN2/3 (0.483) were significantly lower than those of specimens graded as CIN1 (0.786) and normal (0.793) (p < 0.05). We observed that area under the receiver operating characteristic curve (AUC) for E2/E6 ratio (0.844; 95% confidence interval [CI]=0.793–0.895) was higher than that for L1 immunochemistry (0.636; 95% CI=0.562–0.711). A combination of E2/E6 ratio and L1 immunocytochemistry analyses showed the highest AUC (0.871; 95% CI=0.826–0.917) for the prediction of ≥CIN2 lesions. CONCLUSION: To our knowledge, this is the first study to validate HPV L1 capsid protein expression and decreased HPV E2/E6 ratio as valuable predictive markers of ≥CIN2 cervical lesions. Cervical cytology may be analyzed longitudinally on an outpatient basis with noninvasive procedures as against invasive conventional histologic analysis.
Subject(s)
Humans , Area Under Curve , Biomarkers , Capsid Proteins , Carcinoma, Squamous Cell , Uterine Cervical Dysplasia , Epithelial Cells , Genotype , Immunochemistry , Immunohistochemistry , Outpatients , ROC Curve , Squamous Intraepithelial Lesions of the Cervix , Uterine Cervical Neoplasms , Virus IntegrationABSTRACT
PURPOSE: The purpose of this study was to investigate the clinicopathological features of pulmonary metastasis from cervical cancer. MATERIALS AND METHODS: We reviewed the medical records of 56 patients with cervical cancer who developed pulmonary metastasis after radical hysterectomy, postoperative concurrent chemoradiation or systemic chemotherapy between January 1990 and March 2014. RESULTS: Fifty-six patients were diagnosed with pulmonary metastasis from cervical cancer. The prevalence of pulmonary metastasis was 3.6%. The mean event-free duration was 12 months. Twelve patients underwent surgical removal of metastatic lesions. The overall survival (OS) of patients with 4 lesions (25 months, p=0.034). The OS of patients who underwent surgical resection was 53.8 months, longer than that of those who did not (p=0.006). In addition, the OS of patients with adjuvant platinum-based chemotherapy was 32.6 months (p=0.027). CONCLUSION: In this study, we found that the number of metastatic nodules, surgical resection, and postoperative platinum-based chemotherapy can influence clinical outcome. Further studies on prognostic factors and successful treatment modalities are warranted.
Subject(s)
Humans , Drug Therapy , Hysterectomy , Lung , Medical Records , Neoplasm Metastasis , Prevalence , Prognosis , Uterine Cervical NeoplasmsABSTRACT
BACKGROUND: Human papillomavirus (HPV) is a major risk factor for cervical cancer. METHODS: We evaluated the clinical significance of the HPV DNA chip genotyping assay (MyHPV chip, Mygene Co.) compared with the Hybrid Capture 2 (HC2) chemiluminescent nucleic acid hybridization kit (Digene Corp.) in 867 patients. RESULTS: The concordance rate between the MyHPV chip and HC2 was 79.4% (kappa coefficient, κ = 0.55). The sensitivity and specificity of both HPV tests were very similar (approximately 85% and 50%, respectively). The addition of HPV result (either MyHPV chip or HC2) to cytology improved the sensitivity (95%, each) but reduced the specificity (approximately 30%, each) compared with the HPV test or cytology alone. Based on the MyHPV chip results, the odds ratio (OR) for ≥ high-grade squamous intraepithelial lesions (HSILs) was 9.9 in the HPV-16/18 (+) group and 3.7 in the non-16/18 high-risk (HR)-HPV (+) group. Based on the HC2 results, the OR for ≥ HSILs was 5.9 in the HR-HPV (+) group. When considering only patients with cytological diagnoses of “negative for intraepithelial lesion or malignancy” and “atypical squamous cell or atypical glandular cell,” based on the MyHPV chip results, the ORs for ≥ HSILs were 6.8 and 11.7, respectively, in the HPV-16/18 (+) group. CONCLUSIONS: The sensitivity and specificity of the MyHPV chip test are similar to the HC2. Detecting HPV-16/18 with an HPV DNA chip test, which is commonly used in many Asian countries, is useful in assessing the risk of high-grade cervical lesions.
Subject(s)
Humans , Asian People , Uterine Cervical Dysplasia , Diagnosis , DNA , Epithelial Cells , Human papillomavirus 16 , Human papillomavirus 18 , Nucleic Acid Hybridization , Odds Ratio , Oligonucleotide Array Sequence Analysis , Risk Factors , Sensitivity and Specificity , Squamous Intraepithelial Lesions of the Cervix , Uterine Cervical NeoplasmsABSTRACT
PURPOSE: The purpose of this study is to evaluate the impact of high-risk human papillomaviruses (HPVs) other than HPV 16/18 on the natural course of atypical squamous cells of undetermined significance (ASC-US) or low-grade squamous intraepithelial lesion (LSIL). MATERIALS AND METHODS: The study population was derived from the Korean HPV cohort (2010-2014). Women aged 20 to 60 who satisfied the criteria of having both HPV infection and abnormal cervical cytology of either ASC-US or LSIL were recruited from five institutions nationwide. Enrolled patients underwent cervical cytology and HPV DNA testing every 6 months. RESULTS: A total of 1,158 patients were enrolled. The 10 most common HPV types were HPV 16 (12.3%), 58 (10.0%), 56 (8.8%), 53 (8.4%), 52 (7.7%), 39 (6.2%), 18 (6.0%), 51 (5.7%), 68 (5.1%), and 66 (4.6%). Among these patients, 636 women were positive for high-risk HPVs other than HPV 16 or 18, and 429 women were followed for more than 6 months. Cytology evaluations showed progression in 15.3% of women, no change in 22.6%, and regression in 62.1% of women at 12 months. In cases of HPV 58 single infection, a more highly significant progression rate, compared to other high-risk types, was observed at 6 months (relative risk [RR], 3.3; 95% confidence interval [CI], 2.04 to 5.30; p < 0.001) and 12 months (RR, 5.03; 95% CI, 2.56 to 9.91; p < 0.001). CONCLUSION: HPV genotypes numbered in the 50s were frequent in Korean women with ASC-US and LSIL. HPV 58 was the second most common type, with a high progression rate of cervical cytology.
Subject(s)
Female , Humans , Atypical Squamous Cells of the Cervix , Cohort Studies , Genotype , Human papillomavirus 16 , Human Papillomavirus DNA Tests , Squamous Intraepithelial Lesions of the CervixABSTRACT
OBJECTIVE: DNA methylation has been shown to be a potential biomarker for early cancer detection. The aim of this study was to evaluate DNA methylation profiles according to liquid-based Pap (LBP) test results and to assess their diagnostic value in a Korean population. METHODS: A total of 205 patients with various Papanicolaou test results were enrolled to this study (negative, 26; atypical squamous cells of undetermined significance, 39; low grade squamous intraepithelial lesion, 44; high grade squamous intraepithelial lesion (HSIL), 48; and cancer, 48). DNA methylation analysis of four genes, ADCYAP1, PAX1, MAL, and CADM1, was performed on residual cervical cells from LBP samples using a quantitative bisulfite pyrosequencing method. To evaluate the diagnostic performance of the four methylated genes for cancer detection, receiver operating characteristic (ROC) curves were drawn. Sensitivities and specificities were also tested at cutoffs determined from the ROC curves. RESULTS: Cervical cancer cells showed dramatically increased methylation levels for the four genes analyzed. ADCYAP1 and PAX1 also trended toward elevated methylation levels in HSIL samples, although the levels were much lower than those in cancer cells. The sensitivities of methylated ADCYAP1, PAX1, MAL, and CADM1 for the detection of cancer were 79.2%, 75.0%, 70.8%, and 52.1%, and the specificities were 92.0%, 94.0%, 94.7%, and 94.0%, respectively. Methylated ADCYAP1 and PAX1 demonstrated relatively better discriminatory ability than did methylated MAL and CADM1 (area under the curves 0.911 and 0.916 vs. 0.854 and 0.756, respectively). CONCLUSION: DNA methylation status, especially in the ADCYAP1 and PAX1 genes, showed relatively good specificity, ranging from 90% to 94%. The possible additive and complementary roles of DNA methylation testing with respect to conventional cervical cancer screening programs will need to be validated in prospective population-based studies.
Subject(s)
Female , Humans , Alphapapillomavirus/genetics , Atypical Squamous Cells of the Cervix/pathology , Cell Adhesion Molecules/genetics , DNA Methylation , Genotype , Immunoglobulins/genetics , Myelin and Lymphocyte-Associated Proteolipid Proteins/genetics , Paired Box Transcription Factors/genetics , Papanicolaou Test , Pituitary Adenylate Cyclase-Activating Polypeptide/genetics , ROC Curve , Squamous Intraepithelial Lesions of the Cervix/genetics , Uterine Cervical Neoplasms/genetics , Vaginal SmearsABSTRACT
Cervical cancer is the fourth most common cancer in women worldwide, and the human papillomavirus (HPV) is the main causative agent for its development. HPV is a heterogeneous virus, and a persistent infection with a high-risk HPV contributes to the development of cancer. In recent decades, great advances have been made in understanding the molecular biology of HPV, and HPV\'s significance in cervical cancer prevention and management has received increased attention. In this review, we discuss the role of HPV genotyping in cervical cancer by addressing: clinically important issues in HPV virology; the current application of HPV genotyping in clinical medicine; and potential future uses for HPV genotyping.
Subject(s)
Female , Humans , DNA, Viral/analysis , Early Detection of Cancer/methods , Genome, Viral , Genotype , Papillomaviridae/classification , Papillomavirus Infections/complications , Papillomavirus Vaccines/therapeutic use , Uterine Cervical Neoplasms/diagnosisABSTRACT
OBJECTIVE: Infection with high-risk genotypes of human papillomavirus (HR-HPV) is the major cause of invasive cervical cancers. HPV-16 and HPV-18 are known to be responsible for two-thirds of all invasive cervical carcinomas, followed by HPV-45, -31, and -33. Current guidelines only differentiate HPV-16/18 (+) by recommending direct colposcopy for treatment. We tried to evaluate whether there are differences in risk among 12 non-16/18 HR-HPV genotypes in this study. METHODS: The pathology archive database records of 1,102 consecutive gynecologic patients, who had results for cervical cytology and histology and for HPV testing, as determined by HPV 9G DNA chip, were reviewed. RESULTS: Among the 1,102 patients, 346 were non-16/18 HR-HPV (+) and 231 were HPV-16/18 (+). We calculated the odds ratios for ≥cervical intraepithelial neoplasia 2 (CIN 2) of 14 groups of each HR-HPV genotype compared with a group of HR-HPV (–) patients. Based on the odds ratio of each genotype, we divided patients with non-16/18 HR-HPV genotypes (+) into two groups: HPV-31/33/35/45/52/58 (+) and HPV-39/51/56/59/66/68 (+). The age-adjusted odds ratios for ≥CIN 2 of the HPV-31/33/35/45/52/58 (+) and HPV-39/51/56/59/66/68 (+) groups compared with a HR-HPV (–) group were 11.9 (95% CI, 7.6 to 18.8; p<0.001) and 2.4 (95% CI, 1.4 to 4.3; p<0.001), respectively, while that of the HPV-16/18 (+) group was 18.1 (95% CI, 11.6 to 28.3; p=0.003). CONCLUSION: The 12 non-16/18 HR-HPV genotypes can be further categorized (HPV-31/33/35/45/52/58 vs. HPV-39/51/56/59/66/68) by risk stratification. The HPV-31/33/35/45/52/58 genotypes might need more aggressive action. Large scale clinical trials or cohort studies are necessary to confirm our suggestion.
Subject(s)
Adult , Female , Humans , Middle Aged , Uterine Cervical Dysplasia/virology , Colposcopy , DNA, Viral/analysis , Genotype , Human papillomavirus 16/genetics , Human papillomavirus 18/genetics , Papanicolaou Test , Papillomaviridae/genetics , Papillomavirus Infections/virology , Risk Factors , Uterine Cervical Neoplasms/virology , Vaginal SmearsABSTRACT
PURPOSE: Vaginal intraepithelial neoplasia (VAIN), a rare premalignant condition, is difficult to eradicate. We assess the effectiveness of high-dose rate intracavitary brachytherapy (HDR-ICR) in patients with VAIN or carcinoma in situ (CIS) of the vagina after hysterectomy. MATERIALS AND METHODS: We reviewed 34 patients treated for posthysterectomy VAIN or CIS of the vagina by brachytherapy as the sole treatment. All patients underwent a coloposcopic-directed punch biopsy or had abnormal cytology, at least 3 consecutive times. All patients were treated with a vaginal cylinder applicator. The total radiation dose was mainly 40 Gy in 8 fractions during the periods of 4 weeks at a prescription point of the median 0.2 cm (range, 0 to 0.5 cm) depth from the surface of the vaginal mucosa. RESULTS: Acute toxicity was minimal. Seven patients had grade 1/2 acute urinary and rectal complications. There were 15 cases of late toxicity, predominantly vaginal mucosal reaction in 12 patients. Of these patients, two patients suffered from grade 3 vaginal stricture and dyspareunia continuously. After a median follow-up time of 48 months (range, 4 to 122 months), there were 2 recurrences and 2 persistent diseases, in which a second-line therapy was needed. The success rate was 88.2%. The average prescription point in failure patients was 1.1 mm from the surface of the vagina compared to an average of 2.6 mm in non-recurrent patients (p=0.097). CONCLUSION: HDR-ICR is an effective treatment method in VAIN patients. In spite of high cure rates, we should consider issues regarding vaginal toxicity and radiation techniques to reduce the occurrence of failure and toxicity.
Subject(s)
Female , Humans , Biopsy , Brachytherapy , Carcinoma in Situ , Constriction, Pathologic , Dyspareunia , Follow-Up Studies , Hysterectomy , Methods , Mucous Membrane , Prescriptions , Radiotherapy , Recurrence , Vagina , Vaginal NeoplasmsABSTRACT
PURPOSE: Vaginal intraepithelial neoplasia (VAIN), a rare premalignant condition, is difficult to eradicate. We assess the effectiveness of high-dose rate intracavitary brachytherapy (HDR-ICR) in patients with VAIN or carcinoma in situ (CIS) of the vagina after hysterectomy. MATERIALS AND METHODS: We reviewed 34 patients treated for posthysterectomy VAIN or CIS of the vagina by brachytherapy as the sole treatment. All patients underwent a coloposcopic-directed punch biopsy or had abnormal cytology, at least 3 consecutive times. All patients were treated with a vaginal cylinder applicator. The total radiation dose was mainly 40 Gy in 8 fractions during the periods of 4 weeks at a prescription point of the median 0.2 cm (range, 0 to 0.5 cm) depth from the surface of the vaginal mucosa. RESULTS: Acute toxicity was minimal. Seven patients had grade 1/2 acute urinary and rectal complications. There were 15 cases of late toxicity, predominantly vaginal mucosal reaction in 12 patients. Of these patients, two patients suffered from grade 3 vaginal stricture and dyspareunia continuously. After a median follow-up time of 48 months (range, 4 to 122 months), there were 2 recurrences and 2 persistent diseases, in which a second-line therapy was needed. The success rate was 88.2%. The average prescription point in failure patients was 1.1 mm from the surface of the vagina compared to an average of 2.6 mm in non-recurrent patients (p=0.097). CONCLUSION: HDR-ICR is an effective treatment method in VAIN patients. In spite of high cure rates, we should consider issues regarding vaginal toxicity and radiation techniques to reduce the occurrence of failure and toxicity.
Subject(s)
Female , Humans , Biopsy , Brachytherapy , Carcinoma in Situ , Constriction, Pathologic , Dyspareunia , Follow-Up Studies , Hysterectomy , Methods , Mucous Membrane , Prescriptions , Radiotherapy , Recurrence , Vagina , Vaginal NeoplasmsABSTRACT
OBJECTIVE: The purpose of this study was to investigate whether selective cyclooxygenase (COX) inhibitors promote paclitaxel-induced apoptosis in taxane-resistant ovarian cancer cells by suppressing MDR1/P-glycoprotein (P-gp) expression. METHODS: Taxane-resistant ovarian cancer cells were cultured with paclitaxel alone or combined with a selective COX inhibitors. The expression patterns of MDR1/P-gp and the ability of COX inhibitors to inhibit growth of taxane-resistant ovarian cancer cells were measured. The efficacy of prostaglandin E2 (PGE2) supplementation was measured to evaluate the mechanisms involved in suppressing MDR1 gene expression. RESULTS: P-gp was upregulated in taxane-resistant ovarian cancer cells compared to paired paclitaxel-sensitive ovarian cancer cells. An 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that selective COX inhibitors significantly enhanced the cytotoxic effects of paclitaxel in taxane-resistant ovarian cancer cells via a prostaglandin-independent mechanism. These increased apoptotic effects were further verified by measuring an increased percentage of cells in sub-G1 stage using flow cytometry. Selective COX inhibitors suppressed MDR1 and P-gp expression. Moreover, combined treatment with paclitaxel and selective COX inhibitors increased poly (ADP-ribose) polymerase (PARP) cleavage in taxane-resistant ovarian cancer cells. CONCLUSION: Selective COX inhibitors significantly promote paclitaxel-induced cell death in taxane-resistant ovarian cancer cells in a prostaglandin-independent manner. COX inhibitors could be potent therapeutic tools to promote paclitaxel sensitization of taxane-resistant ovarian cancers by suppressing MDR1/P-gp, which is responsible for the efflux of chemotherapeutic agents.
Subject(s)
Apoptosis , Cell Death , Cyclooxygenase Inhibitors , Dinoprostone , Flow Cytometry , Ovarian Neoplasms , ATP Binding Cassette Transporter, Subfamily B, Member 1 , Paclitaxel , Prostaglandin-Endoperoxide Synthases , Tetrazolium Salts , ThiazolesABSTRACT
We have designed a five-year multicentre prospective cohort study in women who are both human papillomavirus (HPV)-positive with either atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL) of cervix. This study aimed to analyze the risk of developing a high-grade squamous intraepithelial lesion (HSIL) from either ASCUS or LSIL in HPV-positive women, so called 'progression' rate, to investigate differences in the progression rates according to HPV type-specific infection, and to evaluate the various factors associated with the persistence or clearance of HPV infection in the Korean population. At present, the study protocol composed of cervical cytology, HPV DNA testing, and questionnaire have been conducted actively since the first participant was enrolled in 2010. This study is the first nationwide Korea HPV cohort study. Our data will provide valuable information about not only the ambiguous cytology results of ASCUS and LSIL but also the effect of the specific HPV type and other various factors on the progression to HSIL. Finally, the results of our study will be helpful and applicable to determine the primary cervical cancer prevention strategies.
Subject(s)
Female , Humans , Uterine Cervical Dysplasia , Cervix Uteri , Cohort Studies , Human Papillomavirus DNA Tests , Korea , Uterine Cervical Neoplasms , Surveys and QuestionnairesABSTRACT
Lymphangioleiomyomatosis (LAM) is a rare idiopathic disease and this is characterized by a proliferation of abnormal smooth muscle cells in the lungs and in the lymphatic system of the thorax and retroperitoneum. The female genital tract is rarely affected by LAM. We report here on the CT and MR imaging findings of extensive LAM involving the uterus and pelvic cavity, and this was seen as multiple cystic uterine and parauterine masses with internal hemorrhage in a young female with tuberous sclerosis complex.
Subject(s)
Adult , Female , Humans , Adnexal Diseases/diagnosis , Diagnosis, Differential , Hysterectomy , Lymphangioleiomyomatosis/diagnosis , Magnetic Resonance Imaging , Tomography, X-Ray Computed , Tuberous Sclerosis/diagnosis , Uterine Neoplasms/diagnosisABSTRACT
OBJECTIVE: The study assessed the immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted cervical cancer vaccine in healthy Korean women aged 15-25 years. METHODS: Phase IIIB, double-blind, randomised (2:1), multi-centre trial was conducted in Korea from June 2007 to March 2008. The study enrolled 225 women in the HPV (N=149) and placebo (N=76) groups who received three doses of HPV-16/18 AS04-adjuvanted vaccine or placebo (aluminium hydroxide) administered intramuscularly at 0, 1, and 6 months and were followed until one month post-dose 3. Serum samples were collected pre-vaccination and one month post-dose 3. Safety and reactogenicity data were collected throughout. RESULTS: In this trial, 208 women completed the study (141 in HPV group; 67 in placebo group). At month 7, all initially seronegative women had seroconverted for HPV-16 and HPV-18 antibodies with anti-HPV-16 and anti-HPV-18 geometric mean titres of 9,351.4 El.U/mL (95% CI, 8,145.5 to 10,735.8) and 4204.1 El.U/mL (95% CI, 3,626.5 to 4,873.6), respectively. Initially seropositive women showed similar increase in geometric mean titre levels. Compliance to the three dose vaccination course was 95.3% in HPV and 89.5% in placebo group. Solicited local (pain) and general (fatigue, myalgia or headache) symptoms were commonly reported in both groups. Three serious adverse events were reported (two in HPV group; one in placebo group), all unrelated to vaccination by the investigator; all recovered. CONCLUSION: The HPV-16/18 AS04-adjuvanted vaccine was highly immunogenic with a clinically acceptable safety profile in Korean women. This study was in line with previous global studies in Europe, North America, and Brazil. (ClinicalTrials.gov number, NCT 00485732.)
Subject(s)
Aged , Female , Humans , Antibodies , Brazil , Compliance , Europe , Human papillomavirus 16 , Human papillomavirus 18 , Korea , North America , Uterine Cervical Neoplasms , VaccinationABSTRACT
For intraoperative consultation of mucinous adenocarcinoma involving the ovary, it would be useful to have approaching methods in addition to the traditional limited microscopic findings in order to determine the nature of the tumors. Mucinous adenocarcinomas involving the ovaries were evaluated in 91 cases of metastatic mucinous adenocarcinomas and 19 cases of primary mucinous adenocarcinomas using both an original algorithm (unilateral > or =10 cm tumors were considered primary and unilateral or =15 cm were primary, respectively. The diagnostic algorithm using size and laterality, in addition to clinical history, preoperative image findings, and operative findings, is a useful adjunct tool for differentiation of metastatic mucinous adenocarcinomas from primary mucinous adenocarcinomas of the ovary.
Subject(s)
Adolescent , Adult , Aged , Female , Humans , Middle Aged , Adenocarcinoma, Mucinous/classification , Algorithms , Neoplasm Staging , Ovarian Neoplasms/classificationABSTRACT
BACKGROUND: Human papillomavirus (HPV) infection can be detected by in situ hybridization (ISH), in which a punctate signal pattern indicates integrated HPV DNA and a diffuse pattern denotes the presence of episomal viral DNA. This study was conducted to evaluate the usefulness of an HPV ISH assay for invasive cervical cancer. METHODS: The HPV ISH assay for high-risk HPV and immunohistochemical staining for p16(INK4a), p53, bcl-2, and Ki-67 were performed in a tissue microarray of 279 cervical cancers. RESULTS: High-risk HPV ISH was positive in 194 (69.5%) of the samples. Punctate, diffuse, and mixed signal patterns were observed in 157 (56.3%), one (0.4%), and 36 cases (12.9%), respectively. Positive results in high-risk HPV ISH were associated with p16 and bcl-2 expression (p = 0.01 and p < 0.01, respectively). According to a Cox regression analysis, HPV infection and its surrogate immunohistochemical markers such as p16, bcl-2, and Ki-67 were not independent prognostic factors, but stage and grade were independent prognostic factors. CONCLUSIONS: Our results confirm that an HPV ISH assay is reasonably sensitive for HPV infection and that it might be useful to identify integrated HPV DNA in formalin-fixed and paraffin-embedded specimens. Further study encompassing HPV type, E2/E6 ratio, and therapeutic modality is necessary to understand the clinical meaning of HPV status in cervical cancer.