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Background/purpose To compare the clinical outcomes of Taiwanese patients with ovarian clear cell carcinomas (CCCs) and serous carcinomas (SCs). Methods We retrieved the clinical records of women with epithelial ovarian cancer (Stage I–IV) who received primary surgeries between 2000 and 2013. Cancer-specific survival (CSS), progression-free survival, and survival after recurrence (SAR) of CCC and SC patients were retrospectively compared. Multivariate analysis was used to identify the independent predictors of survival. Results Of 891 women diagnosed with epithelial ovarian cancer, 169 CCCs and 351 high-grade SCs were analyzed. The 5-year CSS rates of CCC patients were significantly lower than those of SC for both Stage III (22.3% vs. 47.3%, p = 0.001) and Stage IV (0% vs. 24.4%, p = 0.001) disease. In the absence of gross residual malignancies, the 5-year CSS rate was better for CCC (82.3%) than SC (75.2%, p = 0.010). The 5-year SAR rate was significantly lower for CCC than SC (14.3% vs. 24.4%, p = 0.002). Old age and residual malignancies were independent prognostic factors for CSS in the entire cohort of CCC patients. In the subgroup of Stage I CCC, positive cytology was identified as the only adverse prognostic factor for CSS. Conclusion The clinical outcomes of CCC are generally poorer than SC. Complete cytoreduction to no gross residual disease should be ideally achieved in CCC patients. A greater understanding of the molecular pathogenesis of CCC may lead to tailored therapies, ultimately optimizing outcomes.

We aimed to investigate the clinicopathologic features, immunohistochemical studies, and prognosis in patients with endometrial stromal sarcoma (ESS). Clinical information was reviewed retrospectively for cases of ESS (1985-2009). A histologic review and immunohistochemical staining for the estrogen receptor, progesterone receptor, c-Kit, CD-10, Ki-67, and m-TOR were performed. Sixty-one patients (median age, 44 y; range, 22-71) were eligible for analysis (1988 International Federation of Gynecology and Obstetrics Stage I, 43; Stage II, 2; Stage III, 11; Sage IV, 4; unstaged, 1). The median follow-up period for survivors was 73 mo. Of those, the patients who underwent an adnexectomy and a pelvic lymphadenectomy, 15% and 13%, respectively, revealed metastasis. There were 20 relapses/persistence, including 13 (65%) in the pelvis and abdomen and 7 (35%) in distant sites. Eight patients died from ESS at a median duration of 14.5 mo (range, 2-50 mo) after relapse. Five- and 10-yr cancer-specific survival (CSS) rates were 88% and 85%, respectively; and 5- and 10-yr progression-free survival rates were 69% and 57%, respectively. Stage, residual disease, and high proliferative index of Ki-67 were significant prognostic factors for both progression-free survival and CSS in a univariate analysis, in addition to mitotic index for CSS. Multivariate analysis selected only residual disease as an independent variable for progression-free survival and stage and residual disease for CSS. Our results support using clinical Stage I, no residual disease, low proliferative index of Ki-67, and estrogen receptor/progesterone receptor overexpression as potential biomarkers to select patients with ESS for fertility-preservation surgery (5 such patients were alive and free).

There are limited data on the prevalence and distribution of human papillomavirus (HPV) genotypes in vaginal intraepithelial neoplasia (VAIN). We sought to clarify this issue in a series of 450 VAIN cases with a confirmed diagnosis between 1990 and 2006. HPV genotyping was performed using paraffin-embedded specimens and polymerase chain reaction (PCR)-based methods. Multiple HPV types were validated by E6 type-specific PCR and direct sequencing. The HPV genotypes of the vaginal and cervical neoplasms were compared for those with incident VAIN and a history of previous/concomitant cervical neoplasms. Ki-67 was performed for supporting diagnosis of VAIN. Of these 450 VAIN cases (median age, 59 years; range, 19-93), two with missing paraffin blocks and 54 with poor DNA quality were excluded. HPV was detected in 273/394 (69.3%) VAIN, and multiple infections were found in 17.9% of HPV-positive samples. The leading types were HPV16 (35.5%), HPV58 (9.9%), HPV52 (9.9%), HPV39 (8.4%), HPV33 (7.3%) and HPV53 (7.0%). Among the 156 cases with a history of previous cervical neoplasia, 29.0% had concordant HPV genotypes, while synchronous VAIN samples (n = 49) were more likely to harbor concordant genotypes (58.7%) with the concomitant cervical neoplasm (p = 0.0003). Whether those HPV types in the incident VAIN lesions had existed in the vaginal epithelium at the time of the previous cervical neoplasia or a new acquisition needs to be clarified in prospective follow-up studies.

We aimed to assess the distribution of human papillomavirus (HPV) genotypes in high-grade cervical lesions in Taiwan. The study included 1,086 paraffin-embedded, formaldehyde-fixed cervical intraepithelial neoplasia (CIN) 2/3 specimens. HPV genotyping was performed using polymerase chain reaction (PCR)-based methods. Multiple HPV types were validated by E6 type-specific PCR, direct sequencing and/or real-time PCR. HPV DNA was detected in 995 (91.6%) specimens, and multiple HPV types were identified in 192 (19.3%) samples. The leading HPV types were HPV16 (24%), HPV52 (20%), HPV58 (20%), HPV33 (13%), HPV31 (8%) and HPV18 (4.6%). Although the leading six types consisted of 87.6%, HPV16 or 18 comprised only 30.9%. The prevalence of different HPV types showed a significant association with age. In women older than 50 yr, HPV16 and 18 comprised 21.3% (83/389), while HPV52, 58 and 33 represented 55.5% (216/389). In women aged less than 50 yr, HPV16 and 18 comprised 32.1% (224/697, p < 0.0001), while HPV 52, 58 and 33 represented 47.9% (334/697, p = 0.02). The distribution of HPV genotypes was compared with previously reported findings for Taiwanese women with cervical cancer (CC). The overall HPV16 positivity rate was significantly higher in CC than in CIN 2/3 (odds ratio: 2.14, 95% CI: 1.91-2.40). In addition, HPV18, 39 and 45 were significantly overrepresented in CC, whereas HPV52, 58, 33, 31, 35, 51 and 53 were underrepresented. We concluded that an effective vaccine against the most common HPV types could prevent a significant proportion of cervical cancer cases that occur in Taiwan.

Objective Previous studies have shown that SPF1/GP6+ PCR followed by HPV Blot has high sensitivity and high reproducibility for the detection of human papillomavirus (HPV). However, there have been reports of false-negative results. In the present study we endeavoured to improve the diagnostic performance of HPV DNA testing in cervical swab specimens. We also aimed to identify viral load thresholds. Methods We examined DNA from cervical swabs of 7 women with a cervical intraepithelial neoplasia grade 2 or worse (CIN2+) who were negative by HPV DNA testing. For control purposes, 106 cytology negative/HPV-negative samples were included. PCR was performed with either 1μL of DNA solution or different amounts of input DNA (25, 50, and 100ng). We tested two different commercial alkaline phosphatases (ALPs) at two distinct reaction times. The overall conclusions were based on HPV Blot, type-specific PCR, direct sequencing, and real-time quantitative PCR (qPCR). Results All seven patients with CIN2+ disease turned HPV-positive when 100ng of input DNA and E6 type-specific PCR were used. Discrepant and false-negative results were obtained using different amounts of input DNA. Different commercial ALPs showed a significant impact on detection performance. Analysis of viral load indicated that the detection threshold for HPV infection using SPF1/GP6+ PCR plus HPV Blot was approximately 10 2 –10 3 copies. Conclusions Reliable determination of HPV status is crucially dependent on the amount of input genomic DNA.

Little is known about acquisition of human papillomavirus (HPV) and its outcome among older women with negative HPV testing and normal cytology. A longitudinal 3-yr follow-up of nested-cohort subjects (n = 8825) from a population-based cervical cancer screening study whose Pap and HPV tests were negative at baseline were conducted. Every active HPV-negative (n = 413) participant had 12-mo follow-ups of Pap smear and HPV testing. Colposcopy was performed if either HPV-positive or cytology was abnormal. The cytology and histology information of the remaining subjects (passive HPV-negative, n = 8412) was obtained from national registry database. Median age of participants was 45 yr (range, 30-73 yr). The incidence of new acquisition was 4.2/100 woman-years. The 3-yr cumulative total HPV acquisition rate was 11.1% (95% confidence interval [CI]: 8.1-14.1). Increased number of sexual partners (> or =2 vs. 1) of the participant was associated with risk of acquisition (odds ratio [OR]: 5.0, 95% CI: 2.0-12.6) by multivariate analysis. Three cases of > or = cervical intraepithelial neoplasia (CIN) 2 were identified in 3-yr follow-up in active HPV-negative subjects. HPV genotypes in the dysplastic tissue were actually present at baseline samples after reanalysis. From the passive HPV-negative group, only 1 case progressed to CIN2 probably after HPV acquisition. Negative Pap and HPV tests assured a very low risk of developing > or = CIN2 within 3 yr despite incident HPV infection.

We compared the efficacy of human papillomavirus (HPV) DNA detection between a PCR-based genechip (Easychip HPV Blot [hereafter referred to as HPV Blot]; King Car, Taiwan) method and Hybrid Capture II (HCII; Digene, Gaithersburg, MD) in women with previous normal ( n = 146) or abnormal (≥atypical squamous cells of undetermined significance [ASCUS] [ n = 208]) cytology. A total of 354 cervical swab samples were collected for HPV DNA assay by both HCII and SPF1/GP6+ PCR followed by HPV Blot tests. Colposcopy-directed biopsy was performed if clinically indicated. Of the 354 samples, HPV-positive rates by these two methods (HCII and HPV Blot) were 12.6% and 18.2% in 143 normal samples, 36.2% and 45.7% in 105 ASCUS samples, 57.4% and 57.4% in 94 low-grade squamous intraepithelial lesion samples, and 83.3% and 75.0% in 12 high-grade squamous intraepithelial lesion samples, respectively. The concordance of HPV Blot and HCII was 80.8% (286/354), and the agreement between the methods (κ value, 0.68) was substantial. Discrepancies were further investigated by at least one of the following three methods: direct sequencing, type-specific PCR, and HPV Blot genotyping of cervical biopsy tissue. In the 15 HCII-positive samples, HPV Blot detected only non-HCII HPV genotypes; results of further verification methods were consistent with the latter test in the 15 samples. Of the 20 samples with HCII-negative and HPV Blot-positive results, 18 were found to contain the 13 HCII high-risk genotypes by verification methods. In only 16.7% (3/18) of the HCII-positive but HPV Blot-negative samples, further studies detected the 13 HCII genotypes. We conclude that HPV Blot seemed comparable to HCII for detection of HPV DNA in cervical swab samples.

Little is known about acquisition of human papillomavirus (HPV) and its outcome among older women with negative HPV testing and normal cytology. A longitudinal 3-yr follow-up of nested-cohort subjects (n = 8825) from a population-based cervical cancer screening study whose Pap and HPV tests were negative at baseline were conducted. Every active HPV-negative (n = 413) participant had 12-mo follow-ups of Pap smear and HPV testing. Colposcopy was performed if either HPV-positive or cytology was abnormal. The cytology and histology information of the remaining subjects (passive HPV-negative, n = 8412) was obtained from national registry database. Median age of participants was 45 yr (range, 30-73 yr). The incidence of new acquisition was 4.2/100 woman-years. The 3-yr cumulative total HPV acquisition rate was 11.1% (95% confidence interval [CI]: 8.1-14.1). Increased number of sexual partners (or =2 vs. 1) of the participant was associated with risk of acquisition (odds ratio [OR]: 5.0, 95% CI: 2.0-12.6) by multivariate analysis. Three cases ofor = cervical intraepithelial neoplasia (CIN) 2 were identified in 3-yr follow-up in active HPV-negative subjects. HPV genotypes in the dysplastic tissue were actually present at baseline samples after reanalysis. From the passive HPV-negative group, only 1 case progressed to CIN2 probably after HPV acquisition. Negative Pap and HPV tests assured a very low risk of developingor = CIN2 within 3 yr despite incident HPV infection.

Human papillomavirus (HPV) persistence is essential for cervical cancer development. We accrued nested-cohort subjects from a population-based study to investigate the host and viral factors related to outcome of HPV infection. Women (age ≥ 30 years old) with HPV-positive but normal cytology and negative colposcopy were invited to participate. After signing informed consent, every participant completed a structured questionnaire and had 6monthly follow-ups of Pap smear, HPV testing and colposcopy. Total and type-specific HPV clearance rates as well as host and viral factors associated with clearance in 3-year longitudinal followup were analyzed. Adjusted hazard ratios (HRs) of progression to ≥ cervical intraepithelial neoplasia (CIN) 2 according to baseline HPV of the women with normal cytology were calculated from national registry database. Among the 626 eligible women, 526 (median age 47, 29–75) were enrolled and 412 returned for followup at least once. The median follow-up of enrolled subjects was 23 months (range 6.8–39). The 3-year cumulative total HPV clearance rate was 49.0% (95% confidence interval [CI]: 43.3–54.7%). The median 3-year cumulative type-specific HPV clearance rate was 50.0% (range 0–100.0%) with a median time to clearance of 12.4 months (6.4–24.5). Older age was associated with significantly decreased total HPV clearance and decreased type-specific clearance in HPV-18 and -53, while high viral load was associated with decreased total and type-specific clearance. After adjusting confounding variables, the HR of developing CIN2 in baseline HPVpositive women was 34.0-fold (95% CI: 15.5–74.7) as compared to HPV-negative women. ' 2008 Wiley-Liss, Inc.

We conducted a population-based cohort study to evaluate the complementary value of HPV testing to Papanicolaou (Pap) smear and the prevalence and genotype distribution of HPV in Taiwan. In this report, we described the design of the whole study and analyzed the cross-sectional results. Female residents (age >or= 30 years) of Taoyuan, Taiwan were invited. After signing informed consent, every participant had a Pap smear and a HPV testing. Patients with Pap >or= atypical squamous cell of undetermined significance (Group I) or those with HPV-positive but normal cytology (Group II) were referred for a colposcopic examination. A total of 10,014 women were eligible. The overall HPV prevalence was 10.8% (95% confidence interval 10.5%-11.4%) in the study population. A total of 37 types of HPV were identified and the leading three were HPV-52, -18 and -58. There was a significant positive correlation of HPV prevalence with older age, postmenopausal status, current-user of oral contraceptives and never-user of hormone replacement therapy. Past users of oral contraceptives and never users of Pap were associated with higher risk of abnormal Pap, while age 40-49 strata had lower risk. Fifty-nine cases of cervical intraepithelial neoplasia (CIN) 2 from Group I and additional 11 from Group II were identified. The improvement of sensitivity with additional HPV testing was 15.3%. Besides, no specific subgroup was found to most benefit from the combined strategy. The value of adding HPV test to conventional Pap smear has to be evaluated after longer-term follow-up of this population-based cohort.

Purpose Our aim was to evaluate the prognostic significance of human papillomavirus (HPV) genotype in early-stage cervical carcinoma primarily treated with surgery in a large tertiary referral medical center. Patients and Methods Consecutive patients who underwent primary surgery for invasive cervical carcinoma of International Federation of Gynecology and Obstetrics (FIGO) stage I to IIA between 1993 and 2000 were retrospectively reviewed. Polymerase chain reaction (PCR) using a general primer set followed by reverse-blot detection of 38 types of HPV DNA in a single reaction was performed for genotyping. E6 type-specific PCR was performed to validate multiple types. Results A total of 1,067 eligible patients were analyzed. HPV DNA sequences were detected in 95.1% of the specimens, among which 9.6% contained multiple types. HPV 16 was detected in 63.8% of the samples, and HPV 18 was detected in 16.5% of the samples. The median follow-up time of surviving patients was 77 months. By multivariate analysis, FIGO stage, lymph node metastasis, depth of cervical stromal invasion, grade of differentiation, and HPV 18 positivity were significantly related to cancer relapse. FIGO stage II, deep stromal invasion, parametrial extension, HPV 18 positivity, and age older than 45 years were significant predictors for death. Using the seven selected variables from either recurrence-free or overall survival analysis, death-predicting (P < .0001) and relapse-predicting (P < .0001) models classifying three risk groups (low, intermediate, and high risk) were constructed and endorsed by internal validation. Conclusion The independent prognostic value of HPV genotype is confirmed in this study. The prognostic models could be useful in counseling patients and stratifying patients in future clinical trials.