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.
To evaluate the efficacy and toxicity of topical imiquimod for the treatment of persistent human papillomavirus (HPV) infection in patients with or without cervical/vaginal intraepithelial neoplasia (CIN/VAIN). Patients with persistent HPV infection (≥1 year) after a history of treatment for cervical or vaginal neoplasm but normal histology and cytology, abnormal Papanicolaou (Pap) smears without abnormal histology, and untreated histology-documented CIN/VAIN Grade 1/2/3 with HPV-positive testing were recruited. Patients were instructed to apply 250 mg of 5% imiquimod cream intravaginally on consecutive days or at least twice weekly on an outpatient basis for a minimum of 12 doses. A group of age- and previous diagnosis-matched, imiquimod-untreated historical controls (n = 20) were selected. The main outcome measures included HPV DNA detection, cytology, and colposcopy/histology at 6 months after treatment. A total of 72 patients were eligible for analysis. At a median follow-up of 33.6 months, 37 patients (51.4%) had cytological/histological regression and tested HPV-negative. Six patients (8.3%) had progressive cytology/histology with persistent HPV infections. Of the 72 treated patients, 26 patients who had a normal Pap test but were persistently HPV-positive for at least 1 year had a complete regression rate of 65.4%, which was significantly different from the rate (30%) observed in the untreated historical control (p = 0.036). Six patients with histologically proven CIN2/3 or VAIN2/3 had a complete regression rate of 66.6% (4/6). The tolerability of intravaginal self-administered imiquimod is confirmed. Its efficacy in the treatment of women with persistent HPV infection and normal cytology warrants further randomized, controlled trials to determine appropriate dosages and scheduling.
We aimed to define the long-term follow-up results in cervical cancer patients with unexplained squamous cell carcinoma antigen (SCC-Ag) elevation (negative conventional imaging studies, computed tomography or magnetic resonance imaging) after definitive treatment using positron emission tomography (PET).Of the 27 women with unexplained SCC-Ag elevation, 13 died or were alive with disease (12 PET true-positive, one PET false-negative) in our previous report. In this study, we reported long-term follow-up results for all the 14 patients remaining cancer-free at cut-off of our previous analysis (seven with true-negative PET and two with false-positive PET, and five with true-positive PET having received successful curative salvage therapy).The seven patients with true-negative PET studies remained recurrence-free (median follow up, 70 months; range, 11-84). Two patients had pelvic inflammatory disease; their SCC-Ag levels returned to the normal range after eradication of infection. Two other patients had recurrent cystitis, and their SCC-Ag levels normalized at 5 and 36 months, respectively. The two patients with false-positive PET/computed tomography were disease-free 73.5 and 70 months from original PET studies, respectively. In contrast, of the five patients with successful salvage, two are alive without disease (at 80 and 86.7 months), one died of radiation cystitis at 54 months, and two died of their cancer subsequent to previous analysis.Cystitis or pelvic inflammatory disease may cause unexplained elevation of SCC-Ag after definitive treatment. A negative PET study usually indicates absence of disease. PET is a useful tool to identify curable recurrences, especially when SCC-Ag < 4 ng/mL.
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).
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