A multicenter, randomized, open, controlled trial to evaluate the efficacy of Honglilai Vaginal Cream and Premarin Vaginal Cream for Genitourinary Syndrome of Menopause in different subgroups of Chinese postmenopausal women.

AIM: In a randomized, multicenter, open, controlled trial, we compared the effects of Honglilai Vaginal Cream and Premarin Vaginal Cream in different age subgroups and menopausal year subgroups (trial registration numbers: 02003L00493). METHODS: Postmenopausal women with Genitourinary Syndrome of Menopause (GSM) were divided into Honglilai group (n = 319) and Premarin group (n = 116), while subgroups were divided according to their different characteristics of age and menopausal years. Honglilai Vaginal Cream (0.625 mg/g) or Premarin Vaginal Cream (0.625 mg/g) once daily for 3 weeks. RESULTS: In the subgroup of participates >60 years, there were no significant differences of Vaginal Cell Maturation Index (VMI) between the two groups after treatment (p = .171). In the subgroup of 50-59 years, the VMI of Honglilai group was significantly lower than Premarin group (Honglilai group: 74.37 ± 22.76; Premarin group: 80.06 ± 16.15; p = .02). There were no significant differences of Vaginal symptom scores between Honglilai group and Premarin group in every sub-group (p > .05). CONCLUSIONS: Honglilai Vaginal Cream had comparable efficacy with Premarin Vaginal Cream in Chinese women older than 60 years.

[High-risk HPV genotyping PCR testing as a means of cervical cancer and precancerous lesions early screening].

OBJECTIVE: To explored high-risk HPV genotyping PCR testing whether as a feasible means for the early screening of cervical cancer and precancerous lesions. METHODS: From January 2013 to June 2014, 15,192 outpatients in China-Japan Friendship Hospital voluntary were tested by high-risk type HPV genotyping PCR. The average age of them were (33±8) years old. High-risk HPV types genotyping PCR tested by fluorescence PCR technology, in which 13 kinds of high-risk HPV subtypes were detected, including HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68. A total of 4,315 cases of them were tested by the liquid-based cytology (LCT), among them with positive of high-risk HPV genotyping tested by PCR (n=2,366) were biopsy under colposcope (648 cases) in those LCT results were positive or LCT negative but HPV16 positive or LCT negative but had the clear clinical symptoms or and non-HPV16 positive but with clear clinical symptoms. (1) Analysis high-risk HPV infection status of 15 192 women. (2) As the pathological diagnosis was the gold standard in the diagnosis of cervical lesions, analysis of the relationship among high-risk HPV infection, virus loads and cervical lesions. (3) To evaluated the value of high-risk HPV genotyping PCR tested method in screening of cervical cancer and precancerous lesions. RESULTS: ⑴ Of 15,192 cases tested by high-risk HPV genotyping PCR, 2,366 cases were HPV positive (HPV infection), the overall infection rate was 15.57% (2,366/15,192), in which a single subtype of HPV infection in 1,767 cases, infection rate was 11.63% (1,767/15,192), and multiple subtypes of HPV infection (two and more subtypes HPV infection) in 599 cases, infection rate was 3.94% (599/15,192). The HPV16, 52 and 58 infections were the most common HPV subtypes in 13 subtypes, the infection rate was 3.95% (600/15,192), 2.86% (435/15,192) and 2.67% (406/15,192), respectively. (2) The most relevant subtypes with cervical intraepithelial neoplasia (CIN) II and even higher lesion were HPV16, 52 and 58, accounted for 57.7% (154/267) of all above CIN II lesions. The most relevant subtype with the cervical glandular intraepithelial neoplasia (CGIN) II or above lesions was HPV18, 3 cases with CGIN II or above lesions were all single HPV18 infection. The pathologic examination positive percentage of patients which HPV virus loads≤10(3) copys/10(4) cells was 18.2% (25/137), while the pathologic examination positive proportion was 33.3% (247/742) which HPV virus loads≥10(4) copys/10(4) cells, there was statistically significant difference between them (χ2=27.06, P=0.000). (3) Sensitivity, specificity, positive predictive value and negative predictive value for detection of CIN II or above using HPV genotyping PCR were 96.11%, 85.76%, 30.94% and 99.70%, respectively. CONCLUSIONS: There were a guiding significance for high-risk HPV genotyping PCR tested in screening of cervical cancer and precancerous lesion. HPV16, 52 and 58 were related to the severe cervical squamous epithelial lesions, while HPV18 was related to cervical severe glandular cell pathological changes. HPV genotyping is feasible and economical as the first choice of opportunistic screening in tertiary hospitals.

[Randomized, blind, parallel-controlled and multiple-centre clinical trial on the effectiveness and safety of leuprolide acetate in the treatment of endometriosis].

OBJECTIVE: To evaluate the effectiveness and safety of leuprolide acetate in the treatment of endometriosis. METHODS: From Nov. 2007 to Oct. 2012, the patients who confirmed to be endometriosis were randomly divided into test group of 113 cases and control group of 116 cases. The test drug was the sustained-release agent of leuprolide acetate. The control drug was Enantone. The drugs were used for 3 times in total. After treatment, the ovarian mass volumes measured with type-B ultrasound, the scores of the patient's subjective symptoms during non-menstrual and menstruation days, the pelvic signs during non-menstrual days, the changes of hormones [estradiol (E2), FSH, LH], and adverse events were observed. RESULTS: After the treatment, the rate of changes of ovarian mass volume (among them, at 12 weeks after the first injection, the median was -55.83% in the test group, -68.22% in the control group, P = 0.336), the distinct improvement rate of symptom scores and pelvic signs during non-menstrual days [among them, at 12 weeks after the first injection, the rate of lower abdomen pain was 47.5% (48/101) in the test group, 44.0% (44/100) in the control group, P = 0.881], the hormone (E2, FSH, LH) levels [among them, at 12 weeks after the first injection, the serum level of E2, was (33±38) pmol/L in the test group, (38±40) pmol/L in the control group, P = 0.414; the serum level of FSH, was (5.1±2.8) U/L in the test group, (5.3±2.3) U/L in the control group, P = 0.666; the serum level of LH, was (0.6±0.8) U/L in the test group, (0.6±0.9) U/L in the control group, P = 0.907], had no statistically significant difference between the two groups (all P > 0.05). The distinct improvement rate and improvement rate of symptom (lower abdomen pain, low back pain) scores during menstruation days at 12 weeks after the first injection, the rates of lower abdomen pain were 73.9% (34/46), 15.2% (7/46) respectively in the test group, 72.3% (34/47), 2.1% (1/47) respectively in the control group, had statistically significant difference between the two groups (P = 0.026). There was no serious adverse event occurred in both two groups. The incidence rate of adverse event was 33.6% (38/113) in test group, 23.2% (27/116) in control group, there was no significant difference between the two groups (P = 0.082). CONCLUSION: Leuprolide acetate is effective and safe in the treatment of endometriosis.

[Evaluation of variable methods for HPV testing].

OBJECTIVE: To evaluate clinical efficacy of different HPV methods in screening of cervical cancers. METHODS: Between August 2011 and November 2011, 424 women in the China-Japan Friendship Hospital were enrolled in this study. All participants were undergone liquid-based cytology test (LCT), Hybrid capture II (HC-II) and real-time (RT) PCR high risk HPV DNA test for HPV16 and HPV18 genotyping. Those results were classified into two group: 424 women at HC-II group with LCT and HC-II test and 421 women at PCR group with LCT and PCR test. All women with atypical squamous cell of undetermined significance (ASCUS) or above in cytological result with high risk HPV positive at two group underwent cervical biopsy by colposcopy.In the mean time, women with negative in cytological results and with HPV 16 and(or) HPV 18 positive also underwent histo-pathological examination by and colposcopy. The results in two groups were discussed:LCT+HC-II group (424 patients) and LCT+PCR12+2 group (421 patients). RESULTS: (1) There was no significant difference in cervical intraepithelial neoplasia (CIN) II or above disease between LCT+HC-II group and LCT+PCR12+2 group (χ(2) = 3.35, P > 0.05).Sensitivity, specificity, positive predictive value and negative predictive value for detection of CINII or above using HC-II and PCR12+2 were 77.8%, 79.4%, 20.4%, 98.1% and 96.3%, 78.2%, 23.2%, 99.7%, respectively. (2) In LCT+PCR12+2 group, it was found 34 women with HPV16 positive, 5 women with HPV 18 positive including 1 women combined with HPV 16 positive, 74 women with other high risk HPV positive and 309 women with HPV negative. Compared to the infection of other high-risk HPV types, HPV 16 and HPV 18 infection leads to a higher chance of cervical lesions with CIN II or above [51.3% (20/39) and 8.1% (6/74) ]. (3) A significant difference of causing cervical cancer and CINII or above was found among women who were infected with HPV 16 and/or HPV 18 infection, with other high-risk HPV types and negative in high-risk HPV infection (χ(2) = 93.98, P < 0.01). CONCLUSION: LCT combined with PCR genotyping HPV could identify CIN II or above disease efficiently.

Sensitive HPV genotyping based on the flow-through hybridization and gene chip.

Persistent infection of high-risk human papillomavirus (HPV) has been recognized as the direct cause of cervical carcinoma. Therefore, detection and genotyping of HPV are important to cervical-cancer screening. In this study, we have evaluated the efficacy of flow-through hybridization and gene chip (HybriMax) on HPV genotyping through comparison of the results with Hybrid Capture II (HC-II) and in situ hybridization (ISH). 591 women were classified into 6 groups according to their histological diagnoses. The overall accordance rate on 13 types of HPV genotypes between HybriMax and HC-II were 92.5% and 100% in the cancer group. The overall accordance was excellent with the Kappa index (KI) of 0.814. The value of KI in each group was 0.750 (normal cytological diagnosis), 0.781 (chronic cervicitis), 0.80 (condyloma acuminatum), 0.755 (cervical intraepithelial neoplasia (CIN) I), 0.723 (CIN II), and 0.547 (CIN III) (0.75 > KI > 0.4, good; KI ≥ 0.75, excellent). The 10 most common HPV subtype detected by HybriMax were 16, 52/58, 18, 33, 31, 81, 53, 68, and 66 in patients, and 16, 68, 18, 52, 58, 11, 53, 31/39, and 33 in normal controls. In conclusion, HybriMax is an efficient method for HPV genotyping and more suitable for clinical use.

Value-based medicine analysis on loop electrosurgical excision procedure and CO2 laser vaporization for the treatment of cervical intraepithelial neoplasia 2.

AIM: The best treatment option for cervical intraepithelial neoplasia 2 (CIN2) is controversial and there is a lack of studies in value-based medicine. This multicenter comparative study was undertaken to evaluate the effectiveness, cost-effectives and quality of life (QOL) of loop electrosurgical excision procedure (LEEP) and CO(2) laser vaporization for the treatment of CIN2. MATERIAL AND METHODS: A database of LEEP and laser vaporizations performed at three research centers was created. Patients with colposcopic-histopathologically confirmed CIN2 were randomly submitted to LEEP and laser vaporization. Cytology, human papilloma virus (HPV) DNA test and histology were performed, and a questionnaire on QOL was filled out during follow-up. Effectiveness, cost-effectives and QOL were analyzed. RESULTS: Three hundred and thirty-eight women with CIN2 were included in the study. Frequencies of remission, and persistent and recurrent CIN were 89.2%, 7.2%, and 3.6% for LEEP, and 86.7%, 12.6%, 0.70% for laser, respectively. There was no significant difference in remission and persistence of CIN. There was a significant difference in the number of operations, recovery time and costs. Women treated with two methods showed relatively identical QOL. CONCLUSION: Both LEEP and CO(2) laser vaporization are effective and reliable treatments for CIN2, whereas cervical tissue can be obtained for histology by LEEP. Preoperative evaluation and postoperative follow-up are important. Gynecologists should pay attention to QOL of patients with CIN.

Association of abnormal vaginal microflora and HPV infection in cervical precancerous lesions: a retrospective study.

INTRODUCTION: The aim of this study was to analyze the correlation between abnormal vaginal microflora and different types of human papillomavirus (HPV) infection and cervical precancerous lesions during the perimenopausal period. METHODOLOGY: This retrospective study included women patients who underwent liquid-based cytologic test (LBC), HPV test, leucorrhea routine test, or routine urine test at the China-Japan Friendship Hospital between October 2019 and January 2020. A cut-off of 45 years was used as the cut-off age for menopause. The positivity and subtypes of HPV were determined using a chip-based assay. Vaginal microflora was determined using an HB-2012a flow-through hybridization instrument. RESULTS: A total of 132 patients were included in this study. 97 patients were younger than 45 years of age, with a median age of 35 (8.0), and 35 patients ≥ 45 years of age, with a median age of 55 (11.0). There were no significant differences in cytology, type of cervical lesion, HPV type, and common pathogens of the reproductive tract (all p > 0.05). The multivariable analysis showed that only HPV-16 infection lesions (OR: 2.825, 95% CI: 1.121-7.120, p = 0.028), Chlamydia trachomatis infection (OR: 0.142, 95% CI: 0.024-0.855, p =0.033), and Mycoplasma infection (OR: 7.750, 95% CI: 1.603-37.474, p = 0.011) were independent risk factors for cervical precancerous lesions. The menopausal status (with age < 45 or > 45 years as its surrogate) was not associated with cervical precancerous lesions. CONCLUSIONS: Menopause was not associated with cervical precancerous lesions. The results suggest that the prevention and treatment of HPV-16, Chlamydia trachomatis infection, and Mycoplasma infection could be significant to prevent the occurrence of cervical precancerous lesions.

[Pregnancy related cervical cytological changes and clinical management].

OBJECTIVE: To investigate characteristics of cervical cytology and management in pregnant women. METHODS: From Aug. 2006 to Jan. 2010, 5152 pregnant women who received antenatal and postpartum examination underwent cervical cytological screening by liquid-based cytological test (LCT) in China-Japan Friendship Hospital. The cytological diagnosis was in accordance with the Bethesda system (TBS) 2001 diagnosis and classification system. The abnormal LCT results were followed up at 3 months after postpartum. The diagnosis of high-grade squamous intraepithelial lesions (HSIL) and squamous cell carcinoma (SCC) were based on colposcopic examination and biopsy during pregnant. The diagnosis of atypical glandular cells (AGC) was based on curettage and biopsy at postpartum 6 weeks. The histopathology of biopsy were compared and analyzed. RESULTS: (1) Cervical cytological changes related with pregnancy: among 5152 cases, it was found navicular cells in 3215 cases (62.40%), decidual cells in 783 cases (15.20%), reactive glandular cells in 369 cases (7.16%), and trophoblastic cells in 55 cases (1.07%). (2) LCT results: among 5152 cases, the normal samples were 4125 cases (80.07%), the inflammatory samples were 542 cases (10.52%), and the samples of abnormal epithelial cells were 485 cases (9.41%). Among those abnormal cases, 291 cases (5.65%) were in atypical squamous cells (ASC), 153 cases (2.97%) were in low-grade squamous intraepithelial lesions (LSIL), 33 cases (0.64%) were in HSIL, 1 case (0.02%) were in SCC and 7 cases (0.14%) were in AGC. (3) Histological pathology results: all women with HSIL and SCC underwent colposcopic examination and biopsy, it was found 28 cases in cervical intraepithelial neoplasia (CIN)II-III, 1 cases in adenosquamous carcinoma. 7 women underwent curettage and biopsy at postpartum 6 weeks which were diagnosed by AGC, the histopathological diagnosis was all negative. The concordance rate of cytopathologic and histopathologic diagnosis was 71% (29/41). (4) FOLLOW-UP: 485 women with abnormal LCT results were all followed up to 3 months at postpartum. Women with HSIL, SCC and AGC undergoing biopsy showed normal LCT results during follow-up. Those women with ASC and LSIL did not undergo colposcopic examination and biopsy. The regression rate was 72.3% (321/444) at postpartum 3 months. CONCLUSIONS: The navicular cells were primarily morphological characteristics of cytology during pregnant and postpartum women. Some changes were easily confused with malignant lesions. It should be careful discrimination, and avoid excessively diagnosis and misdiagnosis. It suggested that we should follow up those women closely and expand the indication of colposcopic biopsy.

Immunochemical analysis of human papillomavirus L1 capsid protein in liquid-based cytology samples from cervical lesions.

OBJECTIVE: To investigate using detection of human papillomavirus (HPV) L1 capsid protein to predict the course of mild or moderate cervical intraepithelial neoplasia (CIN). STUDY DESIGN: Immunocytochemical analysis using antibody against HPV L1 capsid protein was carried out on 274 Pap tests from women positive for high-risk HPV detected by hybrid capture, with cytologic diagnoses of atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesion (LSIL), atypical squamous cell cannot exclude high-grade squamous intraepithelial lesion (HSIL) (ASC-H), HSIL and squamous cell carcinoma (SCC). Histologic diagnosis was available for patients after initial cytologic diagnosis. RESULTS: L1 capsid protein was positive in 69.79% of cervicitis, 83.53 % of CIN 1, 41.81% of CIN2, 3.13% of CIN3 and 0% of SCC. Cytologic diagnosis revealed a higher expression rate in LSIL than in ASCUS and HSIL + SCC. In 71 ASCUS/LSIL without treatment, no L1-positive cases progressed in cytology; 18.75% of L1-negative cases progressed to ASC-H/HSIL. CONCLUSION: The decreased expression of HPV L1 may correlate with progressed cytopathology. The expressions of HPV L1 in liquid-based cell specimens implied the histopathology diag- nosis of cervix. Expression of HPV L1 may have significance in treating ASCUS and LSIL.

[Comparative study on the effects of LEEP and laser CO(2) vaporization in cervical intraepithelial neoplasia II].

OBJECTIVE: to compare the effect and complications of loop electro-surgical excision procedure (LEEP) and laser CO(2) vaporization in the treatment of cervical intraepithelial neoplasia II. METHODS: a total of 338 CINII women were recruited into this multi-center comparative study. The diagnosis was confirmed by histopathological examination for cervical epithelial cell abnormalities. And colposcopic examination was submitted to LEEP (n = 195) or laser CO(2) vaporization (n = 143) respectively. A post-treatment follow-up of 3, 6 and 12 months was carried out to compare the effect of two methods. RESULTS: among 195 women undergoing LEEP, the frequency of cure, persistent and recurrent CIN was 89.2% (n = 174), 4.1% (n = 8) and 3.6% (n = 7) respectively. And among 143 women receiving laser CO(2) vaporization, the frequency of cure, persistent and recurrent CIN was 86.7% (n = 124), 4.9% (n = 7) and 0.70% (n = 1) respectively. There was no statistical difference in cure rates, persistence or recurrence of CIN (P > 0.05). The recovery time, the operative frequency and intra-operative blood loss were significantly different in two groups. CONCLUSION: both LEEP and CO(2) vaporization are both effective and reliable for the treatment of cervical intraepithelial neoplasia II. However, pathological specimens may be harvested during LEEP. It is of vital importance to conduct preoperative colposcopic assessment and standard postoperative follow-ups.

Human papillomavirus type-distribution in cervical cancer in China: the importance of HPV 16 and 18.

Prophylactic vaccination against HPV 16 and 18 has the potential for effective prevention of high-grade precancer (cervical intraepithelial neoplasia [CIN)] 2/3) and ICC caused by these viruses (globally 50 and 70%, respectively) when employed in women prior to starting sexual activity. To provide data for decisions on HPV vaccination in China, we determined HPV type-distribution in ICC and CIN 2/3 from women of different regions within China. A multicenter study was conducted by randomized sampling of paraffin blocks of 664 ICC (630 squamous cell carcinoma [SCC]; 34 adenocarcinoma [ADC]), 569 CIN 2/3 cases from seven regions of China. Histological diagnosis was confirmed in 1,233 cases by consensus review. HPV DNA was detected using the SPF10 LiPA25 version 1 assay. HPV prevalence was 97.6% in SCC, 85.3% in adenocarcinoma, and 98.9% in CIN 2/3. HPV 16 (76.7%) and HPV 18 (7.8%) were the most common, together accounting for 84.5% of SCC, followed by HPV 31 (3.2%), HPV 52 (2.2%), and HPV 58 (2.2%). HPV positivity in SCC did not differ notably by region. However, SCC cases from women

A study on the mechanism of 5-aminolevulinic acid photodynamic therapy in vitro and in vivo in cervical cancer.

5-Aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) is a new ablation treatment for tumors, while its function mechanism in cervical cancer has not been elucidated. In this study, we investigated the effects of ALA-PDT on the cervical cancer cell line Me180, to search for optimal parameters of PDT. ALA-PDT on proliferation of Me180 was examined by MTT assay to find the optimal function parameters of ALA-PDT. Apoptosis was observed by using AnnexinV-FITC/PI double staining, Hoechst 33342 staining and May-Grünwald-Farbstoff Giemsa staining. Furthermore, we established a tumor model and 6 mice of each group underwent measurement of the tumor size on days 3, 7, 14, and 21 after treatment. The mRNA expression of survivin, bcl-2, p53, bax and bad in Me180 cells were detected by real-time fluorescence reverse transcription-polymerase chain reaction (RT-PCR) in vitro and in vivo. Finally, we compared the effects between topical and intravenous administration. Based on the above studies, we found ALA-PDT induced apoptosis and G0-G1 phase arrest of Me180 cells. The tumor volume of the topical administration and PDT group was the smallest at 7-14 days post-PDT. H&E staining showed remarkable subcutaneous necrosis in the PDT groups. The mRNA expression of survivin and bcl-2 in Me180 cells were suppressed post-PDT. Topical administration of PDT is recommended in treating cervical cancer so as to minimize the side-effects and inconvenience of phototoxic reaction brought by PDT. Our data may contribute to making the mechanism of PDT on cervical cancer clearer and give some useful suggestions for clinical application.

[Detection of multiple human papillomavirus infection in cervical specimens by flow fluorescent hybridization].

OBJECTIVE: To explore the clinical significance of detection of multiple human papillomavirus infection in cervical lesions detected by flow fluorescent hybridization technology with Luminex multi-analytic profiling (xMAP). METHODS: Cervical exfoliated cell specimens were collected from 301 randomly selected women accepting opportunistic screening for cervical lesions with the cytological results and hybrid capture 2 (HC-2) assay>or=atypical squamous cells of uncertain significance (ASC-US), 48 with the pathological diagnosis>or=cervical intraepithelial neoplasia (CIN)2 (case group) and 253 with normal histological result or only inflammation (control group), aged (34+/-9) (21-59). The samples were tested with xMAP technology with blind method. The coincidence of the xMAP and HC-2 was assessed. The HPV genotype, multiple HPV infection rate, and their relationships to the patients' clinical-pathological features were analyzed. RESULTS: The rates of sensitivity, specificity, and accuracy of xMAP technology to detect>or=CIN2 cervical lesions were 80.49%, 80.00%, and 80.07% respectively. The positive and negative predictive values were 47.06% and 96.30% respectively. The Kappa Index for agreement between xMAP technology and HC-2 was 0.56. The prevalence rate of high-risk HPV infection was 28.24% (85/301). The prevalence rate of multiple HPV infection was 11.30% (34/301), significantly lower than that of single type high-risk HPV infection (16.94%, P<0.05). The proportion of multiple HPV infection in total positive HPV results was 35.05% (34/97). The proportion of duplex and treble HPV infection were 29.90% (29/97) and 5.15% (5/97) respectively. The multiple HPV infection rate of the case group was 37.50% (18/48), significantly higher than that of the control group (6.32%, 16/253, P<0.01). The common duplex HPV infection modes were 16+51/58 (n=4), 51/58+52/59 (n=4), 11+16 (n=3), and 11+52/59 (n=3), 18+52/59 (n=3). The common treble HPV infection modes were 11+16+52/59, 16+18+31, 16+18+52/59, 31+33+39, and 31+33+52/59 (all n=1). HPV16, 52/59, 51/58, 18, 11, and 31 were the common types in multiple HPV infections. CONCLUSION: Flow fluorescent hybridization technology is able to detect multiple HPV infection that is associated with cervical lesions and to identify the HPV genotypes.

[Detection of human papillomavirus L1 capsid protein expression in liquid-based cytology samples with abnormal cytology.].

OBJECTIVE: To investigate the possibility of detection of the human papillomavirus (HPV) L1 capsid protein to predict the course of mild or moderate cervical intraepithelial neoplasia (CIN). METHODS: Immunocytochemical analysis using antibody against HPV L1 capsid protein was carried out on 274 samples obtained from women performed TriPath Pap tests, positive for high-risk HPV DNA detected by hybrid capture II (HC-II) or cytologic diagnosed atypical squamous cells of undetermined significance (ASCUS) or more severe. For cytological diagnosed, there were ASCUS 105 cases, low-grade squamous intraepithelial lesions (LSIL) 119 cases, atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion (ASC-H) 9 cases, high-grade squamous intraepithelial lesions (HSIL) 36 cases, and squamous cell carcinoma (SCC) 5 cases. But for the pathologic diagnosed, there were chronic cervicitis 96 cases, CINI 85 cases, CINII 55 cases, CIN III 32 cases, and SCC 6 cases. RESULTS: Of the 274 cases, HPV L1 capsid protein was positive in 69.8% (67/96) of cervicitis, 83.5% (71/85) of CINI, 41.8% (23/55) of CINII, 3.1% (1/32) of CINIII and 0(0/6) of SCC. Cytologic diagnosis revealed a higher expression rate in LSIL (75.6%, 90/119) than that in ASCUS (63.8%, 67/105) or in HSIL + SCC (9.8%, 4/41; all P < 0.01). Of 71 cases with ASCUS and LSIL without treated, none of HPV L1 positive cases (0/55) progressed in cytology, while 19% (3/16) of HPV L1 negative cases progressed to ASC-H, HSIL (P < 0.01). CONCLUSION: The expression rates of HPV L1 protein in liquid-based cell specimen is decreased as the cytopathology diagnosis severe degree, which may imply the histopathology diagnosis of cervix, predict the progression of cervical lesion, and help to treat the cases with ASCUS and LSIL.

[Efficacy and safety of drospirenone-ethinylestradiol on contraception in healthy Chinese women: a multicenter randomized controlled trial].

OBJECTIVE: To evaluate the contraception efficacy, mode of bleeding, side effects and other positive effects of drospirenone-ethinylestradiol (Yasmin) in healthy Chinese women. METHODS: This was a multicenter, randomized, control study of 768 healthy Chinese women who consulted about contraception. The subjects were randomized into Yasmin group (30 microg ethinylestradiol plus 3 mg drospirenone, 573 cases) or desogestrel group (30 microg ethinylestradiol plus 150 microg desogestrel, 195 cases) with the ratio of 3:1. Each individual was treated for 13 cycles. Further visits were required at cycle 4, cycle 7, cycle 10 and cycle 13 of treatment Weight, height, body mass index were evaluated at each visit. The menstrual distress questionnaire (MDQ) was given to the women at baseline, visit 3 (cycle 7) and visit 5 (after cycle 13). RESULTS: The values of basal features were similar between two groups (P > 0.05). The Pearl index (method failure) of Yasmin was 0. 208/hundred women year which was lower than that of desogestrel (0. 601/hundred women year). The mode of bleeding was similar between two groups after trial without showing any significant difference. According to MDQ subscale, the improvement of water retention and increasing appetite during inter-menstrual period and water retention and general well-being during menstrual period in the Yasmin group (-0.297, -0.057, 0.033, 0.150 respectively) was more obvious than that in the desogestrel group (-0.108, 0.023, 0.231, -0.023 respectively) with a significant difference (P < 0.05). Some other values which improved in both two groups, especially the improvement of breast tenderness and pain and skin abnormality in Yasmin group (18.0%, 89/494; 12.6%, 62/494) was more distinct than that in desogestrel group (11.3%, 19/168; 5.4%, 9/168). The mean weight increased in desogestrel group (0.57 kg) while it decreased in Yasmin group (-0.28 kg) with a significant difference (P < 0.01). CONCLUSIONS: Both Yasmin and desogestrel have good efficacy on contraception and similar modes of menstrual bleeding. Yasmin is better than desogestrel in terms of weight control and premenstrual syndrome of oral contraceptive.

Effects of Notch Signaling Pathway in Cervical Cancer by Curcumin Mediated Photodynamic Therapy and Its Possible Mechanisms in Vitro and in Vivo.

Curcumin, as a high effect and low toxicity anti-cancer drug and photosensitiser, has synergistic and complementary effects with photodynamic therapy (PDT). However, due to its unclear mechanism, PDT's application and efficacy were limited. Notch signaling pathway, which is highly correlates with carcinogenesis and development of cervical cancer, could be a potential therapeutic targets to improve the effectiveness of PDT. Therefore, in this study, we explored the effects of Notch signaling pathway in cervical cancer by curcumin mediated PDT with/without Notch receptor blocker (DAPT), and hope to elucidate its mechanism. Firstly, the effect on the proliferation of cervical cancer Me180 cells were detected with MTT assay, and apoptosis were detected with Annexin V-FITC/PI combined with flow cytometry. Secondly, after establishment of nude mice model, dividing the experimental animals into model group, curcumin PDT group, simple DAPT group, and curcumin-PDT+DAPT group, and analyzing tumor volume changes as well as HE staining in each group. mRNA and protein expression of gene Notch-1 and its downstream NF-κB and VEGF were observed with RT-PCR, immunohistochemical staining and Western-blot with/without inhibition of Notch signaling pathway by DAPT, both in vivo and in vitro experiments. We found both DAPT and curcumin-PDT can inhibit the proliferation and induce apoptosis of cervical cancer cell. The two have synergistic effect in vitro and in vivo. This effect can effectively block the conduction of Notch signaling pathway, which is associated with down-regulation of the expression of Notch1 and NF-κB. Notch signaling pathway could be one of the targets of curcumin-PDT photodynamic therapy.

[Effects of 5-aminolevulinic acid photodynamic therapy on cervical cancer: in vivo experiment with nude mice].

OBJECTIVE: To study the effects of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) on human cervical cancer, and to identify the best administration regimen with the least phototoxic reaction. METHODS: Seventy-two BALB/c nude mice underwent subcutaneous injection of human cervical cancer cells of the line Me180 so as to establish animal models, and then randomly divided into 6 equal groups: pure topical administration group (undergoing injection of ALA 60 mg/kg around the tumor), pure intravenous administration group (undergoing injection of ALA 250 mg/kg into the caudal vein), topical administration and PDT group (undergoing injection of ALA 60 mg/kg around the tumor and radiotherapy of 630 nm He-Ne laser 6 h after the drug administration), intravenous administration and PDT group (undergoing injection of ALA 250 mg/kg into the caudal vein and radiotherapy of 630 nm He-Ne laser 6 h after the drug administration), and control group (undergoing none of the treatment). 24 h later 6 mice from each group were killed with their tumors taken out. On the days 3, 7, 14, and 21 after treatment the remaining mice underwent measurement of the tumor size. HE staining and pathological examination were performed. Immunohistochemical study was conducted to detect the protein expression of the apoptosis-inhibiting genes of survivin and vascular endothelial growth factor (VEGF). RT-PCR was used to detect the mRNA expression of the apoptosis-inhibiting gene of Bcl-2 and apoptosis-promoting genes of P53, Bax, and Bad. RESULTS: The tumor volumes after treatment of the pure topical administration and pure caudal vein administration groups were (0.09 +/- 0. 02) cm3 and (0.14 +/- 0.04) cm3 respectively, both significantly smaller than that of the control group [(0.67 +/- 0.06) cm3, both P < 0.01]. The tumor volume of the pure topical administration group 7-14 days after treatment was the smallest. HE staining showed remarkable subcutaneous necrosis in the 2 PDT groups. Immunohistochemistry showed remarkable down-regulation of protein expression of survivin and VEGF in the PDT groups. RT-PCR showed that the mRNA expression levels of survivin and Bcl-2 were both significantly lower than that of the control group (both P < 0.01), and the mRNA expression levels of P53, Bax, and Bad were higher than those of the control group, however, not significantly (all P > 0.05). CONCLUSION: ALA-PDT is effective in treatment of cervical cancer. Topical ALA administration + PDT is recommended in treating cervical cancer so as to minimize the side-effects and inconvenience of phototoxic reaction brought by PDT.

[Application of high-risk human papillomavirus testing in women with abnormal cytology].

OBJECTIVE: To detect the high-risk human papillomavirus (HPV) infectious condition in women with abnormal cytology and evaluate its values in the screening of high grade squamous intraepithelial lesion. METHODS: We used hybrid capture 2 (hc2) method to examine 949 patients with abnormal cervical cytology results [ > or =atypical squamous cells of undetermined significance (ASC-US) according to the 2001 The Bethesda System diagnosis criteria]. All subjects also received colposcopy for tissue studies. RESULTS: Among 949 patients with abnormal cytology, the diagnoses of atypical squamous cells (ASC), low grade squamous intraepithelial lesion (LSIL), and high grade squamous intraepithelial lesion (HSIL) were made in 432, 310, and 207 patients, respectively. The high-risk HPV positive rate in ASC, LSIL, and HSIL were 40.3%, 44.8%, and 89.4%, respectively. The numbers of patients with pathologically confirmed results of negative intraepithelial lesion or malignancy (NILM), cervical intraepithelial neoplasia 1, 2, 3 (CIN 1, 2, 3), and squamous cell carcinoma (SCC) were 335, 388, 118, 101, and 7, and the high-risk HPV positive rate was 17.3%, 66.2%, 92.4%, 97.0%, and 100%, respectively. Among patients with atypical squamous cells of undetermined significance (ASC-US), rate of HSIL in high-risk HPV positive group and negative group were 10.2% and 0.8%, respectively (P < 0.01). In screening HSIL, the sensitivities of cytology [ > or = ASC cannot exclude HSIL (ASC-H)] and cytology ( > or = ASC-H) plus high-risk HPV testing were 0.925 and 0.991, and the specificities were 0.510 and 0.748, respectively (P < 0.01). Sensitivitives of cytology ( > or = LSIL) and cytology (> or = LSIL) plus high risk HPV in detecting HSIL were 0.898 and 0.982, respectively, while the specificitives were 0. 567 and 0.779, respectively (P < 0.01). CONCLUSIONS: The positive rate of high-risk HPV increases with the gravity of cervical lesions. In patients with abnormal cervical cytology, high-risk HPV testing can improve the sensitivity and specificity in the screening of HSIL.

[Clinical evaluation of the xMAP technology in detection of high-risk human papillomavirus].

OBJECTIVE: To evaluate the clinical application value of flexible multi-analyte profiling (xMAP) technology in detecting high-risk human papillomavirus (HR-HPV). METHODS: Totally 1 061 women, aged 21-65 years, were randomly enrolled into the study. Cervical exfoliated cells were used in xMAP technology and hybrid capture II (hc2). Pathological diagnosis was used as golden standard. Consistency of these two methods was assessed. RESULTS: The sensitivity and specificity of xMAP technology were 80.31% and 85.83%, respectively. The positive and negative predictive values were 44.5% and 96.9%, respectively. The Kappa value for consistency between xMAP technology and hc2 was 0.58. CONCLUSIONS: The specificity of xMAP technology is similar to hc2 test, but the sensitivity is inferior to hc2. However, these two methods show good consistency in the detection of HR-HPV.

Distribution of human papillomavirus genotypes in cervical lesions.

The aims of the present study were to investigate the distribution of human papillomavirus (HPV) genotypes in cervical lesions, and the association between different HPV genotypes and cervical lesions. Between January 2013 and June 2014, the HPV type determinations of nucleic acid by use of fluorescence polymerase chain reaction (PCR) method of 15,192 outpatients in China-Japan Friendship Hospital were performed and the infection status was analyzed. The results showed that: i) 2,366 Cases were HPV positive and 12,826 cases were HPV negative, the overall infection rate was 15.57% (2,366/15,192), in which a single genotype of HPV infection rate was 11.63% (1,767/15,192), and multiple genotypes of HPV infection rate was 3.94% (599/15,192); ii) HPV16, HPV52 and HPV58 infections were the most common HPV genotypes, the infection rates were 3.95% (600/15,192), 2.86% (435/15,192) and 2.67% (406/15,192), respectively; and iii) According to the gold standard of histopathological analysis via hematoxylin-eosin staining, HPV16, HPV52 and HPV58 accounted for 58.80% (154/267) of all CIN2 or above squamous epithelial lesions. Furthermore, three cases with pathological changes of the cervical severe glandular epithelium were all HPV18 infection. The difference was statistically significant (χ2=60.74, P<0.001). Single HPV subtype infection was primarily associated with HPV16, HPV52 and HPV58. In conclusion, HPV type detection had a may be important in screening of cervical lesions as a difference in pathogenic ability was noted among different HPV genotypes. As cervical cancer is an infectious disease, HPV testing may help detect more precancerous lesions, thus reducing the morbidity and mortality of cervical cancer. HPV16, HPV52 and HPV58 were associated with severe cervical squamous epithelial lesions; HPV18 was associated with cervical severe glandular cell pathological changes, although it was not the most common HPV genotype in China. When positive, a clinical cervical examination should be conducted, including colposcopy and biopsy.