Objective To investigate the prevalence of high-risk HPV subtypes in different pathological types of cervical cancer, and analyze the attribution of carcinogenic HPV subtypes in different pathological types. Methods A total of 1 541 patients with cervical cancer were treated between February 2009 and October 2016 in Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. The median age at diagnosis was 49 years (ranged 20-82 years old). The numbers of patients with cervical cancer from North China, Northeast China, East China, Central China and other regions (including Northwest, Southwest and South China) were 961, 244, 175, 87 and 74 cases, respectively. Pathological types: 1 337 cases of squamous cell carcinoma (SCC), 87 usual adenocarcinoma (ADC), 23 adenosquamous carcinoma (ASC), 20 mucinous carcinoma (MC), 19 clear cell carcinoma (CCC), 12 endometrioid carcinoma (EC), 25 neuroendocrine carcinoma (NEC), 9 serous carcinoma (SC), 5 villous adenocarcinoma (VADC) and 4 minimal deviation adenocarcinoma (MDAC). The prevalence of high-risk HPV in different regions, age groups at diagnosis and pathological types in cervical cancer were analyzed. The attribution of 13 high-risk HPV subtypes in different pathological types of cervical cancer based on proportional attribution method, and the attribution of high-risk HPV subtypes prevented by 9-valent HPV vaccine in SCC and ADC were calculated. Results (1) The prevalence of high-risk HPV in 1 541 patients with cervical cancer was 86.6% (1 335/1 541). The multiple high-risk HPV infection rate in patients with SCC ≥60 years old (23.0%, 37/161) was significantly higher than those in patients aged 45-59 years old and≤44 years old [11.4% (85/747) vs 11.7% (50/429), P<0.01], and the high-risk HPV infection rates of patients with cervical cancer in North China, Northeast China, East China, Central China and other regions were respectively 86.8% (834/961), 87.7% (214/244), 83.4% (146/175), 83.9% (73/87) and 91.9% (68/74). SCC (86.8%, 1 337/1 541) and ADC (5.6%, 87/1 541) were the most common pathological types in cervical cancer. The high-risk HPV prevalence of SCC, ADC, ASC, MC, NEC and VADC were 90.1% (1 205/1 337), 74.7% (65/87), 87.0% (20/23), 65.0% (13/20), 72.0% (18/25) and 5/5 respectively. The high-risk HPV infection rates of SC, EC, CCC and MDAC were 4/9, 3/12, 2/19 and 0/4 respectively. (2) According to proportional attribution, HPV 16 (69.5%), HPV 18 (5.6%), HPV 58 (2.2%), HPV 31 (1.9%), HPV 52 (1.4%) and HPV 33 (1.3%) were the six common high-risk HPV subtypes in SCC. While, HPV 18 (44.1%), HPV 16 (20.5%), HPV 52 (2.3%), HPV 58 (1.2%) and HPV 51 (1.2%) were the main carcinogenic subtypes in ADC. The main carcinogenic high-risk HPV subtypes of ASC, NEC and MC were HPV 18 and HPV 16. The total attribution of HPV 16, 18, 31, 33, 45, 52 and 58 prevented by 9-valent HPV vaccine in SCC and ADC were 82.6% and 68.1% respectively; the attribution of HPV 45 in SCC and ADC were only 0.8% and 0. Conclusions SCC and ADC are the main pathological types in cervical cancer. SCC, ADC, ASC, MC, NEC and VADC are closely related to high-risk HPV infection. HPV 16 is the main carcinogenic genotypes of SCC. HPV 18 maybe play an important role in the pathogenesis of ADC.

Objective To explore the effects and postoperative prognostic factors in cervical cancer patients received neoadjuvant chemotherapy combined with surgery and post-operative adjuvant therapy. Methods A total of 177 patients with cervical cancer at International Federation of Gynecology and Obstetrics (FIGO) stageⅠb2, Ⅱa2 who underwent neoadjuvant chemotherapy (NACT) followed by surgery with and without adjuvant therapy in Cancer Hospital, Chinese Academy of Medical Sciences were included. Univariate and multivariate analyses of 5-year overall survival (OS) rate and 5-year disease-free survival (DFS) rate were performed. Results Of 177 patients, 133 (75.1%) had stageⅠb2 and 44 (24.9%) hadⅡa2 cancers. After NACT,overall response rate was 63.3% (112/177) including 12 cases of complete response (CR), 100 of partial response (PR) and no progressive disease (PD) case. At a median follow-up of 59.2 months, the 5-year DFS rate was 73.6% and the 5-year OS rate was 86.8%. Univariate analysis revealed that lymph node metastasis, deep stromal invasion and tumor size after NACT significantly affected 5-year DFS rate (P<0.05). Lymph node metastasis, deep stromal invasion and tumor size after NACT significantly affected 5-year OS rate (P<0.05). The multivariate analysis showed that, stromal invasion (outer 1/3 or outer 1/2) was independent risk factor of 5-year DFS rate (P<0.05), and 5-year OS rate was significantly affected by tumor size >3 cm after NACT (P<0.05). Conclusions The effect of NACT in Ⅰb2, Ⅱa2 squamous carcinoma of the uterined cervix is confirmed. The independent risk factor for 5-year DFS rate in patients received NACT and hysterectomy is deep stromal invasion of the cervix. The presence of tumor size>3 cm after NACT adversely affect 5-year OS rate.

Objective: To explore the effects and postoperative prognostic factors in cervical cancer patients received neoadjuvant chemotherapy combined with surgery and post-operative adjuvant therapy. Methods: A total of 177 patients with cervical cancer at International Federation of Gynecology and Obstetrics (FIGO) stage Ⅰ b2, Ⅱ a2 who underwent neoadjuvant chemotherapy (NACT) followed by surgery with and without adjuvant therapy in Cancer Hospital, Chinese Academy of Medical Sciences were included. Univariate and multivariate analyses of 5-year overall survival (OS) rate and 5-year disease-free survival (DFS) rate were performed. Results: Of 177 patients, 133 (75.1%) had stage Ⅰb2 and 44 (24.9%) had Ⅱa2 cancers. After NACT, overall response rate was 63.3% (112/177) including 12 cases of complete response (CR), 100 of partial response (PR) and no progressive disease (PD) case. At a median follow-up of 59.2 months, the 5-year DFS rate was 73.6% and the 5-year OS rate was 86.8%. Univariate analysis revealed that lymph node metastasis, deep stromal invasion and tumor size after NACT significantly affected 5-year DFS rate (P<0.05). Lymph node metastasis, deep stromal invasion and tumor size after NACT significantly affected 5-year OS rate (P<0.05). The multivariate analysis showed that, stromal invasion (outer 1/3 or outer 1/2) was independent risk factor of 5-year DFS rate (P<0.05), and 5-year OS rate was significantly affected by tumor size >3 cm after NACT (P<0.05). Conclusions The effect of NACT in Ⅰ b2, Ⅱ a2 squamous carcinoma of the uterined cervix is confirmed. The independent risk factor for 5-year DFS rate in patients received NACT and hysterectomy is deep stromal invasion of the cervix. The presence of tumor size >3 cm after NACT adversely affect 5-year OS rate.

Objective: The correlation between dosimetric parameters of transposed ovary and different clinical ovarian functional status was assessed in young patients with cervical cancer who needed adjuvant radiotherapy after radical resection of the Ⅰ_B1-Ⅱ_A2 phase of preserved and transposed ovaries. Methods: The function of transposed ovary and relevant clinical symptoms in 86 patients before and 2 years after treatment between 2015 and 2017 were retrospectively analyzed, and the correlation between the dosimetric parameters and functional status of transposed ovaries during radiotherapy was evaluated. Different in vitro measures were adopted to protect the transposed ovaries during postoperative radiotherapy including 68 cases of IMRT or VMAT and 18 cases of two-dimensional and other central radiotherapy. Results: The nearest distance between ovary and PTV was negatively correlated with the ovarian dose ≥V_{5 Gy} (P=0.025). V₈ Gy and D_mean were positively correlated with FSH after treatment (P=0.011, 0.020). The larger the volume of V_{8 Gy} and the large D_mean, the higher the FSH, the worse the ovarian function. In two-dimensional technology, the ovarian dose ≥V_{5 Gy} was significantly lower than that in three-dimensional technique. The average age of those with normal ovarian function after treatment was 33.4 years, whereas the average age of women with ovarian failure was 39.6 years (P=0.007). The number of preserved ovaries and whether synchronous chemotherapy was delivered were similar in patients with different ovarian status, which were correlated with the levels of FSH and E2 (Estradiol) before treatment, that is, the higher the level of FSH before treatment, the lower the E2 of ovarian FSH after treatment, and the higher the level of FSH after treatment, the lower the level of ovarian E2. Patients who retained their ovaries before treatment but suffered from ovarian failure received neoadjuvant chemotherapy with a slightly higher age. Conclusions Age, V_{8 Gy} and D_mean of the transposed ovary, the shortest distance between transposed ovary and PTV, whether neoadjuvant chemotherapy was delivered before surgery and radiotherapy technique affect the protection of the function of transposed ovary.

Objective To assess the clinical value of HPV genotyping in follow-up after treatment for cervical high grade squamous intraepithelial lesion (HSIL). Methods Two hundred and thirty eight patients with HSIL receiving conization in Cancer Hospital, Chinese Academy of Medical Sciences from Dec, 2006 to Jan, 2009 were accrued in our study. All the patients were prospectively observed after conization every 6 months for 3 times or till histologically confirmed recurrence. The items in every visit included pelvic examination, cervical cytology and HPV genotyping. Twenty-one HPV genotypes were detected by PCR-hybridization method. The last follow-up was July 31, 2010, and the median follow-up time was 28.3 months (range 6.5-43.0 months). Kaplan-Meire method as used for analyzed the median recurrent time, and the relationships between HPV status and recurrent disease were calculated by and log-rank test and Cox-regression model. Results Among the 238 patients, 110 cases (46.2%, 110/238) had positive result of HPV DNA testing at any visit. The most common HPV types detected in follow-up were HPV16 (45.6%), HPV58 (26.5%), and HPV52 (16.9%). There was no correlation between recurrent disease and any individual high risk HPV infections (P>0.05). Seventeen recurrent cases (7.1%) were identified in 238 patients within a median recurrent time of 14.9 months (range 6.0-32.1 months). In univariate analyses, HPV positive at any visit, persistent infection, multiple infection, type specific persistent infection and positive HPV at 18 months after conization were indicators for residual/recurrent disease (P<0.05). In multivariate analysis, only multiple HPV infection (HR=8.6, 95%CI:1.8-41.7, P=0.008) and type specific persistent HPV infection (HR=5.1, 95%CI: 1.0-24.8, P=0.042) had an elevated risk of recurrent disease. Conclusions HSIL with multiple HPV infection and type specific persistent HPV infection in follow-up are at high risk of recurrent disease. Patients with HPV turning into negative within 18 months after treatment have a low risk of recurrence.

Objective To investigate the efficacy and prognostic factors in patients with stage Ⅰ b and Ⅱ a cervical carcinoma by radical radiotherapy.Methods Between January 1999 and January 2012,108 patients with stage Ⅰ b and Ⅱ a cervical carcinoma received radical radiotherapy in Cancer Hospital,Chinese Academy of Medical Sciences were included and analyzed retrospectively.Patients of stage Ⅰ b1,Ⅰ b2,Ⅱa1 and Ⅱa2 were 18 (16.7％,18/108),38 (35.2％,38/108),33 (30.6％,33/108) and 19 (17.6％,19/108),respectively.Results The 5-year overall survival rate was 76.2％ and the 5-year disease free survival rate was 75.6％.Totally 25 (23.1％,25/108) patients developed recurrent disease,16 of them (64％,16/25) had local recurrences,6 (24％,6/25) had distant metastases and 3 cases had both local recurrence and distant metastases.Among patients with recurrent disease,23 died and 2 survive with tumor.Totally 24 patients died,23 of them died due to tumor recurrence and the other one died of other reason.The univariate analysis showed that,lymph node metastasis,squamous cell carcinoma antigen (SCC) levels before treatment,SCC levels after treatment 1 month had relation with overall survival time in patients with stage Ⅰ b and Ⅱ a cervical carcinoma (all P ＜ 0.05).The multivariate analysis showed that,lymph node metastasis and SCC levels after treatment 1 month were the independent prognostic factors for overall survival time for the cervical squamous cell carcinoma (OR =2.5,4.4 ; all P ＜ 0.05).Conclusions By means of radical radiotherapy,stage Ⅰ b and Ⅱ a cervical carcinoma patients with lymph node metastasis and SCC levels≥ 1.5 mg/L after treatment one month have poor prognosis.While,stage Ⅰ b and Ⅱ a patients with concurrent chemoradiotherapy after neoadjuvant chemotherapy did not affect the prognosis.The 5-year survival rate with concurrent chemoradiotherapy was higher than that of radiotherapy.

Objective To analyze the clinicopathologic characteristics,treatment and prognostic factors in malignant transformation of mature cystic teratoma(MCT)of ovary.Methods The clinical data of 44 patients with MCT from January 1961 to June 2009 were reviewed.Results The median age of the 44 patients was 48 years(range,16-84 years).Mean tumor size was(16 ±6)cm.Thirty-two cases were diagnosed squamous cell carcinoma(73％,32/44),and 5 of them with the elevated level of serumal squamous cell antigen(SCC-Ag).Three of 37 cases(8％,3/37)were identified with malignant transformation in image examinations.Rapid frozen section examination and multiple-location biopsy were performed in 8 cases,and 5 of them were detected with malignant diseases.Twenty-two patients with disease confined within the unilateral ovary(10 with intact capsule,and 12 with ruptured capsule).Diseases extended extra ovaries in the others 22 patients.The median cumulative overall survivals were 126 and 10 months,respectively.The difference between the two groups was significant(P ＜ 0.01).Twenty-seven patients had no residual tumor after primary surgery.The median cumulative overall survivals between the patients with and without residual tumor were 10 and 84 months respectively,and there were significant difference between two groups(P ＜ 0.01).Seven selected patients with malignant disease confined within unilateral ovary underwent fertility-sparing surgery,and 2 cases of them had successful pregnancies and delivery,while other 4 cases with ruptured capsule recurred.Conclusions The most common pathology type of malignant transformation in mature cystic teratoma of the ovary is squamous cell carcinoma.Comprehensive pre-operation image examination and tumor marker level detection might be of great help in diagnosis.Tumor extension extraovary and residual tumor after surgery are the most significant poor prognostic factors.Early stage patient with ruptured capsule should be very discreet to choose fertility-sparing surgery.

Objective To investigate the relationship between single nucleotide polymorphism (SNP) of Fas ligand (FasL) and fulminant hepatitis B in Han Chinese. Methods HBV infected subjects were enrolled in this case-control study, including 233 cases of inactive HBsAg carrier, 68 patients with fulminant hepatitis B,100 cases of spontaneous hepatitis B clearance, 102 patients with hepatitis B virus (HBV) related cirrhosis and 112 patients with HBV related primary hepatocellular carcinoma. The blood samples and clinical data were collected. FasL-844T/C polymorphisms of enrolled subjects were examined by TaqMan real time fluorescent genotyping polymerase chain reaction (RT-PCR). A adjusted odds ratios (OR)and 95% confidence intervals (CI)were calculated using the Logistic regression model. Results After adjusting the factors of gender and age, binary Logistic regression analyses indicated that the genotype frequencies of FasL-844 CC,CT,TT in inactive HBsAg carriers were 50. 64% ,39. 91% and 9. 44% respectively, and those in cases of fulminant hepatitis B were 79. 41%, 17. 65% and 2. 94%, respectively. The analysis also revealed that FasL-844CC genotype in inactive HBsAg carriers was high risk factor of developing fulminant hepatitis B (OR =4. 729,95%CI:0. 510 - 21. 282,P = 0. 043), while there were no statistic significances in other cases (P>0. 05). Conclusion The inactive HBsAg carriers harboring FasL-844CC may have greater susceptibility to fulminant hepatitis B, which need arouse high attention.

Host genetic, environmental and viral factors are classified as three categories that determine clinical outcomes of hepatitis B virus (HBV) infection. The objective of this study was to detect the associations between polymorphisms rs346473 and rs346482 in Rho GTPase-activating protein 24 (ARHGAP24) gene and disease progression of HBV infection in Han Chinese population. These two SNPs were found by our DNA pooling using Affymetrix Genome-Wide Human Mapping SNP6.0 Array in HBV carriers, and verified by using TaqMan 7900HT Sequence Detection System with 758 progressed HBV carriers versus 300 asymptomatic HBV carriers (AsC) in a discovery phase and 971 progressed HBV carriers versus 328 AsC in a replication phase. Multivariable logistic regression revealed that individuals with genotype TT at variant rs346473 displayed remarkable correlations with disease progression of HBV infection both in the discovery phase (OR, 2.693; 95% CI, 1.928-3.760; P=6.2×10(-9); additive model) and the replication phase (OR, 1.490; 95% CI, 1.104-2.012; P=9.0×10(-3); additive model). These two SNPs were in strong linkage disequilibrium with D'=0.99 and r (2)=0.951, and haplotype TT disclosed an increased susceptibility to HBV progression (OR, 1.980; 95% CI, 1.538-2.545; P=8.1×10(-8)). These findings suggest that polymorphism rs346473 in the ARHGAP24 gene might be a part of the genetic variants underlying the susceptibility of HBV carriers to disease progression.

Host genetic,environmental and viral factors are classified as three categories that determine clinical outcomes of hepatitis B virus (HBV) infection.The objective of this study was to detect the associations between polymorphisms rs346473 and rs346482 in Rho GTPase-activating protein 24 (ARHGAP24) gene and disease progression of HBV infection in Han Chinese population.These two SNPs were found by our DNA pooling using Affymetrix Genome-Wide Human Mapping SNP6.0 Array in HBV carriers,and verified by using TaqMan 7900HT Sequence Detection System with 758 progressed HBV carriers versus 300 asymptomatic HBV carriers (AsC) in a discovery phase and 971 progressed HBV carriers versus 328 AsC in a replication phase.Multivariable logistic regression revealed that individuals with genotype TT at variant rs346473 displayed remarkable correlations with disease progression of HBV infection both in the discovery phase (OR,2.693; 95％ CI,1.928-3.760; P=6.2× 10-9;additive model) and the replication phase (OR,1.490; 95％ CI,1.104-2.012; P=9.0× 10-3; additive model).These two SNPs were in strong linkage disequilibrium with D'=0.99 and r2=0.951,and haplotype TT disclosed an increased susceptibility to HBV progression (OR,1.980; 95％ CI,1.538-2.545;P=8.1× 10-8).These findings suggest that polymorphism rs346473 in the ARHGAP24 gene might be a part of the genetic variants underlying the susceptibility of HBV carriers to disease progression.