Objective To evaluate the 15 years changing trends of prevalence of high risk HPV (HR?HPV) infection and the risks of cervical cancer and precancerous lesions (CIN2+) among a Chinese rural population. Methods The screening cohort with 1 997 women aged 35 to 45 years old was built in 1999 in Xiangyuan County, Shanxi province ( SPOCCS?I) and followed up by cytology and HR?HPV testing in the years of 2005, 2010, and 2014. The changes of HR?HPV prevalence and the risks of cervical precancerous lesions with CIN2+ as the endpoints were analyzed during the past 15 years. Results The detection rates of HPV infection and CIN2+ were 15.7%?22.3% and 1.1%?4.3% for the baseline visit and the other 3 follow?ups, respectively. The cumulative risk of CIN2+ in HR?HPV positive women at baseline was significantly higher than HR?HPV negative women ( P<0.01) during the 15?year follow?up. The risk of CIN2+ in the four?times HPV positive group was 40. 0%, while the group with four?times negative HPV results was 0.6% (Adjusted RR = 55.0, 95% CI: 11.3 to 268.4). Conclusions The prevalence of HR?HPV infection and CIN2+ lesions were high in Xiangyuan county during the 15 years. HR?HPV positivity elevated the risk of CIN2+ compared to women whose HR?HPV test was negative. The risks of CIN2+incidence in 6 years were low among women with negative HR?HPV test. The risk of CIN2+ increased with the numbers of HPV infection events. The screening interval could be extended to 5?6 years.

Objective To evaluate the 15 years changing trends of prevalence of high risk HPV (HR?HPV) infection and the risks of cervical cancer and precancerous lesions (CIN2+) among a Chinese rural population. Methods The screening cohort with 1 997 women aged 35 to 45 years old was built in 1999 in Xiangyuan County, Shanxi province ( SPOCCS?I) and followed up by cytology and HR?HPV testing in the years of 2005, 2010, and 2014. The changes of HR?HPV prevalence and the risks of cervical precancerous lesions with CIN2+ as the endpoints were analyzed during the past 15 years. Results The detection rates of HPV infection and CIN2+ were 15.7%?22.3% and 1.1%?4.3% for the baseline visit and the other 3 follow?ups, respectively. The cumulative risk of CIN2+ in HR?HPV positive women at baseline was significantly higher than HR?HPV negative women ( P<0.01) during the 15?year follow?up. The risk of CIN2+ in the four?times HPV positive group was 40. 0%, while the group with four?times negative HPV results was 0.6% (Adjusted RR = 55.0, 95% CI: 11.3 to 268.4). Conclusions The prevalence of HR?HPV infection and CIN2+ lesions were high in Xiangyuan county during the 15 years. HR?HPV positivity elevated the risk of CIN2+ compared to women whose HR?HPV test was negative. The risks of CIN2+incidence in 6 years were low among women with negative HR?HPV test. The risk of CIN2+ increased with the numbers of HPV infection events. The screening interval could be extended to 5?6 years.

To establish the standardization of clinical verification designs for in vitro diagnostic devices(IVDs) of human papillomavirus, China Food and Drug Administration (CFDA) and United States Food and Drug Administration (FDA) issued guidelines of detailed study designs and effectiveness evaluation for accuracy validation and clinical performance of nucleic acid detection, respectively, including triage of a typical squamous cells of undetermined significance(ASC-US) patients and validation of combined screening and preliminary screening. The design, study population, sample size estimation and statistical analysis of guidelines were moderately different from America to China, however, the evaluation indication was similar. According to the guideline issued by CFDA, prospective design suggested by FDA could be replaced by cross sectional study design to validate the triage of ASC-US patients. Alternatively, prospective design could be used to conduct the HPV product declaration and cellular parallel detection for the same natural population, and the clinical effectiveness of declared products could be validated by at least 3 years follow-up of cytology.

Objective To investigate the prognostic factors for patients with intrahepatic cholangiocarcinoma after surgical resection. Methods The clinicopathological and follow?up data of 123 patients with intrahepatic cholangiocarcinoma who underwent surgical resection in Cancer Hospital, Chinese Academy of Medical Sciences between January 1999 and June 2015 were collected and reviewed, and their survival and prognosis were analyzed with the Kaplan?Meier method and Cox regression model. Results The median follow?up time was 22 months and median recurrence?free survival time was 8.97 months. The 1?, 2?and 3?year recurrence rates were 58. 6%, 68. 9% and 76. 5%, respectively. Cox multivariate regression analysis showed that preoperative rise in CEA, lymph node metastasis, multiple lesions, extrahepatic invasion, and combination of tumor necrosis were significant adverse prognostic factors affecting the postoperative recurrence?free survival in patients with intrahepatic cholangiocarcinoma after surgical resection (P<0.05 for all). The median overall survival time was 21.17 months, and the 1?, 3? and 5?year overall survival rates were 76.6%, 33.2% and 26.1%, respectively. The Cox multivariate regression analysis showed that preoperative rise in CEA, lymph node metastasis, multiple lesions, and extrahepatic invasion were significant adverse prognostic factors affecting the postoperative overall survival in patients with intrahepatic cholangiocarcinoma after surgical resection( P<0.05 for all) . Conclusion Preoperative rise in CEA, lymph node metastasis, multiple lesions and extrahepatic invasion are significant adverse prognostic factors for patients with intrahepatic cholangiocarcinoma after surgical resection.

Objective To investigate the prognostic factors for patients with intrahepatic cholangiocarcinoma after surgical resection. Methods The clinicopathological and follow?up data of 123 patients with intrahepatic cholangiocarcinoma who underwent surgical resection in Cancer Hospital, Chinese Academy of Medical Sciences between January 1999 and June 2015 were collected and reviewed, and their survival and prognosis were analyzed with the Kaplan?Meier method and Cox regression model. Results The median follow?up time was 22 months and median recurrence?free survival time was 8.97 months. The 1?, 2?and 3?year recurrence rates were 58. 6%, 68. 9% and 76. 5%, respectively. Cox multivariate regression analysis showed that preoperative rise in CEA, lymph node metastasis, multiple lesions, extrahepatic invasion, and combination of tumor necrosis were significant adverse prognostic factors affecting the postoperative recurrence?free survival in patients with intrahepatic cholangiocarcinoma after surgical resection (P<0.05 for all). The median overall survival time was 21.17 months, and the 1?, 3? and 5?year overall survival rates were 76.6%, 33.2% and 26.1%, respectively. The Cox multivariate regression analysis showed that preoperative rise in CEA, lymph node metastasis, multiple lesions, and extrahepatic invasion were significant adverse prognostic factors affecting the postoperative overall survival in patients with intrahepatic cholangiocarcinoma after surgical resection( P<0.05 for all) . Conclusion Preoperative rise in CEA, lymph node metastasis, multiple lesions and extrahepatic invasion are significant adverse prognostic factors for patients with intrahepatic cholangiocarcinoma after surgical resection.

Objective: To evaluate the actual efficacy of cervical cancer and precancerous lesions screening approaches in real-world regions with different economic levels in China. Methods: The demonstrative application and effect evaluation of cervical cancer screening program were conducted in 21 hospitals nationwide from 2015 to 2018. Multi-stage sampling method was adopted to divide the country into 7 large areas according to geographical location. Two to four screening sites of two types of cancer (cervical cancer and breast cancer) were selected in each area, and the grassroots screening sites were implemented under the guidance of superior hospitals. In rural areas, women were initially screened using cytology, human papillomavirus (HPV) testing and visual inspection. The women with positive cytology or visual inspection were referred for colposcopy, and the women with positive HPV infection were randomly referred for reflex cytology or visual inspection, or direct colposcopy examination. In urban areas, women were primarily randomized into cytology or HPV testing groups. The women with abnormal cytology or positive HPV 16/18 infection were directly referred for colposcopy examination, whereas the women with positive infection of the other 12 high-risk subtypes of HPV were referred for reflex cytology or colposcopy. All of recruited women would be follow-up and screened by the baseline screening techniques in the third year while the positive women underwent colposcopy examination. The positive rates, referral rates, the detection rates of grade 2 and above of cervical intraepithelial neoplasia (CIN 2+ ) were compared. Results: A total of 63 931 women were recruited at the baseline. Among them, 11 rural sites included 33 823 women: 15 577, 11 157 and 7 089 women were screened by HPV testing, visual inspection via acetic acid or Lugol′s iodine (VIA/VILI) and cytology, respectively. Additionally, 30 108 women were from 10 urban sites: 9 907 and 20 201 women were screened by cytology and HPV subtyping, respectively. The HPV positive rate for urban women was 9.34%, whereas that for rural women was 12.53%. The abnormal rate of cytology for urban women was 5.63%, and that for rural women was 4.24%. The positive rate of VIA/VILI in the rural women was 12.25% Furthermore, the detection rate of CIN2+ at the baseline was 0.56%, and that was statistically higher in HPV-positive group than cytology-positive group (P<0.05). Conclusions All of screening sites completed the baseline screening tasks as expected. The prevalence of HPV infection is higher in rural women than urban women. The performance of HPV testing is better than cytology for detecting CIN2+ cases. This real-world demonstration study provides evidences for cervical cancer prevention and control in different regions.

Objective: To evaluate the clinical performance of HPV genotyping with cytology for detecting cervical precancer among women attending co-testing. Methods: A total of 2 883 females who participated in cervical cancer screening program were recruited from Erdos in 2016. All the participants were tested by cytology and HPV genotyping. In 2017, women with abnormal cytology results or HPV positive were followed up. Pathological cervical intraepithelial neoplasia (CIN) 2+ was the study end-point. Clinical performance indexes were calculated, including sensitivity, specificity, positive predictive value, negative predictive value, referral rate and missed cases. Results: INNO-LiPA resulted in a detection rate of 18.87%(544/2 883) for the 14-type high risk HPV. HPV16 was the most common infectious genotype (4.06%), followed by HPV52 (3.61%), HPV51 (2.50%), HPV58 (1.98%), and HPV18 (1.56%). With more HPV genotypes added into the group, sensitivity increased and the specificity decreased. Addition of HPV16, 58, 33, 39, 52, 18, 31 for detection lead to the maximun value of area under the curve (AUC)=0.913 (95%CI: 0.882-0.944). Compared with traditional screening method by cytology, cotesting decreased the number of missed diagnosis. Meanwhile, the fifth method (co-testing: triage of women with HPV16/18+ , cytological minor abnormalities and HPV58, 33, 39, 52, 31+ or cytological high grade abnormalities) did not increase referral rate (8.99% vs. 8.71%, P=0.525), with five cases of missed diagnosis (sensitivity of 92.1% and specificity of 93.2%). Conclusions Co-testing with triage of women with HPV16/18+ , cytological minor abnormalities and HPV58, 33, 39, 52, 31+ or cytological high grade abnormalities would provide better clinical performance. In co-testing, triage of HPV16/18 was used in women with normal cytology; triage of HPV58, 33, 39, 52 and 31 was used in women with low-grade abnormal cytology; referral colposcopy was used in women with high-grade abnormal cytology, which would provide better clinical performance.