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Cervical cancer is the fourth common cancer in women globally, with the number of new cases accounted for 18.6 % among all the cancer patients, in China. It is well known that the situation of prevention and control programs are quite challenging. Based on the efforts being made in the last 20 years, the etiology and carcinogenesis on cervical cancer had been clearly understood. Breakthroughs had been achieved in the development of prophylactic human papillomovirus vaccine and the technology of in screening. Various screening strategies are already available in areas with different economic status. Nevertheless, the capacity of health care services at the primary care clinics needs to be improved to narrow the gap between the reality and the demands.

Objective: To evaluate the performance of High-risk HPV typing detection in cervical cancer screening. Methods: A total of 3 231 women were recruited as the subjects of cervical cancer screening from Jiyuan city of Henan provinces from June to July 2017. All women underwent HPV DNA test. The women with cytological examination ≥ASCUS or cytological examination negative and HPV 16/18 positive underwent colposcopy biopsy and pathological examination. Pathological diagnosis was used as the gold standard. Sensitivity, specificity, positive predictive value (PPV), negative predictive value(NPV) as well as corresponding 95% confidence interval ( CI ) of HR-HPV and HPV 16/18 were calculated. Results: The mean age of 3 231 subjects selected in this study was 46.84±10.00 (21-64) years old. 524 subjects had the positive results of HR-HPV, including 91 of HPV16 and 15 of HPV18. Pathological test result CIN2+ was the gold standard. The sensitivity and specificity of HR-HPV for cervical precancer lesions screening were 93.75 (95 %CI : 79.85-98.27) and 84.56% (95 %CI : 83.26-85.77), respectively. To compared with HR-HPV, HPV16/18 had low sensitivity (65.63%, 95 %CI : 48.31-79.59)and higher specificity (97.44%, 95 %CI : 96.83-97.93). After age stratification by age 30 and 45, the sensitivity of HPV 16/18 was same with HR-HPV (100%, 95 %CI : 34.24-100.00), the specificity of HPV 16/18 was higher than HR-HPV (98.71%, 95 %CI : 96.27-99.56 vs 84.48%, 95 %CI : 79.27-88.58) in < 30 age group.The sensitivity of HR-HPVin 30-45 and ≥45 age group were higher than HPV16/18 (85.71%, 95 %CI : 48.69-97.43 vs 71.43%, 95 %CI : 35.89-91.78, 95.65%, 95 %CI : 79.01-99.23 vs 60.87%, 95 %CI : 40.79-77.84), but the specificity werelower than HPV16/18 (86.89%, 95 %CI : 84.58-88.90 vs 98.51%, 95 %CI : 97.51-99.11、83.49%, 95 %CI : 81.81-85.04 vs 96.80%, 95 %CI : 95.94-97.48). Conclusions: HR-HPV detection has relatively high sensitivity and specificity in cervical cancer screening. For > 30 years old women, HR-HPV is more recommended in cervical cancer screening. Therefore, HR-HPV detection is an effective method for cervical cancer screening.

Objective: To evaluate the performance of Hybribio human papillomavirus (HPV) typing test kit for high risk HPV-DNA typing detection in screening of cervical precancer lesions. Methods: A total of 9 914 women were recruited in Henan, Shanxi, and Guangdong provinces from June to July 2017. All women underwent HPV DNA test. The women who diagnosed as HPV positive and cytological examination ≥ atypical squamous cells of undetermined significance (ASCUS) or HPV negative and cytological examination≥low-grade squamous intraepithelial lesions (LSIL) underwent colposcopy biopsy and pathological examination. Using the pathological diagnosis as the gold standard, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and 95% confidence interval ( CI ) of high-risk HPV and HPV16/18 tests were calculated. Results: The mean age of 9 914 subjects was (45.0±9.3) years old. Among them, 1 302 subjects were detected as high risk HPV positive, including 211 of HPV16 positive and 64 of HPV18 positive. According to the pathological gold standard of cervical intraepithelial neoplasia grade 2 (CIN2) or worse, the sensitivity and specificity of high risk-HPV and HPV 16/18 for triaging ASCUS women were 90.6% (95% CI: 75.8%-96.8%) and 78.0% (95% CI: 74.5%-81.2%) as well as 56.3% (95% CI: 39.3%-71.8%) and 95.7% (95% CI: 93.8%-97.1%), respectively. The sensitivity and specificity of high risk-HPV and HPV 16/18 for cervical precancer lesions screening were 95.1% (95% CI: 88.1%-98.1%) and 87.6% (95% CI: 86.9%-88.2%) as well as 65.9% (95% CI: 55.1%-75.2%) and 97.8% (95% CI: 97.5%-98.1%), respectively. Conclusions: The Hybribio HPV test kit has a relative high sensitivity and specificity for cervical precancer lesions screening and ASCUS triaging. It is reliable for HPV DNA detection and cervical cancer screening.

Objective: To evaluate the feasible cervical cancer screening strategies in rural China. Methods: The study was based on the health industry scientific research project of National Health Commission in 2015, cervical cancer screening technology and demonstration research suitable for rural areas in China, we collected health economics and epidemiological parameters and established the unscreening model and screening model with Treeage Pro 2011 software. Combining with the data acquired from site investigation, including population screening, treatment-related clinical materials and cost data, we simulated the occurrence and the development of cervical cancer of rural women in China under different screening and intervention programs and predicted the screening effects [cumulative incidence, cumulative risk of disease, life years and quality adjusted life years (QALY) , gains] and costs after 20 years, and using health economic evaluation analysis (cost-effectiveness analysis, cost-utility analysis, cost-benefit analysis). Screening programs included five screening strategies [visual inspection with acetic acid/lugol's iodine (VIA/VILI), careHPV, ThinPrep cytology test (TCT), careHPV+TCT, careHPV+VIA/VILI] and three screening intervals (1-year, 3-year, 5-year), a total of fifteen screening programs. Results: Compared with no screening, fifteen screening programs reduced the cumulative incidence by 22.65%-51.76%. Compared with TCT or VIA/VILI, for the same screening interval, the reduced cumulative incidence, the amounts of life-year saved and QALY and benefits gained of careHPV were the highest. The cost-effectiveness ratios of these screening programs ranged (0.44-3.24)×10(4) Yuan per life-year saved, cost-utility ratios ranged (0.15- 1.01)×10(4) Yuan per QALY, benefit-cost ratios ranged 7.73-59.10. The results of incremental costeffectiveness ratios showed that VIA/VILI every five years, VIA/VILI every three years, careHPV every five years, careHPV every three years and careHPV every year were dominant programs. Conclusions: VIA/VILI screening is cost-effective, careHPV is slightly more expensive but more effective. In rural China, careHPV screening every five years could be recommended. This study provides a basis for the determination of cervical cancer screening methods feasible for rural areas in China.

Objective: To analyze the distribution characteristics of common aeroallergens in patients with allergic rhinitis（AR）in Wuhan. Method: Serum specific IgE（ssIgE）was detected in 1 983 patients with clinically diagnosed AR by Midiwiss Allergen Screen system. Data was analyzed statistically. Result: Among the 1 983 patients，1 507（76.0%）had at least one positive ssIgE. The most common aeroallergens were Dermatophagoides pteronyssinus（62.0%），mixed fungi（32.1%）and house dust（27.3%）.Single positive allergen（43.8%），dual positive allergen（28.1%）and triple positive allergen（15.4%）were the most common combinations. The proportion of single positive allergens in the juvenile group（1 to 17 years old）（35.2%）was lower than adult group（≥18 years old）（46.7%），while the proportion of multiple positive allergens was higher than adult group. The positive rates of mulberry and mixed grass in male group were higher than female group. The positive rates of house dust，cat fur and dog fur in the juvenile group were higher than the adult group，while the positive rate of mulberry，cockroach and mixed grass were lower than the adult group. In the elder group（60-88 years old），the positive rates of Dermatophagoides pteronyssinus and mixed fungi were higher than the other three groups. The positive rates of Dermatophagoides pteronyssinus in summer and autumn were higher than that in winter and spring. The positive rate of mixed grass in autumn was much higher and the positive rate of mixed trees and mulberry trees in spring was higher than summer and autumn. Conclusion: Dermatophagoides pteronyssinus，mixed fungi and house dust were the most common aeroallergens among patients with allergic rhinitis in Wuhan. The distribution characteristics in different genders，ages and seasons were different.., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Objective: To explore the most economically feasible cervical cancer screening strategies in urban China. Methods: A series of Markov models were constructed to evaluate health and economic outcomes of different screening strategies. There were 24 screening strategies including four screening methods: liquid-based cytology (LBC), human papillomavirus (HPV) DNA genotyping, HPV DNA genotyping with LBC triage (HPV DNA+ LBC), HPV DNA genotyping and LBC co-testing (HPV DNA-LBC), along with three intervals (every 1, 3 or 5 years) and two starting age for screening (30 or 35 years old) were compared. Models parameters were obtained from a cervical cancer screening study in urban China and literature reviews. Results: The cumulative incidence and mortality risk of cervical cancer declined over 69% and 82% respectively for each screening strategy as compared with the no screening scenario. LBC every five years starting from 35 years old strategy cost the least (RMB 690 per capita) and could save life years compared with no screening. The cost effectiveness ratios of 24 strategies ranged from -10 903 to 117 992 RMB per life year saved. All strategies were cost-effective compared to no screening. In the incremental cost-effectiveness analysis, LBC every 5 years starting from 30 strategy, HPV DNA genotyping every 3 years starting from 30 strategy, LBC every 3 years starting from 30 strategy and LBC every year starting from 30 strategy were dominant strategies. Conclusions: Screening can effectively prevent cervical cancer. In urban Chinese areas with insufficient socioeconomic resources, LBC every 5 years from 35 years old strategy is recommended. In relatively more affluent areas, LBC every 5 years from 30 years old strategy, LBC every 3 years from 30 years old strategy, HPV DNA genotyping every 3 years from 30 years old strategy, and LBC every year from 30 years old strategy are recommended successively.

Through a brief overview of the origin and development of artificial intelligence, the research progress of artificial intelligence in digestive endoscopy, ophthalmoscopy and electronic colposcopy was summarized, and the importance of its application was clarified. This article induced the main problems and suggestions of artificial intelligence in the development of medical endoscopes, and prospected the future application of artificial intelligence in medical endoscopy diagnosis.

Objective: To account the direct cost of uterine cervix carcinoma treatment in China and to explore the related factors which influence the direct financial burden of the disease. Methods: Data was collected through the medical record system and telephone interviews in 14 county-level hospitals and 9 provincial and municipal hospitals from 14 provinces/municipalities enrolled in the Chinese National Health Industry Research Project in 2015. The direct financial burden of uterine cervix carcinoma treatment consisted of the direct medical cost and the direct non-medical cost of treatment in different pathological cervical cancer stages and precancerous lesions. Multiple liner regression method was used to analyze the factors affecting the costs. Results: The age of the 3 246 patients was (46.40±10.43) years, including 2 423 patients from provincial and municipal hospitals and 823 patients from county-level hospitals. The direct financial burden for one patient of pathological uterine cervix carcinoma stage or precancerous lesion ranged from 10 156.3 yuan to 75 716.4 yuan in provincial and municipal hospitals, and for patients from county-level hospitals, the cost was between 4 927.9 yuan and 47 524.8 yuan per person. There was a wide gap between the direct financial burden of patients in different disease stages. The direct financial burden of patients with precancerous lesions ranged from 4 927.9 yuan per person to 11 243.0 yuan per person, as for patients of pathological uterine cervix carcinoma stages, the direct financial burden was between 29 274.6 yuan and 75 716.4 yuan per person. The factors which influence direct financial burden would include: the levels of the hospital, pathological period, medicare reimbursement, days of treatment, and the methods of treatment ( P< 0.001). Conclusion: The direct financial burden of diseases in patients with pathological uterine cervix carcinoma stage or precancerous lesion differed in different levels of hospital and pathological periods. In addition, medicare reimbursement, days of treatment, and the methods of treatment all had impact on it.

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.

Cervical cancer is the fourth most common cancer in women worldwide. More than 80% of cervical cancer deaths occur in low- and middle-income countries. Global health faces enormous challenges. Prevention and control of cervical cancer have a promising prospect, owing to the etiology of carcinogenesis being clearly understood, great efficacy of HPV prophylactic vaccine being proved, technologies of early detection and treatment being well-established, and the various screening strategies being available for communities with different social and economic status. In this commentary, we focused on China and discussed the challenges and opportunities faced by the grass-roots hospitals and clinics, considering the large population load in China and unbalanced allocation of scarce healthcare resources across the nation. In the framework of "Healthy China 2030" , much needs to be done to prevent and control cervical cancer in the upcoming 12 years.

Objective: To analyze the epidemiological genotype features of human papillomavirus (HPV) in cervical infection and their risks for cervical precancers among women in Shenzhen area. Methods: A total of 2 717 individuals ranging in age from 30~59 years were recruited in 18 community health centers of Shenzhen city from March 1 to June 15, 2015 by a cluster sampling method. The results of genotype of HPV, liquid-based cytology (LBC), colposcopy and pathology were analyzed. The clinical sensitivity and specificity as well as positive (PPV) and negative (NPV) predictive values of the combination of different HPV genotype in screening the cervical intraepithelial neoplasia (CIN) 2 and above were estimated. Results: The HPV infection rate in Shenzhen area was 15.9% (432/2 717). The most common HPV genotype was HPV52 (22.9%), followed by HPV16 (12.7%), HPV53 (10.0%), HPV51 (8.6%) and HPV58 (8.1%). Compared with HPV16/18 genotyping, HPV33/16 genotyping had a higher sensitivity (57.1% vs. 42.9%, P <0.05) and an analogous specificity (87.3% vs. 86.9%, P >0.05) in predicting CIN2+ . The sensitivity of combination of HPV33/16 genotyping and low grade squamous intraepithelial lesion (LSIL) positive tested by LBC in predicting CIN2+ was 75.0%, significantly higher than 64.3% of atypical squamous cells of undetermined significance (ASC-US) positive tested by LBC alone ( P <0.05). The specificities of these two methods mentioned above in predicting CIN2+ were 83.5% and 89.2%, respectively, without statistical difference ( P >0.05). Conclusions: Women infected by HPV have distinct risks for CIN2+ according to different high-risk HPV genotypes. The top five risks were HPV 33, 16, 58, 56, and 68. HPV-positive women triaged by LBC LSIL+ combined with HPV33/16 genotyping may be a potential strategy for cervical cancer screening in developed urban area.

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.

Objective: To explore the role of HPV viral loads in random biopsy under normal colposcopy. Methods: 908 atypical squamous cells of undetermined significance (ASC-US) and HPV positive women, recruited in cluster sampling in 9 provinces including 5 urban areas and 9 rural areas in China from 1999 to 2008 and meeting the inclusion and exclusion criteria were included in this analysis. According to relative light units/cutoff (RLU/CO) value, subjects were stratified as low (286 cases), intermediate (311 cases) and high (311 cases) viral load groups. Risks of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) among different viral load groups were compared with linear trend Chi-square test. Results: Detection rate of CIN3+ in low, intermediate and high viral load groups were 2.1% (6 cases), 2.6% (8 cases) and 6.8% (21 cases) (Chi-square test for trend χ(2)=8.91, P= 0.003) and were 60.3, 74.0 and 201.3 times higher than ASC-US and HPV negative women, respectively. Among 908 subjects, 27.0% (245 cases) were abnormal under colposcopy and 68.6% (623 cases) diagnosed as normal. Under normal colposcopy, detection rate of CIN3+ in low, intermediate and high viral load groups were 0.9% (2 cases), 0.9% (2 cases) and 3.8% (7 cases) (χ(2)=6.42, P= 0.040). Conclusion: HPV viral loads display satisfactory risk stratification ability among ASC-US and HPV positive women under normal colposcopy. Women with high HPV viral loads show a significantly increased detection rate of existing CIN3+ and could be recommended to perform random biopsy for histologic diagnosis.

Objective: To analyze the distribution and associated factors of high-risk genotypes of HPV in cervical infection among women in Shenzhen. Methods: The information on sociodemographic characteristics and HPV genotypes of HPV-positive women who participated cervical screening test from January 2014 to December 2016 was downloaded from Shenzhen Maternity and Child Healthcare Management Information System. According to the pathogenicity, the high-risk HPV genotypes were divided into 15 types including HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66 and 68; and there were 6 low-risk genotypes including HPV 6, 11, 42, 43, 44, and 81. Chi-square tests were applied to compare the proportions of high-risk HPV infection among women who had different sociodemographic characteristics. A non-conditional logistic regression model was used to analyze the associated factors for high-risk HPV infection. Results: In total, all HIV positives received HPV genotyping, with an average age of (38.08±9.38) years old. There were 9 979 (93.9%) high-risk and 645 (6.1%) low-risk HPV infections. The proportions of HPV infections for high-risk type in each year were 91.5%, 93.8%, and 95.6%, increasing with the screening years (χ(2)=54.79, P< 0.001). Multivariate logistic regression analysis showed that compared with women younger than 25 years old, women in other age groups (at age 26 to 30 years, 31 to 35 years, 36 to 40 years, 41 to 45 years, and 50 years or older) had increased risks of high-risk HPV infection, with OR (95 %CI ) of 1.67 (1.20-2.31), 1.49 (1.09-2.03), 1.71 (1.23-2.37), 1.65 (1.19-2.31), and 1.84 (1.26-2.67), respectively; compared with the married, single women had a decreased risk of high-risk HPV infection ( OR (95 %CI ): 0.71 (0.50-1.00)); women received HPV testing in 2015 and 2016 showed higher risk of high-risk HPV infection than those in 2014 ( OR (95 %CI ): 1.43 (1.17-1.74) and 2.03 (1.68-2.46)). The 5 most common HPV genotypes were HPV52 (25.1%, 2 670 cases), followed by HPV16 (19.2%, 2 041 cases), HPV58 (13.3%, 1 413 cases), HPV18 (9.9%, 1 048 cases), and HPV51 (9.3%, 993 cases). Conclusion: Age, marital status, and screening year were associated with high-risk HPV infections. Besides HPV16 and HPV18, the prevention and control on HPV infections for HPV52, HPV58, and HPV51 should be prioritized in Shenzhen area.

Objective: To investigate the human papillomavirus (HPV) positive rate and its usefulness in predicting CIN2+ in women with atypical squamous cells of undetermined significance (ASC-US) cervical cytology. Methods: A pooled analysis was conducted using published data of hospital classification, HPV positive rate and histopathologic diagnosis in ASC-US population during 2005 to 2017 from 104 studies which enrolled 28 923 ASC-US samples. Results: The overall HPV positive rate was 52.09% (range from 12.06% to 88.68%). The HPV positive rate in 79 tertiary hospitals of 21 244 cases was 52.46%, slightly higher than the 50.87% in 22 second-class hospitals of 6 925 cases. There was no significant difference between specialized hospitals and general hospitals. In addition, the positive rate of HC2 conducted in 66 hospitals with 19 791 cases was 53.13%, which was slightly higher than 51.10% of reverse hybridization from 24 hospitals with 6 338 cases. In 73 studies of 18 163 cases with histological diagnosis, the sensitivity of HPV for detecting CIN2+ was 90.16% (95% CI : 88.91% to 91.28%), specificity was 53.08% (95% CI : 53.02% to 54.57%), positive predictive value was 23.24% and negative predictive value was 97.24%. Conclusion: HPV detection is clinically validated for ASC-US triage, but there is a wide variation of HPV positive rate in population of cervical cytological diagnosis as ASC-US in China, suggesting different diagnostic level between regions and hospitals and further improvement is needed.

Objective: To study the expression of p16/mcm2 immunocytochemical dual staining in cervical lesions and its association with high-risk HPV infection, and discuss its clinical value in cervical cancer screening. Methods: From May to December 2015, a total of 1 127 women receiving cervical cancer screening, high-risk HPV (HR-HPV) test and liquid-based cytology test were included in the study. p16/mcm2 immunocytochemical dual staining was performed on residual cytology specimens and the results were compared with histopathology results. Results: p16/mcm2 had a higher expression risk in HPV16/18 group and other HR-HPV group compared with HPV negative group, with OR of 15.95 (95 %CI : 9.59-26.51) and 10.53 (95 %CI : 7.41-14.98), respectively. The positive rate of p16/mcm2 increased with cervical intraepithelial neoplasia (CIN) severity, and was higher in both CIN2 group and CIN3 group than in benign lesion group ( P <0.05). The overall sensitivity of p16/mcm2 to detect CIN2+and CIN3+lesions were 86.1 % and 92.0 % , respectively, and the overall specificity were 46.1 % and 44.4 % , respectively. In group with cytologic diagnoses of atypical squamous cells (ASC) and low-grade squamous intraepithelial lesion (LSIL), the sensitivity to detect CIN2+and CIN3+lesions were 85.7 % and 87.5 % , respectively, and the specificity were 45.5 % and 44.1 % , respectively. Conclusions: p16/mcm2 dual staining has higher sensitivity than cytology test and better specificity than HPV test. It can identify high-grade cervical lesions and guide the classification of CIN. p16/mcm2 might be used as an innovative biomarker for cervical cancer screening.

Objective: to investigate the clinical value of p16/Ki-67 immunocytochemical dual staining (abbreviated as p16/Ki-67 dual staining) in cervical intraepithelial neoplasia (CIN) and cervical cancer screening. Methods: From July to November 2015, a total of 980 women attending cervical cancer screening and receiving high-risk human papillomavirus (HR-HPV) test and thinprep cytologic test (TCT) were included in the study. p16/Ki-67 immunocytochemical dual staining was performed on residual cytologic specimens and compared with histopathology results. Results: The expression risks of p16/Ki-67 in HPV16/18 group and another HR-HPV group were higher than HPV negative group, with an odds ratio of 10.64 (95% CI: 5.66~20.02) and 5.40 (95% CI: 3.62~8.04), respectively. The positive rate of p16/Ki-67 increased with the grade of TCT and histologic diagnosis, and was higher in both CIN2 and CIN3 groups than normal group ( P <0.05). The sensitivity of p16/Ki-67 to detect CIN2+ and CIN3+ lesions was 89.3% and 94.1%, respectively, and the specificity was 69.3% and 66.8%, respectively. The sensitivity of TCT to detect CIN2+ and CIN3+ lesions was 60.7% and 64.7%, respectively, and the specificity was 49.3% and 49.1%, respectively. Conclusions: Compared with TCT, p16/Ki-67 dual staining has higher sensitivity and specificity. It can identify high-grade cervical lesions and guide the classification of CIN. p16/Ki-67 dual staining in conjunction with HPV test may be considered as an efficient method for cervical cancer screening.

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.

Pancreatic cancer is characterized by rapid onset, high malignancy and high mortality, thus its early diagnosis is effective for improving the survival rate of patients. To discuss the values of detection of carbohydrate antigen (CA) 50, CA242 and CA199 in the diagnosis of pancreatic cancer, this study randomly selected 112 patients who were confirmed as having stage Ia~IIb pancreatic ductal adenocarcinoma (PDAC) in the Shandong Provincial Hospital, China, from May 2012 to May 2013 as a malignant group. One hundred patients with benign pancreatic lesions and 90 healthy people were selected in the same period as a benign group and a healthy control group, respectively. The levels of serum CA199, CA242 and CA50 were detected using electrochemiluminescence. Results demonstrated that the levels of serum CA199, CA242 and CA50 of the malignant group were significantly higher than those of the benign group and the healthy control group (P=0.001; P=0.003; P=0.000). The positive rate of the tumor markers of the malignant group was higher than that of the benign group and the healthy control group, and the differences had statistical significance (P=0.006; P=0.004; P=0.005). In the malignant group, sensitivity of CA199 was the highest (81.42%) as was the specificity of CA242 (80.14%). The detection of two or more markers could improve sensitivity (joint detection based on parallel tests) and specificity (joint detection based on serial tests). Thus the levels of serum tumor markers including CA199, CA242 and CA50 could be used as the assisted indicators for the diagnosis of early-stage PDAC. Joint detection of the three tumor markers is of great significance to improve the diagnostic sensitivity and accuracy of early PDAC.

Objective: To analyze the basic characteristics of patients with hepatocellular carcinoma (HCC), and further explore the major factors affecting the prognosis of HCC patients. Methods: A total of 800 HCC patients were randomly selected from the Cancer Hospital, Chinese Academy of Medical Sciences. Their clinical and follow-up information was obtained from medical record. Univariate analysis of variance, Kaplan-Meier method and Cox regression analysis were used to analyze the patients' age at diagnosis and survival time, etc. Results: The average age of diagnosis was 55.04 years among all the 800 HCC patients, and the sex ratio of male to female was 4.48. The infection rates of HBV and HCV were 78.6% (629/800) and 5.8% (46/800), respectively. The smoking rate was 41.0% (328/800) and the alcohol consumption rate was 38.5% (328/800). 259 (32.4%) patients underwent radical treatments with liver resection as major therapy, and 541 (67.6%) patients adopted non-radical treatments with transcatheter arterial chemoembolization (TACE) as major therapy. The 1-, 3- and 5-year survival rates of the HCC patients were 73.2%, 53.7% and 42.4%, respectively. The risk factors for prognosis included alcohol abuse and treatment methods. The HR of alcohol abuse was 1.326 (95% CI: 1.058 to 1.661) and HR of treatment methods was 3.301 (95% CI: 2.483 to 4.387). Conclusions: Men account for the majority of HCC patients, and most patients have a lower age at diagnosis and adopt non-radical treatments. The exposure rates of HBV infection and alcohol abuse of HCC patients are significantly higher than those of general population. The major risk factors affecting prognosis and survival are treatments and alcohol abuse. Alcohol abuse and HBV may have synergistic effects on the survival of HCC patients.

Objective: To evaluate the dynamic variation of genotypes distribution of human papillomavirus (HPV) over 10-year follow-up in a cervical cancer screening cohort. Methods: Based on the Shanxi Province Cervical Cancer Screening Study Ⅰ cohort, we detected HPV genotypes on the well-preserved exfoliated cervical cells from women who were tested HPV positive from year 2005 to year 2014 using reverse linear probe hybridization assay. The changes of prevalence of type-specific HPV over time among the overall population were estimated using linear mixed models. The association between the type-specific HPV and cervical intraepithelial neoplasia grade 2 or worse (CIN2 +) was calculated by linear Chi-square test. Finally, the trends of multiple infections of HPV with the increase of the age were analyzed. Results: During the cervical cancer screening of the overall population from 2005 to 2014, the most common genotypes among the population were HPV16 and 52. The prevalence of HPV16 decreased over time from 4.6 % in 2005 to 2.2 % in 2010 and 2014 ( F =8.125, P <0.001). The prevalence of HPV52 remained pretty stable and HPV33, 51 and 58 slightly decreased then apparently increased. Further stratification analysis by pathological lesions showed the same trend of the HPV prevalence for the histology normal women with the overall population. Of note, for those women with the cervical intraepithelial neoplasia (CIN2 +), the detection rate of HPV16 decreased from 65.22 % in 2005 to 41.03 % in 2010 and finally to 31.58 % in 2014 ( χ (2)=4.420, P =0.036) and that of HPV33 substantially increased. No significant variation was found for other types of HPV. Multiple infection rate varied with the growing age of the women. Conclusions: The genotypes prevalence of HPV tended to vary over time during cervical cancer screening in the context of regular screening combining with immediate treatment for those CIN2 + women. HPV16 prevalence significantly decreased over time, which indicated that the variation of type-specific HPV prevalence should be considered when regular cervical cancer screening was organized using HPV technique.

The incidence and mortality of breast cancer is in an increasing trend. In contrast to the global breast cancer situation, the prevention and control is challenging in China. Some suggestions are presented to the project of breast cancer prevention and control in China. Combining the global screening experiences with the epidemiological features of Chinese female breast cancer, aims to improve the population screening and early detection rate. Standardizing clinical diagnosis and treatment practice, aims to increase the efficacy and decrease the mortality. Intervening lifestyle and dietary behaviors, and intends to reduce risk exposure and incidence. Building national breast cancer registry provides preventive strategies. Great efforts should be made to carry out large sample multicenter clinical trails and translational research on the prevention and cotrol of breast cancer coordiated by health care service and science and technology administrations. Breast cancer prevention and control has a long way to go in China.

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 assess the risk of cervical cancer and high grade cervical intraepithelial in women with negative human papillomavirus (HPV) and cytology atypical squamous cells of undetermined significance (ASC-US) and to provide evidence for clinical management., Methods: We pooled 17 population-based cross-sectional studies which were conducted across China from 1999 to 2008. Totally, 30 371 women aged 17-59 were included in these studies. All women received liquid-based cytology test (LBC), HPV testing (hybrid capture 2 test, HC2) and visual inspection with acetic acid test (VIA). Women with any positive result from above tests were referred to colposcopic examination. Totally, 28 810 women with complete results from HPV, cytology and pathology were included in the final analysis. Women with negative HPV (LBC-/HPV-) or negative cytology (LBC-) results served as the control, respectively. Risk on high grade cervical intraepithelial neoplasia (CIN2+) was calculated for women with HPV negative and ASC-US results (ASC-US/HPV-)., Results: There were 22 003 women with LBC-/HPV-, 24 139 women with LBC-, and 1 834 with ASC-US/HPV- indentified in our study. CIN2+prevalence rates to the above women appeared as 0.05%, 0.36% and 0.16%, respectively. Compared with women with LBC-/HPV- and women with LBC-, the odds ratios (ORs) for CIN2+in women with ASC-US/HPV-were 3.00 (95%CI: 0.85-10.65) and 0.46 (95%CI:0.15-1.45), with adjusted ORs as 4.00 (95%CI: 1.08-14.87) and 0.47(95%CI: 0.15-1.49), respectively., Conclusions: The risk of CIN2+ in women with ASC-US/HPV- was in between the risks of women with LBC-/HPV- or with LBC-. Based on the "equal risk, equal management" principle, women with ASC-US/HPV- were suggested to be followed under the '3-year interval' program, which was the same as for those cytology negative women. However, in areas with limited health resources, the follow-up interval can be extended to 5 years, similar to the management on women with LBC-/HPV-.

The aim of this study was to determine human papillomavirus (HPV) type distribution in women with and without cervical neoplasia from Asia and to estimate the potential future impact of an HPV 16/18 prophylactic vaccine in this region. A meta-analysis was conducted including 79 studies using polymerase chain reaction to detect HPV types. A total of 5954, 1653, 958, and 16,803 women with invasive cervical cancer (ICC), high-grade squamous intraepithelial lesions (HSIL), low-grade squamous intraepithelial lesions (LSIL), and normal cytology or histology were included, respectively. Type-specific prevalence of HPV types 6, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68, 70, 73, and 82 were estimated and stratified by cervical lesion grade. Overall HPV prevalence was 85.9%, 81.0%, 72.9%, and 14.4%, respectively, in women with ICC, HSIL, LSIL, and normal cytology/histology. In ICC, HPV 16 was the predominant type (52.4%), followed by HPV 18, 58, 33, 52, 45, 31, and 35. The estimated HPV 16/18-positive fraction was 66.9%, 40.4%, 26.7%, and 3.3% in women with ICC, HSIL, LSIL, and normal cytology or histology, respectively. In ICC, the estimated HPV 16/18-positive fraction was about 70% in all Asian geographic regions, with the exception of Japan (51.3%). HPV 16/18 vaccines are estimated to provide about 67% protection against ICC in Asia. HPV 58 and 52 were among the five most common types in ICC in eastern and southeastern Asia but not in south central Asia. After HPV 16 and 18, the next most six common HPV types were 58, 33, 52, 45, 31, and 35 that accounted for additional 20% of cervical cancer cases in Asia. For optimal population coverage, these HPV carcinogenic types should be considered for second-generation HPV prophylactic vaccines.

Objectives: In most reports, the prevalence of PD in mainland China is lower than in western populations. To estimate PD prevalence in China, we performed a cross-sectional study in a rural population in Linxian County, China., Primary Outcomes: Clinical diagnosis of PD., Results: Among the 16,488 participants examined, the overall age- and gender-adjusted prevalence rate of PD was 522/100,000 (95% CI: 477-567) assuming no cases of PD would be found among those younger than 50 years of age. The gender-adjusted prevalence rates were 103 (95% CI: 83-123), 621 (95% CI: 572-670), 902 (95% CI: 843-961), and 1744 (95% CI: 1662-1826) per 100,000 in age groups 50-59, 60-69, 70-79, and 80 and above, respectively., Conclusions: The estimated prevalence of PD in Linxian, China is higher than most of those reported from other areas in China, and similar to those reported from non-Asian populations., (Copyright Blackwell Munksgaard 2005.)

Background: Oesophageal squamous cell carcinoma (OSCC) is a common cancer worldwide and has a very high mortality rate. Squamous dysplasia is the precursor lesion for OSCC and it can be seen during routine endoscopy with Lugol's iodine staining. We aimed to examine the risk factors for squamous dysplasia and determine if a risk model could be constructed which would be useful in selecting apparently healthy subjects for endoscopic screening in a high risk population in Linzhou, People's Republic of China., Subjects and Methods: In this cross sectional study, 724 adult volunteers aged 40-65 years were enrolled. All subjects completed a questionnaire regarding potential environmental exposures, received physical and dental examinations, and underwent upper endoscopy with Lugol's iodine staining and biopsy. Subjects were categorised as having or not having histologically proven squamous dysplasia/early cancer. Risk factors for dysplasia were examined using univariate and multivariate logistic regression. The utility of the final multivariate model as a screening tool was assessed using a receiver operating characteristics curve., Results: We found that 230 of 720 subjects (32%) with complete data had prevalent squamous dysplasia. In the final multivariate model, more household members (odds ratio (OR) 1.12/member (95% confidence interval (CI) 0.99, 1.25)), a family history of cancer (OR 1.57 (95% CI 1.13-2.18)), higher systolic blood pressure OR 1.11/10 mm Hg (95% CI 1.03-1.19)), heating the home without a chimney (OR 2.22 (95% CI 1.27-3.86)), and having lost more but not all of your teeth (OR 1.91 for 12-31 teeth lost (95% CI 1.17-3.15)) were associated with higher odds of having dysplasia. Higher household income (OR 0.96/100 RMB (95% CI 0.91-1.00)) was associated with a lower odds of having dysplasia. Although we found several statistically significant associations, the final model had little ability to accurately predict dysplasia status, with maximum simultaneous sensitivity and specificity values of 57% and 54%, respectively., Conclusions: We found that risk factors for dysplasia were similar to those previously identified as risk factors for OSCC in this population. The final model did a poor job of identifying subjects who had squamous dysplasia. Other methods will need to be developed to triage individuals to endoscopy in this high risk population.

Background: Oesophageal squamous cell carcinoma (OSCC) has a very poor prognosis, which is largely due to late diagnosis. Successful early detection strategies will require identification of clinically relevant precursor lesions that can be targets for screening and treatment., Aims: To identify the clinically relevant histological precursors of OSCC., Subjects: A cohort of 682 endoscoped patients from a high risk rural population in Linxian, China., Methods: Subjects were endoscoped and biopsied at baseline and followed for 13.5 years. We estimated the relative risk of developing OSCC for each of the initial histological diagnoses using Cox proportional hazards regression models., Results: A total of 114 (16.7%) patients developed OSCC during the follow up period. After adjusting for potential confounding factors, relative risks (95% confidence intervals) for incidence of this tumour, by initial histological diagnosis, were: normal 1.0 (reference), oesophagitis 0.8 (0.2-3.2), basal cell hyperplasia 1.9 (0.8-4.5), mild dysplasia 2.9 (1.6-5.2), moderate dysplasia 9.8 (5.3-18.3), severe dysplasia 28.3 (15.3-52.3), and carcinoma in situ 34.4 (16.6-71.4)., Conclusions: In this study, squamous dysplasia and carcinoma in situ were the only histological lesions associated with a significantly increased risk of developing OSCC within 13.5 years after endoscopy. There was no evidence that oesophagitis predisposed to this tumour. Increasing grades of dysplasia were strongly associated with increasing risk, indicating that the histological grading was clinically meaningful. The follow up experience of severe dysplasia and carcinoma in situ was equivalent, suggesting that this distinction is not clinically relevant. Documenting these precursor lesions of OSCC should assist in the development of effective prevention, early detection, and treatment strategies for this disease.

The objective of this study was to compare the sensitivity and specificity of a new method for self-sampling for high risk human papillomavirus (HPV) with direct sampling and liquid based cervical cytology. In Shanxi Province, China, 8,497 women (ages 27-56) underwent a self-sample for HPV using a conical-shaped brush placed into the upper vagina and rotated. Three to sixteen months later the women were screened with liquid-based cytology and direct HPV tests. Subjects with any abnormal test underwent colposcopy and multiple biopsies. Mean age was 40.9 years. 4.4 percent of subjects had >or=CIN II, 26% a positive self-sample and 24% a positive direct test for HPV. The sensitivity for detection of >or=CIN II was 87.5% for self-sampling, and 96.8% for the direct test (P < 0.001). The specificity was 77.2% for the self-sample and 79.7% for the direct test. With an abnormal Pap defined as ASCUS or greater the sensitivity of the Pap for the detection of >CIN II was 88.3% and the specificity was 81.2%. We conclude that self-sampling for HPV is less sensitive for >CIN II than the direct test, but similar to liquid based cytology.

OBJECTIVE.: To test a new survey instrument and determine the acceptance and potential barriers of cervicovaginal self-sampling for high-risk human papillomavirus in rural Chinese women. MATERIALS AND METHODS.: Data from thirteen survey questions assessed acceptance of the self-sampling procedure. Pain, comprehension, and cultural beliefs were potential barriers evaluated by the survey. RESULTS.: A total of 1,560 women were surveyed. The average and mode number of steps of the self-sampling procedure recalled was 5 (out of 7). Ninety-one percent preferred performing the test at a clinic versus their home. The major barrier encountered was related to the educational level of the women. CONCLUSIONS.: The measure performed well in this population. The self-collection brush was well accepted by these women. Education is the largest hurdle to overcome in implementing a self-sampling screening program.

Deoxynivalenol (DON) is a mycotoxin frequently found as a contaminant of cereal crops and may be etiologically associated with adverse health effects in developing countries where considerable quantities of contaminated crops are consumed. We investigated the metabolism of DON in rats as a basis to establish methodology for a candidate biomarker of human exposure to this toxin and tested this methodology on urine samples from a potentially highly exposed population. Sprague-Dawley rats received a single dose of [14C]DON (5.0+/-0.1 mg/kg body weight, 5.5+/-0.1 microCi/kg) and the distribution of DON in body fluids was investigated over 72 h. DON and its metabolites were detectable in the plasma of rats with the highest levels at 8 h, at which time approximately 9% was bound to plasma protein. A total of 37% of the administered DON was excreted in the urine and DON-glucuronide was implicated as the major urinary metabolite based on reverse-phase HPLC analysis of beta-glucuronidase- and sulphatase-treated samples. An immunoaffinity column (IAC)-HPLC method was subsequently developed to measure urinary metabolites, with a view to establishing a urine-based human biomarker. Urine samples were collected from female inhabitants of Linxian County, China, a high risk region for oesophageal cancer (OC) and an area of potentially high DON exposure, and Gejiu, a low risk region in China. DON was detected in all 15 samples following beta-glucuronidase treatment and IAC enrichment with the identity of DON being confirmed by mass spectrometry. The mean levels of DON from the suspected high and low exposure regions of China were 37 ng/ml (range 14-94 ng/ml) and 12 ng/ml (range 4-18 ng/ml), respectively. This is estimated to correspond to daily exposures of 1.1-7.4 microg/kg/day and 0.3-1.4 microg/kg/day, respectively. This is the first reported measurement of a urinary biomarker for DON in both animals and humans and should facilitate epidemiological studies of disease associations with this mycotoxin.

Several screening methods for cervical cancer and its precancerous lesion are reviewed. Cervical cancer screening using visual inspection, colposcopy, oncogenic human papillomavirus DNA testing, liquid-based monolayers and automated Pap smear screening instruments are all potentially valuable when used alone or in combination. Newly developed techniques provide an opportunity to extend practical cervical cancer screening to large population in limited resource areas, and help do more cost-effectiveness of screening tests in high risk population.

Objective: The aim of this study was to design a cervical cancer screening algorithm for the developing world that is highly sensitive for cervical intraepithelial neoplasia (CIN) II, III, and cancer and highly specific for CIN II and III, making it possible to ablate the transformation zone without histologic confirmation., Methods: In rural Shanxi Province, China, we examined 1997 women ages 35-45. Each subject underwent a self-test for intermediate and high-risk HPV (by HC-II assay), fluorescence spectroscopy, a liquid-based Pap (read manually and by computer and used as a direct test for HPV), a visual inspection (VIA) diagnosis, and colposcopy with multiple cervical biopsies., Results: Mean age was 39.1 +/- 3.16 years, mean number of births was 2.6 +/- 0.93. Based on tests administered, 4.3% subjects had > or =CIN II. All subjects with > or =CIN II had either a ThinPrep Pap (> or =ASCUS) or a positive HPV direct test. The sensitivity and specificity for the detection of > or =CIN II were, respectively, 83 and 86% for the HPV self-test, 95 and 85% for the HPV direct test, 94 and 78% for the ThinPrep Pap (> or =ASCUS), 77 and 98% for the ThinPrep Pap (> or =HGSIL), 94 and 9% for fluorescence spectroscopy, 71 and 74% for VIA, and 81 and 77% for colposcopy., Conclusion: Based on these data and the existing healthcare infrastructure in China, we believe that further refinement of primary HPV screening using centralized labs is indicated. Self-testing in the local villages may be effective with improvements in the devices and techniques., (Copyright 2001 Academic Press.)

Objective: To determine the association between tooth loss and the risk of developing esophageal squamous cell carcinoma, gastric cardia adenocarcinoma, or gastric non-cardia adenocarcinoma in a prospective study., Methods: Cox proportional hazards regression was used to examine these associations in a 28,868-person cohort followed prospectively for 5.25 years. The baseline questionnaire included questions regarding tooth loss, and individuals reporting lost teeth had their teeth counted by study personnel. The analytic cohort included 620 esophagus, 431 gastric cardia, and 102 gastric non-cardia cancer cases., Results: Tooth loss was associated with a significantly elevated risk of developing all three cancers. When examined as median splits, tooth loss was associated with a relative risk (RR) (95% confidence interval, CI) of 1.3 (1.1-1.6) in the esophagus, 1.3 (1.0-1.6) in the gastric cardia, and 1.8 (1.1-3.0) in the gastric non-cardia. Further analysis demonstrated that this increased risk was most strongly associated with the loss of the first few teeth and was primarily confined to the younger members of our cohort., Conclusions: In this cohort tooth loss increased the risk of developing upper gastrointestinal cancer. We hypothesize that this may be related to alterations in oral bacterial flora and subsequent increases in the in-vivo production of carcinogens such as nitrosamines.

Objective: Ecologic studies of esophageal squamous cell carcinoma (ESCC) have reported an association with consumption of maize contaminated with Fusarium verticillioides, which produce fungal toxins referred to as fumonisins. Fumonisins disrupt sphingolipid metabolism and serum sphingolipids have been proposed as biomarkers of fumonisin exposure. We conducted a prospective nested case-control study to examine the relationship between serum sphingolipids and ESCC incidence., Methods: Cases and controls were selected from a large prospective trial conducted in Linxian, People's Republic of China. Ninety-eight ESCC cases were randomly selected from the 639 incident ESCC ascertained during the initial 5.25 years of follow-up: 185 controls were also randomly selected based on the distribution of cases among six age and sex strata. Concentrations of sphinganine and sphingosine were determined by high-performance liquid chromatography in serum collected at the study baseline., Results: No significant associations were found between serum sphingosine, sphinganine, or the sphinganine/ sphingosine ratio and ESCC incidence in conditional and unconditional logistic regression models with adjustment for age, sex, tobacco use. and alcohol use., Conclusion: Our study is the first prospective study to assess the relationship between sphingolipid levels, as biomarkers of fumonisin exposure, and cancer incidence. We found no significant association between sphingolipid levels and risk of ESCC.

Sphinganine and sphingosine, the two sphingoid base backbones of sphingolipids, are highly bioactive compounds that are of increasing interest to nutritionists because they occur in food and their metabolism can be altered by fungal toxins that contaminate some foods. Nonetheless, no studies of diet and sphinganine or sphingosine concentrations in serum have yet been reported. Here we describe a cross-sectional study of 265 residents of Linxian, People's Republic of China, which examines potential demographic, physiologic and dietary correlates of serum sphinganine and sphingosine in this population. Median concentrations of serum sphinganine and sphingosine were compared among strata for 29 different variables. For sphinganine, no significant differences were found. For sphingosine, significant differences were seen among strata of age, menstruation status, serum cholesterol, carotenoids, retinol, tocopherols, fresh and dried vegetable and fresh fruit consumption. Using multivariate linear regression with stepwise selection, we found that the significant predictors for serum sphingosine included total tocopherols, age, serum selenium and retinol, with a final R(2) = 0.22; for sphinganine, tooth loss was the sole correlate, with R(2) = 0.015. Analyses using ranked sphingolipid data or principal components analysis, to simplify the food variables, did not materially alter these results. This study represents the largest report of human serum sphingolipid concentrations to date and provides insight into potential explanatory variables that can be incorporated into future studies.

Objective: To estimate the sensitivity and specificity of visual inspection using acetic acid as a primary screen for cervical intraepithelial neoplasia (CIN)., Methods: Visual inspection was done on 1997 women aged 35-45 years in a screening trial in rural China. Each women had colposcopy and at least five cervical biopsies (directed biopsy of lesions, one biopsy at 2, 4, 8, or 10 o'clock at the squamocolumnar junction in each normal quadrant, and an endocervical curettage)., Results: Forty-three women had biopsy-proven CIN II, 31 had CIN III, and 12 had invasive cancer. In two women only the endocervix was positive (one with CIN II and one with CIN III). Visual inspection yielded normal results in 1445 women (72%), low-grade intraepithelial neoplasia in 525 (26%), high-grade in 21 (1%), and cancer in six (0.3%). With abnormal visual inspection defined as low-grade intraepithelial neoplasia or worse, the sensitivity for detecting biopsy proven CIN II or worse was 71% (61 of 86, 95% confidence interval [CI] 60%, 80%); the specificity was 74% (1420 of 1911, 95% CI 72%, 76%); the sensitivity was 65% for smaller lesions (37 of 57, 95% CI 51%, 77%), and 89% for larger lesions (24 of 27, 95% CI 71%, 98%) (P =.03)., Conclusion: The sensitivity of visual inspection equaled or exceeded reported rates for conventional cervical cytology. Visual inspection and colposcopy have similar specificity profiles for CIN II and greater. The benefit of an inexpensive point-of-care diagnosis and treatment algorithm will be a powerful incentive to pursue visual inspection for cervical cancer screening in developing countries.

Objective: To determine whether the colposcopic impression is influenced by the colposcopist's knowledge of the referral Papanicolaou smear., Study Design: Using a community hospital database, the accuracy of the colposcopic impression (accuracy = proportion of women with histology greater than cervical intraepithelial neoplasia [CIN] 2 that have colposcopic impressions of greater than CIN 2) when referral smears were atypical squamous cells of uncertain significance (ASCUS), atypical glandular cells of uncertain significance (AGUS) or low grade squamous intraepithelial lesion (LSIL) was compared to that when smears showed high grade squamous intraepithelial lesion (HSIL) or cancer. The analysis was repeated with a screening study database in which colposcopic impression was assigned without knowledge of the Papanicolaou smear. Univariate and logistic regression analysis of the second database determined the relative importance of size and grade of lesion and Papanicolaou result to the accuracy of the colposcopic impression., Results: In the community database, colposcopic accuracy was 60/510 (12%) when smears were ASCUS, AGUS or LSIL and 77/132 (58%) when smears were HSIL or cancer (P < .001); in the second database, it was 2/19 (11%) when smears subsequently were reported as negative, ASCUS, AGUS or LSIL and 33/65 (54%) when smears were HSIL or cancer (P < .005). An accurate colposcopic impression was seen in 5/39 (13%) women with one-quadrant lesions, 8/18 (44%) with two-quadrant lesions and 23/27 (85%) with three- or four-quadrant lesions (P < .005). None of 19 women with smears reported as negative, ASCUS, AGUS or LSIL had lesions involving three or four quadrants of the cervix, while 27/65 (42%) women with smears reported as HSIL or cancer had such lesions (P < .005). With logistic regression, the more quadrants of the cervix involved, the more accurate the colposcopic impression. Once controlled for lesion size, there was no improvement when worst histologic grade or Papanicolaou smear result was considered., Conclusion: Through lesions greater than CIN 2 were more often overlooked when referral smears were negative, ASCUS, AGUS or LSIL than when they were HSIL or cancer, the real reason that the lesions were not detected by colposcopy was that they were small.

Using high-pressure liquid chromatography with ultraviolet-visible diode-array detection, we have analyzed polycyclic aromatic hydrocarbons (PAH) in the dichloromethane extracts of soot deposits from coal-burning stoves in several homes of Henan Province, China--including Linxian County, where esophageal cancer rates are some of the highest in the world. Thirty-two individual polycyclic aromatic compounds, ranging in size from three to eight fused aromatic rings, have been unequivocally identified among the soot extract components--including 20 benzenoid PAH, 6 fluoranthene benzologues, 1 cyclopentafused PAH, 1 indene benzologue, 3 oxygenated PAH, and 1 ring-sulfur-containing aromatic. Most of the identified compounds have been observed before among the products of laboratory coal pyrolysis experiments, but two of the components, the six-ring C24H14 napthol[1,2-b]fluoranthene and the eight-ring C30H16 tribenzo[e,ghi,k]perylene, have never before been documented as products of coal in any system. All of the Henan coal soot extracts are remarkably similar qualitatively in that they contain the same set of identified PAH, but absolute levels of individual species vary by up to 5 orders of magnitude, from sample to sample. The bulk of the identified component mass in all of these soot extracts lies in the five- and six-ring PAH--the largest single class being the family of five-ring C20H12 isomers, to which the samples' most abundant components, benzo[b]fluoranthene and benzo[e]pyrene, belong. The five- and six-ring PAH also account for the majority of the samples' known mutagens. The three strong mutagens identified in these soot samples are the C20H12 benzo[a]-pyrene and two C24H14 PAH, dibenzo[a,e]pyrene and naphtho-[2,1-a]pyrene. Seven moderate mutagens are found among the C20H12, C22H12, C22H14, and C24H14 PAH. A major class of mutagens, the cyclopenta-fused PAH, appears to be absent from these samples, but our detection of an oxidation product of the major mutagen cyclopenta[cd]- pyrene--itself mutagenic--suggests that these soot deposits may contain additional mutagenic cyclopentafused PAH oxidation products as well.

We explored the association between polymorphisms of the DNA repair gene XRCC1 (codons 194, 280, and 399) and lung cancer risk in a case-control study nested within a cohort of tin miners. Cases were those diagnosed with lung cancer over 6 years of follow-up (n = 108). Two controls, matched on age and sex, were selected for each case by incidence density sampling. Of the three polymorphisms, only the XRCC1 Arg280His allele was associated with increased lung cancer risk (odds ratio, 1.8; 95% confidence interval, 1.0-3.4) after adjustment for radon and tobacco exposure. In addition, individuals with the variant Arg280His allele who were alcohol drinkers seemed to be at higher risk for lung cancer compared with those with the homozygous wild-type genotype. Conversely, individuals with the variant Arg194Trp allele who were alcohol drinkers seemed to be at lower risk for lung cancer compared with those with the homozygous wild-type genotype. Polymorphisms of XRCC1 appear to influence risk of lung cancer and may modify risk attributable to environmental exposures.

Recent epidemiology and laboratory studies indicate that regular taking of aspirin and other non-steroidal anti-inflammatory drugs(NSAIDs) may reduce the risk of colorectal, esophageal, stomach and pancreatic cancers and other digestive cancers. Thus, aspirin and other NSAIDs may be an effective chemoprevention agent for digestive cancers. On the other hand, this protection effort may be beneficial to the course of the intervention, regression and prevention of cancer lesions. The possible mechanism of NSAIDs chemoprevention may be: (1) reducing the synthesis of prostaglandin(PG) and inhibiting cyclo-oxygenase(COX) activity; (2) inducing apoptosis in epithelial cells of the gastro-intestinal origin; (3) obstructing signaling transduction pathways of COX and PG. Now, chemoprevention of NSAIDs has become focus of research on cancer secondary prevention, as its protective effects of chemoprevention of digestive cancer have been determined. NSAIDs, especially selective COX-2 inhibitor may be a novel useful chemoprevention agents for digestive cancer and their precursor lesions in future.

Objective: To analyze and predict the trends of incidence and mortality rates of esophageal cancer in areas of Taihang Mountains, and explore the strategies for facilitating the reduction of the incidence and mortality of esophageal cancer., Methods: The data were collected from Linxian and Cixian Counties registries between 1988-1997. The trends of the incidence and mortality rates for esophageal cancer had been fitted and predicted by the model of BP (Back Propagation) Neural Networks. Then Linqi Xiang in Linxian County was taken as an example, to determine the power for reducing incidence and mortality of esophageal cancer using endoscopic technology as an early detection and treatment method., Results: There were slowly declining trends for both incidence and mortality rates during past 10 years in Taihang Mountains. The predicting rates of the esophageal cancer incidence in 2,002 are 115. 70/100,000 for male and 79.88/100,000 for female; mortality rates are 94.00/100,000 and 56.29/100,000 respectively. Both incidence and mortality rates a still in high level. But when using endoscopic technology as an early detection and treatment method, the incidence rate is nearly 1/3 of a control group and the power is 88.30% at the end of eight years. The mortality rate is 1/4 of the control group and power is 89.44% after five years intervention (both powers based on 0.05 significant levels)., Conclusions: The incidence and mortality rates for esophageal cancer are still on high levels in Taihang Mountains. We should continue to enhance our preventive effort there. After using endoscopic technology as an early detection and treatment method, the incidence and mortality rates will be decreased markedly during 5 to 8 years. It is recommended to implement a large-scale secondary prevention strategy in these areas.

Background: From March 1986 through May 1991, we conducted a randomized nutritional intervention trial, the General Population Trial, in Linxian, China, a region with epidemic rates of squamous esophageal and adenomatous gastric cardia cancers. We found that participants who received selenium, beta-carotene, and vitamin E had significantly lower cancer mortality rates than those who did not. In the current study, we examined the relationship between selenium levels measured in pretrial (1985) sera from participants and the subsequent risk of developing squamous esophageal, gastric cardia, and gastric non-cardia cancers during the trial., Methods: This study was designed and analyzed in accord with a stratified case-cohort sampling scheme, with the six strata defined by sex and three age categories. We measured serum selenium levels in 590 case subjects with esophageal cancer, 402 with gastric cardia cancers, and 87 with gastric non-cardia cancers as well as in 1062 control subjects. Relative risks (RRs), absolute risks, and population attributable risk for cancers were estimated on the basis of the Cox proportional hazards models. All statistical tests are two-sided., Results: We found highly significant inverse associations of serum selenium levels with the incidence of esophageal (P: for trend <10(-4)) and gastric cardia (P: for trend <10(-6)) cancers. The RR and 95% confidence interval (CI) for comparison of highest to lowest quartile of serum selenium was 0.56 (95% CI = 0.44-0.71) for esophageal cancer and 0.47 (95% CI = 0.33-0.65) for gastric cardia cancer. The population proportion of these cancers that is attributable to low selenium levels was 26.4% (95% CI = 14.45-38.36). We found no evidence for a gradient of serum selenium associated with incidence of gastric non-cardia cancer (P: for trend =.96), with an RR of 1.07 (95% CI = 0.55-2.08) for the highest to lowest quartile of serum selenium., Conclusions: Our study supports findings from previous prospective studies and randomized trials that variations in selenium levels affect the incidence of certain cancers. In the United States, where intervention trials of selenium are in the planning stages, consideration should be given to including populations at high risk for squamous esophageal and gastric cardia cancers.

Objective: To evaluate the association of prediagnostic serum antioxidants and lung cancer risk we conducted a case-control study nested in an occupational cohort of tin miners., Methods: Male workers free of cancer enrolled in the cohort. During up to 6 years of follow-up, 339 lung cancer cases were diagnosed and, among these cases, those who donated blood prospectively (n = 108) were eligible for this study. For each case, two controls alive and free of cancer at the time of case diagnosis were matched on age and date of blood collection., Results: Overall, we observed no association between serum alpha-tocopherol, gamma-tocopherol or selenium levels and lung cancer risk. However, a significant gradient of decreasing lung cancer risk with increasing serum alpha-tocopherol was apparent for men less than 60 years old (odds ratio by tertile: 1.0, 0.9, 0.2; trend p = 0.002). Alpha-tocopherol was also protective in men who reported no alcohol drinking (OR by tertile: 1.0, 0.6, 0.3; trend p = 0.008)., Conclusion: Although there were no significant overall associations between prospectively collected serum alpha-tocopherol, gamma-tocopherol or selenium and incidence of lung cancer, results from this study suggest that higher alpha-tocopherol levels may be protective in men less than 60 years old and in those who do not drink alcohol.

Objective: Diet validation research was conducted to compare the respondents' reporting of dietary intake in a food frequency questionnaire (FFQ) with intake reported in food recalls. Because the population received annual salary increments that could modify food intake, diet validation studies (DVSs) were conducted during two time intervals., Design: A 99-item FFQ was administered by an interviewer twice in a 1-year interval, and responses to each FFQ item were compared with 28 days of interviewer-administered food recalls that were collected in four 1-week intervals during each season of 1992/93. The second validation study in 1995/96 had a similar design to the earlier one., Setting: A prospective cohort study of lung cancer among tin miners in China was initiated in 1992, with dietary and other risk factors updated annually., Subjects: Among a cohort of high risk tin miners for lung cancer, two different samples (n = 141 in 1992/93, and n = 113 in 1995/96) for each diet validation study were randomly selected from four mine units, that were representative of all worker units., Results: Miners reported a significantly higher average frequency of intake of foods in the food recalls than the FFQ, with few exceptions. Deattenuated Pearson correlation coefficients of the frequency of food intake between the FFQ and food recalls were in the range of -0.40 to 0.72 in both studies, with higher positive correlations for beverages and cereal staples than for animal protein sources, vegetables, fruits and legumes. The percentage of individuals with exact agreement in the extreme quartiles of intake in the food recalls and FFQ ranged from 0 to 100% in both studies., Conclusions: Among Chinese miners, the range in correlations between the food recalls and the FFQ were due to: (i) market availability of foods during the food recall weeks compared to their annual reported intake in the FFQ; (ii) cultural perception of time; and (iii) differences in how the intake of mixed dishes and their multi-ingredient foods were reported in the recalls vs. the FFQ. The range in the percentage of agreement in the same quartiles and the changes in food intake over time may have implications for the analysis of the diet-disease relationship in this cohort.

The United States lung cancer epidemic has not yet been controlled by present prevention and treatment strategies. Overexpression of a Mr 31,000 protein, heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1, had shown promise as a marker of lung cancer. In a pilot study of archived preneoplastic sputum specimens, hnRNP A2/B1 overexpression more accurately detected preclinical lung cancer than standard cytomorphology. In separate, ongoing prospective studies, sputum is collected annually from stage I resected non-small cell lung cancer patients at high risk of developing a second primary lung cancer and Yunnan tin miners at high risk of primary lung cancer. After the first year of follow-up, preclinical detection of lung cancer by routine cytology was compared with hnRNP A2/B1 overexpression as measured by quantitative densitometry of immunostained slides. Up-regulation of hnRNP A2/B1 in sputum specimens accurately predicted the outcome in 32 of 40 primary lung cancer and control patients within 12 months, whereas cytological change suggestive of lung cancer was found in only 1 patient. In the primary lung cancer study, overexpressed hnRNP A2/B1 accurately predicted the outcome in 69 of 94 primary lung cancer and control miners, whereas only 10 with primary lung cancer were diagnosed cytologically. These two prospective studies accurately predicted that 67 and 69% of those with hnRNP A2/B1 up-regulation in their sputum would develop lung cancer in the first year of follow-up, compared with background lung cancer risks of 2.2 and 0.9% (35- and 76-fold increase, respectively). Using sputum cells to monitor hnRNP A2/B1 expression may greatly improve the accuracy of preclinical lung cancer detection.