The Risk Stratification for Cervical Cancer and Precursors of Domestic HPV Testing With HPV 16/18 Genotyping in Women With NILM Cytology in CentralChina: A Cohort Study.

OBJECTIVE: To evaluate the clinical performance and utility for risk stratification of DH3 HPV assay in women (≥30 years) with NILM cytology. METHODS: A prospective cohort was established in Central China between November 8 to December 14, 2016 which consisted of 2180 women aging 30-64 years with NILM cytology. At baseline, all women were screened using DH3 HPV assay. HPV 16/18 positive women would be assigned to colposcopy and biopsied if necessary. Then, hr-HPV positive women without CIN2+ lesions would be followed up by cytology every 12 months for two years. In the 3rd year of follow up, all women that were not biopsy proven CIN2+ would be called back and screened by cytology again. In follow-up period, women with ASC-US and above were referred to colposcopy and biopsied if clinically indicated. CIN2+ was the primary endpoint in analysis. The clinical performance and utility for risk stratification of DH3 HPV assay were assessed by SPSS 22.0 and SAS 9.4. RESULTS: Of 2180 qualified women, the prevalence of hr-HPV was 8.5% (185/2180), 45(2.1%) were HPV 16/18 positive. The clinical performance for HPV16/18 was 91.7% for sensitivity, 98.4% for specificity, respectively against CIN2+ detection at baseline. In four years of study, the corresponding rates of HPV 16/18 were 51.5% and 98.7%, respectively. The cumulative absolute risk for the development of CIN2+ was as high as 37.8% for HPV 16/18 positive women, followed by hr-HPV positive (14.6%), other hr-HPV positive (11.0%) and HPV negative (0.3%) in three years. The relative risk was 125.6 and 3.4 for HPV 16/18 positive group when compared with HPV negative and other hr-HPV positive group, respectively. CONCLUSIONS: DH3 HPV assay demonstrated excellent clinical performance against CIN2+ detection in cervical cancer screening and utility of risk stratification by genotyping to promote scientific management of women with NILM cytology.

The Potential Benefits of HPV E6/E7 mRNA Test in Cervical Cancer Screening in China.

This study aims to evaluate the clinical performance of the HPV E6/E7 mRNA test in cervical cancer screening in China. A hospital-based study was conducted with mRNA, DNA, and liquid-based cytology (LBC) as primary screening tests. Each woman with a positive result received colposcopy with lesion-targeted-biopsy. Histopathological diagnosis was used as the gold standard. The total agreement of HPV DNA and mRNA was 90.7% (95%CI: 87.9, 92.9) with a kappa value of 0.81. The positive rates of HPV DNA, mRNA, and LBC increased with the severity of histopathology diagnosis, from 25.5, 19.1, and 11.4% in normal to 100.0% in SCC, respectively. The sensitivities for mRNA to detect CIN2+ and CIN3+ were 93.8% (95%CI: 89.7-96.4) and 95.7% (95%CI: 91.3-97.9), respectively, which were not different from HPV DNA testing (95.7% [95%CI: 92.0-97.7], 96.3% [95%CI: 92.1-98.3]), but higher than LBC (80.4% [95%CI: 74.5-85.2] and 88.8% [95%CI: 83.0-92.8]). The specificities for mRNA to detect CIN2+ (79.0% [95%CI: 74.2-83.0]) and CIN3+ (70.5% [95%CI: 65.7-74.9]) were higher than HPV DNA testing (71.0% [95%CI: 65.9-75.7], 62.8% [95%CI: 57.8-67.5]), but lower than LBC (84.5% [95%CI: 80.1-88.0] 79.8% [95%CI: 75.4-83.6]). All tests were more effective in women older than 30 years. HPV mRNA test showed excellent agreement with the DNA test, with similar sensitivity and a higher specificity in detecting high-grade cervical lesions. It is promising that mRNA test could be used for the national cervical cancer screening to reduce false positive without losing sensitivity.

Tobacco smoking and trends in histological subtypes of female lung cancer at the Cancer Hospital of the Chinese Academy of Medical Sciences over 13 years.

BACKGROUND: Lung cancer is the leading cause of cancer mortality among women in China, and incidence and mortality continue to rise despite the fact that smoking prevalence is very low among Chinese women. AIM: This study investigated tobacco smoking and trends in histological subtypes of female lung cancer in a central cancer hospital in China. METHODS: Demographic, smoking history and histological information on female lung cancer patients diagnosed or treated from 2000 to 2012 was collected from the Cancer Hospital, Chinese Academy of Medical Science (CHCAMS). The classification of histological subtypes and clinical stages were conducted using the ICD-O-3 and Eighth AJCC Cancer Staging Manuals. Time-trends of histological subtypes were analyzed based on annual percentage change (APC). RESULTS: Overall, 5870 female cases of lung cancer were included in the analysis. The number of female lung cancer patients increased from 509 (2000-2002) to 1744 (2011-2012). The most common histological type of lung cancer was adenocarcinoma (ADC) (72.93%), followed by small cell lung cancer (SCLC) (11.06%), squamous cell carcinoma (SCC) (8.38%) and other (7.63%). Among smokers, the proportion of SCC decreased from 40.5% to 23.7% (P = 0.005), while ADC increased from 35.7% to 50.7% (P = 0.009). In non-smokers, ADC increased from 63.1% to 80.6% (P = 0.006) and SCC decreased from 13.6% to 4.5% (P = 0.016). Among SCC cases, smokers made up a larger proportion of early stage (I/II: 47.1%) compared with late stages (III, 34.3%; IV, 18.6%). CONCLUSION: The number of female lung cancer patients has increased in CHCAMS. In both smoking and non-smoking cases, the proportion of adenocarcinoma increased. Squamous cell carcinomas were more likely to be diagnosed in early stages among smokers.

Performance of Different Combination Models of High-Risk HPV Genotyping in Triaging Chinese Women With Atypical Squamous Cells of Undetermined Significance.

Objective: The purpose of this study was to evaluate the effect of different combination models of high-risk human papilloma viruses (HPV) genotyping in triaging Chinese women with atypical squamous cells of undetermined significance (ASCUS). Methods: We established a screening cohort of 3,997 Chinese women who underwent cervical cytology and HPV genotyping test. Women with ASCUS cytology underwent punch biopsy under colposcopy/endocervical curettage. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of different combination models of HR-HPV genotyping calculated that cervical intraepithelial neoplasia 2 or higher (CIN2+) on histology were endpoints. Results: Of the full sample, 393 women had ASCUS. Among ASCUS women with a CIN2 lesion, the prevalence for HPV were 40.0% (type 16), 10.0% (type 18), 0.0% (type 33), 30.0% (type 52), 40.0% (type 58), and 30.0% (other nine types). For ASCUS women with a CIN3 lesion, the prevalence for HPV were 68.4% (type 16), 15.8% (type 18), 10.5% (type 33), 31.6% (type 52), 15.8% (type 58), and 36.8% (other nine types). Combination model including HPV16/18/33/52/58 for predicting CIN2+ lesion in women with ASCUS had relatively higher sensitivity [93.1% (78.0, 98.1)], specificity [75.8% (71.2, 79.9)], PPV [23.5% (16.7, 32.0)], and NPV [99.3% (97.4, 99.8)] than other combination models. Moreover, the referral rate of HPV16/18/33/52/58 (29.3%) was lower than HR-HPV (36.1%). Conclusions: The study demonstrates that specific HR-HPV types HPV16/18/33/52/58 may be an effective strategy in ASCUS triage. This improves the subsequent selection of ASCUS patients.

Evaluation of p16/Ki-67 dual staining in the detection of cervical precancer and cancer in China.

Background This study aimed to evaluate the clinical performance of p16/Ki-67 dual staining in the detection of cervical intraepithelial neoplasia grade 2 or 3 or worse (CIN2+/CIN3+) in Chinese women. Methods Cervical exfoliated cells were collected from 537 eligible women and were used for liquid-based cytology (LBC), p16/Ki-67 dual staining, and human papillomavirus (HPV) DNA testing. All women received colposcopy with biopsies taken at abnormal sites. Histopathological diagnoses were used as the gold standard. Results p16/Ki-67 staining had a positivity rate of 43.58% overall; the rate increased significantly with histological severity (p <0.001). The sensitivities of p16/ki-67 for detecting CIN2+ and CIN3+ were 88.10% and 91.30%, respectively. Compared with high-risk HPV (HR-HPV), sensitivity of p16/Ki-67 was lower for detecting CIN2+ (88.10% versus 95.71%), but similar for detecting CIN3+ (91.30% versus 96.27%). Specificities of p16/Ki-67 were 85.02% for detecting CIN2+ and 76.86% for detecting CIN3+, values similar to those for LBC (84.71% for CIN2+, 80.05% for CIN3+) but higher than those for HR-HPV (62.77% for CIN2+, 71.25% for CIN3+). All the tests performed better in women>30 years. With respect to the performance of triage for women with ASC-US, sensitivities of p16/Ki-67 were 86.36% for detecting CIN2+ and 83.33% for detecting CIN3+, values similar to those of HR-HPV. However, specificities of p16/Ki-67 were both higher than those of HR-HPV (85.96% versus 67.54% for CIN2+, 79.84% versus 62.90% for CIN3+). Conclusion P16/Ki-67 dual staining could probably provide an optional method for China's national cervical cancer screening, and could also be considered as an efficient method of triage for managing women with ASC-US.

Increased lung cancer mortality rates in the Chinese population from 1973-1975 to 2004-2005: An adverse health effect from exposure to smoking.

BACKGROUND: Lung cancer incidence and mortality rates have increased substantially in China despite improvements in clinical diagnosis and treatment approaches as well as significant advances in the implementation of tobacco-control policies in recent decades. METHODS: Age-standardized mortality rates and age-specific rates of lung cancer in China were estimated for the periods 1973 to 1975, 1990 to 1992, and 2004 to 2005 using data from 3 National Death Surveys. Among patients with lung cancer who were identified from a hospital-based information system, the percentages of ever-smokers were analyzed according to histologic and demographic variables. RESULTS: Age-standardized mortality from lung cancer in China dramatically increased from 7.30 per 100,000 during 1973 through 1975 to 27.62 per 100,000 during 2004 through 2005. Increases in lung cancer age-standardized mortality were consistent among men and women in urban and rural populations. Among men ages 75 to 79 years, lung cancer mortality increased remarkably to 453.67 per 100,000 in 2004 and 2005 (from 246.78 per 100,000 during 1990-1992 and from 53.65 per 100,000 during 1973-1975). Among 6674 patients with lung cancer who were identified from 2003 to 2007 from a hospital-based database, 82.97% of men were ever-smokers (73.35% of men with adenocarcinoma and 91.8% of men with squamous cell carcinoma), and 11.18% of women were ever-smokers (6% of women with adenosquamous carcinoma and 39.02% of women with squamous cell carcinoma). Differences in the numbers of ever-smokers were observed between age groups but not according to the year of diagnosis. CONCLUSIONS: The consistent and rapid increases in lung cancer mortality rates observed in the Chinese population and the high prevalence of exposure to smoking in China prompt a strong call for the implementation of a comprehensive tobacco-control policy and specific public health educational strategies.