The trend of unintentional injury-related mortality among children aged under-five years in China, 2010-2020: a retrospective analysis from a national surveillance system.

BACKGROUND: In this study, we estimated the trend of unintentional injury mortality among children aged under-five years in China during 2010-2020. METHODS: Data were obtained from China's Under 5 Child Mortality Surveillance System (U5CMSS). The total unintentional injury mortality and all specific-causes unintentional injury mortality was calculated, annual numbers of deaths and live births were adjusted by a 3-year moving average under-reporting rate. The Poisson regression model and the Cochran-Mantel-Haenszel method were used to calculate the average annual decline rate (AADR) and the adjusted relative risk (aRR) of the unintentional injury mortality. RESULTS: In 2010-2020, a total of 7,925 unintentional injury-related deaths were reported in U5CMSS, accounting for 18.7% of all reported deaths. The overall proportion of unintentional injury-related deaths to total under-five children deaths has increased from 15.2% to 2010 to 23.8% in 2020 (χ2 = 227.0, p < 0.001), the unintentional injury mortality significantly decreased from 249.3 deaths per 100,000 live births in 2010 to 178.8 deaths per 100,000 live births in 2020, with an AADR 3.7% (95%CI 3.1-4.4). The unintentional injury mortality rate decreased from 2010 to 2020 in both urban (from 68.1 to 59.7 per 100,000 live births) and rural (from 323.1 to 230.0 per 100,000 live births) areas (urban: χ2 = 3.1, p < 0.08; rural: χ2 = 113.5, p < 0.001). The annual rates of decline in rural areas and urban areas were 4.2% (95%CI 3.4-4.9) and 1.5% (95%CI 0.1-3.3), respectively. The leading causes of unintentional injury mortality were suffocation (2,611, 32.9%), drowning (2,398, 30.3%), and traffic injury (1,428, 12.8%) in 2010-2020. The cause-specific of unintentional injury mortality rates decreased with varying AADRs in 2010-2020, except for traffic injury. The composition of unintentional injury-related deaths also varied by age group. Suffocation was the leading cause in infants, drowning and traffic injury were the leading causes in children aged 1-4 years. Suffocation and poisoning has high incidence in October to March and drowning has high in June to August. CONCLUSION: The unintentional injury mortality rate of children aged under-five years decreased significantly from 2010 to 2020 in China, but great inequity exists in unintentional injury mortality in urban and rural areas. Unintentional injuries are still an important public health problem affecting the health of Chinese children. Effective strategies should be strengthened to reduce unintentional injury in children and these policies and programmes should be targeted to more specific populations, such as rural areas and males.

Geographical disparities in infant mortality in the rural areas of China: a descriptive study, 2010-2018.

BACKGROUND: The infant mortality rate (IMR) is considered a basic measure of public health for countries around the world. The specific aim of our study was to provide an updated description of infant mortality rate among different regions in rural China, and assess the trends and causes of the IMR geographical disparities. METHODS: Data were collected from China's Under-5 Child Mortality Surveillance System(U5CMSS). The annual number of deaths and causes of death were adjusted using a 3-year moving average underreporting rate based on annual national data quality control results. The average annual decline rate (AADR) and the relative risk (RR) of the IMR and cause-specific infant mortality were calculated by Poisson regression and the Cochran-Mantel-Haenszel method. Data analysis was completed by SAS software. RESULTS: There was an apparent decrease in infant mortality in rural China from 2010 to 2018, at the AADR of 11.0% (95%CI 9.6-12.4), 11.2% (95%CI 10.3-12.1) and 6.6% (95%CI 6.0-7.3) in the eastern, central and western rural areas, respectively. The IMR was highest in the western rural area, followed by the central and eastern rural areas. Compared with the eastern rural area, the RR of infant mortality in the central rural area remained at 1.4-1.6 and increased from 2.4 (95%CI 2.3-2.6) in 2010-2012 to 3.1 (95% CI 2.9-3.4) in 2016-2018 in the western rural area. Pneumonia, preterm birth /LBW and birth asphyxia were the leading causes of infant deaths in the western rural area. Mortality rates of these three causes fell significantly in 2010-2018 but contributed to a higher proportion of deaths in the western rural area than in the central and western rural ares. CONCLUSIONS: Our study indicated that the infant mortality rate dropped significantly from 2010 to 2018, however, geographical disparities of IMR in rural China are still persist. Therefore, there is an urgent need for public health programmes and policy interventions for infants in western rural China.

[Effectiveness of Different Testing Strategies Applied for Cervical Cancer Screening in Shuangliu District, Chengdu City].

Objective: To evaluate the clinical value of different combination strategies of high-risk HPV (hr-HPV) testing and Thinprep cytology test (TCT), a cervical cytology test, for cervical cancer screening, especially for high or higher-grade squamous intraepithelial lesion (HSIL+) in Shuangliu District, Chengdu City. Methods: The study is a population-based randomized clinical trial. Women aged 35 to 65 years meeting the inclusion criteria were enrolled for the study. At the baseline screening conducted in the first year, the participants were randomly assigned to either cytology test or hr-HPV testing at a ratio of 1∶2. If the paticipants had positive results for the baseline hr-HPV test, they would then undergo either cytology test or colposcopy by random assignment. After 24 months, all participants were called back, and combined screening of cytology test and hr-HPV test were performed. Women who had negative results at baseline screening and who entered and completed the third-year follow-up were selected as the subjects of the study. Based on the aforementioned testing findings, the related data were extracted and four different screening protocols were simulated: 1) combined TCT and hr-HPV screening, with referral for colposcopy when there was positive results for either one of the two; 2) combined TCT and hr-HPV screening, with referral for colposcopy when both tests had positive results at the same time; 3) TCT was done for preliminary screening and those who were found to be positive would then undergo hr-HPV test for triage purpose, with subsequent referral made for colposcopy if the hr-HPV results were positive; 4) hr-HPV was done for preliminary screening and those who were found to be positive would then undergo TCT, with subsequent referral made for colposcopy if TCT results were positive. With the detection of HSIL+ on histological examination as the endpoint event, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under curve ( AUC) of different combination screening models were calculated. Results: A total of 3102 women were screened, and 2967 women were included in the statistical analysis in this study. Among the 2967 women, 979 were randomized to cytology and 1988 to hr-HPV genotyping. For prescreening, the positive rate of the cytology group was 5.6% (55/979), with of HSIL+ positive rate being 0.2% (2/979), while the positive rate of the hr-HPV group was 7.5% (149/1988), with HSIL+ positive rate being 0.9% (18/1988). After 24 months, 2456 women were called back and were given cervical cytology test and hr-HPV test at the same time. Among them, the positive rate of the cytology group was 3.2% (78/2456), while the positive rate of hr-HPV group was 8.7% (215/2456). The overall positive rate of HSIL+ was 0.69%(17/2456). Women with a negative baseline hr-HPV had a lower incidence of HSIL+ lesions in the long term. The strategy of cervical cytology screening combined with hr-HPV test for triage purpose is the best method, with a sensitivity of 88.9%, a specificity of 58.3%, a PPV of 44.4%, a NPV of 93.3%, and an AUC of 0.736, P=0.039 (95% CI: 0.555-0.917). Conclusion: This randomized clinical trial from Shuangliu District, Chengdu City shows that the sensitivity of hr-HPV testing is better than that of cytology test, and the prevalence of HSIL+ in women with negative baseline hr-HPV results is lower than that of women with negative baseline cytology results. The screening program of TCT for prescreening plus subsequent hr-HPV test for triage purpose shows better value for the detection of HSIL+.

Breastfeeding practice in China from 2013 to 2018: a study from a national dynamic follow-up surveillance.

BACKGROUND: Breastfeeding is important for the physical and psychological health of the mother and child. Basic data on breastfeeding practice in China are out-of-date and vary widely. This study aimed to evaluate the progress of breastfeeding practice in China, as well as to explore the bottlenecks in driving better practice. METHODS: This was an observational study. We used data from the Under-5 Child Nutrition and Health Surveillance System in China for the period 2013-2018. The prevalence of early initiation of breastfeeding (EIBF) and exclusive breastfeeding (EBF) were calculated for each year for subgroups of China. The Cochran-Armitage test was used to explore the time trends. The annual percent of change (APC) were calculated by log-linear regression followed by exp transformation. RESULTS: The prevalence of EIBF increased significantly from 44.57% (95% CI: 44.07, 45.07) in 2013 to 55.84% (95% CI: 55.29, 56.38) in 2018 (Ptrend < 0.001), with an APC of 4.67% (95% CI: 3.51, 5.85). And the prevalence of EBF increased rapidly from 16.14% (95% CI: 15.10, 17.18) to 34.90% (95% CI: 33.54, 36.26) (Ptrend < 0.001), with an APC of 14.90% (95% CI: 9.97, 20.04). Increases were observed in both urban and rural areas, with urban areas showing greater APCs for EIBF (6.05%; 95% CI: 4.22, 7.92 v.s. 2.26%; 95% CI: 1.40, 3.12) and EBF (18.21%; 95% CI: 11.53, 25.29 v.s. 9.43%; 95% CI: 5.52, 13.49). The highest EBF prevalence was observed in the East, but the Central area showed the highest APC. The prevalence of EBF decreased with increasing age within the first 6 months, especially after 3 months. CONCLUSION: The prevalence of both EIBF and EBF in China are improving in recent years. The rural and West China could be the key areas in the future actions. More efforts should be made to protect and promote breastfeeding to achieve near- and long-term goals for child health.

Social and environmental risk factors for unintentional suffocation among infants in China: a descriptive analysis.

BACKGROUND: This retrospective study aimed to determine the epidemiological features of deaths caused by unintentional suffocation among infants in China. METHODS: The data used in this study were obtained from China's Under 5 Child Mortality Surveillance System (U5CMSS) from October 1, 2015, to September 30, 2016. A total of 377 children under 1 year of age who died from unintentional suffocation were included in the survey. Primary caregivers were interviewed individually using the Unintentional Suffocation Mortality among Children under 5 Questionnaire. EpiData was used to establish the database, and the results were analysed using SPSS 22.0. RESULTS: Most (85.9%) unintentional infant suffocations occurred in rural areas, and 67.5% occurred in infants 0 to 3 months old. Among the primary caregivers of the infants, most (82.7%) had a junior middle school education or below, and 83.1% of them lacked unintentional suffocation first aid skills. Of the 377 unintentional suffocated-infant deaths, the causes of death were accidental suffocation and strangulation in bed (ASSB) (193, 51.2%), inhalation suffocation (154, 40.8%), other unintentional suffocation (6, 1.6%), and unknown (24, 6.4%). Among the infant deaths due to ASSB, overlaying (88.6%) was the most frequently reported circumstance. A total of 93.8% of cases reported occurred during co-sleeping/bed sharing with parents, and in 72.8% of the cases, the infants were covered with the same quilt as their parents. In our study, most inhalation suffocation deaths (88.3%) involved liquid food (such as breast milk and formula milk). A total of 80.5% of infant deaths reportedly occurred after eating; in 28.2% of those cases, the infants were held upright and patted by their caregivers, and 57.2% of them were laid down to sleep immediately after eating. CONCLUSIONS: To reduce the occurrence of unintentional suffocation, local government should strengthen knowledge and awareness of unintentional suffocation prevention and safety among parents and caregivers. Additionally, health care providers should educate parents and caregivers about safety issues of unintentional suffocation, and relevant policies should be introduced to provide environments and activities that reduce the risk of suffocation, such as promoting the Safe to Sleep Campaign. It is important to enhance the focus on infant unintentional suffocation as a health issue.

Communicable disease mortality trends and characteristics of infants in rural China, 1996-2015.

BACKGROUND: More attention should be paid to communicable disease-specific infant mortality rate (CD-IMR) in rural China. However, few studies have examined specific geographic patterns and trends in CD-IMR in these areas. Our aims were to assess the epidemiological distribution and trends in CD-IMR in rural China for the period 1996-2015. METHODS: We used data from China's Under-5 Child Mortality Surveillance System (U5CMSS). The time trends in communicable disease-specific IMR (CD-IMR) were assessed by Poisson regression model, and the proportion of total infant deaths due to communicable disease was assessed by the Cochran Armitage trend test. Differences in CD-IMR among and within geographic regions were assessed for significance using the Cochran-Mantel-Haenszel test. RESULTS: The overall CD-IMR fell by 86.0% from 1444.3 to 201.5 per 100,000 live births in rural mainland China from 1996 to 2015. The proportion of total infant deaths related to communicable disease fell from 33.4 to 19.7%. Using eastern rural areas as the reference, rate ratios (RRs) of IMR due to all communicable diseases ranged between 1.7 and 3.1 in central rural areas and between 4.4 and 9.8 in western areas during the four study intervals. Acute respiratory infection (ARI) accounted for 71% of deaths, followed by diarrhea and septicemia. CONCLUSIONS: IMR due to communicable disease remains a major public health issue. ARI is the leading cause of mortality, followed by diarrhea. A regional gap remains in the risk of infant exposure to communicable disease in rural China. More attention should be paid to western rural areas.

Social and environmental risk factors for the accidental drowning of children under five in China.

BACKGROUND: Accidental drowning of children under five is a serious problem in China. The present study analyzed data on environmental and sociodemographic factors and on primary caregivers of drowned children to understand factors that may contribute to this problem. METHODS: The present study collected information on 563 cases of drowning in children under five from October 1, 2015, to September 30, 2016, in 334 sampling districts in China. Primary caregivers were interviewed individually using the Drowning Mortality among Children under 5 Questionnaire. RESULTS: Most drowned children under 5 years old were boys, and 71.6% lived within 100 m of a body of water. The drownings primarily occurred in ponds, canals, rivers, and wells, and over 90% of these water bodies had no safety measures. There were 28.1% of primary caregivers who did not provide full-time care for the children, and 83.1% of them had no knowledge of first aid skills for drowning. CONCLUSION: Encouraging kindergarten enrollment and providing safety education for children may reduce drowning in children under 5 years of age. Public water body protection measures should be strengthened to prevent children from drowning. Encouraging primary caregivers to care full-time for the children and learning first aid skills for drowning may also help reduce fatalities.

Injury-related mortality among children younger than 5 years in China during 2009-2016: an analysis from national surveillance system.

BACKGROUND: Epidemiology in injury-related mortality among children younger than 5 years was unreported in China recently. METHODS: Data were obtained from China's Under 5 Child Mortality Surveillance System (U5CMSS) in 2009-2016. Injury-related mortality rates were calculated by residence, age-group, gender and major injury type (drowning, traffic injuries, suffocation, poisoning, falls). The average annual decline rate (AADR) was calculated based on the annual mortality rates by Poisson regression and the relative risk (RR) between urban and rural residence was examined based on the rates of two years for each time point by Cochran-Mantel-Haenszel method. RESULTS: U5CMSS contained 6503 injury-related deaths of children younger than 5 years during the study period, of which 58.6% were male, 86.0% occurred in rural areas, 65.7% were children aged 12-59 months. Deaths were mainly attributed to suffocation (34.3%), drowning (29.6%), traffic injuries (17.7%), falls (7.2%) or poisoning (4.7%). The injury-related mortality rate dropped from 274.7 to 189.2 per 100 000 live births from 2009 to 2016, giving an AADR of 4.53% (95% CI 3.50% to 5.55%). During 2009-2016, the injury-related mortality rate in rural area was higher than that in urban area, the adjusted RRs (aRRs) in infants and children aged 12-59 months were 3.32-6.04 and 4.31-5.49, respectively. CONCLUSION: The rate of injury-related deaths in children younger than 5 years has decreased in China, but it remains high and strong urban-rural disparities still exist. Public health programmes and policy interventions should focus particularly on suffocation among infants and on drowning and traffic injuries among children aged 12-59 months, especially in rural areas.

Prior caesarean section and likelihood of vaginal birth, 2012-2016, China.

OBJECTIVE: To examine the trends and safety of vaginal birth after caesarean section around the period of the one-child policy relaxation in China. METHODS: We used data from China's National Maternal Near Miss Surveillance System between 2012 and 2016. To examine trends in vaginal birth after caesarean section, we used Poisson regression with a robust variance estimator. We also assessed the association between vaginal birth after caesarean section and maternal and perinatal outcomes. FINDINGS: We analysed 871 636 deliveries by women with a previous caesarean section. Both in 2012 and 2016, the rate of vaginal birth after caesarean section was 9.8%. After adjusting for institutional, sociodemographic and obstetric characteristics, the rate increased by 14% between 2012 and 2016 (adjusted relative risk, aRR: 1.14; 95% confidence interval, CI: 1.07-1.21). Compared to women with a repeat caesarean section, women with a vaginal birth after caesarean section experienced lower incidence of uterine rupture (aRR: 0.26, 95% CI: 0.16-0.42), blood transfusion (aRR: 0.68, 95% CI: 0.53-0.87) and admission to the intensive care unit (aRR: 0.36, 95% CI: 0.25-0.52), but higher incidence of intrapartum stillbirths, (aRR: 7.20, 95% CI: 6.09-8.51), newborns with a 5-minute Apgar score less than 7 (aRR: 1.75, 95% CI: 1.54-1.99) and neonatal death before discharge (aRR: 1.90, 95% CI: 1.61-2.24). CONCLUSION: Promotion of vaginal birth after caesarean section could increase the rate even further in China. To ensure the safety of mothers and their newborns, national policies and guidelines on vaginal birth after caesarean section are needed.

The Variable Characteristics of Human Papillomavirus in Squamous Cell Carcinoma and Adenocarcinoma of Cervix in China.

OBJECTIVE: A hospital-based multicenter, retrospective study was conducted to compare the distribution of human papillomavirus (HPV) in squamous cell carcinoma (SCC) and cervical adenocarcinoma (CADC) in China. METHODS: Paraffin-embedded tissue blocks diagnosed as SCC and CADC across China were collected, as well as the total number of diagnosed invasive cervical cancer of the 9 selected centers. DNA enzyme immunoassay, reverse hybridization, and multiplex type-specific polymerase chain reaction were used for HPV genotyping. RESULTS: The ratios of CADC to SCC were increasing from 2005 to 2010, in parallel with HPV prevalence in CADC. In 630 patients with SCC (mean ± SD age, 45.40 ± 10.30) and 718 patients with CADC (mean ± SD age, 46.09 ± 10.59) recruited, HPV prevalence rates were 97.6% and 74.5%, respectively. Human papillomavirus viral load for SCC is significantly higher than that for CADC. Most common HPV types distributed in SCC and CADC were HPV-16 (78.5%, 75.1%-81.6%; 47.1%, 42.9%-51.3%), HPV-18 (8.0%, 6.1%-10.4%; 41.1%, 37.0%-45.3%), HPV-52 (2.3%, 1.4%-3.8%; 5.6%, 4.0%-7.9%), and HPV-45 (1.1%, 0.6%-2.3%; 3.9%, 2.6%-5.9%). Different diagnostic mean ± SD age for HPV-16/HPV-18 versus other high-risk HPV types were observed: SCC (44.5 ± 9.94 vs 51.0 ± 10.83, p < .05) and CADC (44.1 ± 9.44 vs 47.4 ± 10.41, p = .006). For HPV-negative cases, mean ± SD age was 46.1 ± 10.73 in SCC and 50.3 ± 11.85 in CADC, which were older than the positive (45.4 ± 10.31, 44.5 ± 9.64). HPV-16 and HPV-18 were the most frequent HPV types in both histological types, and HPV-18 was more frequent in CADC than in SCC. CONCLUSIONS: Human papillomavirus infection was identified more often in SCC than in CADC. Women with HPV-associated cancers, especially HPV-16/HPV-18, were of a younger age at diagnosis when compared with non-HPV-associated cancers.

Effectiveness of novel, lower cost molecular human papillomavirus-based tests for cervical cancer screening in rural china.

This study examined the efficacy of the OncoE6™ Cervical Test, careHPV™ and visual inspection with acetic acid (VIA) in identifying women at risk for cervical cancer and their capability to detect incident cervical precancer and cancer at 1-year follow-up. In a population of 7,543 women living in rural China, women provided a self-collected and two clinician-collected specimens and underwent VIA. All screen positive women for any of the tests, a ∼ 10% random sample of test-negative women that underwent colposcopy at baseline, and an additional ∼ 10% random sample of test-negative women who did not undergo colposcopy at baseline (n = 3,290) were recruited. 2,904 women were rescreened 1 year later using the same tests, colposcopic referral criteria, and procedures. Sensitivities of baseline tests to detect 1-year cumulative cervical intraepithelial neoplasia Grade 3 or cancer (CIN3+) were 96.5% and 81.6% for careHPV™ on clinician-collected and self-collected specimens, respectively, and 54.4% for OncoE6™ test. The OncoE6™ test was very specific (99.1%) and had the greatest positive predictive value (PPV; 47.7%) for CIN3+. Baseline and 1-year follow-up cervical specimens testing HPV DNA positive was sensitive (88.0%) but poorly predictive (5.5-6.0%) of incident CIN2+, whereas testing repeat HPV16, 18 and 45 E6 positive identified only 24.0% of incident CIN2+ but had a predictive value of 33.3%. This study highlights the different utility of HPV DNA and E6 tests, the former as a screening and the latter as a diagnostic test, for detection of cervical precancer and cancer.

Neonatal mortality in the urban and rural China between 1996 and 2013: a retrospective study.

BACKGROUND: One of the proposed United Nations post-2015 sustainable development goals is to eliminate avoidable neonatal deaths by 2030. This study aims to examine changes in neonatal mortality rate (NMR) and cause-specific NMR in urban and rural areas to guide renewed efforts to further reduce NMR in China. METHODS: This retrospective study used 18 y of consecutive data from the National Under-5 Child Mortality Surveillance System. RESULTS: Urban NMR decreased from 11.0 to 4.0 deaths per 1,000 live births, and rural NMR was decreased births from 26.0 to 8.1 deaths per 1,000 live births between the periods of 1996-1998 and 2011-2013. Rural NMR was about two times as much as urban NMR in 2011-2013. Approximately four-fifths of neonatal deaths occurred within less than 7 d after birth. In 2011-2013, the three leading causes of early neonatal death were premature delivery, intrapartum-related conditions, and congenital abnormalities; the three causes of death in late neonates were classification premature delivery, congenital abnormalities, and pneumonia. CONCLUSION: China has made substantive progress in reducing NMR; however, the disparity in NMR between urban and rural areas still exists. More effort should be made to prevent and manage premature delivery and congenital abnormalities, especially in rural areas.

Effect of a group educational intervention on rural Chinese women's knowledge and attitudes about human papillomavirus (HPV) and HPV vaccines.

BACKGROUND: Statistics regarding HPV prevalence and cervical cancer rates in rural China are high, however, low levels of HPV awareness and HPV-related knowledge pose a great challenge for cervical cancer control. METHODS: The authors conducted an educational intervention study, which was embedded in a cervical cancer screening project in Yangcheng county, Shanxi Province, China from October to December, 2011 and was designed to assess the short-term effectiveness of a hospital-based, brief, HPV-focused session on rural Chinese women's knowledge and attitudes. Student's t-test was used when comparing quantitative variables. Chi-squared test or Fisher's exact tests was used when comparing qualitative variables. RESULTS: We found that following the intervention, significant increases were detected in awareness regarding HPV (5.9 % vs. 59 %, p < 0.001) and cervical cancer (63.0 % vs. 89.2 %, p < 0.001). Changes were also observed regarding women's intention to vaccinate themselves (82.0 % vs. 89.0 %, p = 0.001) and their daughters (82.9 % vs. 88.0 %, p = 0.011), although the impact was more modest compared with the impact on change of awareness. Among women who were aware of HPV, 60.3 % knew that cervical cancer is related to HPV, while only 5.0 % knew the relationship between HPV and genital warts after the educational intervention. CONCLUSIONS: Educational campaigns, particularly those targeting women with limited education and poor access to public media or other educational channels are needed to improve knowledge regarding HPV in the general population.

p16 Immunohistochemistry Interpretation by Nonpathologists as an Accurate Method for Diagnosing Cervical Precancer and Cancer.

OBJECTIVE: We conducted a pilot study of whether nonpathologists could accurately diagnose cervical precancer in biopsies using only a basic light microscope, evaluating p16 immunohistochemistry (p16 IHC) of biopsies, and video-based training for both. MATERIALS AND METHODS: Using biopsies collected as part of a screening study conducted in rural China, we randomly selected 50 biopsies with a precancerous diagnosis of cervical intraepithelial neoplasia grade 2 (CIN2) or more severe (CIN2+) and 50 biopsies with diagnosis of CIN less severe than CIN2, and stained them for p16 using a commercial IHC kit. Twelve nonpathologists of varying educational backgrounds living in Beijing, China received video training and were assigned one of 4 sets of 25 CIN2+ and 25 CIN less severe than CIN2 for evaluation. A pathologist reviewed all 100 cases. RESULTS: The mean sensitivity and specificity of the p16 IHC staining scored by the nonpathologists were 91.7% and 94.1%, respectively, compared to scoring by the pathologist. The readers and the pathologist agreed on p16 IHC scoring for 42 (84%) of the 50 slides of CIN less severe than CIN2 and 37 (74%) of the 50 CIN2+ slides. The mean sensitivity and specificity for consensus CIN2+ of p16 IHC as scored by the readers were 88% and 87%, respectively, versus an overall sensitivity and specificity by the pathologist of 96% and 92%, respectively. CONCLUSIONS: We demonstrated that nonpathologists can accurately diagnose CIN2+ using p16 IHC alone.

The Influence of Human Papillomavirus Genotypes on Visual Screening and Diagnosis of Cervical Precancer and Cancer.

OBJECTIVE: To examine the influence of human papillomavirus (HPV) genotypes on the sensitivity of visual inspection with acetic acid (VIA) for screening, and colposcopy for diagnosis of cervical intraepithelial neoplasia grade 2 (CIN2) or more severe (CIN2+). MATERIALS AND METHODS: Women aged 25 to 65 years from China (n = 7,541) were screened with 6 tests (careHPV and Hybrid Capture 2 on self- and clinician-collected specimens; HPV-16, HPV-18, HPV-45 E6 detection; and VIA). Biopsies from women with a diagnosis of CIN2+ underwent testing for 25 HPV genotypes using SPF10/LiPA. Human papillomavirus genotyping results were classified according to broad categories of cancer risk. RESULTS: Among the 143 women with a diagnosis of CIN2+, the percentage who were HPV16 positive increased with increasing severity of diagnosis: 33.3% for CIN2 (n = 39), 69.1% for CIN3 (n = 94), and 90% for cancer (n = 10). There was a higher percentage of HPV-16 in women with abnormal colposcopic impression (p = .007) and positive VIA (p = .02) than normal colposcopy and negative VIA, respectively. Colposcopy and VIA were more sensitive to detect CIN2+ among HPV-16- and/or HPV-18-positive women than HPV-16-/HPV-18-negative women (67.4% vs 43.1%, p = .008, for colposcopy; and 53.3% vs 37.3%, p = .08, for VIA). CONCLUSIONS: Human papillomavirus type 16 is related to more clear visual acetowhite changes in the epithelium. Therefore, we should expect a reduction of the performance of VIA for cervical cancer screening to identify women with CIN2+, and reduction of the performance of colposcopy to diagnose CIN2+, in vaccinated populations.

Lower cost strategies for triage of human papillomavirus DNA-positive women.

Using human papillomavirus (HPV) testing for cervical cancer screening in lower-resource settings (LRS) will result in a significant number of screen-positive women. This analysis compares different triage strategies for detecting cervical precancer and cancer among HPV-positive women in LRS. This was a population-based study of women aged 25-65 years living in China (n = 7,541). Each woman provided a self-collected and two clinician-collected specimens. The self-collected and one clinician-collected specimen were tested by two HPV DNA tests-careHPV™ and Hybrid Capture 2; the other clinician-collected specimen was tested for HPV16/18/45 E6 protein. CareHPV™-positive specimens were tested for HPV16/18/45 DNA. HPV DNA-positive women underwent visual inspection with acetic acid (VIA) and then colposcopic evaluation with biopsies. The performance for detection of cervical intraepithelial neoplasia grade 3 or cancer (CIN3+) among HPV DNA-positive women was assessed for different triage strategies: HPV16/18/45 E6 or DNA detection, VIA, colposcopic impression, or higher signal strength (≥10 relative light units/positive control [rlu/pc]). The percent triage positive ranges were 14.8-17.4% for VIA, 17.8-20.9% for an abnormal colposcopic impression; 7.9-10.5% for HPV16/18/45 E6; 23.4-28.4% for HPV16/18/45 DNA; and 48.0-62.6% for higher signal strength (≥10 rlu/pc), depending on the HPV test/specimen combination. The positivity for all triage tests increased with severity of diagnosis. HPV16/18/45 DNA detection was approximately 70% sensitive and had positive predictive values (PPV) of approximately 25% for CIN3+. HPV16/18/45 E6 detection was approximately 50% sensitive with a PPV of nearly 50% for CIN3+. Different triage strategies for HPV DNA-positive women provide important tradeoffs in colposcopy or treatment referral percentages and sensitivity for prevalent CIN3+.

Optimal positive cutoff points for careHPV testing of clinician- and self-collected specimens in primary cervical cancer screening: an analysis from rural China.

careHPV, a lower-cost DNA test for human papillomavirus (HPV), is being considered for cervical cancer screening in low- and middle-income countries. However, not a single large-scaled study exists to investigate the optimal positive cutoff point of careHPV test. We pooled data for 9,785 women participating in two individual studies conducted from 2007 to 2011 in rural China. Woman underwent multiple screening tests, including careHPV on clinician-collected specimens (careHPV-C) and self-collected specimens (careHPV-S), and Hybrid Capture 2 on clinician-collected specimens (HC2-C) as a reference standard. The primary endpoint was cervical intraepithelial neoplasia grade 3 or more severe (CIN3+) (n = 127), and secondary endpoint was CIN2+ (n = 213). The area under the curves (AUCs) for HC2-C and careHPV-C were similar (0.954 versus 0.948, P = 0.166), and better than careHPV-S (0.878; P < 0.001 versus both). The optimal positive cutoff points for HC2-C, careHPV-C, and careHPV-S were 1.40, 1.74, and 0.85, respectively. At the same cutoff point, careHPV-C was not significantly less sensitive and more specific for CIN3+ than HC2-C, and careHPV-S was significantly less sensitive for CIN3+ than careHPV-C and HC2-C. Raising the cutoff point of careHPV-C from 1.0 to 2.0 could result in nonsignificantly lower sensitivity but significantly higher specificity. Similar results were observed using CIN2+ endpoint. careHPV using either clinician- or self-collected specimens performed well in detecting cervical precancer and cancer. We found that the optimal cutoff points of careHPV were 2.0 on clinician-collected specimens and 1.0 on self-collected specimens.

A prospective study of age trends of high-risk human papillomavirus infection in rural China.

BACKGROUND: In China, high-risk human papillomavirus (HR-HPV) prevalence is unexpectedly high in older women, but the possible reasons have not been well studied yet. This study investigated the age trends of HR-HPV infection in a prospective study. METHODS: A total of 7397 women aged 25-65 years without cervical precancer or cancer were evaluated during 2010-2011 with a stratified sample of 2791 women re-evaluated after one year. Test results for careHPV and careHPV16/18/45 were used to describe the HR-HPV prevalence, incidence and clearance. Risk factors associated with HR-HPV infections were explored using a logistic regression model. RESULTS: The overall HR-HPV prevalence was 13.1% at baseline, with a peak of 19.3% in women aged 55-59 years. The prevalence of HR-HPV (p for trends < 0.001), HPV16/18/45 (p for trends = 0.002), and HR-HPV other than HPV16/18/45 (p for trends = 0.002) generally increased with increasing age. Number of infections that cleared was generally greater than number of incident infections within age groups. One-year clearance rate decreased with increasing age (p for trends < 0.001), however, incidence rate was unrelated to age (p for trends = 0.159). Risk factors that associated with HR-HPV infection differed between younger and older women. CONCLUSIONS: The greater HR-HPV prevalence in older versus younger women in rural China may be explained by a cohort effect, higher than expected incidence, and/or poorer clearance at older age.

[Value of high risk human papillomavirus viral load in predicting cervical lesions and triaging for high risk (HR)-HPV-positive women].

OBJECTIVE: To evaluate the value of high risk (HR)-HPV viral load in predicting cervical lesions and triaging for HR-HPV positive women. METHODS: The study cohort came from a multicenter cervical cancer screening program. HR-HPV was detected by hybrid capture 2 (HC-2) assay, and viral load was measured by the ratio of relative light units to cut off (RLU/CO). Women were divided into 4 groups according to the RLU/CO value, and CIN diagnostic system was used to describe the severity of cervical lesions. Chi-square trend test was used to analyze the association between viral load and CIN. The absolute and relative risks of CIN2+ in different viral load groups were calculated, and the clinical performance to detect CIN2+ at follow-up by different cut-off values of baseline RLU/CO was also calculated. RESULTS: 2 725 women with complete results of both baseline and follow-up were included in this analysis. The severity of cervical lesions increased with the increasing viral load (P < 0.001). In women with normal or CIN1 diagnosis at baseline, the absolute risk of one-year accumulative CIN2+ was 0.11% in the HR-HPV-negative group, compared with 3.14% in the moderate viral load group and 6.09% in the high viral load group, and the relative risk of 29.05 (95%CI: 6.07-138.99) in the moderate viral load group and 56.34 (95%CI: 12.89-246.30) in the high viral load group. Raising cut-off value of baseline HR-HPV viral load to 15.00, RLU/CO decreased the number of women who need to be followed up at one-year from 774 to 412, with the sensitivity of 91.30% and specificity of 47.94% in detecting CIN2+ at follow-up. CONCLUSIONS: The risk of cervical cancer and precancerous lesions increases with the increasing HR-HPV viral load. Raising the cut-off value of HR-HPV viral load can triage for HR-HPV-positive women, therefore help to allocate the health resources more effectively.

[Evaluation of screening performance of HPV DNA test on specimens from different sites of the female genital tract].

OBJECTIVE: To evaluate the diagnostic performance of different specimens for detecting CIN2(+), and to find the solution of the problem that why the performance of self-collected specimen is worse than cervical specimen collected by physician. METHODS: The cervix, lower 1/3 vagina, upper 1/3 vagina and self-collected specimens from each of the 806 women who took part in this multi-center screening program from May 2006 to April 2007 were tested by hybrid capture 2 (HC2) technique. The diagnostic performance of HC2 on the four specimens for detecting CIN2(+) lesions was calculated. Linear array was performed on the four specimens from 489 out of the 806 women and the diagnostic performance of linear array on the four specimens for detecting CIN2(+) lesions was also calculated. Z test was used to compare the area under ROC and McNemar or χ(2) test was used to compare the sensitivity and specificity of different specimens. RESULTS: The area under ROC of the cervix, 1/3 upper vagina, 1/3 lower vagina and self-collected samples testing by HC2 for detecting CIN2(+) lesions were 0.902, 0.793, 0.769 and 0.773, respectively (P < 0.001). Using 1 RUL/CO as the cut-point of HC2, the sensitivity of the cervix, upper vagina, lower vagina and self-collected samples were 98.0%, 91.8%, 83.7% and 81.6%. Compared with the cervical specimen, the sensitivity of self-collected specimen for detecting CIN2(+) lesions was significantly lower (P = 0.008). Lowering the cutoff value for HC2 test could improve the sensitivity of self-collected specimen, but it significantly compromised the specificity. The sensitivity of self-collected specimen tested by linear array for detecting CIN2(+) lesions was 95.7% and it was not significantly different compared with the sensitivity of cervical specimen (97.9%) tested by HC2. CONCLUSIONS: The performance of self-collected specimen tested by HC2 for detecting CIN2(+) lesions is lower than that of physician-collected cervical specimen, and lowering the cutoff value can't improve its diagnostic performance. Using linear array as the HPV DNA test can significantly improve the screening diagnostic performance of self-collected specimens.