Exploring the potential prompting role of cervical human papilloma virus detection in vulvar lesions: a cross-sectional study in China.

Introduction: The etiology and clinical presentation of vulvar carcinomas, especially vulvar lesions, are not fully understood. Because the vulva and cervix are anatomically connected, human papillomavirus (HPV) is the main cause of cervical lesions. Thus, this study explored the potential characteristics and effects of specific HPV infection types across vulvar lesions and concurrent cervical lesions. Methods: This retrospective, cross-sectional study analyzed patients with cervical HPV or cytological results and concurrent vulvar biopsy who were seen in our hospital colposcopy clinic in Shanxi Province, China, between 2013 and 2023. Data on age, menopause status, vulvar manifestations, and cytology and HPV infection testing results were collected. Attributable fractions and multinominal logistic models were used to evaluate HPV genotyping and clinical characteristics across vulvar lesions. Results: Among the 1,027 participants, 83 (8.1%) had vulvar intraepithelial neoplasia (VIN) of high grade or worse (VIN2+), and 127 (12.4%) had non-neoplastic epithelial disorders of the vulva (NNEDV). A total of 175 patients had either VIN2+ or cervical intraepithelial neoplasia (CIN) lesions of grade 2 or worse (CIN2+). The most common HPV genotypes for VIN2+ or concurrent VIN2+/CIN2+ were HPV16, HPV52, and HPV58, although attributable fractions differed among lesions. Patients with normal cytological or histopathological result were more likely to have NNEDV detected, while abnormal cervical diagnosis was associated with higher detection of VIN2+. Multinominal logistic modeling showed that age and HPV16 infection were risk factors for VIN2+ or concurrent VIN2+/CIN2+; however, only vulvar presentation with depigmentation was a risk factor for NNEDV. Among patients with low-grade CIN1/VIN1, compared with those who were HPV16 negative, those who were HPV16 positive were at 6.63-fold higher risk of VIN2+/CIN2+ [95% confidence interval (CI): 3.32, 13.21]. Vulvar depigmentation was also associated with increased risk of NNEDV (odds ratio: 9.98; 95% CI: 3.02, 33.04). Conclusions: Chinese women may be at specific, high risk for HPV infection types associated with VIN or CIN. The use of cervical cell HPV detection along with vulvar presentation during cervical cancer screening may also contribute to vulvar lesion detection.

Host genetic variants, Epstein-Barr virus subtypes, and the risk of nasopharyngeal carcinoma: Assessment of interaction and mediation.

Epstein-Barr virus (EBV) and human leukocyte antigen (HLA) polymorphisms are well-known risk factors for nasopharyngeal carcinoma (NPC). However, the combined effects between HLA and EBV on the risk of NPC are unknown. We applied a causal inference framework to disentangle interaction and mediation effects between two host HLA SNPs, rs2860580 and rs2894207, and EBV variant 163364 with a population-based case-control study in NPC-endemic southern China. We discovered the strong interaction effects between the high-risk EBV subtype and both HLA SNPs on NPC risk (rs2860580, relative excess risk due to interaction [RERI] = 4.08, 95% confidence interval [CI] = 2.03-6.14; rs2894207, RERI = 3.37, 95% CI = 1.59-5.15), accounting for the majority of genetic risk effects. These results indicate that HLA genes and the high-risk EBV have joint effects on NPC risk. Prevention strategies targeting the high-risk EBV subtype would largely reduce NPC risk associated with EBV and host genetic susceptibility.

Behavioral deviations: healthcare-seeking behavior of chronic disease patients with intention to visit primary health care institutions.

BACKGROUND: Although primary health care (PHC) has been proven to be effective in preventing and treating chronic diseases, the visits rate of PHC institutions is still not ideal. Some patients initially express a willingness to visit PHC institutions but end up seeking health services at non-PHC institutions, and the reasons for this behavior remain unclear. Therefore, the objective of this study is to analyze the factors that contribute to behavioral deviations among chronic disease patients who originally intended to visit PHC institutions. METHODS: Data were collected from a cross-sectional survey among chronic disease patients with original intention to visit PHC institutions in Fuqing City, China. The analysis framework was guided by Andersen's behavioral model. Logistic regression models were employed to analyze the factors affecting the behavioral deviations among chronic disease patients with a willingness to visit PHC institutions. RESULTS: A total of 1,048 individuals were finally included and about 40% of the participants with the original willingness to seek care from PHC institutions finally chose non-PHC institutions in their subsequent visits. The results of logistic regression analyses indicated that at the predisposition factor level, older participants (aOR60-69 = 0.602, P < 0.01; aOR70-75 = 0.475, P < 0.01) were less likely to have behavioral deviations. At the enabling factor level, compared to those covered by Urban Employee Basic Medical Insurance (UEBMI) and not reimbursed, those covered by Urban-Rural Resident Basic Medical Insurance (URRBMI) (aOR = 0.297, P < 0.01), and those answering that reimbursement from medical institutions was convenient (aOR = 0.501, P < 0.01) or very convenient (aOR = 0.358, P < 0.001) were less likely to have behavioral deviations. At the need factor level, participants who visited PHC institutions due to illness last year (aOR = 0.348, P < 0.001) and with polypharmacy (aOR = 0.546, P < 0.01) were less likely to have behavioral deviations compared to those without the visit of PHC institutions and not taking polypharmacy, respectively. CONCLUSIONS: The deviations between the original willingness of PHC institution visits and subsequent behavior among chronic disease patients were associated with a number of predisposing, enabling, and need factors. Developing the health insurance system, strengthening the technical capacity of PHC institutions, and steadily developing a new concept of orderly healthcare-seeking behavior among chronic disease patients, will help promote their access to PHC institutions as well as improve the effectiveness of the tiered medical system for chronic disease care.

Body mass index and body shape before treatment and nasopharyngeal carcinoma prognosis: A population-based patient cohort study in southern China.

A concern of reverse causation exists about the association between nasopharyngeal carcinoma (NPC) prognosis and body mass index (BMI) at diagnosis, while the prognostic impact of BMI measured years before diagnosis is unknown. Therefore, we investigated associations of prediagnosis and pretreatment BMI and body shape on NPC mortality. From a population-based patient cohort in southern China between 2010 and 2013, we included 2526 incident NPC cases with prospective follow-up through 2018. We assessed the associations of BMI and body shape at age 20 years, 10 years before diagnosis, and at diagnosis with NPC mortality, combining strategies of stratification and statistical adjustment to minimize reverse causation. We observed 25% lower all-cause mortality (hazard ratio [HR] 0.75, 95% confidence interval [CI]: 0.64-0.89) and 25% lower NPC-specific mortality (HR 0.75, 95% CI: 0.61-0.91) among overweight vs normal-weight NPC cases at diagnosis. Lean body shapes 1 and 2 at diagnosis were associated with 68% and 23% higher all-cause mortality, respectively, compared to normal body shape 3. No effect modification by cancer stage was detected for associations with all-cause or NPC-specific mortality. Associations with BMI and body shape 10 years before diagnosis were similar but attenuated, while body size and shape at age 20 were not associated with mortality. Being overweight at diagnosis decreased mortality, and thinner body shape increased mortality, compared to normal weight/body shape. These associations may be due to poorer nutrition and treatment intolerance, resulting in treatment discontinuation and worse survival outcomes.

Cancer situation in China: what does the China cancer map indicate from the first national death survey to the latest cancer registration?

BACKGROUND: Over the past four decades, the Chinese government has conducted three surveys on the distribution of causes of death and built cancer registration. In order to shine a new light on better cancer prevention strategies in China, we evaluated the profile of cancer mortality over the forty years and analyzed the policies that have been implemented. METHODS: We described spatial and temporal changes in both cancer mortality and the ranking of major cancer types in China based on the data collected from three national surveys during 1973-1975, 1990-1992, 2004-2005, and the latest cancer registration data published by National Central Cancer Registry of China. The mortality data were compared after conversion to age-standardized mortality rates based on the world standard population (Segi's population). The geographical distribution characteristics were explored by marking hot spots of different cancers on the map of China. RESULTS: From 1973 to 2016, China witnessed an evident decrease in mortality rate of stomach, esophageal, and cervical cancer, while a gradual increase was recorded in lung, colorectal, and female breast cancer. A slight decrease of mortality rate has been observed in liver cancer since 2004. Lung and liver cancer, however, have become the top two leading causes of cancer death for the last twenty years. From the three national surveys, similar profiles of leading causes of cancer death were observed among both urban and rural areas. Lower mortality rates from esophageal and stomach cancer, however, have been demonstrated in urban than in rural areas. Rural areas had similar mortality rates of the five leading causes of cancer death with the small urban areas in 1973-1975. Additionally, rural areas in 2016 also had approximate mortality rates of the five leading causes with urban areas in 2004-2005. Moreover, stomach, esophageal, and liver cancer showed specific geographical distributions. Although mortality rates have decreased at most of the hotspots of these cancers, they were still higher than the national average levels during the same time periods. CONCLUSIONS: Building up a strong primary public health system especially among rural areas may be one critical step to reduce cancer burden in China.

Absolute Risk and Attributable Fraction of Type-Specific Human Papillomavirus in Cervical Cancer and Precancerous Lesions-A Population-Based Study of 6286 Women in Rural Areas of China.

Background: To investigate the human papillomavirus (HPV) genotype distribution among the general population and assess the attribution of HPV genotypes targeted by vaccines to protect against cervical lesions theoretically. Methods: Cervical samples were collected from women aged 21 to 64 years old from Inner Mongolia and Shanxi Province in China who had not been vaccinated against HPV. HPV type-specific absolute risk (AR) to classified cervical lesions was calculated and then the attributable fraction (AF) was estimated, together with the combined contributions of the HPV types, targeted by four available HPV vaccines and five HPV vaccines in clinical trials in China to protect against cervical lesions. Results: A total of 6286 women with an average age of 44.1 years ± 8.41 (range: 21−64) participated in the study. The age distribution of 14 HR-HPV and HPV16/18 all showed a 'U' shape, which peaked in the ≤25 year-group and >55 year-group. The five most common genotypes were HPV16 (4.3%), HPV52 (4.1%), HPV58 (2.1%), HPV51 (2.1%), and HPV66 (1.7%). The prevalence of HPV types 6 and 11 infections was 1.1% and observed with n significant differences across age stratifications in China. AF to CIN2+ was predominated by HPV 16 with 56.2%, followed by HPV58 (12.0%), HPV52 (8.5%), HPV18 (4.3%), and HPV51 (2.9%). HPV52 and 58 in the prophylactic HPV vaccine would enhance the protection against CIN2+ by approximately 20%. Conclusions: Regarding multi-valent HPV vaccine development in China, the HPV types 16, 52, 58, and 18 should be given priority for their high prevalence at the population level, high AR, notable AF, and high relative risk to high-grade cervical lesions.

Changes in High-Risk HPV Infection Prevalence and Associated Factors in Selected Rural Areas of China: A Multicenter Population-Based Study.

Background: The Chinese government has taken action to prevent cervical cancer by implementing the National Cervical Cancer Screening Programme in Rural Areas (NACCSPRA), which was launched in 2009. Numerous studies have demonstrated that long-term cervical cancer screening alters human papillomavirus (HPV) infection rates and cervical disease detection. Nearly 80 million women have been screened over 10 years, representing <30% of the target population; however, in some rural areas, such as Ordos City of Inner Mongolia Autonomous Region, Xiangyuan County of Shanxi Province, and Jinyun County, and Jingning County of Zhejiang Province, programs for prevention and treatment of cervical cancer have been implemented. Numerous studies have demonstrated that long-term cervical cancer screening alters rates of human papillomavirus (HPV) infection and cervical disease detection. In this study, we aimed to determine the infection rates of high-risk HPV (hrHPV) and the detection rate of cervical lesions; and changes in factors associated with cervical cancer, to provide scientific data to inform efforts to eliminate cervical cancer in rural areas. Methods: This was a cross-sectional, population-based, and multi-center survey. Populations from three rural areas of China (Ordos City of Inner Mongolia Autonomous Region, Xiangyuan County of Shanxi Province, and Jinyun County and Jingning County of Zhejiang Province) were selected and 9,332 women aged 20-64 years old were invited to participate in cervical cancer screening by both cytology and HPV testing. The outcomes assessed were: infection rates with hrHPV, HPV16, 18, 16/18, and other 12 hrHPV types (HPV 31,33,35,39,45,51,52,56,58,59,66 and 68); detection rates of cytological and histological lesions; and factors associated with HPV infection. Results: A total of 9,217 women aged 45.62 ± 8.02 years were included in this study. Infection rates with hrHPV, HPV 16, 18, 16/18, and other 12 hrHPV types were 16.3%, 3.0%, 1.5%, 4.3%, and 13.6%, respectively. There were significant differences among the age-specific HPV infection rates (P < 0.05). Infection rates with hrHPV, 16, 18, 16/18, and the other 12 hrHPV types showed a single peak infection mode, with a peak age of 56-65 years old. Age, marital status, number of live births, education level, reproductive disease history, and a history of alcohol consumption were risk factors for hrHPV infection. The detection rate of cytological abnormalities was 12.98% in the study and was higher in women older than 56 years old. The detection rates of cervical intraepithelial neoplasia CIN2+ and CIN3+ in the population were 1.45% and 0.77%, respectively. The highest incidence rates of CIN2+ and CIN3+ were 32.12% and 17.51%, respectively, in the 41-45 years old group. Conclusion: Infection rates with hrHPV, HPV16, and cervical lesions among our screening population were lower than the mean level in rural areas of China. Infection rates with hrHPV, HPV16, 18, and 16/18 showed a single-peak infection pattern, with the peak age of infection being 56-65 years old. Risk factors for hrHPV infection were age, history of alcohol consumption, marital status, reproductive diseases, education level, and the number of live births. Based on these data, we recommend that cervical cancer screening be offered to women older than 30 years in rural areas, particularly those aged 41-45 years.

Influence of Pre-treatment Saliva Microbial Diversity and Composition on Nasopharyngeal Carcinoma Prognosis.

Background: The human microbiome has been reported to mediate the response to anticancer therapies. However, research about the influence of the oral microbiome on nasopharyngeal carcinoma (NPC) survival is lacking. We aimed to explore the effect of oral microbiota on NPC prognosis. Methods: Four hundred eighty-two population-based NPC cases in southern China between 2010 and 2013 were followed for survival, and their saliva samples were profiled using 16s rRNA sequencing. We analyzed associations of the oral microbiome diversity with mortality from all causes and NPC. Results: Within- and between-community diversities of saliva were associated with mortality with an average of 5.29 years follow-up. Lower Faith's phylogenetic diversity was related to higher all-cause mortality [adjusted hazard ratio (aHR), 1.52 (95% confidence interval (CI), 1.06-2.17)] and NPC-specific mortality [aHR, 1.57 (95% CI, 1.07-2.29)], compared with medium diversity, but higher phylogenetic diversity was not protective. The third principal coordinate (PC3) identified from principal coordinates analysis (PCoA) on Bray-Curtis distance was marginally associated with reduced all-cause mortality [aHR, 0.85 (95% CI, 0.73-1.00)], as was the first principal coordinate (PC1) from PCoA on weighted UniFrac [aHR, 0.86 (95% CI, 0.74-1.00)], but neither was associated with NPC-specific mortality. PC3 from robust principal components analysis was associated with lower all-cause and NPC-specific mortalities, with HRs of 0.72 (95% CI, 0.61-0.85) and 0.71 (95% CI, 0.60-0.85), respectively. Conclusions: Oral microbiome may be an explanatory factor for NPC prognosis. Lower within-community diversity was associated with higher mortality, and certain measures of between-community diversity were related to mortality. Specifically, candidate bacteria were not related to mortality, suggesting that observed associations may be due to global patterns rather than particular pathogens.

Occupational exposures and risk of nasopharyngeal carcinoma in a high-risk area: A population-based case-control study.

BACKGROUND: The potential role of occupational exposures in the development of nasopharyngeal carcinoma (NPC) remains unclear, particularly in high-incidence areas. METHODS: The authors conducted a population-based case-control study, consisting of 2514 incident NPC cases and 2586 randomly selected population controls, in southern China from 2010 to 2014. Occupational history and other covariates were self-reported using a questionnaire. Multivariate logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for the risk of NPC associated with occupational exposures. Restricted cubic splines were used to evaluate potentially nonlinear duration-response relations. RESULTS: Individuals who had exposure to occupational dusts (OR, 1.45; 95% CI, 1.26-1.68), chemical vapors (OR, 1.37; 95% CI, 1.17-1.61), exhausts/smokes (OR, 1.42; 95% CI, 1.25-1.60), or acids/alkalis (OR, 1.56; 95% CI, 1.30-1.89) in the workplace had an increased NPC risk compared with those who were unexposed. Risk estimates for all 4 categories of occupational exposures appeared to linearly increase with increasing duration. Within these categories, occupational exposure to 14 subtypes of agents conferred significantly higher risks of NPC, with ORs ranging from 1.30 to 2.29, including dust from metals, textiles, cement, or coal; vapor from formaldehyde, organic solvents, or dyes; exhaust or smoke from diesel, firewood, asphalt/tar, vehicles, or welding; and sulfuric acid, hydrochloric acid, nitric acid, and concentrated alkali/ammonia. CONCLUSIONS: Occupational exposures to dusts, chemical vapors, exhausts/smokes, or acids/alkalis are associated with an excess risk of NPC. If the current results are causal, then the amelioration of workplace conditions might alleviate the burden of NPC in endemic areas. LAY SUMMARY: The role of occupational exposures in the development of nasopharyngeal carcinoma (NPC) remains unclear, particularly in high-incidence areas. The authors conducted a population-based study with 2514 incident NPC cases and 2586 population controls in southern China and observed that occupational exposures were associated with an increased risk of NPC. Duration-response trends were observed with increasing duration of exposure. These findings provide new evidence supporting an etiologic role of occupational exposures for NPC in a high-incidence region.

Residence characteristics and risk of nasopharyngeal carcinoma in southern China: A population-based case-control study.

OBJECTIVES: Given the role of exposures related to residence in the development of nasopharyngeal carcinoma (NPC) has not been well explored, present study aims to investigate the magnitude and pattern of associations for NPC with lifelong residential exposures. MATERIALS AND METHODS: We carried out a multi-center, population-based case-control study with 2533 incident NPC cases and 2597 randomly selected population controls in southern China between 2010 and 2014. We performed multivariate logistic regression to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for the risk of NPC associated with residential exposures. RESULTS: Compared with those living in a building over lifetime, risk of NPC was higher for individuals living in a cottage (OR: 1.56; 95% CI: 1.34-1.81) or in a boat (3.87; 2.07-7.21). NPC risk was also increased in individuals using wood (1.34; 1.03-1.75), coal (1.70; 1.17-2.47), or kerosene (3.58; 1.75-7.36) vs. using gas/electricity as cooking fuel; using well water (1.57; 1.34-1.83), river water (1.80; 1.47-2.21), or spring/pond/stream water (2.03; 1.70-2.41) vs. tap water for source of drinking water; living in houses with smaller-sized vs. larger windows in the bedroom (3.08; 2.46-3.86), hall (1.89; 1.55-2.31) or kitchen (1.67; 1.34-2.08); and increasing exposure to cooking smoke [(1.53; 1.20-1.94) for high exposure)] or burned incense [(1.59; 1.31-1.95) for daily use)]. Weighted Cox regression analysis corroborated these results. CONCLUSION: Poorer residential conditions and household air pollution are associated with an increased risk of NPC. Large-scale studies in other populations or longitudinal studies are warranted to further corroborate these findings.

The diagnostic performance of automated versus handheld breast ultrasound and mammography in symptomatic outpatient women: a multicenter, cross-sectional study in China.

OBJECTIVES: The purpose of this study was to evaluate the diagnostic performance of automated breast ultrasound (ABUS) for breast cancer by comparing it to handheld ultrasound (HHUS) and mammography (MG). METHODS: A multicenter cross-sectional study was conducted between February 2016 and March 2017 in five tertiary hospitals in China, and 1922 women aged 30-69 years old were recruited. Women aged 30-39 years (group A) underwent ABUS and HHUS, and women aged 40-69 (group B) underwent additional MG. Images were interpreted using the Breast Imaging Reporting and Data System (BI-RADS). All BI-RADS 4 and 5 cases were confirmed pathologically. Sensitivities and specificities of all modalities were compared. RESULTS: There were 83 cancers in 677 women in group A and 321 cancers in 1245 women in group B. In the whole study population, the sensitivities of ABUS and HHUS were 92.8% (375/404) and 96.3% (389/404), and the specificities were 93.0% (1411/1518) and 89.6% (1360/1518), respectively. ABUS had a significantly higher specificity to HHUS (p < 0.01), while HHUS had higher sensitivity (p = 0.01). In group B, the sensitivities of ABUS, HHUS, and MG were 93.5% (300/321), 96.6% (310/321), and 87.9% (282/321). The specificities were 93.0% (859/924), 89.9% (831/924), and 91.6% (846/924). ABUS had significantly higher sensitivity (p = 0.02) and comparable specificity compared with MG (p = 0.14). CONCLUSION: ABUS increased sensitivity and had similar specificity compared with mammography in the diagnosis of breast cancer. Additionally, ABUS has comparable performance to HHUS in women aged 30-69 years old. ABUS or HHUS is a suitable modality for breast cancer diagnosis. KEY POINTS: • In breast cancer diagnosis settings, automated breast ultrasound has a higher cancer detection rate, sensitivity, and specificity than mammography, especially in women with dense breasts. • Compared with handheld ultrasound, automated breast ultrasound has higher specificity, lower sensitivity, and comparable diagnostic performance. • Automated breast ultrasound is a suitable modality for breast cancer diagnosis, and may have a potential indication for its further use in the breast cancer early detection.

Intake of Alcohol and Tea and Risk of Nasopharyngeal Carcinoma: A Population-Based Case-Control Study in Southern China.

BACKGROUND: The potential effect of alcohol or tea intake on the risk of nasopharyngeal carcinoma (NPC) remains controversial. METHODS: In a population-based case-control study in southern China, we assessed alcohol or tea intake from 2,441 histopathologically confirmed NPC cases and 2,546 controls. We calculated mean daily ethanol (g/day) and tea intake (mL/day). Fully adjusted ORs with 95% confidence intervals (CI) were estimated using logistic regression; potential dose-response trends were evaluated using restricted cubic spline analysis. RESULTS: Compared with nondrinkers, no significantly increased NPC risk in men was observed among current alcohol drinkers overall (OR, 1.08; 95% CI, 0.93-1.25), nor among current heavy drinkers (OR for ≥90 g/day ethanol vs. none, 1.32; 95% CI, 0.95-1.84) or former alcohol drinkers. Current tea drinking was associated with a decreased NPC risk (OR, 0.73; 95% CI, 0.64-0.84). Compared with never drinkers, those with the low first three quintiles of mean daily current intake of tea were at significantly lower NPC risk (OR, 0.53, 0.68, and 0.65, respectively), but not significant for the next two quintiles. Current daily tea intake had a significant nonlinear dose-response relation with NPC risk. CONCLUSIONS: Our study suggests no significant association between alcohol and NPC risk. Tea drinking may moderately reduce NPC risk, but the lack of a monotonic dose-response association complicates causal inference. IMPACT: Tea drinking might be a healthy habit for preventing NPC. More studies on biological mechanisms that may link tea with NPC risk are needed.

Risk stratification of HPV 16 DNA methylation combined with E6 oncoprotein in cervical cancer screening: a 10-year prospective cohort study.

BACKGROUND: How to best triage human papillomavirus (HPV) positive women remains controversial in an era of HPV primary screening of cervical cancer. Here, we assessed the long-term risk stratification for triaging HPV 16 positive women by standalone HPV 16 methylation and combined with E6 oncoprotein. METHODS: A total of 1742 women underwent screening with HPV DNA testing, cytology, and visual inspection with acetic acid (VIA) in 2005 and were followed for 10 years. Seventy-seven women with HPV 16 positivity determined by HPV genotyping test were examined via E6 oncoprotein detection and bisulfite pyrosequencing for quantitative methylation of L1 and LCR genes of HPV 16. RESULTS: The 10-year cumulative incidence rate (CIR) of cervical intraepithelial neoplasia grade 3 or severe (CIN3+) for HPV 16 positive women was 25.3% (95% CI 14.7-37.3%), which significantly increased in women with high methylation at six sites (CpG 5602, 6650, 7034, 7461, 31, and 37) and in women with positive E6 oncoprotein. A methylation panel based on the above six sites showed a competitive risk stratification compared to cytology (HR 11.5 vs. 8.1), with a higher 10-year CIR of CIN3+ in panel positives (57.2% vs 36.8%) and comparable low risk in panel negatives (5.7% vs 4.8%).The sensitivity and specificity for accumulative CIN3+ was 85.7% (95%CI 60.1-96.0%) and 78.4% (95%CI 62.8-88.6%) for a methylation panel and 57.1% (95%CI 32.6-78.6%) and 86.5% (95%CI 72.0-94.1%) for E6 oncoprotein. The AUC values of methylation standalone and the co-testing of methylation panel and E6 oncoprotein were around 0.80, comparable to 0.68 for cytology, 0.65 for viral load, and superior to 0.52 for VIA (p < 0.05). CONCLUSIONS: Our findings indicated the promising use of HPV 16 methylation alone or combined with E6 oncoprotein for triaging HPV 16 positive women based on the long-term risk stratification ability.

Clinical Performance of Human Papillomavirus Testing and Visual Inspection With Acetic Acid in Primary, Combination, and Sequential Cervical Cancer Screening in China.

BACKGROUND: World Health Organization guidelines recommend screening with human papillomavirus (HPV) testing followed by either treatment of all HPV-positives, or by visual inspection (VIA) for triage to treatment, citing insufficient evidence to recommend either strategy over the other. METHODS: We assessed VIA and HPV testing individually, in combination (HPV-VIA cotesting), and as triage models. Three thousand women were screened in Inner Mongolia, China, concurrently with HPV testing and VIA in a real population setting. Screen-positive women underwent colposcopy, and biopsy, if indicated. Accuracy of screening algorithms for cervical intraepithelial neoplasia grade 2 or higher (CIN-2+) was calculated after controlling for verification bias. HPV testing followed by VIA triage for CIN-2+ detection was compared with Hybrid Capture 2 viral loads triage, measured in relative light units/cutoff. RESULTS: CIN-2+ prevalence was 1.0%. Corrected sensitivity, false negative rate, and specificity for CIN-2+, respectively, for primary HPV testing were 89.7%, 10.3%, and 83.3%; 44.8%, 55.2%, and 92·3% for VIA; 93.1%, 6.9%, and 80.2% for HPV-VIA cotesting; and 41.4%, 58.6, and 95.4% for HPV with VIA triage scenarios. Using relative light units/cutoff of 5 or greater to triage HPV-positive women had twice the sensitivity as VIA triage, with comparable specificity for CIN-2+. CONCLUSIONS: When VIA performs relatively poorly and HPV testing is available, adding VIA to sequential (ie, HPV followed by VIA triage) or primary (HPV-VIA cotesting) screening does not significantly improve CIN-2+ detection beyond primary HPV screening alone. Sequential screening (ie, HPV followed by VIA triage) reduces sensitivity too low for population-based screening programs. The HPV viral loads could offer an alternative low-resource country triage strategy.

Current cancer situation in China: good or bad news from the 2018 Global Cancer Statistics?

Cancer is the leading cause of death in China and depicting the cancer pattern of China would provide basic knowhows on how to tackle it more effectively. In this study we have reviewed several reports of cancer burden, including the Global cancer statistics 2018 and Cancer statistics in China, 2015, along with the GLOBCAN 2018 online database, to investigate the differences of cancer patterns between China, the United States (USA) and the United Kingdom (UK). An estimated 4.3 million new cancer cases and 2.9 million new cancer deaths occurred in China in 2018. Compared to the USA and UK, China has lower cancer incidence but a 30% and 40% higher cancer mortality than the UK and USA, among which 36.4% of the cancer-related deaths were from the digestive tract cancers (stomach, liver, and esophagus cancer) and have relatively poorer prognoses. In comparison, the digestive cancer deaths only took up ≤ 5% of the total cancer deaths in either USA or UK. Other reasons for the higher mortality in China may be the low rate of early-stage cancers at diagnosis and non-uniformed clinical cancer treatment strategies performed by different regions. China is undergoing the cancer transition stage where the cancer spectrum is changing from developing country to developed country, with a rapidly increase cancer burden of colorectal, prostate, female breast cancers in addition to a high occurrence of infection-related and digestive cancers. The incidence of westernized lifestyle-related cancers in China (i.e. colorectal cancer, prostate, bladder cancer) has risen but the incidence of the digestive cancers has decreased from 2000 to 2011. An estimated 40% of the risk factors can be attributed to environmental and lifestyle factors either in China or other developed countries. Tobacco smoking is the single most important carcinogenic risk factor in China, contributing to ~ 24.5% of cancers in males. Chronic infection is another important preventable cancer contributor which is responsible for ~ 17% of cancers. Comprehensive prevention and control strategies in China should include effective tobacco-control policy, recommendations for healthier lifestyles, along with enlarging the coverage of effective screening, educating, and vaccination programs to better sensitize greater awareness control to the general public.

Body mass index, body shape, and risk of nasopharyngeal carcinoma: A population-based case-control study in Southern China.

Whether the association between body size or shape and nasopharyngeal carcinoma (NPC) risk exists or varies by age-specific body size indicators is unclear. In a population-based case-control study conducted in Southern China between 2010 and 2014, self-reported height, weight, and body shape at age 20 and 10 years before interview were collected from 2448 histopathologically confirmed NPC cases and 2534 population-based controls. Body mass index (BMI) was categorized according to the World Health Organization guidelines for Asian populations: underweight (<18.5 kg/m2 ), normal weight (18.5-22.9 kg/m2 ), overweight (23.0-27.4 kg/m2 ), and obese (≥27.5 kg/m2 ). Multivariate odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using logistic regression. Furthermore, restricted cubic spline analysis was employed to examine nonlinear effects of BMI and body shape as continuous covariates. Underweight vs normal weight at age 20 years was associated with a 22% decreased NPC risk (OR, 0.78; 95% CI, 0.67, 0.90), whereas obesity was not significantly associated with NPC risk. Associations with BMI 10 years before the interview were similar. Having the leanest body shape at age 20 years, compared with the mode was not significantly associated with NPC risk (OR, 0.85; 95% CI, 0.62, 1.16), but having a larger body shape was associated with an elevated risk (OR, 1.25; 95% CI, 1.03, 1.52). Increasing BMI revealed positive trends with NPC risk. Despite some indication of significant findings, evidence for a strong association between BMI or body shape and NPC risk is still limited.

Reproductive history and risk of nasopharyngeal carcinoma: A population-based case-control study in southern China.

OBJECTS: Nasopharyngeal carcinoma (NPC) incidence exhibits a remarkable sex disparity, with higher risk among males. Whether this pattern can be partly explained by female reproductive history is unclear. METHODS: A population-based case-control study of NPC was conducted in southern China between 2010 and 2014, including 674 histopathologically verified female NPC cases and 690 female controls randomly selected from population-based registries. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression after adjusting for potential confounders. RESULTS: Women who had 3, 4, or ≥5 pregnancies compared with 2 pregnancies were at significantly increased risk for NPC (ORs 1.56, 1.45 and 1.88, respectively). History of deliveries was similarly associated with a greater risk of NPC. These positive associations were more prominent in women who were younger than 50 years, had less than 10 years of education, or were white-collar workers. Increasing time since menopause was associated with a diminished NPC risk (Ptrend = 0.010). Women more than 15 years after menopause had a 0.35-fold (95% CI: 0.16-0.75) NPC risk compared with those 0-3 years after menopause. CONCLUSION: Contrary to our hypothesis, a history of pregnancy or delivery increased the risk of NPC and the risk decreased with increasing time since menopause. However, the non-linear relationship and no consistent risk patterns across strata indicate that the observed associations are unlikely to be causal, and may at least partially be ascribed to residual confounding by socioeconomic factors.

Durability of clinical performance afforded by self-collected HPV testing: A 15-year cohort study in China.

OBJECTIVE: Self-collected HPV testing could substantially reduce disparities in cervical cancer screening, with slightly lower sensitivity compared to physician-collected specimens cross-sectionally. We aimed to evaluate the comprehensive long-term performance of self-collected HPV testing prospectively. METHODS: In 1999, 1997 women were screened by HPV testing on self-collected and physician-collected samples, cytology and visual inspection with acetic acid (VIA) and followed up in 2005, 2010 and 2014, respectively. HPV testing was performed with Hybrid Capture II. Prospective performance, baseline clinical efficiency, and 15-year cumulative risk of cervical intraepithelial neoplasia grade 2 or higher (CIN2+) were analyzed. RESULTS: Self-collected HPV testing prospectively detected 83.3% (95% CI:74.9%,89.3%), 70.3% (95% CI:62.5%,77.2%) and 63.3% (95% CI:55.7%, 70.2%) of cumulative CIN2+ at 6-year, 11-year and 15-year follow-up, respectively. Relative cumulative sensitivity of physician-collected HPV testing versus self-collected HPV testing was stable over 15 years at about 1.16. Cumulative sensitivity of self-collected HPV testing was comparable to cytology and significantly higher than VIA. Among women positive by self-collected HPV testing at baseline, 26.2% (95% CI:21.5%, 30.9%) developed CIN2+ during 6-year follow-up and no difference was observed with physician-collected HPV testing even 15 years after baseline. Negative self-collected HPV results provided greater protection against CIN2+ than VIA and ascertained CIN2+ cumulative incident rates as low as 1.1% at the 6-year follow-up. CONCLUSIONS: Self-collected HPV testing demonstrates lower sensitivity than physician-collected HPV testing but performs comparably to cytology prospectively and provides satisfactory assurance against CIN2+, indicating an alternative role in cervical cancer primary screening with five-year interval as an option especially in low-resource settings.

A multicenter hospital-based diagnosis study of automated breast ultrasound system in detecting breast cancer among Chinese women.

OBJECTIVE: The automated breast ultrasound system (ABUS) is a potential method for breast cancer detection; however, its diagnostic performance remains unclear. We conducted a hospital-based multicenter diagnostic study to evaluate the clinical performance of the ABUS for breast cancer detection by comparing it to handheld ultrasound (HHUS) and mammography (MG). METHODS: Eligible participants underwent HHUS and ABUS testing; women aged 40-69 years additionally underwent MG. Images were interpreted using the Breast Imaging Reporting and Data System (BI-RADS). Women in the BI-RADS categories 1-2 were considered negative. Women classified as BI-RADS 3 underwent magnetic resonance imaging to distinguish true- and false-negative results. Core aspiration or surgical biopsy was performed in women classified as BI-RADS 4-5, followed by a pathological diagnosis. Kappa values and agreement rates were calculated between ABUS, HHUS and MG. RESULTS: A total of 1,973 women were included in the final analysis. Of these, 1,353 (68.6%) and 620 (31.4%) were classified as BI-RADS categories 1-3 and 4-5, respectively. In the older age group, the agreement rate and Kappa value between the ABUS and HHUS were 94.0% and 0.860 (P<0.001), respectively; they were 89.2% and 0.735 (P<0.001) between the ABUS and MG, respectively. Regarding consistency between imaging and pathology results, 78.6% of women classified as BI-RADS 4-5 based on the ABUS were diagnosed with precancerous lesions or cancer; which was 7.2% higher than that of women based on HHUS. For BI-RADS 1-2, the false-negative rates of the ABUS and HHUS were almost identical and were much lower than those of MG. CONCLUSIONS: We observed a good diagnostic reliability for the ABUS. Considering its performance for breast cancer detection in women with high-density breasts and its lower operator dependence, the ABUS is a promising option for breast cancer detection in China.

Risk of high-risk human papillomavirus infection and cervical precancerous lesions with past or current trichomonas infection: a pooled analysis of 25,054 women in rural China.

BACKGROUND: Trichomonas vaginitis (TV) infection has obviously been implicated in gynecological morbidity but still unclear in cervical lesions. OBJECTIVE: To evaluate the risk of hr-HPV infection and cervical intraepithelial neoplasia grade 2 or worse (CIN2 + ) by TV infection. STUDY DESIGN: The pooled study was conducted among 12 population-based, cervical cancer screening studies throughout China (N = 24,054). HPV was detected by Hybrid Capture®2 (HC2) test. Past TV infection was measured by self-reporting, current TV infection was diagnosed by liquid-based cytology (LBC), cervical lesions was diagnosed by histopathology. RESULTS: Respective prevalence of hr-HPV and CIN2+ were 17.4% and 3.3%. Out of 24,054 women, 14.6% reported past TV infection, and out of 11,853 women, 9.9% had current TV infection. Current TV-positive women had an increased risk for hr-HPV (OR 1.31, 95%CI: 1.11-1.56). The risk of CIN2+ decreased for hr-HPV positive women with current TV infection (adjusted OR 0.50, 95% CI: 0.30-0.84) and past TV infection (adjusted OR 0.68, 95% CI: 0.54-0.86). Among hr-HPV negative women, no significant associations were observed between past or current TV infection and risk of CIN2+. CONCLUSIONS: Women infected with HPV are more likely to be infected by other types of sexually transmitted diseases. Current TV-positive women had an increased risk for hr-HPV infection compared to currently TV-negative women. Both past and current TV-positive women had a decreased risk for CIN2+, especially among high-risk HPV positive women. More direct investigation into the interaction between TV, HPV, inflammatory signals, and risk of carcinogenesis are further needed.