Spatial consistency of co-exposure to air and surface water pollution and cancer in China.

Humans can be exposed to multiple pollutants in the air and surface water. These environments are non-static, trans-boundary and correlated, creating a complex network, and significant challenges for research on environmental hazards, especially in real-world cancer research. This article reports on a large study (377 million people in 30 provinces of China) that evaluated the combined impact of air and surface water pollution on cancer. We formulate a spatial evaluation system and a common grading scale for co-pollution measurement, and validate assumptions that air and surface water environments are spatially connected and that cancers of different types tend to cluster in areas where these environments are poorer. We observe "dose-response" relationships in both the number of affected cancer types and the cancer incidence with an increase in degree of co-pollution. We estimate that 62,847 (7.4%) new cases of cancer registered in China in 2016 were attributable to air and surface water pollution, and the majority (69.7%) of these excess cases occurred in areas with the highest level of co-pollution. The findings clearly show that the environment cannot be considered as a set of separate entities. They also support the development of policies for cooperative environmental governance and disease prevention.

Reinforcement learning for individualized lung cancer screening schedules: A nested case-control study.

BACKGROUND: The current guidelines for managing screen-detected pulmonary nodules offer rule-based recommendations for immediate diagnostic work-up or follow-up at intervals of 3, 6, or 12 months. Customized visit plans are lacking. PURPOSE: To develop individualized screening schedules using reinforcement learning (RL) and evaluate the effectiveness of RL-based policy models. METHODS: Using a nested case-control design, we retrospectively identified 308 patients with cancer who had positive screening results in at least two screening rounds in the National Lung Screening Trial. We established a control group that included cancer-free patients with nodules, matched (1:1) according to the year of cancer diagnosis. By generating 10,164 sequence decision episodes, we trained RL-based policy models, incorporating nodule diameter alone, combined with nodule appearance (attenuation and margin) and/or patient information (age, sex, smoking status, pack-years, and family history). We calculated rates of misdiagnosis, missed diagnosis, and delayed diagnosis, and compared the performance of RL-based policy models with rule-based follow-up protocols (National Comprehensive Cancer Network guideline; China Guideline for the Screening and Early Detection of Lung Cancer). RESULTS: We identified significant interactions between certain variables (e.g., nodule shape and patient smoking pack-years, beyond those considered in guideline protocols) and the selection of follow-up testing intervals, thereby impacting the quality of the decision sequence. In validation, one RL-based policy model achieved rates of 12.3% for misdiagnosis, 9.7% for missed diagnosis, and 11.7% for delayed diagnosis. Compared with the two rule-based protocols, the three best-performing RL-based policy models consistently demonstrated optimal performance for specific patient subgroups based on disease characteristics (benign or malignant), nodule phenotypes (size, shape, and attenuation), and individual attributes. CONCLUSIONS: This study highlights the potential of using an RL-based approach that is both clinically interpretable and performance-robust to develop personalized lung cancer screening schedules. Our findings present opportunities for enhancing the current cancer screening system.

Prevalence and risk factors of oral human papillomavirus infection among 4212 healthy adults in Hebei, China.

BACKGROUND: Human papillomavirus (HPV) infection is an essential cause of oropharyngeal squamous cell carcinoma that is increasing in incidence worldwide. However, little is known about the epidemiology of oral HPV infection among healthy adults in China. METHODS: A study in northern China was conducted in 2021 as baseline data of Diverse Life-Course Cohort (DLCC). Residents who aged above 20 were eligible to participate. Oral swab specimens and questionnaires were collected from 4226 participants. HPV DNA in oral exfoliated cells was tested by Nested Polymerase Chain Reaction approach and sequencing. Univariate and multivariate analyses were performed to assess the associations between exposure factors and oral HPV infection. RESULTS: Overall prevalence of oral HPV infection was 4.08% (95%CI, 3.69%-4.68%). The most prevalent HPV type detected was HPV-81 (1.35%; 95% CI, 1.00%-1.70%), followed by HPV-16 (0.64%; 95% CI, 0.40%-0.88%). Oral HPV infection presented a bimodal pattern with respect to age in male and female participants. Oral HPV prevalence of male participants was significantly higher than prevalence of female participants (5.0% versus 3.6%, P = 0.041). Prevalence of oral HPV was higher among current smokers (OR = 1.59; 95% CI, 1.11-2.29; P = 0.039) and current drinkers (OR = 1.60; 95% CI, 1.14-2.25; P = 0.023). Current alcohol consumption was independently associated with oral HPV infection (OR = 1.74; 95% CI, 1.22-2.50; P = 0.010). CONCLUSIONS: Among healthy adults aged above 20 in Hebei, China, the prevalence of high-risk HPV infection was 1.92% (95%CI, 1.51%-2.34%). Oral HPV prevalence was independently associated with alcohol consumption. More tailored prevention strategies are needed to prevent oral HPV infection through smoking cessation, reduction of alcohol consumption, and HPV vaccination.

Epidemiology of Oral Human Papillomavirus Infection among Diverse Chinese Adults in Typical Areas of China: Findings from the DLCC Study.

BACKGROUND: Human papillomavirus (HPV) infection is a predominant cause of oropharyngeal squamous cell carcinoma. However, there is limited knowledge about the epidemiology of oral HPV infections among adults in China. METHODS: We collected data from a prospective cohort that enrolled participants in Mainland China. A total of 9,867 participants ages at least 20 years provided oral swab specimens in typical areas of China (Hebei and Guangdong provinces) in 2021. HPV DNA in oral exfoliated cells was tested using nested PCR and sequencing. Prevalence among subpopulations was compared. Multivariable logistic regression models were employed to assess possible factors influencing oral HPV infection. RESULTS: The overall prevalence of oral HPV infection was 3.0% [95% confidence interval (CI): 2.68-3.36]. Among those infected, 1.3% (1.08-1.53) were infected with high-risk HPV types. Men had a higher age-standardized HPV infection prevalence (3.6%, 2.96-4.29) compared with their female counterparts (2.7%, 2.35-3.12). People in Hebei had a higher age- and sex-standardized prevalence (4.1%, 3.50-4.70) than those in Guangdong (2.2%, 1.80-2.56). Generally, men (OR and 95% CI: 1.42, 1.09-1.85) and people in Hebei (2.01, 1.53-2.65) had higher odds of any type of HPV infection. In addition, people living in urban areas had a 2.15-fold (1.43-3.26) higher odds of high-risk HPV infection. CONCLUSIONS: This study reveals a low prevalence of oral HPV infection with significant geographic and sex differences among Chinese population. IMPACT: This is the first study to report the epidemiologic characteristics of oral HPV infection among Chinese adults in diverse geographic areas with large sample size.

Smoking-related cancer death among men and women in an ageing society (China 2020-2040): a population-based modelling study.

BACKGROUND: China is experiencing a postpeak smoking epidemic with accelerating population ageing. Understanding the impacts of these factors on the future cancer burden has widespread implications. METHODS: We developed predictive models to estimate smoking-related cancer deaths among men and women aged ≥35 years in China during 2020-2040. Data sources for model parameters included the United Nations World Population Prospects, China Death Surveillance Database, national adult tobacco surveys and the largest national survey of smoking and all causes of death to date. The main assumptions included stable sex-specific and age-specific cancer mortality rates and carcinogenic risks of smoking over time. RESULTS: In a base-case scenario of continuing trends in current smoking prevalence (men: 57.4%-50.5%; women: 2.6%-2.1% during 2002-2018), the smoking-related cancer mortality rate with population ageing during 2020-2040 would rise by 44.0% (from 337.2/100 000 to 485.6/100 000) among men and 52.8% (from 157.3/100 000 to 240.4/100 000) among women; over 20 years, there would be 8.6 million excess deaths (0.5 million more considering former smoking), and a total of 117.3 million smoking-attributable years of life lost (110.3 million (94.0%) in men; 54.1 million (46.1%) in working-age (35-64 years) adults). An inflection point may occur in 2030 if smoking prevalence were reduced to 20% (Healthy China 2030 goal), and 1.4 million deaths would be averted relative to the base-case scenario if the trend were maintained through 2040. CONCLUSIONS: Coordinated efforts are urgently needed to curtail a rising tide of cancer deaths in China, with intensified tobacco control being key.

Optimizing the timing of diagnostic testing after positive findings in lung cancer screening: a proof of concept radiomics study.

BACKGROUND: The timeliness of diagnostic testing after positive screening remains suboptimal because of limited evidence and methodology, leading to delayed diagnosis of lung cancer and over-examination. We propose a radiomics approach to assist with planning of the diagnostic testing interval in lung cancer screening. METHODS: From an institute-based lung cancer screening cohort, we retrospectively selected 92 patients with pulmonary nodules with diameters ≥ 3 mm at baseline (61 confirmed as lung cancer by histopathology; 31 confirmed cancer-free). Four groups of region-of-interest-based radiomic features (n = 310) were extracted for quantitative characterization of the nodules, and eight features were proven to be predictive of cancer diagnosis, noise-robust, phenotype-related, and non-redundant. A radiomics biomarker was then built with the random survival forest method. The patients with nodules were divided into low-, middle- and high-risk subgroups by two biomarker cutoffs that optimized time-dependent sensitivity and specificity for decisions about diagnostic workup within 3 months and about repeat screening after 12 months, respectively. A radiomics-based follow-up schedule was then proposed. Its performance was visually assessed with a time-to-diagnosis plot and benchmarked against lung RADS and four other guideline protocols. RESULTS: The radiomics biomarker had a high time-dependent area under the curve value (95% CI) for predicting lung cancer diagnosis within 12 months; training: 0.928 (0.844, 0.972), test: 0.888 (0.766, 0.975); the performance was robust in extensive cross-validations. The time-to-diagnosis distributions differed significantly between the three patient subgroups, p < 0.001: 96.2% of high-risk patients (n = 26) were diagnosed within 10 months after baseline screen, whereas 95.8% of low-risk patients (n = 24) remained cancer-free by the end of the study. Compared with the five existing protocols, the proposed follow-up schedule performed best at securing timely lung cancer diagnosis (delayed diagnosis rate: < 5%) and at sparing patients with cancer-free nodules from unnecessary repeat screenings and examinations (false recommendation rate: 0%). CONCLUSIONS: Timely management of screening-detected pulmonary nodules can be substantially improved with a radiomics approach. This proof-of-concept study's results should be further validated in large programs.

Global evolution of research on pulmonary nodules: a bibliometric analysis.

Aim: To provide a historical and global picture of research concerning lung nodules, compare the contributions of major countries and explore research trends over the past 10 years. Methods: A bibliometric analysis of publications from Scopus (1970-2020) and Web of Science (2011-2020). Results: Publications about pulmonary nodules showed an enormous growth trend from 1970 to 2020. There is a high level of collaboration among the 20 most productive countries and regions, with the USA located at the center of the collaboration network. The keywords 'deep learning', 'artificial intelligence' and 'machine learning' are current hotspots. Conclusions: Abundant research has focused on pulmonary nodules. Deep learning is emerging as a promising tool for lung cancer diagnosis and management.

Developing a toolbox for identifying when to engage senior surgeons in emergency general surgery: A multicenter cohort study.

BACKGROUND: Having a senior surgeon present for high-risk patients is an important safety measure in emergency surgery, but 24-h consultant cover is not efficient. We aimed to develop a user-friendly toolbox (risk identification, outcome prediction and patient stratification) to support when to involve a senior surgeon. MATERIALS AND METHODS: We included 11,901 general surgery patients (10.0% emergencies) in a multicenter prospective cohort in China (2015-2016). Patient information and surgeons' seniority were compared between emergency and elective surgery with the same procedure codes. Risk indicators common in these two surgical timings and specific to emergency surgery were identified, and their clinical importance was evaluated by a working group of 48 experienced surgeons. Predictive models for mortality and morbidity were built using logistic regression models. Stratification rules were created to balance patients' risk and surgeons' caseload with an Acute Call Team (ACT) model. RESULTS: Emergency patients had significantly higher risks of mortality (3.6% vs 0.6%) and morbidity (7.8% vs 4.3%) than elective patients, but disproportionally fewer senior surgeons (59.9% vs 91.4%) were present. Using three risk indicators (American Society of Anesthesiologists score, age, blood urea nitrogen), C-statistic (95% CI) for prediction of emergency mortality was high [0.90 (0.84-0.96)]. It was less complex but equally accurate as two existing and validated models (0.86 [0.79-0.93] and 0.86 [0.77-0.95]). Using five indicators, C-statistic (95% CI) was moderate for prediction of overall morbidity [0.77 (0.72-0.83)], but high for severe morbidity [0.92 (0.88-0.97)]. Based on stratification rules of the ACT model, patient mortality and morbidity were 0.5% and 5.3% in the low-risk stratum (composing 64.6% of emergency caseload), and 15.9% and 29.0% in the very high-risk stratum (6.9% of caseload). CONCLUSION: These findings show the practical feasibility of using a risk assessment tool to direct senior surgeons' involvement in emergency general surgery.

Population-based projections of blood supply and demand, China, 2017-2036.

OBJECTIVE: To estimate the long-term effect of the changing demography in China on blood supply and demand. METHODS: We developed a predictive model to estimate blood supply and demand during 2017-2036 in mainland China and in 31 province-level regions. Model parameters were obtained from World Population Prospects, China statistical yearbook 2016, China's report on blood safety and records from a large tertiary hospital. Our main assumptions were stable age-specific per capita blood supply and demand over time. FINDINGS: We estimated that the change in demographic structure between 2016 (baseline year) and 2036 would result in a 16.0% decrease in blood supply (from 43.2 million units of 200 mL to 36.3 million units) and a 33.1% increase in demand (from 43.2 million units to 57.5 million units). In 2036, there would be an estimated shortage of 21.2 million units. An annual increase in supply between 0.9% and 1.8% is required to maintain a balance in blood supply and demand. This increase is not enough for every region as regional differences will increase, e.g. a blood demand/supply ratio ≥ 1.45 by 2036 is predicted in regions with large populations older than 65 years. Sensitivity analyses showed that increasing donations by 4.0% annually by people aged 18-34 years or decreasing the overall blood discard rate from 5.0% to 2.0% would not offset but help reduce the blood shortage. CONCLUSION: Multidimensional strategies and tailored, coordinated actions are needed to deal with growing pressures on blood services because of China's ageing population.

Cost-effectiveness comparison of routine transfusion with restrictive and liberal transfusion strategies for surgical patients in China.

BACKGROUND AND OBJECTIVES: A health industry standard recommending restrictive transfusion is to be in effect in China in April 2019. We aim to explore its potential economic and clinical impacts among surgical patients. MATERIALS AND METHODS: A decision tree model was applied to compare cost-effectiveness of current routine transfusion in China, a restrictive (transfusion at Hb < 8 g/dl or ischaemic symptoms) and a liberal (transfusion at Hb < 10 g/dl) strategy. Parameters were estimated from empirical data of 25 227 surgical inpatients aged ≥30 years in a multicenter study and supplemented by meta-analysis when necessary. Results are shown for cardio-cerebral-vascular (CCV) surgery and non-CCV (orthopaedics, general, thoracic) surgery separately. RESULTS: Per 10 000 patients in routine, restrictive, liberal transfusion scenarios, total spending (transfusion and length of stay related) was 7·67, 7·58 and 9·39 million CNY (1 CNY × 0.157 = 1 US dollar) for CCV surgery and 6·35, 6·70 and 8·09 million CNY for non-CCV surgery; infectious and severe complications numbered 354, 290, and 290 (CCV) and 315, 286, and 330 (non-CCV), respectively. Acceptability curves showed high probabilities for restrictive strategy to be cost-effective across a wide range of willingness-to-pay values. Such findings were mostly consistent in sensitivity and subgroup analyses except for patients with cardiac problems. CONCLUSION: We showed strong rationale, succeeding previous findings only in cardiac or joint procedures, to comply with the new standard as restrictive transfusion has high potential to save blood, secure safety, and is cost-effective for a wide spectrum of surgical patients. Experiences should be further summarized to pave the way towards individualized transfusion.

Is exposure to tobacco associated with extrahepatic cholangiocarcinoma epidemics? A retrospective proportional mortality study in China.

BACKGROUND: Extrahepatic cholangiocarcinoma (ECC) has become one of the most rapidly increasing malignancies in China during recent decades. The relationship between tobacco exposure and ECC epidemics is unclear; this study aimed to explore this relationship. METHODS: We included 55,806 participants aged 30 years or older from the National Mortality and Smoking Survey of China. Smoking in participants and spouses was defined as 1 cigarette or more per day for up to 1 year. Spouses' smoking was taken as a measure of exposure to passive smoking. Smoking information in 1980 was ascertained and outcomes were defined as ECC mortality during 1986-1988. RESULTS: We found that either passive or active smoking increased the risk of death from ECC by 20% (risk ratio [RR], 1.20; 95% confidence interval [CI], 0.99-1.47), compared with no exposure to any tobacco. This risk was a notable 98% (RR, 1.98; 95% CI, 1.49-2.64) for individuals exposed to passive plus active smoking. These findings were highly consistent among men and women. Pathology-based analyses showed dose-response relationships of ECC with pack-years for all types of smoking exposure (Ps for trend < 0.05); the RR reached 2.75 (95% CI, 1.20-6.30) in individuals exposed to combined smoking with the highest exposure dose. The findings were similar for non-pathology-based analysis. CONCLUSIONS: This study indicates that tobacco exposure increases ECC risk. Given the dramatic increase of exposure to secondhand smoke and patients with ECC, an inadequate provision of smoke-free environments could be contributing to ECC epidemics and could further challenge public health and medical services, based on the current disease spectrum.

Challenges and research opportunities for lung cancer screening in China.

Following publication of the results of the National Lung Screening Trial in the United States, a randomized controlled trial in Italy (ITALUNG) and two simulation studies in China reported similar findings in 2017 favoring lung cancer screening with low-dose computed tomography among smokers. With such advances in lung cancer screening, worldwide interest has gradually shifted from evaluating whether refining lung cancer screening protocols is effective in preventing deaths. However, there are several practical problems to be resolved, including the balance of enrollment criteria and cost effectiveness, precise measurements to reduce false positive findings, risk-based optimization of screening frequency, challenges associated with cancer heterogeneity, strategies to combine image screening with novel biomarkers, dynamic monitoring of the natural history of cancer, accurate identification and diagnosis of cases among huge populations, and the impact of tobacco control policy and environment protection. As one in three individuals with lung cancer worldwide resides in China, these questions pose great challenges as well as research opportunities for population screening programs in China.

Mortality outcomes of low-dose computed tomography screening for lung cancer in urban China: a decision analysis and implications for practice.

BACKGROUND: Mortality outcomes in trials of low-dose computed tomography (CT) screening for lung cancer are inconsistent. This study aimed to evaluate whether CT screening in urban areas of China could reduce lung cancer mortality and to investigate the factors that associate with the screening effect. METHODS: A decision tree model with three scenarios (low-dose CT screening, chest X-ray screening, and no screening) was developed to compare screening results in a simulated Chinese urban cohort (100,000 smokers aged 45-80 years). Data of participant characteristics were obtained from national registries and epidemiological surveys for estimating lung cancer prevalence. The selection of other tree variables such as sensitivities and specificities of low-dose CT and chest X-ray screening were based on literature research. Differences in lung cancer mortality (primary outcome), false diagnoses, and deaths due to false diagnosis were calculated. Sensitivity analyses were performed to identify the factors that associate with the screening results and to ascertain worst and optimal screening effects considering possible ranges of the variables. RESULTS: Among the 100,000 subjects, there were 448, 541, and 591 lung cancer deaths in the low-dose CT, chest X-ray, and no screening scenarios, respectively (17.2% reduction in low-dose CT screening over chest X-ray screening and 24.2% over no screening). The costs of the two screening scenarios were 9387 and 2497 false diagnoses and 7 and 2 deaths due to false diagnosis among the 100,000 persons, respectively. The factors that most influenced death reduction with low-dose CT screening over no screening were lung cancer prevalence in the screened cohort, low-dose CT sensitivity, and proportion of early-stage cancers among low-dose CT detected lung cancers. Considering all possibilities, reduction in deaths (relative numbers) with low-dose CT screening in the worst and optimal cases were 16 (5.4%) and 288 (40.2%) over no screening, respectively. CONCLUSIONS: In terms of mortality outcomes, our findings favor conducting low-dose CT screening in urban China. However, approaches to reducing false diagnoses and optimizing important screening conditions such as enrollment criteria for screening are highly needed.

Passive smoking and stroke in men and women: a national population-based case-control study in China.

An association between passive smoking and stroke is unclear in China, particularly the association with hemorrhagic stroke. This study included 16205 deaths due to stroke aged ≥30 years and 16205 non-stroke controls randomly selected and frequency-matched to cases on gender and age. Smoking of spouses, defined as ≥1 cigarette per day for up to 1 year, was taken as a measure of exposure to passive smoking of subjects that was retrospectively ascertained by interviewing surviving spouses. After adjustment for variables, passive smoking increased the risk of death by 10% (odds ratio (OR), 1.10; 95% confidence interval (CI), 1.05-1.16) for all strokes, by 10% (OR, 1.10; 95% CI, 1.04-1.16) for hemorrhagic stroke, and by 12% (OR, 1.12; 95% CI, 1.03-1.23) for ischemic stroke, compared with non-exposure. This finding was highly consistent in men or women and in smokers or non-smokers, and was generally consistent among zones of China despite geographic diversity. The risk significantly increased with exposure-years and quantity of cigarettes smoked daily by spouses. This study indicated that passive smoking is associated with deaths from all-type strokes. It is highly advisable for the government to promote strong tobacco prevention and cessation programs and smoke-free environments.

Can CT Screening Give Rise to a Beneficial Stage Shift in Lung Cancer Patients? Systematic Review and Meta-Analysis.

OBJECTIVES: To portray the stage characteristics of lung cancers detected in CT screenings, and explore whether there's universal stage superiority over other methods for various pathological types using available data worldwide in a meta-analysis approach. MATERIALS AND METHODS: EMBASE and MEDLINE were searched for studies on lung cancer CT screening in natural populations through July 2015 without language or other filters. Twenty-four studies (8 trials and 16 cohorts) involving 1875 CT-detected lung cancer patients were enrolled and assessed by QUADAS-2. Pathology-confirmed stage information was carefully extracted by two reviewers. Stage I or limited stage proportions were pooled by random effect model with Freeman-Tukey double arcsine transformation. RESULTS: Pooled stage I cancer proportion in CT screenings was 73.2% (95% confidence interval: 68.6%, 77.5%), with a significant rising trend (Ptrend<0.05) from baseline (64.7%) to ≥5 repeat rounds (87.1%). Relative to chest radiograph and usual care, the increased stage I proportions in CT were 12.2% (P>0.05), and 46.5% (P<0.05), respectively. Pathology-specifically, adenocarcinomas (66%) and squamous cell lung cancers (17%) composed the majority of CT-detected lung cancers, and had significantly higher stage I proportions relative to chest radiograph (bronchioloalveolar adenocarcinomas, 80.9% vs 51.4%; other adenocarcinomas, 58.8% vs 38.3%; squamous cell lung cancers, 52.3% vs 38.3%; all P<0.05). However, the percentage of small cell lung cancer was lower using CT than other detection routes, and no significant difference in limited stage proportion was observed (6.8% vs 10.8%, P>0.05). CONCLUSION: CT screening can detect more early stage non-small cell lung cancers, but not all of them could be beneficial as there are a considerable number of indolent ones such as bronchioloalveolar adenocarcinomas. Still, current evidence is lacking regarding small cell lung cancers.