Human papillomavirus infection and the risk of cancer at specific sites other than anogenital tract and oropharyngeal region: an umbrella review.

BACKGROUND: Despite numerous studies having evaluated the associations between human papillomavirus (HPV) infection and risk of specific cancers other than anogenital tract and oropharyngeal, the findings are inconsistent and the quality of evidence has not been systematically quantified. We aimed to summarise the existing evidence as well as to evaluate the strength and credibility of these associations. METHODS: We conducted an umbrella review of systematic reviews and meta-analyses of observational studies. PubMed, EMBASE, and Web of Science were searched from inception to March 2024. Studies with systematic reviews and meta-analyses that examined associations between HPV or HPV-associated genotypes infection and specific cancers were eligible for this review. The quality of the methodology was evaluated using A Measurement Tool to Assess systematic Reviews (AMSTAR). The credibility of the evidence was assessed using GRADE. The protocol was preregistered with PROSPERO (CRD42023439070). FINDINGS: The umbrella review identified 31 eligible studies reporting 87 associations with meta-analytic estimates, including 1191 individual studies with 336,195 participants. Of those, 29 (93.5%) studies were rated as over moderate quality by AMSTAR. Only one association indicating HPV-18 infection associated with an increased risk of breast cancer (odds ratio [OR] = 3.48, 95% confidence interval [CI] = 2.24-5.41) was graded as convincing evidence. There were five unique outcomes identified as highly suggestive evidence, including HPV infection increased the risk of oral squamous cell carcinoma (OR = 7.03, 95% CI = 3.87-12.76), oesophageal cancer (OR = 3.32, 95% CI = 2.54-4.34), oesophageal squamous cell carcinoma (OR = 2.69, 95% CI = 2.05-3.54), lung cancer (OR = 3.60, 95% CI = 2.59-5.01), and breast cancer (OR = 6.26, 95% CI = 4.35-9.00). According to GRADE, one association was classified as high, indicating that compared with the controls in normal tissues, HPV infection was associated with an increased risk of breast cancer. INTERPRETATION: The umbrella review synthesised up-to-date observational evidence on HPV infection with the risk of breast cancer, oral squamous cell carcinoma, oesophageal cancer, oesophageal squamous cell carcinoma, and lung cancer. Further larger prospective cohort studies are needed to verify the associations, providing public health recommendations for prevention of disease. FUNDING: National Key Research and Development Program of China, Natural Science Foundation of China, Outstanding Scientific Fund of Shengjing Hospital of China Medical University, and 345 Talent Project of Shengjing Hospital of China Medical University.

Unraveling reproductive and maternal health challenges of women living with HIV/AIDS in Vietnam: a qualitative study.

BACKGROUND: Human Immunodeficiency Virus (HIV) remains a significant public health concern worldwide. Women living with HIV/AIDS (WLHA) have the additional and unique need to seek sexual and reproductive health services. WLHA's maternal health journeys can be shaped by the cultural norms and resources that exist in their society. This study sought to understand if and how WLHA's family planning, pregnancy, and motherhood experiences could be influenced by the patriarchal culture, gender roles, and HIV stigma in Vietnam, specifically. METHODS: Between December 2021 and March 2022, 30 WLHA with diverse socioeconomic backgrounds and childbirth experiences were interviewed in Hanoi, Vietnam. These semi-structured interviews covered topics including HIV stigma, gender norms, pregnancy experiences, and child-rearing challenges. Interviews were audio recorded, transcribed, and analysed using ATLAS.ti. RESULTS: Qualitative analyses of participant quotes revealed how limited information on one's health prospects and reproductive options posed a significant challenge to family planning. Societal and familial expectations as well as economic circumstances also influenced reproductive decision-making. WLHA often encountered substandard healthcare during pregnancy, labor, and delivery. Stigma and lack of provider attentiveness resulted in cases where women were denied pain relief and other medical services. Communication breakdowns resulted in failure to administer antiretroviral therapy for newborns. Motherhood for WLHA was shadowed by concerns for not only their own health, but also the wellbeing of their children, as HIV stigma affected their children at school and in society as well. Many WLHA highlighted the constructive or destructive role that family members could play in their childbirth decision-making and care-giving experiences. CONCLUSIONS: Overall, this study underscores the complex ways that cultural expectations, family support, and stigma in healthcare impact WLHA. Efforts to educate and engage families and healthcare providers are warranted to better understand and address the needs of WLHA, ultimately improving their reproductive and maternal health.

HIV-related stigma and discrimination have consequential impacts on health and quality of life for women living with HIV (WLHA). WLHA in Vietnam must navigate the additional challenges of a traditionally patriarchal and hierarchical society. Women typically face less educational and occupational opportunities and are often expected to defer to expectations of family and virtue. Stigma among family members, friends, employers, and healthcare providers poses a significant challenge to WLHA autonomy, especially as it relates to their reproductive health decision-making and maternal health experiences. This study aims to better understand the experiences of WLHA throughout family planning, pregnancy, and motherhood. The findings will hopefully shed light on strategies to empower WLHA and to combat HIV- and gender-based stigma not only in Vietnam, but also globally.

Global epidemiology of early-onset liver cancer attributable to specific aetiologies and risk factors from 2010 to 2019.

Background: Considering its emergence as a public health concern worldwide, with potential spatial-temporal heterogeneities, we aimed to determine the global burden of early-onset liver cancer attributable to aetiologies and concomitant risk factors. Methods: We used data from the Global Burden of Diseases Study 2019 to determine age-standardised disability-adjusted life-year (DALY) rates for early-onset liver cancer by aetiologies and the population DALYs attributable to concomitant risk factors between 2010 and 2019. We also calculated estimated annual percentage changes (EAPCs) to measure temporal trends. Results: There were 2.9 million DALYs related to early-onset liver cancer globally in 2019. East Asia contributed over half of DALYs, which increased annually by 1.23% (95% confidence interval (CI) = 0.71, 1.76) between 2010 and 2019. Non-alcoholic steatohepatitis was the only growing aetiology. The proportion of DALYs attributed to metabolic risks increased by 22.50% (95% CI = 14.33, 38.13), while behavioral risks remained stable. Obesity surpassed smoking as the most prevalent nondeterministic aetiological risk factor from 2010 to 2019, while the population DALY attributable to hepatitis B combined with obesity increased by 29.93% (95% CI = 8.49, 60.77) in the same period, making it the principal joint contributor. Conclusions: Early-onset liver cancer poses considerable disability and continues to increase in many regions, especially in East Asia. Metabolic risk factors, particularly when hepatitis B and obesity coexist, are the fastest-growing contributors to this type of cancer. More targeted interventions are imperative to curb the growing burden of early-onset liver cancer due to metabolic risks.

N6-methyladenosine related gene expression signatures for predicting the overall survival and immune responses of patients with colorectal cancer.

N6-methyladenosine (m6A) modification has been demonstrated to exhibit a crucial prognostic effect on colorectal cancer (CRC). Nonetheless, potential mechanism of m6A in survival rate and immunotherapeutic response remains unknown. Here we investigated the genes associated with m6A regulators and developed a risk score for predicting the overall survival (OS) of CRC patients. RNA-seq transcriptomic profiling data of COAD/READ samples were obtained from The Cancer Genome Atlas (TCGA) database. Absolute Shrinkage and Selection Operator (LASSO)- Cox regression analysis was conducted to identify the m6A-related gene expression signatures and the selected genes were inputted into stepwise regression to develop a prognostic risk score in TCGA, and its predictive performance of CRC survival was further validated in Gene Expression Omnibus (GEO) datasets. According to our results, the risk score comprising 18 m6A-related mRNAs was significantly associated with CRC survival in both TCGA and GEO datasets. And the stratified analysis also confirmed that high-risk score acted as a poor factor in different age, sex, T stage, and tumour, node, metastasis (TNM) stages. The m6A-related prognostic score in combination with clinical characteristics yielded time-dependent area under the receiver operating characteristic curve (AUCs) of 0.85 (95%CI: 0.79-0.91), 0.84 (95%CI: 0.79-0.90) and 0.80 (95%CI: 0.71-0.88) for the prediction of the 1-, 3-, 5-year OS of CRC in TCGA cohort. Furthermore, mutation of oncogenes occurred more frequently in the high-risk group and the composition of immune cells in tumour microenvironment (TME) was significantly distinct between the low- and high-risk groups. The low-risk group had a lower microsatellite instability (MSI) score, T-cell exclusion score and dysfunction score, implying that low-risk patients may have a better immunotherapy response than high-risk patients. In summary, a prognostic risk score derived from m6A-related gene expression signatures could serve as a potential prognostic predictor for CRC survival and indicator for predicting immunotherapy response in CRC patients.

Age-Specific Prevalence of Anal and Cervical Human Papillomavirus Infection and High-Grade Lesions in 11 177 Women by Human Immunodeficiency Virus Status: A Collaborative Pooled Analysis of 26 Studies.

BACKGROUND: Age-specific data on anal, and corresponding cervical, human papillomavirus (HPV) infection are needed to inform female anal cancer prevention. METHODS: We centrally reanalyzed individual-level data from 26 studies reporting HPV prevalence in paired anal and cervical samples by human immunodeficiency virus (HIV) status and age. For women with HIV (WWH) with anal high-grade squamous intraepithelial lesions or worse (HSIL+), we also investigated concurrent cervical cytopathology. RESULTS: In HIV-negative women, HPV16 prevalence decreased significantly with age, both at anus (4.3% at 15-24 years to 1.0% at ≥55 years; ptrend = 0.0026) and cervix (7.4% to 1.7%; ptrend < 0.0001). In WWH, HPV16 prevalence decreased with age at cervix (18.3% to 7.2%; ptrend = 0.0035) but not anus (11.5% to 13.9%; ptrend = 0.5412). Given anal HPV16 positivity, concurrent cervical HPV16 positivity also decreased with age, both in HIV-negative women (ptrend = 0.0005) and WWH (ptrend = 0.0166). Among 48 WWH with HPV16-positive anal HSIL+, 27 (56%) were cervical high-risk HPV-positive, including 8 with cervical HPV16, and 5 were cervical HSIL+. CONCLUSIONS: Age-specific shifts in HPV16 prevalence from cervix to anus suggest that HPV infections in the anus persist longer, or occur later in life, than in the cervix, particularly in WWH. This is an important consideration when assessing the utility of cervical screening results to stratify anal cancer risk.

An adaptive design to screen, treat, and retain people with opioid use disorders who use methamphetamine in methadone clinics (STAR-OM): study protocol of a clinical trial.

BACKGROUND: Methamphetamine use could jeopardize the current efforts to address opioid use disorder and HIV infection. Evidence-based behavioral interventions (EBI) are effective in reducing methamphetamine use. However, evidence on optimal combinations of EBI is limited. This protocol presents a type-1 effectiveness-implementation hybrid design to evaluate the effectiveness, cost-effectiveness of adaptive methamphetamine use interventions, and their implementation barriers in Vietnam. METHOD: Design: Participants will be first randomized into two frontline interventions for 12 weeks. They will then be placed or randomized to three adaptive strategies for another 12 weeks. An economic evaluation and an ethnographic evaluation will be conducted alongside the interventions. PARTICIPANTS: We will recruit 600 participants in 20 methadone clinics. ELIGIBILITY CRITERIA: (1) age 16+; (2) Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) scores ≥ 10 for methamphetamine use or confirmed methamphetamine use with urine drug screening; (3) willing to provide three pieces of contact information; and (4) having a cell phone. OUTCOMES: Outcomes are measured at 13, 26, and 49 weeks and throughout the interventions. Primary outcomes include the (1) increase in HIV viral suppression, (2) reduction in HIV risk behaviors, and (3) reduction in methamphetamine use. COVID-19 response: We developed a response plan for interruptions caused by COVID-19 lockdowns to ensure data quality and intervention fidelity. DISCUSSION: This study will provide important evidence for scale-up of EBIs for methamphetamine use among methadone patients in limited-resource settings. As the EBIs will be delivered by methadone providers, they can be readily implemented if the trial demonstrates effectiveness and cost-effectiveness. TRIAL REGISTRATION: ClinicalTrials.gov NCT04706624. Registered on 13 January 2021. https://clinicaltrials.gov/ct2/show/NCT04706624.

The Health Impact of MAFLD, a Novel Disease Cluster of NAFLD, Is Amplified by the Integrated Effect of Fatty Liver Disease-Related Genetic Variants.

BACKGROUND & AIMS: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a newly proposed disease category that derived from non-alcoholic fatty liver disease. The impact of MAFLD on health events has not been investigated. METHODS: UK Biobank participants were diagnosed for whether MAFLD presented at baseline. Five genetic variants (PNPLA3 rs738409 C/G, TM6SF2 rs58542926 C/T, GCKR rs1260326 T/C, MBOAT7 rs641738 C/T, and HSD17B13 rs72613567 T/TA) were integrated into a genetic risk score (GRS). Cox proportional hazard model was used to examine the association of MAFLD with incident diseases. RESULTS: A total of 160 979 (38.0%, 95% confidence interval [CI] 37.9%, 38.2%) participants out of 423 252 were diagnosed as MAFLD. Compared with participants without MAFLD, MAFLD cases had multivariate adjusted hazard ratio (HR) for liver cancer of 1.59 (95% CI, 1.28, 1.98), cirrhosis of 2.77 (2.29, 3.36), other liver diseases of 2.09 (1.95, 2.24), cardiovascular diseases of 1.39 (1.34, 1.44), renal diseases of 1.56 (1.48, 1.65), and cancers of 1.07 (1.05, 1.10). The impact of MAFLD, especially on hepatic events, was amplified by high GRS, of which the genetic variations in PNPLA3, TM6SF2, and MBOAT7 play the principal roles. MAFLD case with normal body weight is also associated with an increased risk of hepatic outcomes, but the genetic factor seems do not influence the risk in this subpopulation. CONCLUSIONS: MAFLD is independently associated with an increased risk of both intrahepatic and extrahepatic events. Fatty liver disease related genetic variants amplify the effect of MAFLD on disease outcomes.

Metabolic dysfunction-associated fatty liver disease and the risk of 24 specific cancers.

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a significant health issue closely associated with multiple metabolic dysfunctions. The association between MAFLD and cancer risk is yet unknown. METHODS: UK Biobank study participants were diagnosed for the presence of MAFLD at baseline. A multivariable Cox regression model was performed to examine the associations of MAFLD with incident events in 24 specific cancers. RESULTS: We included 352,911 individuals (37.2% with MAFLD), among whom 23,345 developed cancers. Compared with non-MAFLD, MAFLD was significantly associated with 10 of the 24 examined cancers, including corpus uteri (hazard ratio [HR] = 2.36, 95% CI 1.99-2.80), gallbladder (2.20, 1.14-4.23), liver (1.81, 1.43-2.28), kidney (1.77, 1.49-2.11), thyroid (1.69, 1.20-2.38), esophagus (1.48, 1.25-1.76), pancreas (1.31, 1.10-1.56), bladder (1.26, 1.11-1.43), breast (1.19, 1.11-1.27), and colorectal and anus cancers (1.14, 1.06-1.23). The associations of MAFLD with liver, esophageal, pancreatic, colorectal and anal and bladder cancers and malignant melanoma were strengthened in males, and associations with kidney, thyroid, and lung cancers were increased in females. The associations of MAFLD with the risk of liver, kidney, and thyroid cancers remained significant after further adjusting for the waist circumference or body mass index and the number of metabolic syndrome components based on the main models. The risk-increasing allele of PNPLA3 rs738409 significantly amplified the association of MAFLD with the risk of liver and kidney cancers. CONCLUSION: MAFLD is associated with an increased risk of a set of cancers, but the effect substantially varies by site. MAFLD deserves higher priority in the current scheme of cancer prevention.

HCV infection status and care seeking among people living with HIV who use drugs in Vietnam.

HCV co-infection is widespread among people living with HIV who use drugs (PLHWUD). However, HCV testing was inconsistently implemented among PLHWUD. The low infection awareness and mental health challenges together impede PLHWUD's treatment-seeking. The study used baseline data of a randomized controlled trial conducted in Vietnam. HCV infection status was collected through self-report and medical record review. A linear mixed-effects regression model was used to examine the relationships between PLHWUD's perceived barriers to seeking healthcare, their depressive symptoms, and the consistencies in HCV status reports. Among the 181 PLHWUD in the study, one-third (64; 35.4%) had inconsistent self-reports and medical records of HIV infection status. The agreement between the two records was fair (Kappa statistics = 0.43). PLHWUD with consistent HCV infection confirmed by both medical records and self-reports perceived lower levels of healthcare-seeking barriers than those with discrepant HCV reports (estimated difference = -1.59, SE = 0.71, P = 0.027). Depressive symptoms were significantly correlated with healthcare-seeking barriers among those with discrepant HCV results (estimate = 0.17, SE = 0.06, P = 0.007). There is an urgent need to extend HCV screening efforts and increase HCV awareness among PLHWUD. Explicit HCV result notification and integrated mental health support are recommended to facilitate patients' access to needed care.

Risk prediction model for lung cancer incorporating metabolic markers: Development and internal validation in a Chinese population.

BACKGROUND: Low-dose computed tomography screening has been proved to reduce lung cancer mortality, however, the issues of high false-positive rate and overdiagnosis remain unsolved. Risk prediction models for lung cancer that could accurately identify high-risk populations may help to increase efficiency. We thus sought to develop a risk prediction model for lung cancer incorporating epidemiological and metabolic markers in a Chinese population. METHODS: During 2006 and 2015, a total of 122 497 people were observed prospectively for lung cancer incidence with the total person-years of 976 663. Stepwise multivariable-adjusted logistic regressions with Pentry  = .15 and Pstay  = .20 were conducted to select the candidate variables including demographics and metabolic markers such as high-sensitivity C-reactive protein (hsCRP) and low-density lipoprotein cholesterol (LDL-C) into the prediction model. We used the C-statistic to evaluate discrimination, and Hosmer-Lemeshow tests for calibration. Tenfold cross-validation was conducted for internal validation to assess the model's stability. RESULTS: A total of 984 lung cancer cases were identified during the follow-up. The epidemiological model including age, gender, smoking status, alcohol intake status, coal dust exposure status, and body mass index generated a C-statistic of 0.731. The full model additionally included hsCRP and LDL-C showed significantly better discrimination (C-statistic = 0.735, P = .033). In stratified analysis, the full model showed better predictive power in terms of C-statistic in younger participants (<50 years, 0.709), females (0.726), and former or current smokers (0.742). The model calibrated well across the deciles of predicted risk in both the overall population (PHL  = .689) and all subgroups. CONCLUSIONS: We developed and internally validated an easy-to-use risk prediction model for lung cancer among the Chinese population that could provide guidance for screening and surveillance.

The association between fasting blood glucose trajectory and cancer risk in Chinese population without diabetes.

To examine the associations between fasting blood glucose (FBG) trajectories, the changes in FBG over time and the risk of cancer, particularly for gastrointestinal cancer, we enrolled 69,742 participants without diabetes from the Kailuan cohort. FBG trajectories (2006-2010) were modeled by group-based trajectory modeling, and five trajectories were identified: low-increasing (n = 6,275), moderate-stable (n = 44,120), moderate-increasing (n = 10,149), elevated-decreasing (n = 5,244) and elevated-stable (n = 3,954). A total of 1,364 cancer cases were accumulated between 2010 and 2015, including 472 gastrointestinal cancer cases. We used Cox proportional hazards regression models to evaluate the associations between FBG trajectory patterns and the risk of cancer. We further assessed the associations while carefully controlling for initial body mass index (BMI) in 2006 and for changes in BMI during 2006-2010. Relative to the moderate-stable group, we found a higher hazard ratio (HR) for overall cancer in the low-increasing group (HR = 1.26, 95% confidence interval (CI) 1.06-1.50); and for gastrointestinal cancer in the elevated-stable group (HR = 1.66, 95% CI 1.22-2.26). Moreover, among participants with an initial BMI ≥25 kg/m2 , a positive association with the low-increasing group was observed for both overall cancer and gastrointestinal cancer (HR = 1.54, 95% CI 1.17-2.04; HR = 1.65, 95% CI 1.02-2.66; respectively); among participants with a stable BMI (4.40% loss-5.15% gain), a positive association with the elevated-stable group was observed both for overall cancer and gastrointestinal cancer (HR = 1.43, 95% CI 1.10-1.87; HR = 1.95, 95% CI 1.33-2.86; respectively). Our study observed that FBG trajectories were associated with cancer risk among participants without diabetes, and BMI may modify the associations.

The disparities in gastrointestinal cancer incidence among Chinese populations in Shanghai compared to Chinese immigrants and indigenous non-Hispanic white populations in Los Angeles, USA.

Gastrointestinal cancer patterns are distinct among populations. Our study aims to compare the incidence and risk of gastrointestinal cancers between Chinese American and non-Hispanic whites in Los Angeles, CA, USA, to those of people indigenous to Shanghai to elucidate the changing patterns of gastrointestinal cancers. Cancer incidence data from 1988 to 2012 were extracted from the Cancer Incidence in Five Continents plus database. The age standardized incidence and estimated annual percentage change were calculated to estimate the temporal trends of gastrointestinal cancers. Traditional Poisson regression models and three-factor constrained Poisson regression models were applied to compare the gastrointestinal cancer risk across populations. The incidences of oesophageal, stomach, liver and gall bladder cancers were higher among indigenous Chinese residents of Shanghai than among the other two populations in Los Angeles. While the incidences of colorectal and pancreatic cancer were higher among non-Hispanic whites, Chinese American immigrants were considered to be at an intermediate level for most gastrointestinal cancers. The gender-specific gastrointestinal cancer disparities across populations, especially between Shanghai Chinese and non-Hispanic US whites, were significant regardless of age, period or cohort scale. However, the regional differences in gastrointestinal cancer rates decreased over time. Most gastrointestinal cancer patterns in Chinese American immigrants were more aligned to those of their new country of residence than to those of their original country. The disparities in gastrointestinal cancers across populations indicate that environmental factors might play a key role in cancer genesis. Shift in environmental exposures may result in significant changes in gastrointestinal cancer incidence.

Development of a risk score for colorectal cancer in Chinese males: A prospective cohort study.

To build a simple predictive model as a guide to stratify average-risk population for colonoscopy examinations. We collected data from 92 923 males without a prior history of cancer enrolled in the Kailuan Cohort Study of China. Risk factors included in the evaluation of colorectal cancer (CRC) were collected by questionnaire-based interviews at the baseline. Logistic regression coefficients for incident CRC predictors were converted into risk scores by the absolute value of the smallest coefficient in the model and rounding up to the nearest integer. Receiver operating characteristic (ROC) analysis with the leave-one-out cross-validation method was applied to evaluate model performance. In the 10-year follow-up, 353 CRC patients were in the cohort. Age, alcohol consumption, waist circumference, occupational sitting time, and history of diabetes were selected for the scoring system, and the adjusted area under the ROC was 0.66. Population in the highest risk group (16-19 points) had a 33.12-fold (95% CI: 13.44-81.59) higher risk of CRC than those in the lowest risk group. When we defined 13 points as the cut-off, the sensitivity and specificity of the scoring system for CRC were 67.99% and 62.42%, respectively. A simple scoring system for CRC has been developed to identify men at an increased relative risk of CRC within 10 years using several well-established risk factors, which allows selection of asymptomatic candidates for priority of CRC screening and saving the health resource in cancer prevention and control.

Cervical determinants of anal HPV infection and high-grade anal lesions in women: a collaborative pooled analysis.

BACKGROUND: Cervical cancer screening might contribute to the prevention of anal cancer in women. We aimed to investigate if routine cervical cancer screening results-namely high-risk human papillomavirus (HPV) infection and cytohistopathology-predict anal HPV16 infection, anal high-grade squamous intraepithelial lesions (HSIL) and, hence, anal cancer. METHODS: We did a systematic review of MEDLINE, Embase, and the Cochrane library for studies of cervical determinants of anal HPV and HSIL published up to Aug 31, 2018. We centrally reanalysed individual-level data from 13 427 women with paired cervical and anal samples from 36 studies. We compared anal high-risk HPV prevalence by HIV status, cervical high-risk HPV, cervical cytohistopathology, age, and their combinations, using prevalence ratios (PR) and 95% CIs. Among 3255 women with anal cytohistopathology results, PRs were similarly calculated for all anal HSIL and HPV16-positive anal HSIL. FINDINGS: Cervical and anal HPV infections were highly correlated. In HIV-negative women, anal HPV16 prevalence was 41% (447/1097) in cervical HPV16-positive versus 2% (214/8663) in cervical HPV16-negative women (PR 16·5, 95% CI 14·2-19·2, p<0·0001); these values were 46% (125/273) versus 11% (272/2588) in HIV-positive women (4·4, 3·7-5·3, p<0·0001). Anal HPV16 was also associated with cervical cytohistopathology, with a prevalence of 44% [101/228] for cervical cancer in HIV-negative women (PR vs normal cytology 14·1, 11·1-17·9, p<0·0001). Anal HSIL was associated with cervical high-risk HPV, both in HIV-negative women (from 2% [11/527] in cervical high-risk HPV-negative women up to 24% [33/138] in cervical HPV16-positive women; PR 12·9, 95% CI 6·7-24·8, p<0·0001) and HIV-positive women (from 8% [84/1094] to 17% [31/186]; 2·3, 1·6-3·4, p<0·0001). Anal HSIL was also associated with cervical cytohistopathology, both in HIV-negative women (from 1% [5/498] in normal cytology up to 22% [59/273] in cervical HSIL; PR 23·1, 9·4-57·0, p<0·0001) and HIV-positive women (from 7% [105/1421] to 25% [25/101]; 3·6, 2·5-5·3, p<0·0001). Prevalence of HPV16-positive anal HSIL was 23-25% in cervical HPV16-positive women older than 45 years (5/20 in HIV-negative women, 12/52 in HIV-positive women). INTERPRETATION: HPV-based cervical cancer screening programmes might help to stratify anal cancer risk, irrespective of HIV status. For targeted secondary anal cancer prevention in high-risk groups, HIV-negative women with cervical HPV16, especially those older than 45 years, have a similar anal cancer risk profile to that of HIV-positive women. FUNDING: International Agency for Research on Cancer.

Disparities by province, age, and sex in site-specific cancer burden attributable to 23 potentially modifiable risk factors in China: a comparative risk assessment.

BACKGROUND: Understanding disparities in the burden of cancer attributable to different risk factors is crucial to inform and improve cancer prevention and control. In this report, we estimate the site-specific population-attributable fractions (PAFs) for 23 potentially modifiable risk factors across all provinces in China. METHODS: In this comparative risk assessment study, we used 2014 cancer mortality data for adults from 978 county-level surveillance points in 31 provinces of mainland China. Risk-factor prevalence estimates were obtained from representative surveys. We used summary relative risks obtained from several recent large-scale pooled analyses or high-quality meta-analyses of studies in China. We calculated PAFs using multiple formulae incorporating exposure prevalence and relative risk data stratified by age, sex and province and then combined to create summary PAFs by sex, cancer site, and risk factors. FINDINGS: About 1 036 004 cancer deaths (45·2% of all cancer deaths [95% CI 44·0-46·4]) in China in 2014 in adults aged 20 years or older were attributable to 23 evaluated risk factors. The PAF was higher in men (51·2% [95% CI 50·0-52·4]) than in women (34·9% [33·6-36·2]), with the leading risk factors being active smoking in men and low fruit intake in women. By province, the PAF in both sexes combined ranged from 35·2% in Shanghai to 52·9% in Heilongjiang, while the PAF varied from 40·9% in Shanghai to 56·4% in Guangdong among men and from 26·9% in Shanghai to 48·0% in Heilongjiang among women. The highest PAF among men was smoking in all 31 provinces, whereas among women it varied among low fruit intake (14 provinces), hepatitis B virus infection (seven provinces), smoking (six provinces), excess bodyweight (three provinces), and human papilloma virus infection (one province). INTERPRETATION: The PAFs of cancers attributable to potentially modifiable risk factors vary substantially across provinces in China. Regional adoption of effective primary cancer prevention strategies has a vast potential to reduce the burden of cancer and disparities in China. Smoking, poor diet, and infection warrant particular policy attention as they contributed a large proportion to the total cancer burden. FUNDING: National Science and Technology Basic Research Special Foundation of China.

Type-Specific Anal Human Papillomavirus Prevalence Among Men, According to Sexual Preference and HIV Status: A Systematic Literature Review and Meta-Analysis.

Background: Anal human papillomavirus (HPV) infection, most notably HPV16, the central cause of anal cancer, is increased by anal sexual intercourse and worsened by human immunodeficiency virus (HIV)-positivity. Methods: A systematic review and meta-analysis of type-specific anal HPV prevalence in men, compared according to sexual preference, HIV status, and, when available, anal cytopathology. Results: Seventy-nine eligible studies included: 1805 HIV-negative men who have sex with women (MSW), 924 HIV-positive MSW, 8213 HIV-negative men who have sex with men (MSM), and 12758 HIV-positive MSM. Irrespective of anal cytopathology, HPV16 prevalence was significantly higher in MSM than MSW, both among HIV-negative (14% vs 3%; prevalence ratio (PR) 4.7; 95% confidence interval [CI] 2.5-8.9) and HIV-positive men (30% vs 11%; PR = 2.8; 95% CI, 1.9-4.1). Likewise, HPV16 was significantly higher in HIV-positive than HIV-negative men, both among MSW (PR = 3.5; 95% CI, 1.6-7.7) and MSM (PR = 2.1; 95% CI, 1.8-2.5). Anal HPV16 prevalence was similar between HIV-positive MSW and HIV-negative MSM. For MSM, anal HPV16 prevalence was significantly higher from studies with anal cytopathology, suggesting population sampling effects. Conclusion: Sexual preference and HIV infection are independent strong determinants of male anal HPV16 infection, confirming HIV-positive MSM as priorities for anal cancer prevention.

Family Related Factors and Concurrent Heroin Use in Methadone Maintenance Treatment in China.

BACKGROUND: The use of heroin during Methadone Maintenance Treatment (MMT) is a challenging problem that contributes to poor treatment outcomes. Families may play an important role in addressing concurrent heroin use during MMT, especially in collectivist societies such as China. OBJECTIVES: In this study, we explored the relationship between family-related factors and concurrent heroin use during MMT in China. METHODS: This study was conducted at 68 MMT clinics in five provinces of China. There were 2,446 MMT clients in the analysis. Demographic information, MMT dosage, family members' heroin use status, family support of MMT, family problem, and self-reported heroin use were collected in a cross-sectional survey. The most recent urinalysis of opiate use was obtained from clinical records. RESULTS: Of the 2,446 participants, 533 (21.79%) self-reported heroin use in the previous seven days or had a positive urine morphine test result in the clinic record. Participants whose family member[s] used heroin were 1.59 times (95% CI: 1.17, 2.15) more likely to use concurrently during treatment. Those with family members who totally support them on the MMT were less likely to use (AOR: 0.75, 95% CI: 0.60, 0.94). Having more family problems was positively associated with concurrent heroin use (AOR: 2.01, 95% CI: 1.03, 3.93). CONCLUSIONS: The results highlight the importance of the family's role in concurrent heroin use during MMT programs. The study's findings may have implications for family-based interventions that address concurrent heroin use.

Human papillomavirus types from infection to cancer in the anus, according to sex and HIV status: a systematic review and meta-analysis.

BACKGROUND: Data on carcinogenicity of human papillomavirus (HPV) types in the anus are needed to inform anal cancer prevention through vaccination and screening. This is particularly the case for people infected with HIV, who are at an increased risk of anal cancer. METHODS: We did a systematic review of studies published from January, 1986, to July, 2017, in MEDLINE, Embase, and the Cochrane Library on anal HPV infection, without any language restrictions. Eligible studies reported type-specific HPV prevalence by strata of cytopathological or histopathological anal diagnosis, sex, and HIV status. Data requests were made to authors when necessary. We did a meta-analysis of type-specific HPV prevalence across the full spectrum of anal diagnoses, from normal cytology to anal cancer. We assessed the main outcome of type-specific HPV prevalence ratios [PR], calculated across strata of anal diagnoses, gender, or HIV status, by use of generalised linear models. FINDINGS: 95 studies were identified from the search, published between 1992-2017, from which 18 646 individuals fulfilled the criteria for inclusion in the analyses: 8534 people with normal cytology, 5730 with low-grade lesions, 2024 with high-grade lesions, and 2358 with anal cancer. HPV prevalence varied in normal cytology from 42% in HIV-negative women to 76% in HIV-positive men and, for each diagnosis, was higher in individuals who were HIV positive than those who were HIV negative. HPV16 positivity increased with diagnosis severity, being the only HPV type accounting for more HPV infection in anal cancer than normal cytology, both in individuals who were HIV negative (PR 5·0, 95% CI 3·8-6·6, p<0·0001) and those who were HIV positive (2·3, 1·9-2·7, p<0·0001). HPV16 positivity increased even between high-grade lesions and anal cancer, whereas other high-risk HPV types accounted for high proportions of low-grade or high-grade lesions but their prevalence decreased in anal cancer. However, HPV16 was less frequent in HIV-positive than HIV-negative anal cancer, both in men (PR 0·8, 95% CI 0·7-0·9, p<0·0001) and women (0·8, 0·6-1·0, p=0·063), and in HIV-positive versus HIV-negative high-grade lesions in women (0·6, 0·5-0·9, p=0·0077). Type-specific attribution of the non-HPV16 fraction of HIV-positive anal cancer is hindered by a high prevalence of multiple HPV infections. INTERPRETATION: HPV16 is by far the most carcinogenic HPV type in the anus, with enrichment of HPV16 even from high-grade lesions to anal cancer, both in individuals who are HIV negative and those who are HIV positive. Nevertheless, the fraction of anal cancer attributable to HPV16 is smaller in the HIV-positive population. FUNDING: International Agency for Research on Cancer.

Commune Health Workers' Methadone Maintenance Treatment (MMT) Knowledge and Perceived Difficulties Providing Decentralized MMT Services in Vietnam.

BACKGROUND: With the initial establishment of countrywide methadone maintenance therapy (MMT) system, Vietnam is in the process of expanding and decentralizing the MMT program to community-based healthcare settings. OBJECTIVE: The study aimed to measure the MMT-related knowledge and perceived difficulties in treating patient who use drugs (PWUD) among community-based healthcare providers, e.g., commune health workers (CHW), and examine its correlated factors. METHODS: A total of 300 CHW from 60 communes in two provinces of Vietnam completed a survey using Audio Computer-Assisted Self-Interview (ACASI) method. Twelve true-or-false questions were used to assess the CHW's MMT-related knowledge. The CHW's background characteristics and perceived difficulties treating PWUD were recorded. RESULTS: The mean MMT knowledge score was 8.2 (SD = 1.2; range: 5-11). Misconceptions toward the benefits, procedure, and side effects of MMT were prevalent. The participants perceived varying degrees of difficulties in recruiting, engaging, and communicating with PWUD. With all covariates holding constant, younger age (standardized ẞ = -0.166; p = 0.0078) was associated with less MMT-related knowledge. Number of PWUD seen in a month and MMT-related knowledge was associated with less perceived difficulties treating PWUD. Conclusions/importance: The finding shed lights on the CHW's knowledge gap, which need to be addressed to facilitate the decentralization of MMT services in Vietnam. In preparation for a decentralized MMT service delivery model, specially designed training is warranted to equip CHW with knowledge and confidence to provide MMT-related services to PWUD.

An evaluation of clinical performance of FTA cards for HPV 16/18 detection using cobas 4800 HPV Test compared to dry swab and liquid medium.

BACKGROUNDS: Effective dry storage and transport media as an alternative to conventional liquid-based medium would facilitate the accessibility of women in the low-resource settings to human papillomavirus (HPV)- based cervical cancer screening. OBJECTIVE: To evaluate analytical and clinical performance of indicating FTA™ Elute Cartridge (FTA card) for the detection of HPV16/18 and cervical precancerous lesions and cancer compared to dry swab and liquid medium. STUDY DESIGN: Ninety patients with abnormal cytology and/or HPV infection were included for analysis. Three specimens of cervical exfoliated cells from each woman were randomly collected by FTA card, dry swab or liquid-based medium prior to colposcopy examination. The subsequent HPV DNA tests were performed on cobas 4800 HPV platform. RESULTS AND CONCLUSIONS: High-risk HPV (hrHPV) positivity rate was 63.3%, 62.2% and 65.6% for samples collected by FTA card, dry swab and liquid medium, respectively. The overall agreements and kappa values for the detection of hrHPV, HPV 16 and HPV 18 between FTA card and liquid-based medium were 88.9% (κ=0.76), 97.8% (κ=0.94) and 100% (κ=1.0),respectively; between FTA card and dry swab were 92.1% (κ=0.83), 94.5% (κ=0.87) and 100% (κ=1.0), respectively. The performances of hrHPV tested by FTA card, dry swab, and liquid-based medium for detecting CIN2+ were comparable in terms of the sensitivity and specificity. The specificity of detection of CIN2+ by HPV16/18 increased by approximately 40% compared to hrHPV for any medium albeit at cost of a moderate loss of sensitivity. Dry medium might offer an alternative to conventional liquid-based medium in the HPV-based cervical cancer screening program especially in low-resource settings but still needs further evaluation.