Efficacy and immunogenicity of AS04-HPV-16/18 vaccine in females with existing cervical HR-HPV infection at first vaccination: A pooled analysis of four large clinical trials worldwide.

Females with existing high-risk HPV (HR-HPV) infections remain at risk of subsequent multiple or recurrent infections, on which benefit from HPV vaccines was under-reported. We pooled individual-level data from four large-scale, RCTs of AS04-HPV-16/18 vaccine to evaluate efficacy and immunogenicity in females DNA-positive to any HR-HPV types at first vaccination. Females receiving the AS04-HPV-16/18 vaccine in the original RCTs constituted the vaccine group in the present study, while those unvaccinated served as the control group. Vaccine efficacy (VE) against new infections and associated cervical intraepithelial neoplasia (CIN) 2+ in females DNA-negative to the considered HR-HPV type but positive to any other HR-HPV types, VE against reinfections in females DNA-positive to the considered HR-HPV type but cleared naturally during later follow-up, and levels of anti-HPV-16/18 IgG were assessed. Our final analyses included 5137 females (vaccine group = 2532, control group = 2605). The median follow-up time was 47.88 months (IQR: 45.72-50.04). For the prevention of precancerous lesions related to the non-infected HR-HPV types at baseline, VE against HPV-16/18 related CIN 2+ was 82.70% (95% CI: 63.70-93.00%). For the prevention of reinfections related to the infected HR-HPV types following natural clearance, VE against HPV-16/18 12MPI was non-significant (p > .05), albeit robust immunity persisted for at least 48 months. Females with existing HR-HPV infections at first vaccination still benefit from vaccination in preventing precancers related to the non-infected types at baseline. VE against reinfections related to the infected types following natural clearance remains to be further investigated.

Cost-effectiveness of the screen-and-treat strategies using HPV test linked to thermal ablation for cervical cancer prevention in China: a modeling study.

BACKGROUND: Self-sampling HPV test and thermal ablation are effective tools to increase screening coverage and treatment compliance for accelerating cervical cancer elimination. We assessed the cost-effectiveness of their combined strategies to inform accessible, affordable, and acceptable cervical cancer prevention strategies. METHODS: We developed a hybrid model to evaluate costs, health outcomes, and incremental cost-effectiveness ratios (ICER) of six screen-and-treat strategies combining HPV testing (self-sampling or physician-sampling), triage modalities (HPV genotyping, colposcopy or none) and thermal ablation, from a societal perspective. A designated initial cohort of 100,000 females born in 2015 was considered. Strategies with an ICER less than the Chinese gross domestic product (GDP) per capita ($10,350) were considered highly cost-effective. RESULTS: Compared with current strategies in China (physician-HPV with genotype or cytology triage), all screen-and-treat strategies are cost-effective and self-HPV without triage is optimal with the most incremental quality-adjusted life-years (QALYs) gained (220 to 440) in rural and urban China. Each screen-and-treat strategy based on self-collected samples is cost-saving compared with current strategies (-$818,430 to -$3540) whereas more costs are incurred using physician-collected samples compared with current physician-HPV with genotype triage (+$20,840 to +$182,840). For screen-and-treat strategies without triage, more costs (+$9404 to +$380,217) would be invested in the screening and treatment of precancerous lesions rather than the cancer treatment compared with the current screening strategies. Notably, however, more than 81.6% of HPV-positive women would be overtreated. If triaged with HPV 7 types or HPV16/18 genotypes, 79.1% or 67.2% (respectively) of HPV-positive women would be overtreated with fewer cancer cases avoided (19 cases or 69 cases). CONCLUSIONS: Screen-and-treat strategy using self-sampling HPV test linked to thermal ablation could be the most cost-effective for cervical cancer prevention in China. Additional triage with quality-assured performance could reduce overtreatment and remains highly cost-effective compared with current strategies.

Clinical performance of a newly developed domestic urine-based HPV test for cervical cancer screening in China.

Although urine-based human papillomavirus (HPV) detection is promising in cervical cancer screening, it has not yet been well-developed. Women aged 30-65 were invited to participate in the current study to provide one urine and two paired vaginal samples. Urine was detected by polymerase chain reaction (PCR)-based HPV test (urine-based HPV test). Two vaginal samples were tested by careHPV and GenPlex® HPV genotyping assay, respectively. Women with vaginal HPV positive were called back for colposcopy and biopsied if clinically indicated. The consistency was 79.0% (κ = 0.563) and 80.5% (κ = 0.605) between the urine-based HPV test, careHPV test, and GenPlex® HPV genotyping assay. Against CIN2 detection, the careHPV test showed 77.4% sensitivity, and 71.0% specificity, while the GenPlex® HPV genotyping assay had a sensitivity of 100% and a specificity of 58.7%. For urine-based HPV test, the corresponding rates were 96.8% and 58.7%. Moreover, no significant differences were observed between the urine-based HPV test and careHPV test (p = 0.3395) and GenPlex® HPV genotyping assay (p = 0.338). The newly developed urine-based HPV test demonstrated acceptable consistency and comparable clinical performance with referenced HPV tests for vaginal samples. Therefore, urine-based HPV detection could be a useful alternative for women with difficulties to access cervical cancer screening.

Combined risk factors and risk of upper gastrointestinal cancer mortality in the Linxian general population.

We aimed to explore the association of combined risk factors with risk of death from upper gastrointestinal (UGI) cancer, including esophageal squamous cell carcinoma (ESCC), gastric cardia carcinoma (GCC) and gastric noncardia carcinoma (GNCC) in the Linxian Nutrition Intervention Trial (NIT) cohort. The NIT cohort included 29 584 healthy adults. A combined risk score (CRS) was calculated using a point system method based on 10 risk factors collected at baseline, including gender, smoking, alcohol drinking, body mass index, family history of UGI cancer, drinking tap water, tooth loss and consumption of fresh fruit, eggs and meat. Possible score ranged from 0 to 31, and higher score indicated as poorer health status. Subjects were divided into three groups by the CRS (<12 points, 12 to 20 points and >20 points). The group of CRS <12 points was considered as the reference. During the 30-year follow-up, we identified 4553 UGI cancer deaths. Compared to subjects with a CRS <12 points, the adjusted HRs for CRS of 12 to 20 points and >20 points were 1.69 (95% CI: 1.56-1.83) and 3.06 (95% CI: 2.82-3.33) for UGI cancer mortality, respectively (Ptrend < .001). Comparable associations were also observed for ESCC, GCC and GNCC mortality. Results remained similar across different age groups (Pinteraction > .05). All HRs observed in the second half follow-up period were stronger than that observed in the first half follow-up period. Our study indicated that higher CRS was associated with increased risk of UGI cancer mortality. Appropriate measures should be taken to reduce unhealthy lifestyles.

Arsenic, tobacco use, and lung cancer: An occupational cohort with 27 follow-up years.

BACKGROUND: We explored the shape of the exposure-response relationship of arsenic-related lung cancer and the interaction between arsenic and tobacco use. METHODS: A total of 3278 tin miners with at least 10 years of arsenic exposure were enrolled since 1992 and followed up for 27 years. After excluding radon-exposed miners and former smokers, 1620 miners were included into the sub-cohort. Lung cancer risks were estimated by modeling total exposure and intensity of arsenic exposure. RESULTS: The cohort experienced 73,866 person-years and 414 lung cancer cases. Firstly, the ERR/mg/m3-year was 0.0033 (95% CI: 0.0014-0.0045) in arsenic concentration <3 mg/m3 and 0.0056 (95% CI: 0.0035-0.0073) in arsenic concentration ≥3 mg/m3. After adjusting for cumulative arsenic exposure, and the ERR/mg/m3 increased with increasing intensity (0.129 (95% CI: 0.039, 0.189)). Secondly, an unique aspect of this population was the early age at first arsenic exposure for workers. Results showed that lung cancer incidence risk from exposed in childhood (<13 years) was non-significantly greater than those in other age groups (13-17 and ≥ 18 years). Finally, the most likely joint effects of inhaled arsenic and tobacco use was sub-multiplicative. CONCLUSION: This study enlightened us that for fixed cumulative arsenic exposure, higher concentration over shorter duration might be more deleterious than lower concentration over longer duration. Substantial reductions in the lung cancer burden of smokers exposed to arsenic could be achieved by reductions in either exposure.

Quantitative evaluation of radon, tobacco use and lung cancer association in an occupational cohort with 27 follow-up years.

BACKGROUND: Occupational radon cohorts provide important information about exposure at residential level, which are difficult to observe prospectively. However, evidence about radon-related lung cancer risks from initial exposure in childhood or interaction between radon and smoking is still limited. METHODS: A total of 6017 tin miners with at least 10 years of underground radon exposure were enrolled beginning in 1992 and followed for up to 27 years. Lung cancer risks were estimated by modeling total and intensity of radon exposure. RESULTS: A total of 933 lung cancer cases occurred in this cohort over 89,092 person-years of follow up. Excess relative risk increased by 0.96% per cumulative working level month (WLM). A unique aspect of this population was the early age at first radon exposure for workers. Results showed that lung cancer risk from initial radon exposure in childhood (<13 years old) was greater than risk when first exposure occurred at later ages (13-17, 18-24, and ≥ 25 years old). Moreover, risk declined with years since last exposure and attained age, but increased with age at last exposure. Importantly, these patterns were stable after adjustment for tobacco use or arsenic exposure. For joint effects of radon and other agents, our results support sub-multiplicative as the most likely model for interaction between radon and tobacco use or arsenic exposure. CONCLUSION: This study highlights the possible importance of radon exposure in childhood in cancer etiology and suggests another potential strategy to mitigate the global lung cancer burden.

Association Between Common Vaginal Infections and Cervical Non-Human Papillomavirus (HPV) 16/18 Infection in HPV-Vaccinated Women.

BACKGROUND: How vaginal infections such as bacterial vaginosis, Candida spp, and Trichomonas vaginalis affect persistence of human papillomavirus (HPV) infection is not well established. Our study aimed to evaluate the association between common vaginal infections and cervical non-HPV16/18 infection, as risk factors associated with persistence of nonvaccine HPV types will become increasingly relevant in the setting of HPV vaccination. METHODS: We performed an analysis in 2039 AS04-HPV16/18-vaccinated women enrolled in a phase II/III trial in China, who were HPV DNA negative at month 0 and 6 and had at least 1 subsequent follow-up visit. Vaginal infections were detected in liquid-based cytology according to the diagnostic criteria of the Bethesda System. Associations between vaginal infections and incident and 6-month persistent non-HPV16/18 infections in the cervix were evaluated using generalized estimating equations, adjusting for the age at initial vaccination, as well as HPV types in the persistence analysis. RESULTS: Study visits with any vaginal infection had a statistically significant increased risk of incident non-HPV16/18 infection compared to those without vaginal infections (odds ratio [OR], 1.44 [95% confidence interval {CI}, 1.09-1.92]). However, vaginal infections were not associated with 6-month persistent non-HPV16/18 infection (OR, 1.02 [95% CI, .62-1.69]). CONCLUSIONS: Our study suggests that common vaginal infections are not associated with persistence of non-HPV16/18 infection among HPV16/18-vaccinated women.

Efficacy of point-of-care thermal ablation among high-risk human papillomavirus positive women in China.

Thermal ablation is a point-of-care ablative treatment technique for cervical intraepithelial neoplasia (CIN). However, limited information is available about its efficacy in low- and middle-income countries. We evaluated the efficacy of thermal ablation in treatment of CIN detected through high-risk human papillomavirus (HPV) screening in China. Women positive on high-risk HPV and having colposcopically suspected lesions eligible for ablation underwent colposcopy, biopsy and thermal ablation in one visit. Women ineligible were recalled for large loop excision of transformation zone (LLETZ) when histopathology results were high-grade CIN. Posttreatment follow-up at 6 months or more was with HPV test and cytology followed by colposcopy and biopsy for HPV and/or cytology-positive women. Cure was defined as either negative cytology and HPV test or absence of histopathology proved CIN in any positive women. Of total 218 HPV-positive women treated with thermal ablation (n = 170) or LLETZ (n = 48), 196 reported for follow-up evaluation. For women with histologically confirmed CIN at baseline (thermal ablation-104; LLETZ-38), cure rates were 84.6% for thermal ablation and 86.8% for LLETZ. Cure rates after thermal ablation were 90.3% for CIN grade one (CIN1) and 76.2% for CIN grade two or worse (CIN2+). HPV clearance rate was 80.4% in women undergoing thermal ablation, which was lower for HPV16/18 compared to other oncogenic types (67.6% vs 85.7%). HPV test had a negative predictive value (NPV) of 98.7% to detect CIN2+ at follow-up and the positive predictive value (PPV) was 40.4%. Thermal ablation is effective to treat CIN as well as to clear the high-risk HPV infection. HPV test has high PPV and NPV in following up patients posttreatment.

Inequalities in Cervical Cancer Screening Uptake Between Chinese Migrant Women and Local Women: A Cross-Sectional Study.

INTRODUCTION: Uptake of cervical cancer screening services in Chinese migrant workers is unknown and may be lower than non-migrant workers in China. METHODS: We conducted a cross-sectional study among migrant and non-migrant women aged 21-65 at 7 provinces across China and administered a questionnaire investigating knowledge and attitudes regarding cervical cancer, human papillomavirus (HPV), and HPV vaccine. We used multivariable logistic regression to evaluate odds of previous cervical cancer screening in migrant workers. RESULTS: 737 women participated in the study. Mean age was 41.9 ± 7.2 years. 50.2% of the participants were migrant workers. 27.6% of the migrant workers reported previous cervical cancer screening compared to 33.2% of local participants. 36.6% migrant workers reported awareness of HPV compared to 40.2% of local participants. In adjusted analysis migrant status was not associated with increased odds of previous cervical cancer screening (aOR = 1.11 95%CI: 0.76-1.60). High school or higher education compared to less than high school education and employer-sponsored insurance compared to uninsured were associated with increased odds of previous cervical cancer screening (aOR = 2.15 95%CI: 1.41-3.27 and aOR = 1.67 95% CI: 1.14-2.45, respectively). Having heard of HPV compared to no awareness of HPV was associated with increased odds of cervical cancer screening (aOR = 2.02 95%CI: 1.41-2.91). Awareness of HPV among migrant workers was associated with increased odds of cervical cancer screening compared to migrant and local participants without awareness (aOR = 2.82 95% CI: 1.70-4.69 and 2.97 95%CI: 1.51-5.83, respectively). CONCLUSIONS: Efforts to increase education opportunities, provide insurance, and promote HPV awareness could increase cervical cancer screening uptake in migrant women in China.

Cardiotoxicity induced by Cochinchina momordica seed extract in zebrafish.

Momordica cochinchinensis (Lour.) Spreng is an indigenous South Asian edible fruit, and seeds of Momordica cochinchinensis have been used therapeutically in traditional Chinese medicine. Previous studies have shown that M. cochinchinensis seed (Momordicae Semen) has various pharmaceutical properties such as antioxidant and anti-ulcer effects as well as contains secondary metabolites with potential anticancer activities such as triterpenoids and saponins. Recent studies reported that water extract and ethanol extract of M. cochinchinensi seed were tested on mammals using an acute toxic classic method as OECD guidelines 420. No matter injected intravenously or intramuscularly, animals died within several days. In this study, zebrafish embryos were exposed to various doses of Cochinchina momordica seed extract (CMSE) from 2 dpf (days post fertilization, dpf) to 3 dpf. CMSE-induced cardiotoxicity such as pericardial edema, cardiac apoptosis, increased ROS production, cardiac neutrophil infiltration, decreased blood flow velocity, and reduced expression of three marker genes of cardiac functions were found in zebrafish roughly in a dose-dependent manner. These results suggest that CMSE may induce cardiotoxicity through pathways involved in inflammation, oxidative stress, and apoptosis.

Triage options to manage high-risk human papillomavirus-positive women: A population-based cross-sectional study from rural China.

Improvement in managing HPV-positive women is urgently needed. Based on a population-based study which included 2112 women aged 49 to 69 from Shanxi, China, we aimed to evaluate the clinical performance of multiple triage strategies based on liquid-based cytology (LBC), p16INK4a , viral load and partial genotyping, as a single or combined strategy for detecting cervical intraepithelial neoplasia grade 2/3 or higher (CIN2+/CIN3+) in women who tested positive by Hybrid Capture 2 (HC2). Among 452 HC2-positive women, the test positivity of LBC (ASC-US+), p16INK4a , HPV16/18 and HPV16/18/31/33/45 were 39.6%, 38.5%, 18.0% and 40.0%, respectively. Compared to LBC (ASC-US+) triage, a single triage strategies using p16INK4a or extended genotyping (SureX HPV16/18/31/33/45) achieved comparable sensitivity (relative sensitivity: 1.08, 95% confidence interval [CI]: 0.93-1.26 and 0.96, 95% CI: 0.76-1.22) and specificity (relative specificity: 1.05, 95% CI: 0.96-1.14 and 1.02, 95% CI: 0.92-1.14) for CIN3+. Viral load triage using a ≥50 RLU/CO cut-point also yielded similar results with LBC (ASC-US+). Among combined triage strategies, HPV16/18 genotyping with reflex p16INK4a showed higher sensitivity and slightly lower specificity than LBC (ASC-US+) for CIN3+ detection, however, the differences were not statistically significant. Of note, after a negative result by p16INK4a or LBC among HPV16/18 negative women, the posttest probability of CIN3+ was lower than 1%. Our study suggested that p16INK4a , extended genotyping and increased viral load cut-point could be promising alternatives to cytology triage. Combined triage algorithms of HPV16/18 with reflex p16INK4a or cytology, if negative, are associated with the substantial low posttest risk sufficient to release women to next screening round.

Comparative performance evaluation of different HPV tests and triaging strategies using self-samples and feasibility assessment of thermal ablation in 'colposcopy and treat' approach: A population-based study in rural China.

Human papillomavirus (HPV) test, self-sampling and thermal ablation for cervical intraepithelial neoplasia (CIN) have been developed separately to increase screening coverage and treatment compliance of cervical cancer screening programmes. A large-scale study in rural China screened 9,526 women with their combinations to explore the optimal cervical cancer-screening cascade in the real-world. Participants received careHPV and polymerase chain reaction (PCR) HPV tests on self-collected samples. Women positive on either HPV test underwent colposcopy, biopsy and thermal ablation in a single visit. Samples positive on either HPV test were retested for genotyping. Absolute and relative performance of HPV tests, triage strategies, 'colposcopy and thermal ablation' approach were statistically evaluated. PCR HPV test detected 33.3% more CIN grade two or worse (CIN2+) at a cost of 28.1% more colposcopies compared to careHPV. Sensitivities of PCR HPV and careHPV tests to detect CIN2+ were 96.7 and 72.5%. Specificities for the same disease outcome were 82.1 and 86.0%. Triaging HPV-positive women with HPV16/18 genotyping considerably improved the positive predictive value for CIN2+ (4.8-5.0 to 18.2-19.2%). Ninety-six women positive on HPV and having abnormal colposcopy were eligible for thermal ablation and all accepted same-day treatment, contributing to 64.6% being treated appropriately (CIN1+ on histopathology), which reached up to 84.8% among women positive on HPV 16/18 triage. No serious side-effects/complications were reported. The combination of PCR HPV test followed by HPV 16/18 triaging on self-collected samples and colposcopy of triage positive women followed by immediate thermal ablation might be the appropriate screening cascade for rural China.

Outcomes in women with biopsy-confirmed cervical intraepithelial neoplasia grade 1 or normal cervix and related cofactors: A 15-year population-based cohort study from China.

OBJECTIVE: To estimate long-term outcomes of biopsy-confirmed cervical intraepithelial neoplasia grade 1 (CIN1) or normal cervix and identify the cofactors during disease progression. METHODS: In 1999, a cervical cancer screening cohort in Shanxi, China, enrolled 1997 women aged 35-45. They were followed up at year 6, 11, and 15 after enrollment with high-risk human papillomavirus (hrHPV) DNA testing, liquid-based cytology, and visual inspection with acetic acid. Progression, persistence, and regression rates were calculated, stratified by baseline hrHPV and cytological status. Risk factors associated with hrHPV acquisition, persistence, and progression were examined. RESULTS: The cumulative rates of progression to CIN2+ among CIN1 over 6, 11, and 15 years were 7.5%, 21.4%, and 24.0%, respectively; the regression rates to normal cervix were 85.0%, 76.7%, and 72.9%, respectively. Over 6, 11, and 15 years, 0.7%, 2.9%, and 5.2% of normal cervix developed CIN2+, respectively, but over 90% remained normal after 15 years. CIN1 or normal cervix positive for hrHPV had significantly higher progression rates to CIN2+ than those without hrHPV. Similarly, the severity of cytological status was found to be associated with an increased risk of developing CIN2+. Women who had an earlier sexual debut were at a higher risk of acquiring new HPV infection and repeated HPV infections. CONCLUSIONS: Clinical follow-up strategies for women with CIN1 or normal cervix could be adjusted accordingly based on hrHPV/cytology status.

Eight-type human papillomavirus E6/E7 oncoprotein detection as a novel and promising triage strategy for managing HPV-positive women.

The management of HPV-positive women becomes particularly crucial in cervical cancer screening. Here we assessed whether detection of E6 or E7 oncoproteins targeting eight most prevalent HPV types could serve as a promising triage option. Women (N = 1,416) aged 50-60 from Shanxi, China underwent screening with HPV testing and liquid-based cytology (LBC), with any positive results referring to colposcopy and biopsy if necessary. Women with HPV-positive results received further tests using DNA-based genotyping, E6 or E7 oncoprotein detection targeting HPV16/18 (for short: E6 (16/18) Test) or HPV16/18/31/33/35/45/52/58 (for short: E6/E7 (8 types) Test), respectively. Among HPV-positive women, E6/E7 (8 types) oncoproteins had lower positivity (17.37%) compared to DNA-based genotyping for same eight types (58.30%) and LBC with ASC-US threshold (50.97%); HPV16 was the genotype showing the highest frequency (8.49%) for oncoprotein detection followed by HPV52 (3.47%), 58 (2.32%), 33 (1.54%), 18 (1.16%), 45 (0.77%), 35 (0.39%) and 31 (0%). For detection of cervical intraepithelial neoplasia Grade 3 or higher (CIN3+), E6/E7 (8 types) Test had similar sensitivity (100.00%) and superior specificity (85.94%) as well as positive predictive value (PPV, 22.22%) compared to both LBC and DNA-based genotyping (8 types); For detection of CIN2+, E6/E7 (8 types) Test was less sensitive (67.74%) but still more specific (89.47%) and risk predictive with PPV of 46.67%. Notably, E6/E7 (8 types) Test remarkably decreased the number of colposcopies needed to detect one CIN2+ and CIN3+ (2.14 and 4.50). E6/E7 oncoprotein detection showed a good "trade-off" between sensitivity and specificity with more efficient colposcopy referrals, which is of great importance to maximize the benefits of HPV-based screening program, especially applicable for the areas with high HPV prevalence and low-resources.

Effect of Several Negative Rounds of Human Papillomavirus and Cytology Co-testing on Safety Against Cervical Cancer: An Observational Cohort Study.

Background: Current U.S. cervical cancer screening and management guidelines do not consider previous screening history, because data on multiple-round human papillomavirus (HPV) and cytology "co-testing" have been unavailable. Objective: To measure cervical cancer risk in routine practice after successive negative screening co-tests at 3-year intervals. Design: Observational cohort study. Setting: Integrated health care system (Kaiser Permanente Northern California, Oakland, California). Patients: 990 013 women who had 1 or more co-tests from 2003 to 2014. Measurements: 3- and 5-year cumulative detection of (risk for) cervical intraepithelial neoplasia grade 3, adenocarcinoma in situ, and cervical cancer (≥CIN3) in women with different numbers of negative co-tests, overall and within subgroups defined by previous co-test results or baseline age. Results: Five-year ≥CIN3 risks decreased after each successive negative co-test screening round (0.098%, 0.052%, and 0.035%). Five-year ≥CIN3 risks for an HPV-negative co-test, regardless of the cytology result, nearly matched the performance (reassurance) of a negative co-test for each successive round of screening (0.114%, 0.061%, and 0.041%). By comparison, ≥CIN3 risks for the cytology-negative co-test, regardless of the HPV result, also decreased with each successive round, but 3-year risks were as high as 5-year risks after an HPV-negative co-test (0.199%, 0.065%, and 0.043%). No interval cervical cancer cases were diagnosed after the second negative co-test. Independently, ≥CIN3 risks decreased with age. Length of previous screening interval did not influence future ≥CIN3 risks. Limitation: Interval-censored observational data. Conclusion: After 1 or more negative cervical co-tests (or HPV tests), longer screening intervals (every 5 years or more) might be feasible and safe. Primary Funding Source: National Cancer Institute Intramural Research Program.

Training Future Leaders: Experience from China-ASEAN Cancer Control Training Program.

Cancer care professionals are pivotal in translating the knowledge into action in the continuum of cancer control process. Unfortunately, in China and the Association of South-east Asian Nations (ASEAN), limited training opportunities are available for health professionals in the area of cancer prevention and control. Therefore, the Cancer Hospital, Chinese Academy of Medical Sciences (CICAMS), and the International Agency for Research on Cancer (IARC) collaboratively designed and held the China-ASEAN Cancer Control and Prevention Training Program to provide continuing education opportunities for cancer professionals from China and ASEAN countries. The aim of this article is to report on the effectiveness and quality of the program and share our experience. A total of 36 participants from 12 countries completed the whole course including 1-month online learning and 1-week face-to-face workshop and cancer control facility tour in October 2017. After completion of the program, all participants were invited to fill out a questionnaire and to provide their comments on the training course. Out of 36 participants, 33 completed the evaluation form and they rated the training course highly in terms of satisfaction, value, and likelihood of recommending it to other colleagues. Additionally, all participants provided very detailed and practical comments on the course. Such an intensive, short-term, and comprehensive training program is expected to help participants establish a broader view of cancer prevention and control within the wider health services and be involved in national cancer control programs in a more efficient way. This training course could serve as a model for other institutes dedicated to nurturing future leaders in cancer control.

Human papillomavirus viral load as a useful triage tool for non-16/18 high-risk human papillomavirus positive women: A prospective screening cohort study.

OBJECTIVE: ASCCP cervical cancer screening guidelines recommend triaging high-risk human papillomavirus (hrHPV) positive women with cytology and genotyping, but cytology is often unavailable in resource-limited areas. We compared the long-term risk of cervical cancer and precancers among type-specific hrHPV-positive women triaged by viral load to cytology and visual inspection with acetic acid (VIA). METHODS: A cohort of 1742 Chinese women was screened with cytology, VIA, and Hybrid Capture 2 (HC2) test and followed for ten years. All HC2-positive samples were genotyped. Viral load was measured by HC2 relative light units/cutoff (RLU/CO). Ten-year cumulative incidence rate (CIR) of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) for type-specific hrHPV viral load was estimated using Kaplan-Meier methods. RESULTS: Baseline hrHPV viral load stratified by specific genotypes was positively correlated with prevalent cytological lesions. Ten-year CIR of CIN2+ was associated with cytological lesions and viral load. Among HPV 16/18-positive women, ten-year CIR of CIN2+ was high, even with normal cytology (15.3%), normal VIA (32.4%), viral load with RLU/CO<10 (23.6%) or RLU/CO<100 (33.8%). Among non-16/18 hrHPV positive women, ten-year CIR of CIN2+ was significantly stratified by cytology grade of atypical squamous cell of undetermined significance or higher (2.0% VS. 34.6%), viral load cutoffs at 10 RLU/CO (5.1% VS. 27.2%), at 100 RLU/CO (11.0% VS. 35.5%), but not by VIA (19.1% VS. 19.0%). CONCLUSIONS: Our findings support the guidelines in referring all HPV16/18 positive women to colposcopy and suggest triaging non-16/18 hrHPV positive women using viral loads in resource-limited areas where cytology screening was inaccessible.

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.

Impact of International Collaborative Training Programs on Medical Students' Research Ability.

International collaborative training programs for graduate students are widespread, but studies on their educational impact are limited. As an advanced cancer institute in China, Cancer Hospital Chinese Academy of Medical Science (CHCAMS) attaches great importance to international exchanges and cooperation within graduate education. The Department of Epidemiology of CHCAMS has been involved in several existing international training programs and has also launched a short-term training program in cooperation with foreign universities and institutes from 2008. Fogarty International Clinical Research Scholars and Fellows (FICRS-F) Program and the Fulbright-Fogarty Fellowship Program are the most typical examples of our practice in international cooperation on graduate education over these years. Our department has gained substantial experience in graduate-level international collaborative training, focused on cancer epidemiology. This paper is a brief introduction to the practice of different programs in our department and students' achievements during and after training. Moreover, we attempt to serve as a reference and help promote the training of graduate students pursuing careers in cancer research or global health by other universities or research institutes.

Evaluation of multiple primary and combination screening strategies in postmenopausal women for detection of cervical cancer in China.

As China's population ages, the importance of determining prevalence of cervical disease and accurate cervical cancer screening strategies for postmenopausal women is increasing. Seventeen population-based studies were analyzed to determine prevalence of cervical neoplasia in postmenopausal women. All women underwent HPV DNA testing, visual inspection with acetic acid (VIA) and cytology testing. Diagnostic values for primary and combinations screening methods included sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), referral rate and area under curve (AUC) were calculated using directed biopsy or four quadrants biopsy as reference standard. Premenopausal and postmenopausal women had equal HPV infection and cervical neoplasia rates (p > 0.05). HPV DNA testing CIN3+ sensitivity, specificity, PPV, NPV, referral rate and AUC were 97.9% (95% CI: 90.2-99.9%), 84.2% (95% CI: 82.8-85.5%), 9.9% (95% CI: 7.4-12.8%), 100% (95% CI: 99.8-100%), 17.2% (95% CI: 15.9-18.7%), 0.911, respectively. VIA values were 41.7% (95% CI: 28.4-55.9%), 94.5% (95% CI: 93.6-95.3%), 11.8% (95% CI: 7.5-17.3%), 98.9% (95% CI: 98.5-99.3%), 6.2% (95% CI: 5.3-7.1%) and 0.681, respectively. Values for VIA with HPV triage were 39.6% (95% CI: 26.6-53.8%), 99.2% (95% CI: 98.8-99.5%), 45.2% (95% CI: 30.8-60.4%), 98.9% (95% CI: 98.5-99.3%), 1.5% (95% CI: 1.1-2.0%) and 0.694, respectively. VIA and HPV DNA co-test values were 100% (95% CI: 94.0-100%), 79.5% (95% CI: 78.0-81.0%), 8.0% (95% CI: 6.0-10.3%), 100% (95% CI: 99.9-100%), 21.9% (95% CI: 20.4-23.4%) and 0.898, respectively. VIA sensitivity decreases significantly in postmenopausal women compared to premenopausal performance. HPV DNA testing maintains performance between pre- and postmenopausal women and is the most accurate primary modality for screening postmenopausal populations in low resource areas of China.