Search

Lung cancer screening may provide a "teachable moment" for the smoking cessation and relapse prevention. However, the impact of lung cancer screening on smoking initiation in non-smokers has not been reported.A baseline smoking behavior survey was conducted in 2000 participants who were screened by low-dose computed tomography (LDCT) from 2014 to 2018. All participants were re-surveyed on their smoking behavior in 2019. Of these, 312 participants were excluded, leaving 1688 participants in the final analysis. The smoking initiation rate in baseline non-smokers, the relapse rate in baseline former smokers, and the abstinence rate in baseline current smokers were calculated, respectively. The associations between screening results, demographic characteristics, and smoking behavior change were analyzed using multivariable logistic regression.From 2014 to 2019, smoking prevalence significantly decreased from 52.6% to 49.1%. The prevalence of smoking initiation, relapse, and abstinence in baseline non-smokers, former, and current smokers was 16.8%, 22.9%, and 23.7%, respectively. The risk of smoking initiation in baseline non-smokers was significantly higher in those with negative screening result (adjusted OR = 2.97, 95% CI: 1.27-6.94). Compared to smokers who only received baseline screening, the chance of smoking abstinence in baseline current smokers was reduced by over 80% in those who attended 5 rounds of screening (adjusted OR = 0.15, 95% CI:0.08-0.27). No significant associations were found between smoking relapse and prior screening frequency, with at least one positive screening result. Age, gender, occupational exposure, income, and smoking pack years were also associated with smoking behavior changes.The overall decreased smoking prevalence indicated an overwhelming effect of "teachable moment" on "license to smoke." A tailored smoking cessation strategy should be integrated into lung cancer screening.

Cumulative risk of CIN2+ and 95% confidence interval after one positive test of type-specific hrHPV by multiple infections status.

PDF file - 107K, Supplemental Tables 1A and 1B: Agreement between worst study histopathologic diagnosis. Supplemental Table 2: The relationship of E6 and DNA detection of human papillomavirus (HPV) genotypes 16, 18, and/or 45 (HPV16/18/45) on cervical exfoliated cells with HPV genotypes detected in the tissue of cervical intraepithelial neoplasia grade 2 (CIN2), grade 3 (CIN3), and cervical cancer, overall (all) and by clinical site.

New, lower-cost tests that target high-risk human papillomavirus (HR-HPV) have been developed for cervical cancer screening in lower-resource settings but large, population-based screening studies are lacking. Women ages 25 to 65 years and living in rural China (n = 7,543) self-collected a cervicovaginal specimen, had 2 cervical specimens collected by a clinician, and underwent visual inspection after acetic acid (VIA). The self- and one clinician-collected specimens underwent HR-HPV DNA testing by careHPV (QIAGEN) and Hybrid Capture 2 (HC2; QIAGEN) and the other clinician-collected specimen was tested for HPV16, 18, and 45 E6 using OncoE6 (Arbor Vita Corporation). Women who screened positive for any test and a random sample of those negative on all tests underwent colposcopic evaluation. The percent test positive was 1.8% for HPV E6 oncoprotein, between 14% and 18% for HR-HPV DNA testing, and 7.3% for VIA. The sensitivity for cervical intraepithelial neoplasia grade 3 or more severe (CIN3+; n = 99) was 53.5% for OncoE6, 97.0% for both careHPV and HC2 testing of the clinician-collected specimen, 83.8% for careHPV testing and 90.9% for HC2 testing of the self-collected specimen, and 50.5% for VIA. OncoE6 had the greatest positive predictive value (PPV), at 40.8% for CIN3+, compared with the other tests, which had a PPV of less than 10%. OncoE6 tested 70.3% positive for HPV16, 18, or 45-positive CIN3+ and tested negative for all HPV16-, 18-, or 45-negative CIN3+ (P < 0.0001). HPV E6 oncoprotein detection is useful for identifying women who have cervical precancer and cancer. Cancer Prev Res; 6(9); 938–48. ©2013 AACR.

PDF - 70K, Transition Probability of The Adjusted Models Between States at 1, 3, 5 and 10 Years With 95% CI.

Background: It is important to understand the natural history of cervical cancer, which has implications for cancer prevention and management. However, a dearth of studies on the long-term development of cervical cancer exists in China.Methods: We investigated the natural history of cervical cancer in Chinese women by creating a multistate model using 11 years of follow-up data from the Shanxi Province Cervical Cancer Screening Study I conducted from 1999 to 2010. In 1999, a total of 1,997 eligible women, ages 35 to 45 years, were enrolled in Xiangyuan County, Shanxi Province. Participants were followed up in 2005 and 2010, respectively.Results: The average time a subject spent in CIN1 before transiting into another state was 1.4693 years [95% confidence interval (CI): 1.1215–1.9251] and the average time a subject spent in CIN2 was 2.9822 years (95% CI: 1.9790–4.4938). A subject's transition probability from CIN1 to normal increased with time. However, the transition probability from CIN1 to CIN2 was relatively lower, with 3-, 5-, and 10-year transition probabilities of 0.1415, 0.1066, and 0.0437. Comparison of 5-year transition probabilities between CIN2 to normal/CIN1 and CIN2 to CIN3+ yielded a ratio of 2.74.Conclusions: Women with CIN1 had a substantial tendency for regression. Similarly, women with CIN2 had a higher probability of regression to normal/CIN1 than progression to CIN3+. Findings in this study may have significant implications for the development and evaluation of formal cervical cancer preventive strategies in China.Impact: This study may serve as a valuable reference to future research on other multistate cancer processes. Cancer Epidemiol Biomarkers Prev; 23(7); 1298–305. ©2014 AACR.

Objectives To evaluate the clinical performance of liquid‐based cytology (LBC), HPV tests and visual inspections with acetic acid or Lugol's iodine (VIA/VILI) as primary screening and triage strategies among Chinese women living with HIV (WLHIV). Methods WLHIV aged 18 years and older were recruited from HIV/AIDS treatment clinic in Yunnan, China from 2019 to 2020. Women were screened with self‐ and physician‐sampling for HPV tests, LBC, and VIA/VILI. Women positive for any HPV or with cytological abnormalities were recalled for colposcopy examination and biopsy when necessary. Clinical performance of primary and triage strategies for detecting cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was evaluated. Results For primary screening, sensitivity of physician‐HPV tests was 100%, 89.5%, and 100% for hybrid capture 2 (HC2), cobas, and Sansure HPV, and specificity was 80.4%, 85.1%, and 72.0%, respectively. Self‐HPV test achieved considerable performance with physician‐HPV. Sensitivity and specificity were 61.1% and 96.3% for LBC (atypical squamous cells of undetermined significance or worse [ASCUS+]), 40.0% and 77.3% for VIA/VILI. For triaging HPV‐positive women, LBC (ASCUS+), HPV‐16/18 genotyping, and VIA/VILI‐elevated specificity with sensitivity declined 30%–50% compared with HPV screening alone. Restricted HPV genotyping triage (HPV‐16/18/31/33/45/52/58) demonstrated the optimal accuracy (89.5% sensitivity, 81.9% specificity), and was similar to HPV‐16/18 with reflex LBC (ASCUS+). Combination antiretroviral therapies (cARTs)

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 and20 points). The group of CRS12 points was considered as the reference. During the 30-year follow-up, we identified 4553 UGI cancer deaths. Compared to subjects with a CRS12 points, the adjusted HRs for CRS of 12 to 20 points and20 points were 1.69 (95% CI: 1.56-1.83) and 3.06 (95% CI: 2.82-3.33) for UGI cancer mortality, respectively (P

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.

This Escherichia coli-produced bivalent HPV 16 and 18 vaccine was well tolerated and effective against HPV 16 and 18 associated high-grade genital lesions and persistent infection in interim analysis of this phase 3 trial. We now report data on long-term efficacy and safety after 66 months of follow-up.This phase 3, double-blind, randomised, controlled trial was done in five study sites in China. Eligible participants were women aged 18-45 years, with intact cervix and 1-4 lifetime sexual partners. Women who were pregnant or breastfeeding, had chronic disease or immunodeficiency, or had HPV vaccination history were excluded. Women were stratified by age (18-26 and 27-45 years) and randomly (1:1) allocated by software (block randomisation with 12 codes to a block) to receive three doses of the E coli-produced HPV 16 and 18 vaccine or hepatitis E vaccine (control) and followed-up for 66 months. The primary outcomes were high-grade genital lesions and persistent infection (longer than 6 months) associated with HPV 16 or 18 in the per-protocol susceptible population. This trial was registered with ClinicalTrials.gov, NCT01735006.Between Nov 22, 2012, and April 1, 2013, 8827 women were assessed for eligibility. 1455 women were excluded, and 7372 women were enrolled and randomly assigned to receive the HPV vaccine (n=3689) or control (n=3683). Vaccine efficacy was 100·0% (95% CI 67·2-100·0) against high-grade genital lesions (0 [0%] of 3310 participants in the vaccine group and 13 [0·4%] of 3302 participants in the control group) and 97·3% (89·9-99·7) against persistent infection (2 [0·1%] of 3262 participants in the vaccine group and 73 [2·2%] of 3271 participants in the control group) in the per-protocol population. Serious adverse events occurred at a similar rate between vaccine (267 [7·2%] of 3691 participants) and control groups (290 [7·9%] of 3681); none were considered related to vaccination.The E coli-produced HPV 16 and 18 vaccine was well tolerated and highly efficacious against HPV 16 and 18 associated high-grade genital lesions and persistent infection and would supplement the global HPV vaccine availability and accessibility for cervical cancer prevention.National Natural Science Foundation of China, National Key RD Program of China, Fujian Provincial Project, Fundamental Funds for the Central Universities, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, and Xiamen Innovax.

To address the value of visual inspection where HPV-based screening is not yet available, we evaluated the real-world effectiveness of visual inspection with acetic acid (VIA) and with Lugol's iodine (VILI) as a primary screening method for cervical cancer in rural China.A total of 206 133 women aged 30-59 years received two rounds of VIA/VILI screening for cervical cancer in 2006-2010. Women with positive screening results underwent colposcopy and direct biopsy, and were treated if cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was diagnosed. Clinical effectiveness of VIA/VILI was evaluated by process and outcome measures.The VIA/VILI positivity rate, biopsy rate and detection rate of CIN2+ in the second round were significantly lower than in the first round. The 2-year cumulative detection rate of CIN2+ varied from 0.53% to 0.90% among the four cohorts initiated in 2006, 2007, 2008, and 2009. The first round of screening detected 60%-83% of CIN2, 70%-86% of CIN3, and 88%-100% of cervical cancer. Over 92% of CIN2+ were found at the early stage.Multiple rounds of visual inspection with continuous training and quality assurance could act as a temporary substitutional screening method for cervical cancer in resource-restricted settings.

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.

Background Cervical cancer is preventable and curable by detected early and managed effectively. To explore the most economical and effective cervical cancer screening strategies would lay a solid foundation for reducing the health and economic burden of cervical cancer. Methods A Markov model was established for a cohort of 100,000 female to simulate the natural history of cervical cancer. 18 screening strategies were estimated including careHPV, Thin prep cytologic (TCT), Visual inspection with acetic acid/ Lugol's iodine (VIA / VILI), careHPV in series with VIA / VILI, careHPV in series with TCT, three methods parallel connection every 1, 3, 5 years respectively. Model outcomes included cumulative risk of incidence and death of cervical cancer, quality-adjusted life years (QALYs), cost-effectiveness ratios (CERs), incremental cost-effectiveness ratios (ICERs), cost-utility ratios (CURs) and benefits. Results According to the results of epidemiological analysis, careHPV similar to the parallel connection every 1 year achieved highest epidemiological effects via reducing the cumulative risk of onset and death by more than 98 %. In health-economic terms, CER among all the screening strategies ranged from -756.34 to 113040.3 Yuan per year and CUR ranged from -169.91 to 11968.27 Yuan per QALY. The benefit ranged from -1629 to 996 Yuan. The incremental cost-effectiveness analysis showed that three methods in parallel every 1 year, TCT every 1 year, VIA/VILI every 1, 3, 5 years and careHPV every 5 years were dominant strategies. Conclusion Considering the economic and health benefits of all the strategies, our results suggested careHPV every 3 or 5 years and VIA/VILI every 1 or 3 years eventually were more appropriate as screening methods in rural 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.

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.

Background Human papillomavirus (HPV) attributable cancer burden is currently unknown in China, which is essential to evaluate the potential benefit of existing HPV https://www.sciencedirect.com/topics/medicine-and-dentistry/vaccine and to inform cancer control policy. Methods We extracted data of cancer incidence and mortality in 2014 from Chinese Cancer Registry Annual Report, and data of national population from National Bureau of Statistics. HPV‐attributable cancer burden was estimated by incorporating cancer rates and population forecasts by sex, cancer site, age and geographical area, and then combined to corresponding population attributable fractions. Results We estimated that there were 110 894 HPV‐attributable new cancer cases in China in 2014, including 99 253 cervical cancers, 4449 noncervical cancers in females and 7192 cancers in males. The age‐standardized incidence of HPV‐attributable cancers in China was 5.69 per 100 000 persons, being slightly higher in rural than urban areas. Specifically, 51.1% of HPV‐attributable cervical cancers were diagnosed in women aged 40‐54 years, while 75.8% of noncervical cancers were diagnosed at 45‐79 years of age. Among males, 53.4% of cancers were diagnosed at 55‐74 years of age. Thirty five thousand six hundred and eighty three HPV‐attributable cancer deaths were estimated, including 29 683 due to cervical cancer, and 2307 and 3693 due to noncervical cancer in females and males, respectively. Conclusions The cancer burden attributable to HPV in China is substantial. HPV vaccination and cervical screening should be prioritized., Human papillomavirus (HPV) attributable cancer burden is currently unknown in China; we estimated HPV‐attributable cancer cases and deaths by sex, cancer site, age and geographical area. There is a pressing need for these data to inform evidence‐based policy with regard to HPV vaccination and screening programs.

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 (

Multiple barriers impede the transformation of evidence-based research into implementation of cervical cancer screening in ASEAN countries. This review is the first of its kind to show the disease burden of cervical cancer, progress till date to implement screening and corresponding challenges, and propose tailored solutions to promote cervical cancer prevention in ASEAN. In 2020, approximately 69 000 cervical cancer cases and 38 000 deaths happened in ASEAN, and more than 44% and 63% increases on new cases and deaths are expected in 2040. Only four countries have initiated population-based cervical cancer screening programs, but the participation rate is less than 50% in some countries and even lower than 10% in Myanmar and Indonesia. Inequity and unavailability in service delivery, lack of knowledge and awareness, limited follow-up and treatment capacity, and funding sustainability affect successful scale-up of cervical cancer screening most in ASEAN. Implementing HPV detection-based primary screening, appropriate management of screen-positives, enhancing health education, integrating health services can accelerate reduction of cervical cancer burden in ASEAN. Achieving high screening coverage and high treatment compliance will help ASEAN countries remain aligned to cervical cancer elimination strategies.

Background Cervical cancer is a major public health concern in China. We report the end‐of‐study results of a phase II/III trial to assess the efficacy, immunogenicity, and safety of the AS04‐human papillomavirus (HPV)‐16/18 vaccine in Chinese women aged 18‐25 years followed for up to 72 months after first vaccination. Results of approximately 57 months following first vaccination have been previously reported. Methods Healthy 18‐25‐year‐old women (N = 6051) were randomized (1:1) to receive three doses of AS04‐HPV‐16/18 vaccine or Al(OH)3 (control) at Months 0‐1‐6. Vaccine efficacy against HPV‐16/18 infection and cervical intraepithelial neoplasia (CIN), cross‐protective vaccine efficacy against infections and lesions associated with nonvaccine oncogenic HPV types, immunogenicity, and safety were assessed. Efficacy was assessed in the according‐to‐protocol efficacy (ATP‐E) cohort (vaccine N = 2888; control N = 2892), total vaccinated cohort for efficacy (TVC‐E; vaccine N = 2987; control N = 2985) and TVC‐naïve (vaccine N = 1660; control N = 1587). Results In initially HPV‐16/18 seronegative/DNA‐negative women, vaccine efficacy against HPV‐16/18‐associated CIN grade 2 or worse was 87.3% (95% CI: 5.5, 99.7) in the ATP‐E, 88.7% (95% CI: 18.5, 99.7) in the TVC‐E, and 100% (95% CI: 17.9, 100) in the TVC‐naïve. Cross‐protective efficacy against incident infection with HPV‐31, HPV‐33 and HPV‐45 was 59.6% (95% CI: 39.4, 73.5), 42.7% (95% CI: 15.6, 61.6), and 54.8% (95% CI: 19.3, 75.6), respectively (ATP‐E). At Month 72, >95% of initially seronegative women who received HPV vaccine in the ATP cohort for immunogenicity (N = 664) remained seropositive for anti‐HPV‐16/18 antibodies; anti‐HPV‐16 and anti‐HPV‐18 geometric mean titers were 678.1 EU/mL (95% CI: 552.9, 831.5) and 343.7 EU/mL (95% CI: 291.9, 404.8), respectively. Serious adverse events were infrequent (1.9% vaccine group [N = 3026]; 2.7% control group [N = 3025]). Three and zero women died in the control group and the vaccine group respectively. New onset autoimmune disease was reported in two women in the vaccine group and two in the control group. Conclusions This is the first large‐scale randomized clinical trial of HPV vaccination in China. High and sustained vaccine efficacy against HPV‐16/18‐associated infection and cervical lesions was demonstrated up to Month 72. The vaccine had an acceptable safety profile. Combined with screening, prophylactic HPV vaccination could potentially reduce the high burden of HPV infection and cervical cancer in China. Trial registration NCT00779766., Cervical cancer is one of the most aggressive forms of cancer that women can suffer from. The presence of human papillomavirus (HPV) is responsible for almost all cases of cervical cancer. For these reasons, the world health organization recommends that HPV vaccines should be included in national vaccination programs. From the first licensure of the first HPV vaccine in 2006 to the development of new HPV vaccines, the latter have been studied in clinical trials and demonstrated to decrease in the number of cervical cancers while remaining acceptably safe. Many developed countries have included HPV vaccination in their program. These countries reported a decrease of cervical cancer cases. Many countries from the less developed regions are still yet to introduce HPV vaccination. The novelty: In 2016, the Chinese authorities approved licensure of the first HPV vaccine for use in China to help prevent cervical cancer and based their decision on clinical trials conducted in China. We present here the final results of the key clinical trial of this HPV vaccine that involved around 6000 Chinese women over 6 years. The impact: Chinese women represent almost 10% of the worldwide population at risk of cervical cancer. Latest estimations from 2016 indicate that 111 000 new cervical cancer cases are reported every year in China. This number could be reduced with the HPV vaccination.

Background The high cost and insufficient supply of human papillomavirus (HPV) vaccines have slowed the pace of controlling cervical cancer. A phase III clinical trial was conducted to evaluate the efficacy, safety, and immunogenicity of a novel Escherichia coli-produced bivalent HPV-16/18 vaccine. Methods A multicenter, randomized, double-blind trial started on November 22, 2012 in China. In total, 7372 eligible women aged 18–45 years were age-stratified and randomly assigned to receive three doses of the test or control (hepatitis E) vaccine at months 0, 1, and 6. Co-primary endpoints included high-grade genital lesions and persistent infection (over 6 months) associated with HPV-16/18. The primary analysis was performed on a per-protocol susceptible population of individuals who were negative for relevant HPV type-specific neutralizing antibodies (at day 0) and DNA (at day 0 through month 7) and who received three doses of the vaccine. This report presents data from a prespecified interim analysis used for regulatory submission. Results In the per-protocol cohort, the efficacies against high-grade genital lesions and persistent infection were 100.0% (95% confidence interval = 55.6% to 100.0%, 0 of 3306 in the vaccine group vs 10 of 3296 in the control group) and 97.8% (95% confidence interval = 87.1% to 99.9%, 1 of 3240 vs 45 of 3246), respectively. The side effects were mild. No vaccine-related serious adverse events were noted. Robust antibody responses for both types were induced and persisted for at least 42 months. Conclusions The E coli-produced HPV-16/18 vaccine is well tolerated and highly efficacious against HPV-16/18–associated high-grade genital lesions and persistent infection in women.

Objective This study evaluated the feasibility of different cervical cancer screening strategies in urban China. Methods A Markov model was constructed to simulate a hypothetical cohort of 100,000 females aged 30−59 years in a 20-year period. Screening strategies included liquid-based cytology (LBC) every three years, human papillomavirus (HPV) DNA testing every three and five years, respectively, and a combination of HPV DNA testing and LBC (HPV+LBC) every three and five years, respectively. Model outcomes included cumulative incidence over 20 years, cumulative risk of cervical cancer, costs, life year saved (LYS), quality-adjusted life years (QALYs) and benefits. The cost-effectiveness ratios (CERs), incremental cost-effectiveness ratios (ICERs), cost-utility ratios (CURs), and benefit-cost ratios (BCRs) were used as outcomes in the health economic evaluation analysis. Univariate sensitivity analyses were performed to examine the stability of the results. Results The cumulative incidence of the five screening strategies ranged from 833.02 to 1,158.07 cases per 100,000 females. HPV DNA testing was most effective in reducing the cumulative risk of cervical cancer, saving life years and QALYs and gaining benefits. The CERs of HPV DNA testing every three and five years, and LBC every three years were considered to be very cost-effective if they were below China’s GDP per capita. The CERs of HPV+LBC were considered to be cost-effective if they were below three times GDP per capita. The incremental cost-effectiveness analysis showed that HPV DNA testing every three and five years, LBC every three years and HPV+LBC every five years were dominant strategies. Conclusions The findings of this study indicated that HPV DNA testing every five years or LBC every three years should be recommended in urban China.

Objective Precise prevention is more desired for cervical cancer due to the huge population, high prevalence of human papillomavirus (HPV) infection in China and the vision of screen-and-treat strategies in low- and middle-income countries (LMICs). Considerations of combining type-specific prevalence and attribution proportion to high-grade cervical intraepithelial neoplasia are informative to more precise and effective region-specific cervical cancer prevention and control programs. The aim of the current study was to determine the genotype distribution of HPV and attribution to cervical precancerous lesions among women from rural areas in North China. Methods A total of 9,526 women participated in the cervical cancer screening project in rural China. The samples of women who tested positive for HPV were retested with a polymerase chain reaction (PCR)-based HPV genotyping test. The attribution proportion of specific high-risk human papillomavirus (HR-HPV) types for different grades of cervical lesions was calculated by using the type contribution weighting method. Results A total of 22.2% (2,112/9,526) of women were HR-HPV positive and HPV52 (21.7%) was the most common HR-HPV genotype, followed by HPV58 (18.2%), HPV53 (18.2%) and HPV16 (16.2%). The top three genotypes detected in HR-HPV-positive cervical intraepithelial neoplasia (CIN)1 were HPV16 (36.7%), HPV58 (20.4%), HPV56 (15.3%). Among CIN2+, the most frequent genotypes were HPV16 (75.6%), HPV52 (17.8%), HPV58 (16.7%). HPV16, 56, 58, 53, 52, 59, 68, and 18 combined were attributed to 84.17% of all CIN1 lesions, and HPV16, 58, and 52 combined were attributed to 86.98% of all CIN2+ lesions. Conclusions The prevalence of HR-HPV infection among women from rural areas in North China was high and HPV16, HPV58, HPV52 had paramount attributable fraction in CIN2+. Type-specific HPV prevalence and attribution proportion to cervical precancerous lesions should be taken into consideration in the development of vaccines and strategy for screening in this population.

BACKGROUND Biomarkers highly predictive of cervical cancer are urgently needed for triaging human papillomavirus (HPV)-positive women. METHODS A total of 1997 women aged 35-45 years in Shanxi, China, were recruited in 1999, and follow-up visits were conducted in 2005, 2010, and 2014. HPV load was measured by the Hybrid Capture 2 assay. Findings were determined by relative light units/cutoff (RLU/CO) and categorized into 4 groups: negative (

Background The World Health Assembly has adopted a global strategy to eliminate cervical cancer. However, neither the optimal pathway nor the corresponding economic and health benefits have been evaluated. We take China as an example to assess the optimal pathway towards elimination and the cost-effectiveness of tailored actions. Methods A validated hybrid model was used to assess the costs and benefits of alternative strategies combining human papillomavirus vaccination, cervical screening, and treatment of pre-invasive lesions and invasive cancer for females with different immunization history. All Chinese females living or projected to be born during 2015–2100, under projected trends in aging, urbanization, and sexual activity, were considered. Optimal strategies were determined by cost-effectiveness efficiency frontiers. Primary outcomes were cervical cancer cases and deaths averted and incremental cost-effectiveness ratios (ICERs). We employed a lifetime horizon from a societal perspective. One-way and probabilistic sensitivity analyses evaluate model uncertainty. Results The optimal pathway represents an integration of multiple tailored strategies from females with different immunization history. If China adopts the optimal pathway, the age-standardized incidence of cervical cancer is predicted to decrease to fewer than four new cases per 100,000 women (i.e., elimination) by 2047 (95% confidence interval 2043 to 2050). Compared to the status quo, the optimal pathway would avert a total of 7,509,192 (6,922,744 to 8,359,074) cervical cancer cases and 2,529,873 (2,366,826 to 2,802,604) cervical cancer deaths in 2021–2100, with the discounted ICER being $− 339 (− 687 to − 79) per quality-adjusted life-year. Conclusions By adopting an optimal pathway from 2021 (namely, the year of the first Chinese Centennial Goals) onwards, cervical cancer could be eliminated by the late 2040s (namely, ahead of the second Chinese Centennial Goals) while saving net economic costs in China.

Cervical cancer screening with cytology suffers from low sensitivity, whereas the efficiency of human papillomavirus (HPV)-based screening is limited by low specificity. The authors evaluated a novel p16In total, 2112 women aged 49 to 69 years from Shanxi, China were screened from March to July 2019. HPV testing, liquid-based cytology (LBC), and p16p16With minimal colposcopy referrals, p16

ObjectivesTo explore the prevalence and risk factors of anogenital human papillomavirus (HPV) infection and neoplasia among women living with HIV (WLHIV) in China.MethodsA cross-sectional survey was conducted from 2019 to 2020, 409 WLHIV aged 18 years and older were recruited from an HIV treatment clinic in Yunnan, China. Cervical and anal samples were collected for HPV testing of 15 HPV genotypes and cytological interpretation. Women positive for cervical HPV or cytological abnormalities were recalled for colposcopy examination and biopsy when necessary. Prevalence of anogenital HPV infection and neoplasia were compared by logistic regression.ResultsHPV prevalence was 34.2% (140/409) for cervical and 34.7% (142/409) for anal (high-risk HPV being 30.6% (125/409) and 30.3% (124/409), respectively). The most frequent genotypes were HPV-52, HPV-16 and HPV-58 in the cervix, HPV-52, HPV-53 and HPV-39 in the anus, with strong correlation between cervical and anal positivity, both overall and at a type-specific level. Cervical HPV was most associated with short duration of combination antiretroviral therapies (cART) (≤2 vs >2 years, adjusted OR (aOR)=2.25, 95% CI: 1.22 to 4.12) and high initial HIV viral load (≥1000 vs ConclusionsCervical and anal HPV were strongly correlated and, together with associated neoplasia, were highly prevalent among WLHIV in China. Early initiation of cART to avoid severe immunodeficiency should decrease anogenital HPV prevalence and related cancer burden among WLHIV. Incorporating anogenital cancer prevention services into HIV/AIDS care is warranted.

Background Only clinically validated HPV assays can be accepted in cervical cancer screening. Objectives To update the list of high-risk HPV assays that fulfil the 2009 international validation criteria (Meijer-2009). Data Sources PubMed/Medline, Embase, Scopus, references from selected studies; published in January 2014-August 2020. Study eligibility criteria HPV test validation studies and primary screening studies, involving testing with an index HPV test and a comparator HPV test with reporting of disease outcome (occurrence of histologically confirmed cervical precancer [CIN2+]). Methods Overview tables of relative sensitivity and specificity, including non-inferiority statistics and test reproducibility; random-effect meta-analyses of the relative sensitivity and specificity for CIN2+ on index-vs comparator HPV tests. Participants Women participating in cervical cancer screening. Interventions Testing with an index and a comparator HPV test of clinician-collected cervical specimens and assessment of disease outcome ( Methods Assessment of relative clinical accuracy (including non-inferiority statistics index vs comparator assay) and test reproducibility; random effects meta-analyses of the relative sensitivity and specificity of index vs comparator tests. Results Seven hrHPV DNA tests consistently fulfilled all validation criteria in multiple studies using predefined test positivity cut-offs (Abbott RealTime High Risk HPV, Anyplex II HPV HR Detection, BD Onclarity HPV Assay, Cobas 4800 HPV Test, HPV-Risk Assay, PapilloCheck HPV-Screening Test and Xpert HPV). Another assay (Alinity m HR HPV Assay) was fully validated in one validation study. The newer Cobas 6800 HPV Test, was validated in two studies against Cobas 4800. Other tests partially fulfilled the international validation criteria (Cervista HPV HR Test, EUROArray HPV, Hybribio’s 14 High-Risk HPV, LMNX Genotyping Kit GP HPV, MALDI-TOF, RIATOL qPCR and a number of other in-house developed assays) since the non-inferior accuracy was reached after a posteriori cut-off optimisation, inconsistent accuracy findings in different studies, and/or insufficient reproducibility assessment. The APTIMA HPV Assay targeting E6/E7 mRNA of hrHPV was fully validated in one formal validation study and showed slightly lower pooled sensitivity but higher specificity than the standard comparator tests in seven screening studies. However, the current international validation criteria relate to DNA assays. The additional requirement for longitudinal performance data required for non-DNA based HPV assays was not assessed in this review. Conclusions Eleven hrHPV DNA assays fulfil all requirements for use in cervical cancer screening using clinician-collected specimens.

Background: Currently, knowledge of the protective effects of natural acquired immunity against human papillomavirus (HPV) is mostly based on studies using binding antibodies (IgG) as biomarkers due to the labor-consuming characteristics of neutralizing antibodies assays, and the conclusions from different studies are inconsistent. Methods: In a phase III clinical trial of the Escherichia coli-produced HPV-16/18 bivalent vaccine, participants were tested for neutralizing antibodies and IgG antibodies with pseudovirion-based neutralization assay and L1 virus-like particle-based ELISA, respectively. HPV-16 and HPV-18 infections were identified using cervical specimens periodically collected during the over 5·5 years of follow-up. Data of the 3,634 women aged 18-45 years in the control arm were used to evaluate the protective effects of the type-specific neutralizing antibodies as well as the IgG antibodies. Findings: For the persistent infection (PI) endpoints of HPV-16/18 lasting for over 6/12 months, the prevalence of type-specific neutralizing antibodies was highly protective (6 m PI: RR = 0·16, 95% CI: 0·04, 0·63; 12 m PI: RR = 0·23, 95% CI: 0·06, 0·95), while the prevalence of IgG antibodies was associated with minor and nonsignificant protection (6 m PI: RR = 0·71, 95% CI: 0·44, 1·16; 12 m PI: RR = 0·76, 95% CI: 0·43, 1·36). Women with neutralizing antibodies had a lower risk of subsequent homotypic infection, irrespective of their IgG status. In contrast, women with positive IgG while negative neutralizing antibodies showed a similar risk of subsequent infection as those with neither neutralizing nor IgG antibodies. Interpretation: The findings indicate that naturally acquired neutralizing antibodies are associated with a substantially reduced risk of subsequent homotypic infection. Funding: National Natural Science Foundation of China ; The Fujian Province Health Education Joint Research Project; Xiamen Science and Technology Major Project; Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; and Xiamen Innovax. Declaration of Interest: We declare no competing interests. Ethical Approval: Written informed consent was obtained from all participants, and the trial was conducted in accordance with Good Clinical Practice and was approved by independent ethics committees.

BACKGROUND Cervical cancer screening with cytology suffers from low sensitivity, whereas the efficiency of human papillomavirus (HPV)-based screening is limited by low specificity. The authors evaluated a novel p16INK4a immunocytology approach in cervical cancer screening compared with HPV-based and cytology-based screening. METHODS In total, 2112 women aged 49 to 69 years from Shanxi, China were screened from March to July 2019. HPV testing, liquid-based cytology (LBC), and p16INK4a immunocytology were performed on samples from all women. Any positive result triggered a referral to colposcopy with biopsy, if indicated. Screening performance for detecting cervical intraepithelial neoplasia grade 2 and 3 or worse (CIN2+/CIN3+) was evaluated using multiple algorithms. RESULTS p16INK4a had a lower positive rate (10.0%) than LBC abnormality (vs 12.1%; P = .004) and a high-risk HPV positivity (21.4%; P < .001). For the detection of CIN3+, the relative sensitivity of p16INK4a compared with HPV and LBC was 0.93 (95% CI, 0.82-1.07) and 1.12 (95% CI, 0.95-1.32), respectively. The specificity of p16INK4a was significantly higher than that for HPV and LBC, with a relative specificity of 1.13 (95% CI, 1.11-1.16) and 1.02 (95% CI, 1.01-1.04), respectively. In addition, p16INK4a alone yielded a clinical performance very similar to that of the current mainstream strategy of using HPV16/18 with reflex cytology (ASC-US+, atypical squamous cells of undetermined significance or worse). The immediate risk of CIN3+ was 14.6% if p16INK4a results were positive and 0.2% if p16INK4a results were negative. CONCLUSIONS With minimal colposcopy referrals, p16INK4a screening demonstrated promising utility for risk stratification and yielded a better balance between sensitivity and specificity compared with HPV and LBC primary screening. Moreover, with accuracy and efficiency similar to what is achieved using mainstream cotest algorithms, p16 may simplify the screening practice. More evidence will be required before clinical recommendation.

BackgroundColposcopy diagnosis and directed biopsy are the key components in cervical cancer screening programs. However, their performance is limited by the requirement for experienced colposcopists. This study aimed to develop and validate a Colposcopic Artificial Intelligence Auxiliary Diagnostic System (CAIADS) for grading colposcopic impressions and guiding biopsies.MethodsAnonymized digital records of 19,435 patients were obtained from six hospitals across China. These records included colposcopic images, clinical information, and pathological results (gold standard). The data were randomly assigned (7:1:2) to a training and a tuning set for developing CAIADS and to a validation set for evaluating performance.ResultsThe agreement between CAIADS-graded colposcopic impressions and pathology findings was higher than that of colposcopies interpreted by colposcopists (82.2% versus 65.9%, kappa 0.750 versus 0.516,p p p > 0.05). The CAIADS also demonstrated a superior ability in predicting biopsy sites, with a median mean-intersection-over-union (mIoU) of 0.758.ConclusionsThe CAIADS has potential in assisting beginners and for improving the diagnostic quality of colposcopy and biopsy in the detection of cervical precancer/cancer.

Human papillomavirus (HPV) vaccines are efficacious against HPV infections and associated lesions in women HPV-naïve at vaccination. However, vaccine efficacy (VE) against oncogenic, high-risk HPV (HR-HPV) types in women infected with any other HR-HPV type at first vaccination (baseline) remains unclear. This post-hoc analysis of a phase II/III study (NCT00779766) evaluated AS04-adjuvanted HPV-16/18 (AS04-HPV-16/18) VE against HR-HPV type infection in 871 Chinese women aged 18–25 years over a 72-month follow-up period. Study participants were DNA-negative at baseline to HR-HPV type(s) considered for VE and DNA-positive to any other HR-HPV type. Initial serostatus was not considered. Baseline DNA prevalence was 14.6% for any HR-HPV type and 10.6% excluding HPV-16/18. In the total vaccinated cohort for efficacy, VE against 6-month and 12-month HPV-16/18 persistent infections (PIs) in women DNA-negative to HPV-16/18 but DNA-positive to any other HR-HPV type at baseline was 100.0% (95% Confidence Interval [CI]: 79.8–100.0) and 100.0% (95%CI: 47.2–100.0), respectively. VE against HPV-16/18 incident infections in women DNA-positive to one vaccine type but DNA-negative to the other one at baseline was 66.8% (95%CI: −18.9–92.5). VE against HPV-31/33/45 incident infections, in women DNA-positive to HPV-16/18 and DNA-negative to the considered HPV type at baseline was 71.0% (95%CI: 27.3–89.8). No HPV-16/18 PIs were observed in vaccinated women with non-vaccine HPV A7/A9 species cervical infection at baseline. These findings indicated that women with existing HR-HPV infection at vaccination might still benefit from the AS04-HPV-16/18 vaccine. However, this potential benefit needs further demonstration in the future.

Background It is widely acknowledged that HPV prophylactic vaccine could prevent new infections and their associated lesions among women who are predominantly HPV-naive at vaccination. Yet there still remains uncertainty about whether HPV vaccination could benefit to individuals who have undergone surgery for cervical disease. Methods This post-hoc analysis intends to focus on intent-to-treat participants who underwent excision treatment at baseline and the follow-up period in a phase II/III, double-blind, randomized trial (ClinicalTrials.gov, number NCT00779766) conducted in Jiangsu province, China. We evaluate the impact of HPV vaccination on preventing women from subsequent infection and cervical lesions (LSIL+ and CIN2+) after excision treatment. Results One hundred sixty-eight (vaccine, n = 87; placebo, n = 81) performed excisional treatment in this clinical trial. We observed a significant effect of vaccination on acquiring 14 high-risk HPV (HR-HPV) infection after treatment (vaccine efficacy: 27.0%; 95% CI 4.9, 44.0%). The vaccine efficacy against new infections after treatment for 14 HR-HPV infection was estimated as 32.0% (95%CI 1.8, 52.8%), and was 41.2% (95%CI -162.7, 86.8%) for HPV16/18 infection. The accumulative clearance rates of the vaccine group and placebo group were 88.9 and 81.6% for HPV16/18 infection (P = 0.345), 63.4, 48.7% for 14 HR-HPV infection (P = 0.062), respectively. No significant difference was observed on the persistent rate of HPV16/18, 14 HR-HPV infection and occurrence rate of LSIL+ between the two groups. Conclusions No significant evidence from this study showed that HPV-16/18 AS04-adjuvanted vaccine could lead to viral faster clearance or have any effect on the rates of persistent infection among women who had excision treatment. However, the vaccine may still benefit post-treatment women with “primary prophylactic” effect. Further research is required in clarifying the effect of using the prophylactic HPV vaccine as therapeutic agents. Trial registration ClinicalTrials.gov identifier: NCT00779766. Date and status of trial registration: October 24, 2008. Completed; Has Results.

Women are anticipated to go through more than two rounds of cervical screening in their lifetime. Human papillomavirus (HPV) testing is increasingly used as the primary cervical cancer screening test. However, triage strategies for HPV-positive women were usually evaluated at baseline screening. We assessed the effect of sequential rounds of cervical screening on several algorithms for HPV triage. A total of 1,997 women ages 35–45 years were enrolled in 1999 in Shanxi, P.R. China and followed up three times at approximately 5-year intervals. Cervical intraepithelial neoplasia (CIN) grade 2 or worse (CIN2+) prevalence by prior HPV results and performance of 12 triage algorithms with cytology, genotyping, and prior HPV were examined among 229 HPV-positive women at the fourth round. CIN2+ prevalence varied from 56.5% (95% confidence interval, 36.8%–74.4%) following 15 years HPV persistence to 3.5% (1.2%–9.9%) with an incident HPV within 15 years. Triage with cytology (with threshold of atypical squamous cells of undetermined significance) yielded positive predictive value (PPV) of 21.4% (13.8%–29.0%), entailing immediate colposcopic referral, and negative predictive value (NPV) of 97.4% (94.6%–100%), permitting retesting at short intervals. Triage with genotyping (16/18/31/33/45/52/58) or prior HPV results showed comparable performance with cytology. Among 11 triage algorithms with similar NPV to cytology, triage with prior HPV results and reflex genotyping (16/18) achieved highest PPV of 28.9% (18.8%–39.1%) and lowest colposcopy referral of 33.2% (27.4%–39.5%). HPV persistence across rounds is an effective risk stratifier in HPV-positive women. Mainstream cytology and genotyping, with or without consideration of prior HPV results, remain effective for HPV triage at fourth round. Prevention Relevance: The study highlights the sustained effectiveness of mainstream HPV triage methods, such as cytology and genotyping, after sequential rounds of cervical screening. It also suggests that use of HPV persistence across rounds can improve management of HPV-positive women in cervical cancer screening.

Objectives: Cervical cancer is a leading cause of cancer-related mortality in women in China. This analysis is a quantitative evidence synthesis pooling information about each cervical cancer risk factor. Methods: A meta-model was developed to estimate the risk of cervical cancer for a woman aged 18–85 years in Mainland China based on her risk profile at the time of assessment. The meta-model was built using findings of a systematic literature review that identified 21 case–control studies reporting data on 105 groups of cervical cancer risk factors in Chinese women. Extracted risk factors were ranked, and 17 were selected by Chinese clinical experts for inclusion in the meta-model. Risk equations were developed for each selected study. Predicted risks for each study were dependent on the risk profile under consideration and study-specific risks were pooled to an overall risk estimate using a random-effects meta-analysis. Sensitivity analysis was conducted using 100 artificial patient profiles (in the absence of patient data). Results: Predicted risks for the 100 profiles suggested that the model had good face validity and could differentiate between high and non-high cervical cancer risk profiles. Conclusion: This innovative meta-model approach assesses cervical cancer risk in Chinese women from a holistic perspective and could be adapted for other diseases and settings.

Background Human papillomavirus (HPV) vaccine has been increasingly discussed in mainland China since its first approval in 2016. To date, nearly all studies assessing HPV vaccine perceptions and attitudes were implemented during pre-licensure period. Therefore, the nationwide post-marketing survey was conducted to update knowledge, attitudes and practice on HPV vaccine among general population in mainland China. Methods Participants aged 18–45 years living in mainland China were recruited in April 2019 by multi-stage non-randomized sampling. Sociodemographic factors, HPV and HPV vaccine related awareness, knowledge, attitudes, vaccine uptake and potential obstacles were assessed in questionnaires. Bivariate analysis and multivariate regression were used to identify disparity among subgroups with different sociodemographic characteristics. Results 4,000 women (32.1 ± 7.81y) and 1,000 men (31.8 ± 7.96y) were included in final analysis. Less than one third of participants had heard of HPV (female: 31%; male: 22%) and HPV vaccine (female: 34%; male: 23%). Knowledge score was also unfavorable on HPV (female: 3 out of 13; male: 1.8 out of 13) and HPV vaccine (female: 3 out of 6; male: 2 out of 5). Only 3% females had been vaccinated three years after HPV licensure in China, although willingness to get vaccinated among those unvaccinated were high (mean willingness score ± SD: female: 3.3 ± 0.97; male: 3.0 ± 0.98). Industry of employment and household income were the major factors related to awareness and knowledge of vaccine, whereas HPV and HPV vaccine awareness were key influential factors for willingness. The main obstacles of vaccination were safety concerns, lack of knowledge, and high price of HPV vaccines. Conclusions Findings highlight a lack of vaccine awareness, knowledge, and poor uptake in mainland China and underscore the necessity of health education campaigns. The identified priority groups, contents to be delivered and practical obstacles could furthermore provide insight into health education to reduce disparities and accelerate HPV vaccine roll-out in China.

On Nov 17, 2020, WHO launched a global initiative to accelerate the elimination of cervical cancer through the implementation of HPV vaccination, cervical cancer screening and treatment for precancer and cancer. China has the largest burden of cervical cancer in the world, but only has a national cervical cancer screening program in rural areas since 2009. Here, we aimed to evaluate the effectiveness and cost-effectiveness of cervical cancer screening in urban China, using Shenzhen City as an example.We use an extensively validated platform ('Policy1-Cervix'), calibrated to data from Shenzhen city and Guandong Province. We evaluated a range of strategies that have previously been implemented as pilot studies in China, or recommended as guidelines within China and globally, spanning primary HPV, cytology and co-testing strategies. We additionally considered alternate triaging methods, age ranges and screening intervals, resulting in 19 algorithms in total.Of the 19 strategies considered, the most effective approach involved primary HPV testing. At 3- to 10-yearly intervals, primary HPV testing reduced the age-standardized cancer mortality rate by 37-71 %. The most cost-effective strategy was 5-yearly primary HPV testing with partial genotyping triage for ages 25-65, discharging to 10-yearly screening for low-risk women (ICER = US$7191/QALYS using 2018 costs; willingness-to-pay threshold1xGDP [US$9771]). This strategy gave an incidence and mortality reduction of 56 % and 63 %, respectively. This remained the most cost-effective strategy under most conditions in sensitivity analysis.Primary HPV testing would be cost-effective in Shenzhen and could more than halve cervical cancer incidence rates to 6 per 100,000 over the long term. In order to achieve rates below 4 per 100,000, the elimination threshold set by the World Health Organization, vaccination will likely also be necessary.

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