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Abstract The human papillomavirus (HPV) vaccine is the first vaccine developed specifically targeting the prevention of cervical cancer. For more than 15 years, China has expedited a series of efforts on research and development of the domestically manufactured HPV vaccines, producing local population-based evidence, promoting free HPV vaccination from pilots, and launching action plans to tackle barriers in the scale-up of HPV vaccination. To further roll out the HPV vaccination program in China, several challenges should be addressed to support the steps forward. The availability of more locally manufactured HPV vaccines, pricing negotiation and local evidence supporting the efficacy of one-dose schedule would greatly alleviate the continued supply and financial constraints in China. Meanwhile, more attention should be paid to girls living in low-resource areas and males to ensure equal access to the HPV vaccination. Furthermore, linkage to secondary prevention and further real-world monitoring and evaluation are warranted to inform effective cervical cancer prevention strategies in the post-vaccine era. Graphical Abstract

Abstract 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.

Over recent years in China, the incidence and mortality of cancer have increased significantly, bringing a heavy economic burden on patients, patients' families and society. In this paper, we analyze main causes and heavy economic burden of cancer in China from aspects of disease characteristics and related social factors, and put forward suggestions on reducing the economic burden of cancer in China in the future.

Abstract Background 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. Methods 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. Results 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. Conclusions 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.

Cervical cancer is the commonest cancer affecting women worldwide. During the last decades, the incidence and mortality rates of cervical cancer have increased in China. This research aims to assess the overall and genotype-specific prevalence of the human papillomavirus (HPV) infection among Chinese women with normal cervix, considering age, and geographic location. We selected studies about HPV prevalence in women from Chinese in Mainland China with normal cervix and abnormal cervical lesions, published between January 1995 and December 2020. The HPV prevalence was analyzed using meta-analysis based on the following: cytological and histological diagnoses, regions, and ages. The overall HPV prevalence in 856,535 women was 14.3%, 95% confidence interval (CI) and it increased from 8.2% to 16.5% in studies published from 2006 to 2020. The prevalence of high-risk (HR) and low-risk (LR) HPV types was 11.3% and 2.7%, respectively. The commonest types of HPV in women from Mainland China were HPV 16 (2.6%), 52 (2.4%), 58 (1.7%), 18 (0.9%), and 33 (0.8%). According to the geographical analysis, the prevalence of different HPV genotypes varied by region, Central China had the highest overall HPV prevalence. HPV16 was the commonest type in all the regions except in South China and East China, where HPV52 was found to be common. Regarding diagnosis, the HPV infection led to cervical cancer diagnosis by cytology and histology with 90.1% and 91.5% rates, respectively. HPV16 and HPV18 were common types associated with cervical cancer diagnosed by cytology and histology. HPV 16, 58, 52, 18, and 33 were the commonest types found in women with normal cervixes from Mainland China. The prevalence of different HPV genotypes varied by age group and region.

BackgroundTo explore the patterns of the exposure-response relationship between arsenic exposure and cardiovascular disease (CVD) mortality and investigate the effect of cigarette smoking on the association.MethodsSeven thousand seven hundred thirty-five tin miners with at least 10 years of arsenic exposure were enrolled since 1992 and followed up for 27 years. Each individual's air arsenic exposure at workplace was calculated by time weighted average arsenic concentration × exposure months. Detailed information on smoking was collected at baseline, and information on smoking status was collected for five consecutive years from 1992 to 1996. Hazard ratio (HR) and 95% confidence interval (CI) for the risk of CVD were estimated using Cox proportional hazards models.ResultsA total of 1,046 CVD deaths occurred in this cohort over 142,287.7 person-years of follow up. We firstly reported that for equal cumulative exposure, participants exposed to higher concentrations over shorter duration had a higher risk of CVD mortality than those exposed to lower concentration over longer duration. The HR and 95% CI were 1.38 (95%CI: 1.03–1.85) in participants exposed to arsenic concentration (45.5–99.5 mg/m3), 1.29 (95%CI: 1.02–1.67) in 99.5–361.0 mg/m3. Further, participants with age at first exposure

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 (

BackgroundThis special cohort reveals the effect of smoking cessation in occupational miners exposed to radon and arsenic.MethodsA total of 9,134 tin miners with at least 10 years of underground radon and arsenic exposure were enrolled beginning in 1992 and followed for up to 27 years. Detailed smoking information was collected at baseline, and information on smoking status was consecutively collected from 1992 to 1996. The Cox proportional hazards model was used to explore the relationship between time since smoking cessation and lung cancer.ResultsA total of 1,324 lung cancer cases occurred in this cohort over 167,776 person-years of follow-up. Among populations exposed to radon and arsenic, miners after quitting smoking for 10 years or more had almost halved their lung cancer risk [adjusted hazard ratio (HR) = 0.55, 95% CI: 0.38–0.79], compared with current smokers. Among miners after quitting smoking for 5 years or more, lung cancer incidence approximately halved (HR = 0.52, 95% CI: 0.30–0.92) for squamous cell lung carcinoma, while it showed no significant decline for adenocarcinoma (HR = 0.79, 95% CI: 0.34–1.85).ConclusionSmoking cessation for 10 years or more halved lung cancer incidence among miners exposed to radon and arsenic, and the benefit was more pronounced among squamous cell lung carcinoma.

Abstract 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.

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.

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.

Objective: We performed a pooled analysis to examine cigarette smoking and household passive smoke exposure in relation to the risk of human papillomavirus (HPV) infection and cervical intraepithelial neoplasia grade 2+ (CIN2+). Methods: Data were pooled from 12 cross-sectional studies for cervical cancer screenings from 10 provinces of China in 1999-2007. A total of 16,422 women were analyzed, along with 2,392 high-risk-HPV (hr-HPV) positive women and 381 CIN2+ cases. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression models controlling for sexual and non-sexual confounding factors. Results: There was an excess risk between active smoking and hr-HPV infection and CIN2+. Adjusted OR for ever smokers vs. never smokers was 1.45 (95% CI=1.10-1.91), for hr-HPV infection and 1.89 (95% CI=1.03-3.44), for CIN2+. Passive smoking had a slightly increased risk on the hr-HPV infection with adjusted OR 1.11 (1.00-1.24), but no statistical association was observed between passive smoke exposure and CIN2+. Compared with the neither active nor passive smokers, both active and passive smokers had a 1.57-fold (95% CI=1.14-2.15) increased risk of HPV infection and a 1.99-fold (95% CI=1.02-3.88) risk of CIN2+. Conclusion: Our large multi-center cross-sectional study found active smoking could increase the risk of overall hr-HPV infection and CIN2+ adjusted by passive smoking and other factors. Passive smoking mildly increased the risk of HPV infection but not the CIN2+. An interaction existed between passive tobacco exposure and active smoking for hr-HPV infection and the CIN2+. [ABSTRACT FROM AUTHOR]

Objective: To investigate the extent of the cross-reactivity of hybrid capture 2 (HC2) assay and evaluate the potential effect of cross-reactivity on the long-term risk for cervical cancer and precancers. Methods: Based on the Shanxi Province Cervical Cancer Screening Study-I (SPOCCS-I) cohort from 2005 to 2014 in Shanxi, China, SPF10-line probe assay (LiPA) was performed in all 598 HC2 positive and 300 random-selected HC2 negative cervical specimens. Tenyear cumulative incidence rate (CIR) of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) of these two tests was evaluated using Kaplan-Meier methods. Possible human papillomavirus (HPV) types to be cross-reacted by HC2 were also analyzed. Results: The overall agreement between HC2 and SPF10-LiPA for detecting carcinogenic HPV was 73.27%. The highest 10-year cumulative risk of CIN2+ was observed in both HC2 positive and LiPA-carcinogenic HPV positive women (25.70%; 95% confidence interval [CI]=23.55%- 27.91%), followed by HC2 positive but LiPA-non-carcinogenic HPV positive women (9.97%; 95% CI=8.57%-11.50%), HC2 negative but LiPA-carcinogenic HPV positive (2.56%; 95% CI=2.44%-2.70%) and HC2 positive but LiPA-HPV negative (1.85%; 95% CI=1.78%-1.92%) women. The proportion of cross-reactivity of HC2 with untargeted carcinogenic types was 8.9%, most of which were attributable to HPV26, 73, 82, 69, 71, 53, 11, 43, and 54. Conclusion: The noticeable high risk of CIN2+ in women infected with cross-reacted noncarcinogenic HPV and low risk in those with miss-to-detective carcinogenic HPV supported an overall good clinical performance of HC2 for a general cervical cancer screening. [ABSTRACT FROM AUTHOR]

Objective: To explore the genotype distribution of high-risk human papillomavirus (HRHPV) and its attribution to different grades of cervical lesions in rural China, which will contribute to type-specific HPV screening tests and the development of new polyvalent HPV vaccines among the Chinese population. Methods: One thousand two hundred ninety-two subjects were followed based on the Shanxi Province Cervical Cancer Screening Study I (SPOCCS-I), and screened by HPV DNA testing (hybrid capture® 2 [HC2]), liquid-based cytology (LBC), and if necessary, directed or random colposcopy-guided quadrant biopsies. HPV genotyping with linear inverse probe hybridization (SPF10-PCR-LiPA) was performed in HC2 positive specimens. Attribution of specific HR-HPV type to different grades of cervical lesions was estimated using a fractional contribution approach. Results: After excluding incomplete data, 1,274 women were included in the final statistical analysis. Fifteen point two percent (194/1,274) of women were HR-HPV positive for any of 13 HR-HPV types (HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68) and the most common HR-HPV types were HPV16 (19.1%) and HPV52 (16.5%). The genotypes most frequently detected in HR-HPV-positive cervical intraepithelial neoplasia grade 1 (CIN1) were HPV52 (24.1%), HPV31 (20.7%), HPV16 (13.8%), HPV33 (13.8%), HPV39 (10.3%), and HPV56 (10.3%); in HR-HPV-positive cervical intraepithelial neoplasia grade 2 or worse (CIN2+): HPV16 (53.1%), HPV58 (15.6%), HPV33 (12.5%), HPV51 (9.4%), and HPV52 (6.3%). HPV52, 31, 16, 33, 39, and 56 together contributed to 89.7% of HR-HPV-positive CIN1, and HPV16, 33, 58, 51, and 52 together contributed to 87.5% of CIN2+. Conclusion: In summary, we found substantial differences in prevalence and attribution of CINs between different oncogenic HPV types in a rural Chinese population, especially for HPV16, 31, 33, 52, and 58. These differences may be relevant for both clinical management and the design of preventive strategies. [ABSTRACT FROM AUTHOR]

Background: Human papillomavirus (HPV) 16 and 18 are the two most common HPV oncogenic types that can be prevented by vaccination. This study aimed at assessing the cost-effectiveness of 3 doses of the bivalent HPV vaccine in rural and urban settings in China. Methods: A Markov model was adapted to reflect the lifetime of a modelled 100,000 12-year-old girls cohort in rural and urban settings in China. Input parameters were obtained from published literature, official reports and a two-round expert review panel. Clinical and economic outcomes of vaccination at age 12 with screening was compared to screening only. In the base case analysis, a 3 % discount rate, the vaccine cost of 247 CNY (US$ 39, PAHO vaccine cost in 2013), two rounds of screening in a life time and 70 % coverage for both screening and vaccination were used. One-way, two-way and probabilistic sensitivity analyses were performed. We used different thresholds of cost-effectiveness to reflect the diversity of economic development in China. Results: Vaccination in addition to screening could prevent 60 % more cervical cancer cases and deaths than screening only. The incremental cost effectiveness ratio varied largely when changing cost of vaccination and discount in one way analysis. Vaccination was very cost-effective when the vaccine cost ranged 87-630 CNY (US$ 13.8-100) in rural and 87-750 CNY (US$ 13.8-119) in urban; and remained cost-effective when the vaccine cost ranged 630-1,700 CNY (US$ 100-270) in rural and 750-1,900 CNY (US$ 119-302) in urban in two way analysis. Probabilistic sensitivity analyses showed that model results were robust. Conclusions: In both rural and urban, the vaccination cost and discounting are important factors determining the cost-effectiveness of HPV vaccination; policy makers in China should take these into account when making a decision on the introduction of HPV vaccine. In areas with a high burden of cervical cancer and limited screening activities, HPV vaccination should be prioritized. However, the vaccine cost needs to be reduced in order to make it very cost-effective and affordable as well, in particular in poverty areas with high disease burden. [ABSTRACT FROM AUTHOR]

Background: An association between high-risk human papillomavirus (HR-HPV) oncoprotein expression and viral persistence has been suggested by the outcome of etiology studies, but there are no epidemiologic studies evaluating that link. Methods: We performed a 3-year prospective study in which 2,498 Chinese women ages 25 to 65 years were screened by six screening tests, including the OncoE6 Cervical Test (Arbor Vita Corporation) in 2011 (baseline). Six-hundred and ninety women who were positive for any of the tests and a random sample of 164 women with all negative results received colposcopy, and cervical specimens for the cobas 4800 HPV test ("cobas," Roche Molecular Systems) were collected before colposcopy; of this group, 737 cervical specimens were collected to perform cobas and OncoE6 Cervical Test in 2014 (follow-up). Twenty-four cases of HPV16/18 E6 positives and 204 selected controls at baseline, 13 cases of HPV16/18 E6 positive and another 204 selected controls at follow- up were analyzed separately using unconditional logistical regressionmodels to estimate ORs and 95% confidence intervals (CI). Results: Compared with women who were HPV16 E6 oncoprotein negative at baseline, women in the E6-positive group had a much higher risk of HPV persistence (adjusted OR, 54.64; 95% CI, 7.19-415.09) at 3-year follow-up; a statistically strong association was also found between HPV16/18 HPV persistence and E6 oncoprotein expression detected at follow-up (adjusted OR, 360.57; 95% CI, 28.30-4,593.55). Conclusions: A single detection of HPV16/18 E6 oncoprotein expression was strongly associated with viral persistence. Impact: HPV16/18 E6 oncoprotein constitutes a marker for risk of HPV persistence. [ABSTRACT FROM AUTHOR]

Background: The cost-effectiveness of human papillomavirus (HPV) vaccination in women pre-sexual debut has been demonstrated in many countries. This study aimed to estimate the cost-effectiveness of a 3-dose bivalent HPV vaccination at ages 12 to 55 year in both rural and urban settings in China.Methods: The Markov cohort model simulated the natural history of HPV infection and included the effect of screening and HPV vaccination over the lifetime of a 100,000 female cohort. Transition probabilities and utilities were obtained from published literature. Cost data were estimated by Delphi panel using healthcare payers' perspective. Vaccine cost was assumed Hong Kong listed price. Vaccine efficacy (VE) was based on the PATRICIA trial data assuming VE irrespective of HPV type at all ages on incident HPV. Costs and outcomes were discounted at 3 %. Cervical cancer cases and incremental cost-effectiveness ratio (ICER) for vaccination and screening compared with screening alone were estimated for each vaccination age. Reduced VE in women post-sexual debut were investigated in scenario analyses.Results: With 70 % vaccination coverage, a reduction of cancer cases varying from 585 to 33 in rural and 691 to 32 in urban were estimated at ages 12 to 55, respectively. The discounted ICERs of vaccination at any age under 23 years in rural and any age under 25 years in urban were lower than the current threshold. Scenario analyses with lower VE post-sexual debut confirmed the results with age 20 in rural and 21 in urban had consistent lower ICERs. The more 'catch-up' cohorts vaccinated at the start of a program, the more cancer lesions are avoided in the long-term.Conclusions: Vaccination at any age under 23 years old in rural and any age under 25 years old in urban were cost-effective. Catch-up to the age of 25 years in rural and urban could still be cost-effective. [ABSTRACT FROM AUTHOR]

Background: Liquid-state specimen carriers are inadequate for sample transportation in large-scale screening projects in low-resource settings, which necessitates the exploration of novel non-hazardous solid-state alternatives. Studies investigating the feasibility and accuracy of a solid-state human papillomavirus (HPV) sampling medium in combination with different down-stream HPV DNA assays for cervical cancer screening are needed.Methods: We collected two cervical specimens from 396 women, aged 25-65 years, who were enrolled in a cervical cancer screening trial. One sample was stored using DCM preservative solution and the other was applied to a Whatman Indicating FTA Elute® card (FTA card). All specimens were processed using three HPV testing methods, including Hybrid capture 2 (HC2), careHPV™, and Cobas®4800 tests. All the women underwent a rigorous colposcopic evaluation that included using a microbiopsy protocol.Results: Compared to the liquid-based carrier, the FTA card demonstrated comparable sensitivity for detecting high grade Cervical Intraepithelial Neoplasia (CIN) using HC2 (91.7 %), careHPV™ (83.3 %), and Cobas®4800 (91.7 %) tests. Moreover, the FTA card showed a higher specificity compared to a liquid-based carrier for HC2 (79.5 % vs. 71.6 %, P = 0.015), comparable specificity for careHPV™ (78.1 % vs. 73.0 %, P > 0.05), but lower specificity for the Cobas®4800 test (62.4 % vs. 69.9 %, P = 0.032). Generally, the FTA card-based sampling medium's accuracy was comparable with that of liquid-based medium for the three HPV testing assays.Conclusions: FTA cards are a promising sample carrier for cervical cancer screening. With further optimization, it can be utilized for HPV testing in areas of varying economic development. [ABSTRACT FROM AUTHOR]

Background: Controversy remains whether a pattern of cervical intraepithelial neoplasia exists on the cervix. Our study aims at determining if the prevalence of histologically proven lesions differs by cervical four-quadrant location or by 12 o'clock surface locations of diagnosis. Methods: We conducted a retrospective, histopathological study of 19 different population based cervical cancer screening studies from 1999 to 2010 by Cancer Hospital of Chinese Academy of Medical Sciences. The Institutional Review Board for human research subjects at CHCAMS approved all of the studies. During the colposcopy procedure, participant received either 4-quadrant biopsy or directed biopsy with/without endocervical curettage. Data of all samples were stratified by the methods of sampling. Kruskal-Wallis test was used to determine overall distribution of normal/CIN1, CIN2 and CIN3+ on the cervix. Results: In total, 53,088 cervical samples were included in distribution analysis. 66.9 % samples were obtained by random biopsy, 16.1 % were by directed biopsy, and 17.0 % were by endocervical curettage. 95.9%of the biopsied samples were diagnosed as normal/CIN1, 2.0 % were CIN2, and 2.1 % were CIN3 + . CIN2 and CIN3+ were most often found in quadrants 2 and 3 (KW 2 = 46.6540, p < 0.0001) and at the 4- and 7-o'clock positions by directed biopsy (ORCIN2 = 2.572, 1.689, ORCIN3+ = 3.481, 1.678, respectively), and at the 5-, 6-, 7-, 9- and 12-o'clock positions by random biopsy. CIN3+ was least often found at the 11-o'clock position by directed biopsy (OR = 0.608). Conclusions: Our results suggest a predisposition of specific locations on the cervix to CIN occurrence. Quadrants 2 and 3, especially the 4- and 7-o'clock positions should be preferentially targeted during biopsy. The decision for random biopsy should be reconsidered in future studies. [ABSTRACT FROM AUTHOR]

Background In China, high-risk human papillomavirus (HR-HPV) prevalence is unexpectedly high in older women, but the possible reasons have not been well studied yet. This study investigated the age trends of HR-HPV infection in a prospective study. Methods A total of 7397 women aged 25-65 years without cervical precancer or cancer were evaluated during 2010-2011 with a stratified sample of 2791 women re-evaluated after one year. Test results for careHPV and careHPV16/18/45 were used to describe the HR-HPV prevalence, incidence and clearance. Risk factors associated with HR-HPV infections were explored using a logistic regression model. Results The overall HR-HPV prevalence was 13.1% at baseline, with a peak of 19.3% in women aged 55-59 years. The prevalence of HR-HPV (p for trends < 0.001), HPV16/18/45 (p for trends = 0.002), and HR-HPV other than HPV16/18/45 (p for trends = 0.002) generally increased with increasing age. Number of infections that cleared was generally greater than number of incident infections within age groups. One-year clearance rate decreased with increasing age (p for trends < 0.001), however, incidence rate was unrelated to age (p for trends = 0.159). Risk factors that associated with HR-HPV infection differed between younger and older women. Conclusions The greater HR-HPV prevalence in older versus younger women in rural China may be explained by a cohort effect, higher than expected incidence, and/or poorer clearance at older age. [ABSTRACT FROM AUTHOR]

Background: Due to the potential of human papillomavirus (HPV) vaccination for decreasing cervical cancer rates in Mainland China, where some of the highest incidences in the world have been reported, our study aimed to assess HPV and HPV vaccine knowledge, and to evaluate the effect of a brief educational intervention on HPV knowledge and vaccine acceptability in Chinese undergraduate students and employed women. Methods: This multi-center, cross-sectional study was conducted across five representative cities of the five main geographical regions of Mainland China. Participants were selected from one comprehensive university and three to four companies in each city for a total of six comprehensive universities and 16 companies. A 62-item questionnaire on HPV knowledge and HPV vaccine acceptability was administered to participants before and after an educational intervention. The intervention consisted of an informative group lecture. Results: A total of 1146 employed women and 557 female undergraduate students were surveyed between August and November 2011. Baseline HPV knowledge was low among both groups— 320/1146 (28%) of employed women and 66/557 (12%) of students had heard of HPV, while only 237/1146 (21%) of employed women and 40/ 557 (7.2%) of students knew that HPV is related to cervical cancer. After educational instruction, 947/1061 (89%) of employed women and 193/325 (59%) of students knew the relationship between HPV and cervical cancer (χ2 = 1041.8, p < 0.001 and χ2 = 278.5, p < 0.001, respectively). Post-intervention, vaccine acceptability increased from 881/1146 (77%) to 953/1061 (90%), (p = <0.001) in employed women and 405/557 (73%) in students to 266/325 (82%), (p < 0.001). Women in both groups cited concerns about the HPV vaccine’s safety, efficacy, and limited use to date as reasons for being unwilling to receive vaccination. 502/1146 (44%) of women were willing to vaccinate their children at baseline, which increased to 857/1061 (81%) post-intervention, p < 0.001. Conclusions: Incorporation of our lecture-based education initiative into a government-sponsored or school-based program may improve HPV-related knowledge and HPV vaccine acceptability. Further studies are needed to evaluate and standardize HPV education programs in China. [ABSTRACT FROM AUTHOR]

Background: Cost estimation is a central feature of health economic analyses. The aim of this study was to use a micro-costing approach and a societal perspective to estimate aggregated costs associated with cervical cancer screening, diagnosis and treatment in rural China. Methods: We assumed that future screening programs will be organized at a county level (population ~250,000), and related treatments will be performed at county or prefecture hospitals; therefore, this study was conducted in a county and a prefecture hospital in Shanxi during 2008-9. Direct medical costs were estimated by gathering information on quantities and prices of drugs, supplies, equipment and labour. Direct non-medical costs were estimated via structured patient interviews and expert opinion. Results: Under the base case assumption of a high-volume screening initiative (11,475 women screened annually per county), the aggregated direct medical costs of visual inspection, self-sampled careHPV (Qiagen USA) screening, clinician-sampled careHPV, colposcopy and biopsy were estimated as US$2.64,$7.49,$7.95,$3.90 and $5.76, respectively. Screening costs were robust to screening volume (<5% variation if 2,000 women screened annually), but costs of colposcopy/biopsy tripled at the lower volume. Direct medical costs of Loop Excision, Cold-Knife Conization and Simple and Radical Hysterectomy varied from $61-544, depending on the procedure and whether conducted at county or prefecture level. Direct non-medical expenditure varied from $0.68-$3.09 for screening/ diagnosis and $83-$494 for pre-cancer/cancer treatment. Conclusions: Diagnostic costs were comparable to screening costs for high-volume screening but were greatly increased in lower-volume situations, which is a key consideration for the scale-up phase of new programs. The study's findings will facilitate cost-effectiveness evaluation and budget planning for cervical cancer prevention initiatives in China. [ABSTRACT FROM AUTHOR]

Background: A new lower-cost rapid-throughput human papillomavirus (HPV) test (careHPV, Qiagen, Gaithersburg, USA) has been shown to have high sensitivity for the detection of high grade cervical intraepithelial neoplasia. Methods: We assessed the outcomes and cost-effectiveness of careHPV screening in rural China, compared to visual inspection with acetic acid, when used alone (VIA) or in combination with Lugol's iodine (VIA/VILI). Using data on sexual behaviour, test accuracy, diagnostic practices and costs from studies performed in rural China, we estimated the cost-effectiveness ratio (CER) and associated lifetime outcomes for once-lifetime and twice-lifetime screening strategies, and for routine screening at 5-yearly, 10-yearly and IARC-recommended intervals. The optimal age range for once-lifetime screening was also assessed. Results: For all strategies, the relative ordering of test technologies in reducing cervical cancer incidence and mortality was VIA (least effective); VIA/VILI; careHPV@1.0 pg/ml and careHPV@0.5 pg/ml (most effective). For oncelifetime strategies, maximum effectiveness was achieved if screening occurred between 35-50 years. Assuming a participation rate of ~70%, once-lifetime screening at age 35 years would reduce cancer mortality by 8% (for VIA) to 12% (for careHPV@0.5) over the long term, with a CER of US$557 (for VIA) to $959 (for careHPV@1.0) per life year saved (LYS) compared to no intervention; referenced to a 2008 GDP per capita in Shanxi Province of $2,975. Correspondingly, regular screening with an age-standardised participation rate of 62% (which has been shown to be achievable in this setting) would reduce cervical cancer mortality by 19-28% (for 10-yearly screening) to 43-54% (using IARC-recommended intervals), with corresponding CERs ranging from $665 (for 10-yearly VIA) to $2,269 (for IARC-recommended intervals using careHPV@1.0) per LYS. Conclusions: This modelled analysis suggests that primary careHPV screening compares favourably to visual inspection screening methodologies in rural China, particularly if used as part of a regular screening program. [ABSTRACT FROM AUTHOR]

Long-term follow-up evaluations of cervical screening approaches are limited in low-resource areas. This prospective study assessed the risk of future cervical intraepithelial neoplasia grade 2 or worse (CIN2+) associated with baseline human papillomavirus (HPV) and cytologic status. In rural China, 1,997 women were screened with 6 screening tests, including colposcopic evaluations, and underwent biopsies in 1999. In December 2005, 1,612 women with cervical intraepithelial neoplasia grade 1 or less at baseline were rescreened by visual inspection, liquid-based cytology, and HPV-DNA testing. All women underwent colposcopy at follow-up, with biopsies taken from women with visually apparent lesions or cytologic abnormalities. Twenty women developed incident CIN2+. The crude relative risk of CIN2+ for baseline HPV-positive women was 52 (95% confidence interval: 12.1, 222.5). The crude relative risk of CIN2+ was 167 (95% confidence interval: 21.9, 1,265) for baseline and follow-up repeatedly HPV-positive women compared with repeatedly HPV-negative women. Among 1,374 baseline HPV-negative women, 2 and no incident CIN2+ cases were detected in baseline cytologically normal and abnormal subgroups, respectively. Among 238 baseline HPV-positive women, 6 of 18 incident cases of CIN2+ developed in the cytologically normal group. This study demonstrates that a single oncogenic HPV-DNA test is more effective than cytology in predicting future CIN2+ status. [ABSTRACT FROM PUBLISHER]

Objectives: Human papillomavirus is the necessary cause of cervical cancer, in particular the human papillomavirus-16/18 strains, which have been detected in ~70% of all cervical cancer cases worldwide. This study aims to assess whether other cofactors, which might be specific for the Chinese population, are involved in the development of cervical cancer. These findings may support the future direction of cervical cancer prevention. Study Design: Systematic literature review. Methods: The following databases were searched: MEDLINE, MEDLINE-IN-PROCESS, EMBASE, China National Knowledge Infrastructure, Wanfang Data and Chongqing VIP Information. The target population were adolescents or adults from mainland China. All observational studies irrespective of intervention or comparator reporting risk factors for cervical cancer were included. The Newcastle-Ottawa Scale was used to assess study quality. The impact of each outcome was reported in numerical terms. Results: A total of 2,676 articles were screened. A total of 21 articles met the inclusion criteria. All studies were case-controlled designs mostly conducted in hospitals of South-Eastern China. A total of 18 studies reported lifestyle behaviours as significant influencing factors in the development of cervical cancer. Sexual behaviour, gestational factors, screening history, disease history and socio-demographics status were reported as significant risk factors for cervical cancer development. Conclusion: This review provides an up-to-date insight of current cervical cancer risk factors in China. Due to the heterogeneity of the results, further evaluation is recommended to determine the association of these risk factors to the overall risk of cervical cancer.

Aim: To assess the efficacy of random biopsy in diagnosing those high-grade squamous intraepithelial lesions or carcinomas (HSIL+) missed by colposcopy-directed biopsy, and to identify the scenarios of cervical cancer screening when random biopsy is necessary. Patients/interventions: Data from 1997 women who participated in the Shanxi Province Cervical Cancer Screening Study I (SPOCCS I) were reviewed. Each woman received human papillomavirus (HPV) testing with the second-generation hybrid capture, liquid-based cytology, four-quadrant biopsy and endocervical curettage. The final diagnosis was based on the most severe pathological result obtained. The efficacy of random biopsy and colposcopy-directed biopsy was evaluated on the basis of the final pathological results. Results: For women with severe cytological abnormalities (HSIL+) and negative colposcopy, the yield of HSIL+ diagnosed by random biopsy was 25%. On the other hand, the yield of HSIL+ diagnosed by random biopsies in the negative quadrant was no more than 4% when the colposcopy was positive, regardless of the cytological findings. For women with negative HPV, no HSIL+ was found by random biopsy. For women with severe cytological abnormalities (HSIL+) and positive HPV, the yield of HSIL+ diagnosed by random biopsy was 35% when colposcopy was negative. For women with low-grade intraepithelial lesion (LSIL) and positive HPV, the yield of HSIL+ diagnosed by random biopsy was 12.5% when colposcopy was negative. Conclusion: Random biopsy is not effective in the negative quadrant in women with positive colposcopy, but should be performed in women with cytological HSIL+ but negative colposcopy, or in those with cytological LSIL or HGSL+ and positive HPV but negative colposcopy. [ABSTRACT FROM AUTHOR]