Importance:Lung cancer (LC) remains the leading cause of cancer-related mortality worldwide, with tobacco smoking being the primary risk factor. However, the long-term LC risk among individuals with negative low-dose computed tomography (LDCT) findings and the role of tobacco smoking in risk stratification remain poorly understood, limiting evidence-based guidance for subsequent screening intervals. Objective:To evaluate the association of tobacco smoking with long-term LC risk after a negative baseline LDCT finding and to inform optimized screening strategies. Design, Setting, and Participants:This population-based, prospective cohort study was conducted under the Cancer Screening Program in Urban China. Individuals aged 40 to 74 years with negative baseline LDCT findings (October 1, 2013, to December 31, 2021) were included, with follow-up until December 2023. All participants were monitored for LC incidence. Exposures:Self-reported smoking status, pack-years, and time since quitting. Main Outcomes and Measures:The primary outcome was LC incidence, analyzed using Kaplan-Meier methods and multivariable Cox proportional hazards regression models. The association between smoking exposure and LC risk was assessed, with time-stratified analyses and dose-response associations. Results:Among 30 565 participants (14 761 never smokers and 15 804 smokers; mean [SD] age, 57.1 [7.7] years; 15 693 [51.3%] female), 76 LC cases occurred during 139 011.51 person-years (crude incidence rate, 54.67 of 100 000 person-years). Smokers had higher LC risk than never smokers (adjusted hazard ratio [AHR], 2.73; 95% CI, 1.49-5.01), driven by those with a smoking history of 20 pack-years or more (eg, ≥30 pack-years: AHR, 3.22; 95% CI, 1.85-5.58). There was no elevated risk at 2 years (AHR, 2.07; 95% CI, 0.91-4.69), but risk was significantly increased at 3 years (AHR, 2.54; 95% CI, 1.19-5.41) and onward. A nonlinear dose-response association was found between pack-years and LC risk, with risk surpassing clinically relevant thresholds at approximately 20 pack-years (eg, 20 to <30 pack-years: AHR, 2.48; 95% CI, 1.14-5.40). Females exhibited higher susceptibility than males at comparable exposure (≥30 pack-years: AHR, 5.78 [95% CI,1.87-17.83] for females vs 1.36 [95% CI, 0.18-10.39] for males). Significant risk was seen in those aged 50 to 54 years (≥30 pack-years) and 55 to 74 years (≥20 pack-years). Short-term cessation (<15 years) was not significantly associated with reduced LC risk. Conclusions and Relevance:In this cohort study, smokers with negative baseline LDCT findings exhibited a substantially elevated long-term LC risk, which became significant only after 2 years after screening. These findings suggest support for extending the initial screening interval and implementing personalized long-term monitoring based on smoking history.

BACKGROUND:Co-testing with human papillomavirus (HPV) DNA testing plus liquid-based cytology is still used in parts of China, although many screening programmes are moving toward HPV-based strategies. We aimed to compare co-testing with HPV-based and cytology-only approaches in routine county services in resource-limited areas. METHODS:We analysed a screening cohort of 33,387 women aged 35-64 years from four primary care sites. Because all women received both HPV testing and cytology, we reconstructed four strategies within the same population: co-testing, HPV primary screening with cytology triage, HPV-only, and cytology-only. For each strategy we estimated detection of cervical intraepithelial neoplasia grade 2 or worse (CIN2 + ), referrals for specialist examination of the cervix, and cytology workload per 1000 women screened. RESULTS:Here we show that co-testing detects 6.7 CIN2+ cases per 1000 women screened, compared with 6.5 for HPV primary screening with cytology triage, 4.3 for HPV-only, and 4.9 for cytology-only. However, co-testing requires more resources than HPV primary screening with cytology triage, including 33.1 additional colposcopy referrals and 888.8 extra cytology slides per 1,000 women screened, with little gain in detection. Cytology-only increases referrals while detecting fewer CIN2+ cases, whereas HPV-only reduces referrals but detects fewer CIN2 + . CONCLUSIONS:In resource-limited county programmes, HPV primary screening with cytology triage provides the most favourable balance between detecting cervical pre-cancer and limiting unnecessary procedures. These findings support transitioning from routine co-testing to HPV-based screening tailored to local capacity.

Background:The World Health Organization (WHO) guidelines on cervical cancer screening recommends colposcopy as one of the methods to triage human papillomavirus (HPV)-positive women. We aimed to assess the diagnostic accuracy of colposcopy in this context. Methods:In this systematic review and meta-analysis, we searched for articles reporting the diagnostic accuracy of colposcopy in women with a positive HPV screening test, published in PubMed, Embase or the Cochrane library up to Oct 20, 2025. We included cross-sectional or longitudinal studies if the number of true and false positive and negatives could be derived or obtained after contacting the authors. Studies were excluded if the study population was not representative of a screening population. We collected data on colposcopy triage (index) together with data on cytology triage (comparator), if available, and assessed risk of bias using an adapted Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 checklist. The pooled sensitivity and specificity to detect cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and grade 3 or worse (CIN3+) were calculated, as well as the relative sensitivity and specificity of colposcopy triage compared to cytology triage, using a bivariate logistic random effects model. Heterogeneity was measured using τ2 and I2. Sample size effects were assessed by Deeks' funnel plots and regression test. Certainty of evidence was assessed using the GRADE tool. This study was registered in PROSPERO, CRD42023389772. Findings:The literature search identified 5774 records. After screening, we included 11 studies (13,311 participants) in the review, but restricted the primary analysis to 8 studies (10,632 participants) that had complete follow-up after colposcopy triage. The pooled sensitivity for CIN2+ and CIN3+ using colposcopy (low-grade colposcopic impression) were 84.4% (95% CI: 79.0%-88.6%) and 86.9% (95% CI: 81.7-90.8%), respectively. The pooled specificity for < CIN2 was 64.3% (95% CI: 57.4%-70.7%). While heterogeneity between studies was high, with I2 up to 95.5%, most studies reported a similar or higher sensitivity and lower specificity compared to cytology (at the lowest cut-off): the pooled relative sensitivity for CIN2+ and CIN3+ were 1.74 (95% CI: 1.53-1.97) and 1.58 (95% CI: 1.35-1.85). The relative specificity for < CIN2 was 0.67 (95% CI 0.61-0.72). Certainty of evidence was considered low to very low due to subjectivity in the assessment of colposcopy, cytology and the reference standard, as well as the high inter-study heterogeneity and the risk of reference standard misclassification. Interpretation:Studies consistently reported good sensitivity but low specificity of colposcopy to triage women with a positive HPV screening test, showing colposcopy may be an acceptable triage test. While our findings are consistent with current WHO guidelines, low certainty of evidence and risk of over-treatment should be carefully considered. Funding:World Health Organization; Horizon 2020 Framework Programme for Research and Innovation of the European Commission the European Joint Action EUCanScreen and the European Commission Initiative on Cervical Cancer.

Exogenous chemical exposures are a global health concern due to their hepatotoxic potential, yet the extent to which endogenous metabolic disruption bridges these exposures to long-term liver cancer risk remains unclear. In a nested case-control study within a prospective Chinese cohort (n = 200), we conducted a metabolome-wide association analysis integrating 254 serum exogenous chemical residues with 478 endogenous metabolites to characterize pre-diagnostic metabolic disorders occurring up to 10 years before liver cancer onset and to delineate exposure-risk relationships. Individuals who later developed liver cancer exhibited pronounced metabolic perturbations, particularly involving bile acid metabolism, acylcarnitine pathways, glycerophospholipid turnover, sphingomyelin composition, and acylglycerol metabolism. A candidate early-warning panel comprising Phe/Tyr, FFA 24:1, PC (16:0_20:5), TG (18:1_18:1_21:0), and TG (18:3_17:1_18:2) was identified for liver cancer risk stratification. Exposure to salmeterol, diethylstilbestrol, and dibutyl phosphate showed positive associations with liver cancer risk, and mediation analysis highlighted tyrosine, PC (19:0_18:2), and SM (d18:1/24:1) as significant intermediators, suggesting hepatocarcinogenesis arises from the combined impact of exogenous chemical exposure and endogenous metabolic disorders. Overall, these findings indicate that early disturbances in bile acid, lipid, and amino acid metabolism precede clinical diagnosis by years and may serve as mechanistic links and early-warning biomarkers for exposure-related liver carcinogenesis.

Supplementary Table 1: Study population and exclusion criteria by cohorts as established by the ACC reproductive factor working group

Objective This study aimed to validate the prognostic discriminatory power of the revised International Federation of Gynecology and Obstetrics (FIGO) 2018 staging system and to evaluate the association between regional lymph node resection (RLNR) and survival in cervical cancer (CC) patients who underwent RLNR followed by chemotherapy and radiotherapy. Methods In this retrospective cohort study utilizing the Surveillance, Epidemiology, and End Results (SEER) database (2000–2018), patients were categorized into early-stage (IA/IB1-IB2/IIA1) and locally advanced-stage (IB3/IIA2-IIB/III/IVA) groups. Survival outcomes were analyzed using Kaplan–Meier, univariate and multivariate Cox regression (including time-dependent), and year-of-diagnosis stratified analyses, applied to crude, inverse probability of treatment weighting (IPTW)-weighted, and propensity score matching (PSM)-matched models. Results The FIGO 2018 system revealed significant survival differences between IB1 vs IB2 and IIIC1 vs IIIA/IIIB (all p < 0.001). In early-stage patients, RLNR conferred no significant survival benefit. However, in locally advanced-stage patients, RLNR with primary surgery was associated with better survival than RLNR alone. In the cohort without primary surgery, RLNR alone was consistently identified as a prognostic factor versus non-surgery across all three analytical models (IPTW as primary, PSM as sensitivity; all p<0.001). The hazard ratios for RLNR alone versus non-surgery were all below 1.000, and year-of-diagnosis stratified analyses further supported this protective association, with consistently directional estimates. Conclusion This study suggested the prognostic value of the FIGO 2018 staging system and hypothesized that RLNR is a prognostic factor for better survival compared with chemotherapy and radiotherapy alone in locally advanced-stage CC, although the limitations of a retrospective study must be acknowledged.

Existing evidence regarding the impact of vaccination on the natural history of high-risk human papillomavirus (HPV) infections remains limited, understanding such effects is essential for optimizing cervical cancer screening in post-vaccination era. Using 10-year follow-up data from a phase 3 randomized trial of the Escherichia coli-produced HPV-16/18 bivalent vaccine (NCT01735006) and its extension study (NCT05045755, NCT04969445), we compared the spectra and natural history (persistence, clearance, and progression) of high-risk HPV infections between vaccinated and unvaccinated females aged 18-45 years. Data was analyzed using the Cox regression and the competing risk model. Our findings indicate that vaccination reduces the burden of HPV-16/18-associated lesions (HR = 0.12, p = 0.0041) primarily by preventing incident infections (HR = 0.45, p < 0.0001) and modifying the natural history of breakthrough infections (enhancing clearance: 98.5% vs. 93.8%, p < 0.0001; and attenuating progression: 1.5% vs. 6.2%, p = 0.0420). Conversely, the elevated burden of HPV-52-associated lesions (HR = 3.06, p = 0.0303) observed in the vaccine group stems mainly from altered natural history (reduced clearance: 90.3% vs. 97.9%, p = 0.0144; and increased progression: 9.7% vs. 2.1%, p = 0.0421), rather than an increase in incidence (HR = 1.09, p = 0.2669). In this work, the observed shifts in HPV infection profiles and natural history between vaccinated and unvaccinated populations suggest that cervical cancer screening recommendations may warrant adjustment for vaccinated individuals.

Background and objectiveThe disease burden of colorectal cancer (CRC) in China is relatively heavy, and although the multidisciplinary treatment (MDT) model can improve efficacy and resource efficiency, there are inequalities in its accessibility. The aim of this study was to investigate the key factors affecting access to MDT among patients with stage III to stage IV CRC.MethodsA multi-stage stratified sampling method is adopted to conduct a cross-sectional survey of 4,589 stage III-IV colorectal cancer (CRC) patients across 19 hospitals nationwide.ResultsOnly 796 (17.3%) of the 4,589 patients with stage III-IV CRC included in this study participated in MDT, with more males (61.4%) than females (38.6%). Univariate analysis showed that:patients’ location, medical visits to provincial-capital-city-hospitals and prefecture-level-city-hospitals, education background, number of medical institutions been visited, family income, patients’ circumstance of disease, initial diagnosis stage, whether metastasis occurred at initial diagnosis, endoscopic interventional therapy, chemotherapy, targeted therapy, traditional Chinese medicine(TCM) or palliative treatment, and treatment efficacy (p<0.05) are factors influencing patient participation in MDT. Multivariate analysis shows that patients in North China (OR: 2.69, 95% CI: 1.98-3.67), Central China (OR: 1.59, 95% CI: 1.15-2.21), Southwest China (OR: 5.19, 95% CI: 3.78-7.11), and Northwest China (OR: 2.28, 95% CI: 1.51-3.43) are more likely to participate in MDT. Patients treated at city-level hospitals (OR: 1.84, 95% CI: 1.50-2.26) and those receiving care at two hospitals (OR: 1.28, 95% CI: 1.02-1.61) also show higher MDT participation rates. Those in the recurrent treatment phase (OR: 3.21, 95% CI: 1.56-6.58) are significantly more likely to engage in MDT. Additionally, patients undergoing chemotherapy (OR: 2.62, 95% CI: 1.75-3.93), targeted therapy (OR: 1.38, 95% CI: 1.10-1.73), or traditional Chinese medicine (TCM)/palliative treatment (OR: 1.76, 95% CI: 1.41-2.22) have an increased likelihood of MDT participation. There is a positive association between participation in MDT and the overall health-related quality of life (HRQOL) score in colorectal cancer patients.ConclusionDifferent regions, healthcare organizations, patients’ stage of treatment, modalities of treatment and quality of life influence access to MDT for patients with Stage IV CRC, while MDT care is significantly associated with better quality of life.

Tailored cervical cancer screening strategies are essential, particularly in resource-limited settings. This study aimed to assess the genotype-specific impact of high-risk human papillomavirus (HR-HPV) infections on cervical cytological progression over a 3-year interval among Chinese women, thereby providing evidence for more precise and individualized screening approaches. A multicenter cohort was established in 2017 across three Chinese provinces. Participants underwent baseline HPV genotyping and cytological examination, with genotyping for five high-risk types (HPV16, 18, 33, 52, and 58), and follow-up evaluations conducted from 2018 to 2020. Cytological progression was defined as a transition from normal cytology (negative for intraepithelial lesion or malignancy, NILM) at baseline to low-grade squamous intraepithelial lesion (LSIL) or worse at the final follow-up. A total of 7240 women were included to evaluate the cytological progression. The overall progression rate was 0.7%, with a notably higher rate among HR-HPV-positive women (2.1%) compared to HR-HPV-negative women (0.5%). Specifically, HPV16, HPV52, and HPV58 were significantly associated with an increased risk of progression, with adjusted odds ratios (aORs) of 6.26 (95% CI: 2.62-14.95), 6.68 (95% CI: 3.30-13.53), and 4.24 (95% CI: 1.51-11.94), respectively. Moreover, women with persistent infections with HPV16, HPV52, and HPV58 had approximately 8-fold, 6-fold, and 5-fold higher risks of progression, respectively, compared with women without infections. Stratified management based on high-risk genotypes-particularly HPV16, HPV52, and HPV58-may help prioritize colposcopy and more intensive follow-up for women at elevated risk, which could contribute to cervical cancer prevention efforts. Trial Registration: Chinese Clinical Trial Registry Center of the World Health Organization International Clinical Trials Registry Platform number: ChiCRT2200055287.

Background:Cervical cancer remains a major public health concern in Mongolia, where screening coverage is estimated at approximately 38%, well below recommended levels, and access to timely diagnosis varies. This study examined temporal trends in incidence and mortality and assessed the impact of COVID-19-related disruptions on cancer detection. Methods:A nationwide population-based study was conducted using data from Mongolia's national health information system (H-Info). All cervical cancer cases (ICD-10: C53.0-C53.9) and related deaths from 2014 to 2024 were included. Age-standardized incidence (ASIR) and mortality rates (ASMR) were calculated using the WHO world standard population as reference. Temporal trends were analyzed using log-linear and segmented regression models. The mortality-to-incidence ratio (MIR) was used as an ecological indicator of population-level cancer outcomes. Results:A total of 3,990 cases and 1,370 deaths were identified. Incidence increased between 2014 and 2016, declined thereafter, and dropped sharply during 2020-2022 (APC -29.4%), before rebounding in 2023-2024. In contrast, mortality declined gradually over the study period. MIR increased during the pandemic and declined following service recovery. Conclusions:Cervical cancer incidence in Mongolia is highly sensitive to disruptions in screening and diagnostic services. Divergent trends between incidence and mortality likely reflect reduced detection during the pandemic rather than true changes in disease burden. These findings highlight the importance of maintaining continuity of cancer screening and diagnostic services during health-system disruptions.

Evidence shows HPV vaccination reduces infection, precancer and cervical cancer, yet coverage in health-resource-limited of China remains uncertain. We assessed awareness, uptake and correlates among women attending cervical screening, and examined associations with screening outcomes. We conducted a cross-sectional study in eight county sites in 2023-2024 among women aged 35-64 y. A standardized questionnaire captured sociodemographic factors, awareness and vaccination. Cervical samples were tested for hrHPV. Outcomes were awareness, vaccination, hrHPV, HPV16/18 and CIN2+. Associations were estimated using modified Poisson models with site fixed effects and HC3 robust errors. Adjusted prevalence ratios (aPRs) and covariate-standardized marginal estimates were reported. We included 93,027 unique participants. Awareness was 45.15% and vaccination 6.73%. hrHPV prevalence was 11.38% and CIN2+ detection was 0.70%. In 2024 versus 2023, awareness was lower (40.66% vs 51.34%) while vaccination was higher (7.61% vs 5.53%; aPR 1.25, 95% CI 1.18-1.32). Awareness and uptake declined with age; coverage was 23.23% at ages 35-39 and 0.29% at ages 60-64. Urban residence and higher education were associated with uptake (urban aPR 1.19, 95% CI 1.11-1.27; bachelor's or higher aPR 1.73, 95% CI 1.58-1.90). The age-by-year interaction was significant, with standardized gains concentrated at ages 35-49. Vaccination was associated with lower HPV16/18 infection (aPR 0.66, 95% CI 0.52-0.85) but not with overall hrHPV or CIN2+. HPV vaccine awareness and uptake were low among women aged 35-64 y in health-resource-limited areas, with strong age, educational and urban-rural gradients and marked site heterogeneity. Uptake increased in 2024, mainly at ages 35-49, and vaccination was associated with a lower prevalence of HPV16/18 infection.

Supplementary Table 3: Pooled relative risks for recategorized age at menarche and age at menopause & incident thyroid cancer risk, Overall and papillary type

Supplementary Table 2: Distribution of total cases according to histology according to participating cohorts

Supplementary Figure 3: Forest plots of the pooled hazard ratios (HRs) and 95% confidence intervals (CIs) generated by combining cohort-specific HRs for the association between reproductive factors and the overall risk of thyroid cancer in the Asia Cohort Consortium. A - Forest plot for the pooled HRs and CIs for breastfeeding status and thyroid cancer risk, overall B - Forest plot for the pooled HRs and CIs for postmenopausal status and thyroid cancer risk, overall C - Forest plot for the pooled HRs and CIs for age at menopause and thyroid cancer risk, overall

Medical artificial intelligence (AI) has advanced rapidly, yet a comprehensive quantitative overview of its clinical evaluation landscape remains lacking. We conducted a scoping review of 218 systematic reviews published between September 2023 and September 2024, from which 4667 primary studies were identified and classified by research stage, geography, specialty, and study design. Most studies were preclinical (88.2%, 4114/4667), while only 2.4% (113/4667) were randomized controlled trials (RCTs). Research was highly geographically concentrated: the top 10 contributing countries accounted for 75.5% of total country contributions, of which the United States and China contributed 47.5%. Among all primary studies, neoplasms (32.5%, 1518/4667) and musculoskeletal disorders (14.1%, 656/4667) were the most common, whereas digestive (38.1%, 43/113) and circulatory diseases (12.4%, 14/113) accounted for most RCTs. Among RCTs, 67.3% (76/113) were single-center, and 71.7% (81/113) did not report adherence to any reporting guideline. Overall, 82.3% (93/113) of RCTs reported favorable outcomes, although methodological concerns were common, particularly in allocation concealment and blinding. These findings indicate that medical AI research remains heavily skewed toward early-stage development, with limited high-quality clinical evidence. Strengthening trial design, multicenter collaboration, and reporting transparency will be critical to support the safe and equitable integration of AI into clinical practice.

Inappropriate cervical cancer screening practices, including over- and under-screening, pose significant healthcare burdens in low-resource settings. This study analyzed screening behaviors and determinants among 33,362 women aged 35-64 in Wuxiang County, China, using longitudinal cohort data. Screening events were classified as guideline-adherent, over-screened, under-screened, or unscreened based on prior methods (HPV, cytology, or co-testing) and results, using cause-specific frailty models for analysis. Overall, only 19.9% of events were guideline-adherent, while 29.5% were over-screened and 50.6% were under- or unscreened. Notably, the implementation of a county-wide Electronic Medical Record (EMR) platform in 2022 coincided with a sharp decline in over-screening from 36.7% to 15.7%. Compared with primary HPV testing, prior co-testing increased the hazard of both over- and under-screening, whereas prior cytology was strongly associated with under-screening. Women with low-grade abnormalities (≤CIN1) showed a substantially higher risk of under-screening compared to those with negative results. Additionally, community residents were more prone to over-screening, while village residents faced higher under-screening risks. These findings suggest that transitioning to HPV-based screening and integrating EMR systems effectively reduces unnecessary testing, though enhanced reminder systems are crucial to address persistent under-screening in resource-constrained regions.

Deep learning (DL) systems could improve diagnostic accuracy and efficiency in detecting cervical atypia, but their effectiveness remains insufficiently explored. This multicentre, randomised crossover trial evaluated the clinical utility of a DL system in cervical cytopathology. A total of 1,920 women aged 18 years or older undergoing liquid-based cytology for cervical cancer screening were included, and their slides were digitized and randomly assigned (1:1) to two reading sequences. Four non-expert cytopathologists with 1-3 years of experience assessed slides using DL assistance for one group and manual microscopy for the other, and then switched roles after a four-week washout period. Each slide was evaluated twice in a randomly shuffled order. DL significantly improved sensitivity (85.7% vs 71.3%, p < 0.001), with a difference of 14.3% (95% CI: 7.6% to 21.1%), exceeding the 5% superiority margin. Specificity was comparable (86.5% vs 85.1%, p = 0.238), and non-inferiority was supported, as the lower limit of the 95% CI for the difference (1.4%; 95% CI: -1.0% to 3.8%) was above the pre-specified margin of -5%. Reading time was markedly reduced with DL (175 seconds vs 31 seconds, p < 0.001). DL assistance could enhance both sensitivity and efficiency while rigorously preserving specificity in cervical cytology interpretation. Trial registration: ChiCTR2300078722.

Supplementary Methods 1: Details on the development of the Asia Cohort Consortium reproductive factor working group protocol

BACKGROUND:Cecolin, a bivalent human papillomavirus (2vHPV) vaccine produced with Escherichia coli, has demonstrated safety and efficacy and is now widely used globally. We aimed to report the efficacy, safety, and immunogenicity profile of the nine-valent (9vHPV) vaccine, Cecolin 9. METHODS:We conducted a multicentre, double-blind, randomised, controlled, phase 3 trial at five local health centres in the Jiangsu and Sichuan provinces in China. Eligible participants were healthy, non-pregnant women aged 18-45 years with an intact cervix, no previous HPV vaccination, and between one and four lifetime sexual partners. Participants were stratified by age (18-29 and 30-45 years) and randomly assigned (1:1) with an interactive web response system (central randomisation with block sizes of eight) to receive three doses of either the 9vHPV vaccine (vaccine group) or the 2vHPV vaccine (control group) at day 0, month 1, and month 6. All participants, investigators, and laboratory personnel were masked to group assignment. The coprimary outcomes were immunogenicity, defined as non-inferiority of neutralising antibodies against HPV 16 and 18 at month 7 in the per-protocol set, and persistent infection (≥12 months), associated with HPV 31, 33, 45, 52, and 58 in the modified intention-to-treat population. Non-inferiority was identified for the lower limit of the 95% CI of the geometric mean concentration (GMC) ratio (9vHPV vs 2vHPV) at a margin of 0·5 and a seroconversion rate difference (9vHPV - 2vHPV) at a margin of -5%. Both criteria had to be met to establish non-inferiority. This trial is registered with ClinicalTrials.gov (NCT04537156) and follow-up is ongoing. FINDINGS:Between Sept 5 and Dec 10, 2020, 11 024 individuals were screened, of whom 9327 (84·6%) eligible women were randomly assigned to the vaccine group (4663 [50·0%]) and the control group (4664 [50·0%]). In the per-protocol set, antibody responses against HPV 16 and 18 in the vaccine group were non-inferior to those in the control group. The GMC ratio was 0·60 (95% CI 0·56-0·66) for HPV 16 and 0·64 (0·58-0·70) for HPV 18; the difference in seroconversion rates was 0·0% (95% CI -0·49 to 0·48) for HPV 16 and -0·12% (-0·67 to 0·33) for HPV 18. In the modified intention-to-treat population, 9vHPV vaccine efficacy against 12-month persistent infection associated with HPV types 31, 33, 45, 52, and 58 was 98·2% (95% CI 89·6-100). Adverse reactions were reported by 2432 (52·1%) of 4664 participants in the vaccine group and by 1966 (42·2%) of 4663 in the control group. Serious adverse events occurred at a similar rate between the vaccine group (512 [11·0%]) and the control group (481 [10·3%]); none were considered related to vaccination. INTERPRETATION:The E coli-produced 9vHPV vaccine was well tolerated, immunogenic, and highly protective against vaccine-targeted HPV types. Given its low production cost, this vaccine has the potential to improve global access to high-valency HPV vaccination. FUNDING:National Key R&D Program of China, National Natural Science Foundation of China, Natural Science Foundation of Beijing Municipality, Natural Science Foundation of Xiamen Municipality, Fundamental Research Funds for the Central Universities, and Xiamen Innovax. TRANSLATION:For the Chinese translation of the abstract see Supplementary Materials section.

BACKGROUND:Cervical cancer remains a significant health burden in China. National policies now allow human papillomavirus (HPV) DNA as a primary screening test, but many health resource-limited counties have not adopted it because programs cannot fund reagents or laboratory platforms. We conducted a multicenter study in 10 pilot counties where HPV DNA screening was introduced with project-supported reagents, platforms, and training. METHODS:We analyzed data from 10 pilot counties designated by the National Cervical Cancer Prevention Program. A total of 63,223 women aged 35 to 64 years were screened with three strategies: (i) cytology alone, (ii) HPV DNA testing with cytology triage, and (iii) HPV DNA testing with visual inspection with acetic acid/Lugol iodine (VIA/VILI) triage. Key indicators included screen positivity rate, colposcopy rate, cervical intraepithelial neoplasia (CIN) 2+ detection, positive predictive value (PPV), and number needed to refer (NNR). Inverse probability weighting was used to adjust for loss to follow-up. RESULTS:HPV-based strategies were superior to cytology across all indicators. CIN2+ detection was two to three times higher, with the highest PPV in the HPV + cytology group (21.9%) and the lowest NNR (5.73), indicating higher referral efficiency. Loss to follow-up rate was also significantly reduced under the HPV + VIA/VILI strategy. These advantages were most prominent among women aged ≥45 years. CONCLUSIONS:Within the first year of implementation, HPV DNA-based screening is feasible and more effective in health resource-limited areas of China and flexible triage models can be adapted. IMPACT:The findings support the integration of HPV DNA testing into national cervical cancer screening programs and highlight needs for robust follow-up systems in underserved populations.