OBJECTIVE:To evaluate the 5-year efficacy of thermal ablation (TA) for cervical intraepithelial neoplasia (CIN) and high-risk HPV (hrHPV) clearance in Chinese women. METHODS:A total of 17,202 women aged 20-65 years were recruited to screening cohorts in 2017-2018 from 3 rural counties in Shanxi and Inner Mongolia and an urban area in Shenzhen with follow-up evaluations until 2022. The hrHPV-positive women with ablation-eligible lesions on colposcopy underwent biopsy and TA (n = 228) in one visit. A loop electrosurgical excision procedure (LEEP) or cold knife conization (CKC) was recommended for ineligible women with high-grade CIN on histology (n = 106 and 41, respectively), while untreated hrHPV-positive women served as controls. Treated women had annual hrHPV testing and cytology. Untreated women had annual hrHPV testing. Positive cases were referred for colposcopy, with biopsy performed when indicated. Cure rates and hrHPV clearance rates were analyzed using Kaplan-Meier and competing risk models with sub-distribution hazard ratios (SHRs) assessing treatment effects. RESULTS:The 5-year cure rate for CIN1 regressing to normal was 79.0% after TA treatment and the 5-year cure rate for CIN2 regressing to CIN1/normal was 87.9%, comparable to LEEP (90.3%) and CKC (94.4%) for CIN2 (P = 0.54). The TA cure (66.0%) was significantly lower for CIN3 than LEEP and CKC (97.0% and 94.1%; P = 0.006). TA achieved 98.0% 5-year hrHPV clearance in CIN1/normal cases, which was higher than untreated women (87.7%; SHR = 0.81, 95% CI = 0.73-0.90), particularly for HPV16 (SHR = 0.67), HPV31 (SHR = 0.56), and HPV33 (SHR = 0.65). The 5-year hrHPV clearance after TA was comparable to LEEP and CKC for CIN2/3. CONCLUSIONS:TA provides durable efficacy for CIN1 and CIN2 and promotes hrHPV clearance, reducing progression risk. It could complement excisional treatments for CIN2 and enhance treatment accessibility in low-resource settings.

Lung Adenocarcinoma (LUAD) is a leading cause of cancer-related mortality worldwide. The relationship between metabolic reprogramming and immune infiltration has been identified as having a crucial impact on LUAD progression. The aim of this study is to achieve a deeper understanding of the interplay between the immune system and metabolism in the LUAD microenvironment. A total of 213 treatment-naïve LUAD patients from two independent cohorts were enrolled. Using the proteomic data from one of the cohorts (n = 103), three molecular subtypes of LUAD were identified based on their immune signatures, clinical characteristics, metabolic reprogramming, and genomic features were analyzed. The data from the other cohort (n = 110) were used to validate the findings. Three subtypes with distinct immune environment (IM1-IM3) were identified in LUAD based on the proteomic dataset, each of which has distinctive clinical, immune, and metabolic characteristics. Among these subtypes, IM2, which has the highest immune infiltration and is more likely to benefit from immunotherapy. In contrast, IM3 was found to have the poorest prognosis, exhibits active hypoxia and glycosaminoglycan biosynthesis, and is thought to be associated with extracellular matrix remodeling and epithelial-mesenchymal transition activation. Additionally, the active glycosaminoglycan biosynthesis pathway in the IM3 subtype was associated with an immune-desert microenvironment. This study presents the proteomic immune stratification of LUAD, revealing the possible link between immune cells and reprogramming of LUAD metabolisms, which may be a viable therapeutic strategy to improve LUAD immunotherapy.

This study investigated the differences in vaginal microbiota and metabolism between HPV positive and HPV negative women based on the stratification of vaginitis. This was a case-control study. A total of 164 women were included in this study analysis with a ratio of 1:3 for HPV positive and HPV negative women. The V3-V4 region of the 16S rRNA gene was amplified by polymerase chain reaction (PCR) followed by sequencing with Illumina. Untargeted metabolomic sequencing was conducted by the liquid chromatography-mass spectrometry (LC-MS) system. Specific microbial species and differentially expressed metabolites associated with these differences were explored. We found that a statistically significant difference existed in the bacterial structure between HPV positive and HPV negative women (R = 0.2177, p = 0.001), and HPV positivity was associated with the enrichment of Lactobacillus iners among women diagnosed with vaginitis. However, this difference was not observed in women without vaginitis. Regarding metabolic differences, HPV positive women with vaginitis displayed elevated levels of organic acids and their derivatives, accompanied by decreased lipid levels in their vaginal secretions. Conversely, HPV positive women without vaginitis showed higher lipid levels and lower concentrations of organic acids and their derivatives. Among women with vaginitis, Lactobacillus iners was positively correlated with biogenic amine, organic acids and derivatives and negatively correlated with kessyl glycol. Among women without vaginitis, Lactobacillus iners was negatively correlated with pelargonic acid. The disparity in the abundance and metabolites of vaginal microbiota between HPV positive and HPV negative women could be affected by whether the woman has been diagnosed with vaginitis. Metabolic differences indicated that antioxidant therapy holds promising prospects for potential application in the management and treatment of HPV infections. Further in-depth research into the molecular mechanisms is crucial for clarifying the precise role that vaginal microbiota and metabolites play in HPV infection.

ObjectiveClinical investigators are essential for assessing the clinical value, safety, and efficacy of innovative drugs. However, comprehensive data on their competency levels are limited in China. This study aimed to evaluate the current status and key determinants of clinical investigators' competencies.MethodsWe conducted a multicenter, cross-sectional study in 40 tertiary hospitals in Beijing in August 2023, enrolling 1397 clinical investigators. Competency was assessed via a self-administered questionnaire, and influencing factors were identified using multivariate logistic regression.ResultsThe median overall competency score was 103 (range: 32-160). Among 194 principal investigators (PIs), prominent competency scores ranged from 25 to 120, with a median of 93. Several factors were significantly associated with higher competency, including advanced education (doctoral degree: aOR = 1.75, 95% CI: 1.21-2.55), professional title (midlevel title: aOR = 1.77, 95% CI: 1.20-2.59; senior-level title: aOR = 2.91, 95% CI: 1.78-4.75), experience leading clinical trials (>= 1 trial as PI: aOR = 2.38, 95% CI: 1.69-3.36), and GCP training frequency (at least semiannually: aOR = 1.39, 95% CI: 1.07-1.81).ConclusionsEfforts should target areas of underperformance, particularly by encouraging the pursuit of advanced degrees, senior professional accreditation, PI experience, and regular GCP training. Competency development requires systematic training rather than mere seniority. Consistent GCP training and adherence to international competency standards are crucial for elevating trial quality and facilitating China's integration into global drug development.

There is limited evidence of the relationship between cognitive changes and all-cause mortality. And it has no report of population-attributable fraction (PAF) of mortality due to cognitive impairment in Chinese elderly. In light of this, we comprehensively examined the relationship between cognitive impairment and all-cause mortality after 20-year follow-up among the elderly Chinese. This is an epidemiological survey with a 20-year prospective cohort study design. A total of 9093 participants came from the Chinese Longitudinal Healthy Longevity Survey 1998–2018 waves. Cox proportional hazards regressions were performed to analyze the relationship between baseline cognitive impairment status, the rate of change in the MMSE scores over two years and subsequent all-cause mortality. We observed a dose–response relationship between cognition and mortality. Compared to those with no impairment, elderly with mild (AHR = 1.11, 95

The relationship between gut microbiota and metabolic syndrome (MetS) has attracted significant attention, with MetS comprising components like abdominal obesity, dysglycemia, dyslipidemia, and hypertension. The dietary index for gut microbiota (DI-GM) has also been developed as a standardized tool for assessing a balanced diet for the gut microbiota. Additionally, the interplay between aging and metabolism is important for understanding disease development. Nevertheless, the intrinsic regulatory mechanisms of factors such as aging in the association between the DI-GM and MetS have not been thoroughly investigated. Participants were recruited from multiple cycles of National Health and Nutrition Examination Surveys (NHANES). In this study, weighted logistic regression models, restricted cubic spline (RCS) and subgroup analyses were employed to investigate the association between DI-GM index, categorized as unfavorable or beneficial to gut microbiota, and the prevalence of MetS as well as its components. Mediation analysis models analyzed the mediating roles of biological age advance index (KDM-BAA) and body mass index (BMI). Sensitivity analyses were performed to assess the robustness of the models. Candidate genes related to aging and BMI mediators in this association were retrieved using the GeneCards database (evidence: literature/database annotations). GO and KEGG enrichment was conducted to reveal the potential regulatory mechanisms. Top ten topologically central genes were prioritized as potential regulators by protein–protein interaction (PPI) network and cytoHubba-MCC algorithm. GeneMANIA co-expression network and friends analysis refined the functional annotations of these genes, thereby providing clear hypotheses for subsequent experimental validation. A total of 6086 participants was enrolled. The DI-GM score was significantly negatively correlated with the prevalence of MetS (odd ratio (OR) = 0.91, 95

Objective:This study aimed to investigate cervical cancer screening participation, knowledge of cervical cancer and screening, attitudes toward relevant healthcare services, and associated factors among migrant Burmese women in Mangshi, a county on the China-Myanmar border in Southwest China's Yunnan province. Methods:A cross-sectional study was conducted in Mangshi Maternal and Child Health Hospital from October 2020 to December 2021. Migrant Burmese women attending routine gynecological examinations were recruited via convenient sampling. An interviewer-administered questionnaire was utilized to collect data. Logistic regressions were utilized to assess factors associated with cervical cancer screening participation and knowledge level. Results:Among 1504 participants, 31.3 % ever attended cervical cancer screening. In the recommended age group of 25-64 years, the participation rate was 35.2 %. Screening participation was associated with age, marital status, occupation, and history of genital tract infection. Approximately 20.9 % had heard of human papillomavirus, 23.2 % knew cervical cancer is preventable, and 41.6 % had heard of cervical cancer screening. Awareness of risk factors, screening techniques, and symptoms was limited. The median knowledge score was 2.0 out of 19.0. Knowledge level was associated with education, age at menarche, number of sexual partners, and history of genital tract infection. Most (99.7 %) participants were willing to attend cervical cancer screening, but only 84.5 % would accept therapy if necessary. The most common barrier to therapy was unaffordable cost. Conclusions:Migrant Burmese women in Mangshi had suboptimal screening participation and inadequate cervical cancer knowledge. Screening policies should prioritize socioeconomically disadvantaged women. Enhancing targeted health education is essential.

The intermitochondrial cement (IMC) and chromatoid body (CB) are posited as central sites for piRNA activity in mice, with MIWI initially assembling in the IMC for piRNA processing before translocating to the CB for functional deployment. The regulatory mechanism underpinning MIWI translocation, however, has remained elusive. We unveil that piRNA loading is the trigger for MIWI translocation from the IMC to CB. Mechanistically, piRNA loading facilitates MIWI release from the IMC by weakening its ties with the mitochondria-anchored TDRKH. This, in turn, enables arginine methylation of MIWI, augmenting its binding affinity for TDRD6 and ensuring its integration within the CB. Notably, loss of piRNA-loading ability causes MIWI entrapment in the IMC and its destabilization in male germ cells, leading to defective spermatogenesis and male infertility in mice. Collectively, our findings establish the critical role of piRNA loading in MIWI translocation during spermatogenesis, offering new insights into piRNA biology in mammals.

To construct a competency model for clinical investigators involved in the process of new drug development, providing a reference for the training, selection and assessment of clinical investigators. The Behavioral Event Interview (BEI) method was used to interview 12 excellent clinical investigators and 8 clinical investigators of average performance. Each competency characteristic was extracted from the interview text by semantic coding. Total frequency, total score, average score and highest score were calculated for each competency element. Category agreement coefficient, coefficient of reliability and Spearman correlation coefficient were used to assess the consistency of two coders for coding and classification. Independent-samples Mann-Whitney U test was applied to compare the differences in competency elements between the group of excellent clinical investigators and the group of average investigators. The average coefficient of category agreement was 0.671, and the average coefficient of reliability was 0.803. No significant differences were observed between the two groups in the aspect of interview time (P = 0.190) and the interview words (P = 0.184), indicating comparability between the two groups. However, there was a clear performance difference between the excellent and average groups. In addition, we found that the competency model for clinical investigators contained 24 prominent competence elements and 8 benchmark competency elements. Clinical investigator is a medical professional who is involved in a highly research-intensive and practical job, where prominent competency element largely reflects clinical practice skills, innovation and awareness of Good Clinic Practice (GCP). Our results provide a reference for assessing clinical investigators’ competencies, encouraging and guiding them to modify their behaviors according to the competency model, and also cultivating clinical investigators so as to improve the competence level of clinical investigators.

AIMS:To identify driver methylation genes and a novel subtype of lung adenocarcinoma (LUAD) by multi-omics and elucidate its molecular features and clinical significance.METHODS:We collected LUAD patients from public databases, and identified driver methylation genes (DMGs) by MethSig and MethylMix algrothms. And novel driver methylation multi-omics subtypes were identified by similarity network fusion (SNF). Furthermore, the prognosis, tumor microenvironment (TME), molecular features and therapy efficiency among subtypes were comprehensively evaluated.RESULTS:147 overlapped driver methylation were identified and validated. By integrating the mRNA expression and methylation of DMGs using SNF, four distinct patterns, termed as S1-S4, were characterized by differences in prognosis, biological features, and TME. The S2 subtype showed unfavorable prognosis. By comparing the characteristics of the DMGs subtypes with the traditional subtypes, S3 was concentrated in proximal-inflammatory (PI) subtype, and S4 was consisted of terminal respiratory unit (TRU) subtype and PI subtype. By analyzing TME and epithelial mesenchymal transition (EMT) features, increased immune infiltration and higher expression of immune checkpoint genes were found in S3 and S4. While S4 showed higher EMT score and expression of EMT associated genes, indicating S4 may not be as immunosensitive as the S3. Additionally, S3 had lower TIDE and higher IPS score, indicating its increased sensitivity to immunotherapy.CONCLUSION:The driver methylation-related subtypes of LUAD demonstrate prognostic predictive ability that could help inform treatment response and provide complementary information to the existing subtypes.

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

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.

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.

Objective: We assessed the longitudinal risk of developing cervical intraepithelial neoplasia (CINs) with self sampling human papillomavirus (HPV) tests, based on polymerase chain reaction (PCR) and signal amplification (careHPV), to explore the appropriate intervals for cervical cancer screening.Methods: A prospective study was conducted in China during 20172020. Participants were invited for PCR and careHPV tests with self-samples at baseline. Women positive in either HPV test underwent colposcopy and biopsy if necessary. Women with baseline CIN grade one (CIN1) or less were followed up over 3 years. The absolute risk was assessed by the immediate risk (IR) and cumulative risk (CR), and the relative risk was assessed by the hazard ratio (HR) with a 95% confidence interval (CI).Results: A total of 8,126 women were included in the final analysis. Women positive for the PCR HPV test had comparable IRs of CIN2+ and CIN3+ to those positive on the careHPV test. With triage by HPV genotyping, women with HPV 16/18 infection had the highest IRs of CIN2+ (21.15%) and CIN3+ (9.67%). For CR, women negative for PCR HPV test had a lower risk of CIN2+ than that reported in women negative on careHPV test (0.57% versus 0.98%, HR = 0.58, 95% CI: 0.38, 0.87), but no significant difference was found in the CRs of CIN3+ between them (0.25% versus 0.39%, HR = 0.64, 95% CI: 0.34, 1.20). Among women with CIN1 or less at baseline, women who were persistent or recurrent positive on careHPV or PCR HPV test had a higher risk of developing CIN3+ (11.36%-14.59%), compared with women remained HPV negative from baseline throughout follow-up (<= 0.28%).Conclusions: Routine screening with 3-year intervals is acceptable for self-sampling HPV tests based on PCR or careHPV test. Women positive on HPV16/18 triaging at baseline or with CIN1 or less at baseline while being persistent or recurrent positive on careHPV or PCR HPV test during 3-year follow-up require immediate colposcopy or treatment.

Triaging of women positive for high-risk human papillomavirus (hrHPV) on self-collected samples requires a molecular reflex test to avoid recall for cytology or visual tests. We assessed triage performance and predictive value of human gene methylation panel (ZNF671/ASTN1/ITGA4/RXFP3/SOX17/DLX1) alone and with combination of HPV16/18 genotyping in a longitudinal screening study. Out of 9526 women at baseline, 1758 women positive for hrHPV on self-collected samples followed up yearly were included in the current analysis. Satisfactory risk stratification to detect cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was demonstrated by the methylation panel with an odds ratio (OR) of 11.3 among methylation-positive women compared to methylation-negative counterparts. Triaging with methylation panel reduced colposcopy referral rate by 67.2% with sensitivity and specificity of 83.0% and 69.9% to detect CIN2+. The corresponding values for the combining methylation and HPV 16/18 were 96.6% and 58.3%. The cumulative 3-year incident CIN2+ risk was 6.8% (95% CI: 4.9%-8.6%) for hrHPV positive women, which was reduced to 4.5% (95% CI: 2.7%-6.3%) and 2.9% (95% CI: 1.2%-4.5%) for women negative on methylation triaging alone and negative on the combined strategy. The corresponding risk for women positive for both methylation and HPV 16/18 reached 33.7% (95% CI: 19.0%-45.8%). Our study demonstrated the satisfactory triage performance and predictive value of the methylation panel, especially in combination with HPV 16/18 genotyping. The substantially lower risk of CIN2+ among the triage negative women over the next 3 years suggests that the interval for repeat HPV test can be safely extended to at least 2 years.

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.

目的:探讨细胞学、高危型人乳头瘤病毒(high risk human papillomavirus,hrHPV)分型对于阴道镜结果正常或低级别鳞状上皮内病变(low-grade squamous intraepithelial lesion,LSIL)妇女的风险预测作用.方法:基于1999年6月在山西省建立的宫颈癌筛查队列,以2005年随访时阴道镜结果为正常或低度病变的596例妇女为研究对象,于2010年和2014年进行随访.分析hrHPV阴性组、hrHPV阳性组、HPV16/18阳性组、细胞学LSIL以下组和细胞学LSIL及以上组发生宫颈上皮内瘤样病变2级及以上(cervical intraepithelial neoplasia grade 2 or worse,CIN2+)的瞬时、5年和9年累积风险和相对危险度.结果:细胞学LSIL以下组发生CIN2+的瞬时、5年和9年累积风险分别为0.2％、2.8％和4.2％,细胞学LSIL及以上组相应的风险分别为14.7％(RR=73.8,95％CI为9.7～561.5)、40.0％(RR=16.0,95％CI为8.2～31.1)和51.4％(RR=15.0,95％CI为8.3～27.0).hrHPV阴性组发生CIN2+的瞬时风险、5年和9年累积风险较低,分别为0.6％、2.7％和3.8％,hrHPV阳性和HPV16/18阳性组发生CIN2+的风险逐渐升高,其中HPV16/18阳性组的相应风险分别为13.2％(RR=23.4,95％CI为5.1～106.9)、36.9％(RR=15.4,95％CI为6.9～34.3)和42.6％(RR=14.1,95％CI为6.8～29.2).结论:阴道镜结果正常或LSIL妇女,若细胞学结果为LSIL及以上或HPV16/18阳性,未来进展为高度宫颈癌前病变的风险较高,细胞学和HPV16/18分型可用于该人群的临床分流管理.

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 ( <1.0), low (range, 1.0 to <10.0), moderate (range, 10.0 to <100.0), and high (range, 100.0-∞). Cumulative incidence rates (CIRs) and adjusted hazard ratios (aHRs) for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) were calculated for viral load subgroups, using survival analysis. RESULTS Among 1739 women with normal or CIN1 pathological findings at baseline, 15-year CIRs for CIN2+ for those who were HPV negative and those with low, moderate, and high HPV loads groups were 3.1%, 8.4%, 19.9%, and 22.0%, respectively (Ptrend <.001). Compared with women who were negative for HPV from baseline through follow-up, those who had decreasing, increasing, or stable moderate/high loads had aHRs of 9.1, 38.7, or 379.7, respectively, for CIN2+. There was no significant difference between triage based on cytologic findings (for those with atypical squamous cells of undetermined significance or more-severe findings) and that based on a moderate/high HPV load for HPV primary screening (P = .343). CONCLUSION A moderate/high HPV load may accelerate the progression of cervical precancers and potentially could be used as a triage indicator for HPV-positive women.