Cervical cancer prevention in China: where are we now, and what's next?

Cervical cancer(CC) epidemiology CC, the fourth most frequently diagnosed malignancy in women worldwide, is a major global health challenge, particularly in low-resource regions. Approximately 88.1% of the 604,000 CC new cases occurred in low-and middle-income countries in 2020, and more than 90% of the 342,000 CC deaths occurred in low-and middle-income countries in 2020~1.

中国肺癌低剂量CT筛查指南(2023年版)

肺癌是导致中国癌症死亡的首要原因。近年来低剂量计算机断层扫描(low-dose computed tomography,LDCT)筛查的效果进一步被证实,并且在高危人群选择、筛查间隔及结节管理的研究方面取得了显著进展。本研究的目的是对2018年中国肺癌LDCT筛查指南进行修订。由国家卫健委任命的中国肺癌早诊早治专家组专家及中国西部肺癌研究协作中心部分专家,共同参与了2023版中国肺癌筛查指南的修订工作。专家们根据近年来国内外LDCT肺癌筛查进展,结合我国肺癌流行病学特征,共同修订了本次肺癌筛查指南。本指南对以下方面进行了修订:(1)高危人群定义中考虑了除吸烟外其他肺癌危险因素;(2)对LDCT扫描参数进行了修改和补充;(3)扩大了部分筛查阴性个体的筛查间隔;(4)将部分阳性结节的随访时间由3个月调整为6个月;(5)强调了多学科诊疗(multi-disciplinary treatment,MDT)在阳性结节管理、肺癌诊断和治疗中的作用。本次修订将使得LDCT筛查指南更适应我国国情,并使筛查、干预与治疗路径更为明确。未来应进一步基于新兴技术,包括生物标志物及人工智能研究,优化肺癌LDCT筛查方法及技术。

Estimation of economic burden throughout course of cervical squamous intraepithelial lesion and cervical cancer in China:A nationwide multicenter cross-sectional study

Objective: Cervical squamous intraepithelial lesion(SIL) and cervical cancer are major threats to females' health and life in China, and we aimed to estimate the economic burden associated with their diagnosis and treatment.Methods: A nationwide multicenter, cross-sectional, hospital-based survey was conducted in 26 qualified hospitals across seven administrative regions of China. We investigated females who had been pathologically diagnosed with SIL and cervical cancer, and included five disease courses(“diagnosis”, “initial treatment”,“chemoradiotherapy”, “follow-up” and “recurrence/progression/metastasis”) to estimate the total costs. The median and interquartile range(IQR) of total costs(including direct medical, direct non-medical, and indirect costs), reimbursement rate by medical insurance, and catastrophic health expenditures in every clinical stage were calculated.Results: A total of 3,471 patients in different clinical stages were analyzed, including low-grade SIL(LSIL)(n=549), high-grade SIL(HSIL)(n=803), cervical cancer stage ⅠA(n=226), ⅠB(n=610), ⅡA(n=487), ⅡB(n=282), Ⅲ(n=452) and Ⅳ(n=62). In urban areas, the estimated total costs of LSIL and HSIL were $1,637.7(IQR:$956.4-$2,669.2) and $2,467.1(IQR:$1,579.1-$3,762.3), while in rural areas the costs were $459.0(IQR:$167.7-$1,330.3) and $1,230.5(IQR:$560.6-$2,104.5), respectively. For patients with cervical cancer stage ⅠA,ⅠB, ⅡA, ⅡB, and Ⅲ-Ⅳ, the total costs were $15,034.9(IQR:$11,083.4-$21,632.4), $19,438.6(IQR:$14,060.0-$26,505.9), $22,968.8(IQR:$16,068.8-$34,615.9), $26,936.0(IQR:$18,176.6-$41,386.0) and $27,332.6(IQR:$17,538.7-$44,897.0), respectively. Medical insurance covered 43%-55% of direct medical costs for cervical cancer patients, while the coverage for SIL patients was 19%-43%. For most cervical cancer patients, the expense was catastrophic, and the extent of catastrophic health expenditure was about twice large for rural patients than that for urban patients in each stage.Conclusions: The economic burden of SIL and cervical cancer in China is substantial, with a significant proportion of the costs being avoidable for patients with LSIL. Even for those with medical insurance, catastrophic health expenditures are also a major concern for patients with cervical cancer, particularly for those living in rural areas.

Cervical cancer: Epidemiology, risk factors and screening

Cervical cancer is one of the leading causes of cancer death among females worldwide and its behavior epidemiologically likes a venereal disease of low infectiousness. Early age at first intercourse and multiple sexual partners have been shown to exert strong effects on risk. The wide differences in the incidence among different countries also influenced by the introduction of screening. Although the general picture remains one of decreasing incidence and mortality, there are signs of an increasing cervical cancer risk probably due to changes in sexual behavior. Smoking and human papillomavirus(HPV) 16/18 are currently important issues in a concept of multifactorial, stepwise carcinogenesis at the cervix uteri. Therefore, society-based preventive and control measures, screening activities and HPV vaccination are recommended. Cervical cancer screening methods have evolved from cell morphology observation to molecular testing. High-risk HPV genotyping and liquid-based cytology are common methods which have been widely recommended and used worldwide. In future, accurate,cheap, fast and easy-to-use methods would be more popular. Artificial intelligence also shows to be promising in cervical cancer screening by integrating image recognition with big data technology. Meanwhile, China has achieved numerous breakthroughs in cervical cancer prevention and control which could be a great demonstration for other developing and resource-limited areas. In conclusion, although cervical cancer threatens female health, it could be the first cancer that would be eliminated by human beings with comprehensive preventive and control strategy.

中国大陆人群对人乳头瘤病毒预防性疫苗的认知和态度

目的:了解中国大陆人群对人乳头瘤病毒(human papillomavirus,HPV)预防性疫苗的认知和态度,并寻找可能的影响因素,为HPV疫苗在我国进一步推广应用提供参考依据。方法:2009年5月至2012年5月在中国大陆,针对普通公众、医务人员和在校学生开展全国性大规模横断面流行病学调查研究,通过调查问卷收集研究对象的基本情况、对HPV疫苗的认知和态度等信息,采用χ2检验、Logistic回归方法进行统计学分析。结果:研究共回收18 677份有效问卷,研究对象的中位年龄为32(15～79)岁。在疫苗认知方面,仅24.5%的研究对象曾听闻HPV预防性疫苗,14.1%知道HPV疫苗可预防宫颈癌等疾病。83.5%的受调查者表示愿意为自己、配偶或孩子接种疫苗,其中比较了解疫苗的人群、农村人群和女性人群对疫苗接种的态度更为积极(校正后OR值分别为2.81、2.14和1.25)。不愿接种HPV疫苗人群主要的担心是疫苗的安全性(占64.7%)。有关疫苗价格,66.3%的受调查者能够接受的最高定价低于300元。结论:中国大陆人群对HPV疫苗认知度较低,但对疫苗接种普遍态度积极。应加强开展人群有关知识的健康教育,消除对HPV疫苗安全性等的顾虑,在接种疫苗时给予一定的优惠政策是必要的。

A multicenter hospital-based diagnosis study of automated breast ultrasound system in detecting breast cancer among Chinese women

Objective: The automated breast ultrasound system(ABUS) is a potential method for breast cancer detection;however, its diagnostic performance remains unclear. We conducted a hospital-based multicenter diagnostic study to evaluate the clinical performance of the ABUS for breast cancer detection by comparing it to handheld ultrasound(HHUS) and mammography(MG).Methods: Eligible participants underwent HHUS and ABUS testing; women aged 40–69 years additionally underwent MG. Images were interpreted using the Breast Imaging Reporting and Data System(BI-RADS).Women in the BI-RADS categories 1–2 were considered negative. Women classified as BI-RADS 3 underwent magnetic resonance imaging to distinguish true-and false-negative results. Core aspiration or surgical biopsy was performed in women classified as BI-RADS 4–5, followed by a pathological diagnosis. Kappa values and agreement rates were calculated between ABUS, HHUS and MG.Results: A total of 1,973 women were included in the final analysis. Of these, 1,353(68.6%) and 620(31.4%)were classified as BI-RADS categories 1–3 and 4–5, respectively. In the older age group, the agreement rate and Kappa value between the ABUS and HHUS were 94.0% and 0.860(P<0.001), respectively; they were 89.2% and0.735(P<0.001) between the ABUS and MG, respectively. Regarding consistency between imaging and pathology results, 78.6% of women classified as BI-RADS 4–5 based on the ABUS were diagnosed with precancerous lesions or cancer; which was 7.2% higher than that of women based on HHUS. For BI-RADS 1–2, the false-negative rates of the ABUS and HHUS were almost identical and were much lower than those of MG.Conclusions: We observed a good diagnostic reliability for the ABUS. Considering its performance for breast cancer detection in women with high-density breasts and its lower operator dependence, the ABUS is a promising option for breast cancer detection in China.

阴道镜结果正常或低度病变妇女发生宫颈癌前病变的前瞻性风险分层研究

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(cervi cal 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。

A study on service capacity of primary medical and health institutions for cervical cancer screening in urban and rural areas in China

Objective: To provide a decision-making basis for sustainable and effective development of cervical cancer screening.Methods: This cross-sectional study assesses the service capacity to conduct cervical cancer screening with a sample of 310 medical staff, medical institutions and affiliated township health centers from 20 countylevel/district-level areas in 14 Chinese provinces in 2016.Results: The county-level/district-level institutions were the main prescreening institutions for cervical cancer screening. More medical staff have become engaged in screening, with a significantly higher amounts in urban than in rural areas(P<0.05). The number of human papillomavirus(HPV) testers grew the fastest(by 225% in urban and 125% in rural areas) over the course of the project. HPV testing took less time than cytology to complete the same number of screening tasks in both urban and rural areas. The proportion of mid-level professionals was the highest among the medical staff, 40.0% in urban and 44.7% in rural areas(P=0.406), and most medical staff had a Bachelor’s degree, accounting for 76.3% in urban and 52.0% in rural areas(P<0.001). In urban areas, 75.0% were qualified medical staff, compared with 68.0% in rural areas, among which the lowest proportion was observed for rural cytology inspectors(22.7%). The medical equipment for cervical pathology diagnosis in urban areas was better(P<0.001). HPV testing equipment was relatively adequate(typing test equipment was 70% in urban areas, and non-typing testing equipment was 70% in rural areas).Conclusions: The service capacity of cervical cancer screening is insufficient for the health needs of the Chinese population. HPV testing might be an optimal choice to fill the needs of cervical cancer screening given current Chinese medical health service capacity.

Accuracy of triage strategies for human papillomavirus DNA-positive women in low-resource settings:A cross-sectional study in China

Objective: Care HPV is a human papillomavirus(HPV) DNA test for low-resource settings(LRS).This study assesses optimum triage strategies for care HPV-positive women in LRS.Methods: A total of 2,530 Chinese women were concurrently screened for cervical cancer with visual inspection with acetic acid(VIA),liquid-based cytology and HPV testing by physician-and self-collected care HPV,and physician-collected Hybrid Capture 2(HC2).Screen-positive women were referred to colposcopy with biopsy and endocervical curettage as necessary.HPV-positivity was defined as ≥1.0 relative light units/cutoff(RLU/CO) for both care HPV and HC2.Primary physician-HC2,physician-care HPV and self-care HPV and in sequential screening with cytology,VIA,or increased HPV test-positivity performance,stratified by age,were assessed for cervical intraepithelial neoplasia(CIN) grade 2/3 or worse(CIN2/3+) detection.Results: The sensitivities and specificities of primary HPV testing for CIN2+ were: 83.8%,88.1% for physiciancare HPV; 72.1%,88.2% for self-care HPV; and 97.1%,86.0% for HC2.Physician-care HPV test-positive women with VIA triage had a sensitivity of 30.9% for CIN2+ versus 80.9% with cytology triage.Self-care HPV testpositive women with VIA triage was 26.5% versus 66.2% with cytology triage.The sensitivity of HC2 test-positive women with VIA triage was 38.2% versus 92.6% with cytology triage.The sensitivity of physician-care HPV testing for CIN2+ decreased from 83.8% at ≥1.0 RLU/CO to 72.1% at ≥10.00 RLU/CO,while the sensitivity of selfcare HPV testing decreased from 72.1% at ≥1.0 RLU/CO to 32.4% at ≥10.00 RLU/CO; similar trends were seen with age-stratification.Conclusions: VIA and cytology triage improved specificity for CIN2/3 than no triage.Sensitivity with VIA triage was unsuitable for a mass-screening program.VIA provider training might improve this strategy.Cytology triage could be feasible where a high-quality cytology program exists.Triage of HPV test-positive women by increased test positivity cutoff adds another LRS triage option.

hrHPV DNA载量分型和E6蛋白对宫颈癌前病变进展的预测作用

目的:探讨预测高危型人乳头瘤病毒(high risk human papillomavirus,hrHPV)阳性和宫颈上皮内瘤样病变1级(cervical in-traepithelial neoplasia grade 1,CIN1)妇女进展的生物学标志物。方法:2010年10月至2012年8月在山西省、河南省和江西省招募7 543名妇女,采用hrHPV DNA检测和E6蛋白检测(Onco E6)等方法进行宫颈癌筛查,任一结果阳性者转诊阴道镜并取活检,于1年后随访。纳入基线hrHPV阳性或病理诊断CIN1者。结果:共纳入794例满足条件妇女,1年后88例妇女病理级别发生进展。基线hrHPV DNA中高载量者进展的风险是低载量者的2.9倍(95%CI为1.8~4.8),hrHPV16/18/45、E6蛋白阳性者进展的风险分别是阴性者的2.4倍(95%CI为1.5~3.9)、2.9倍(95%CI为1.5~5.9),其进展至宫颈上皮内瘤样病变2级及以上(cervical intraepi-thelial neoplasia grade 2 or worse,CIN2+)的绝对风险分别为4.9%(95%CI为3.2~7.4)、9.0%(95%CI为5.5~14.3)、18.8%(95%CI为10.2~31.9)。hrHPV16/18/45中高载量且E6蛋白(Onco E6)阳性妇女进展的绝对风险高达32.4%(11/34)。结论:hrHPV DNA中高载量、hrHPV16/18/45分型以及E6蛋白(Onco E6)可作为妇女hrHPV阳性和CIN1进展的生物学标志物,特别是hrHPV中高载量且E6蛋白(Onco E6)阳性妇女,临床应给予密切随访。

Economic evaluation of cervical cancer screening strategies in urban China

Objective:This study evaluated the feasibility of different cervical cancer screening strategies in urban China.Methods:A Markov model was constructed to simulate a hypothetical cohort of 100,000 females aged 30-59 years in a 20-year period.Screening strategies included liquid-based cytology(LBC)every three years,human papillomavirus(HPV)DNA testing every three and five years,respectively,and a combination of HPV DNA testing and LBC(HPV+LBC)every three and five years,respectively.Model outcomes included cumulative incidence over 20 years,cumulative risk of cervical cancer,costs,life year saved(LYS),quality-adjusted life years(QALYs)and benefits.The cost-effectiveness ratios(CERs),incremental cost-effectiveness ratios(ICERs),costutility ratios(CURs),and benefit-cost ratios(BCRs)were used as outcomes in the health economic evaluation analysis.Univariate sensitivity analyses were performed to examine the stability of the results.Results:The cumulative incidence of the five screening strategies ranged from 833.02 to 1,158.07 cases per100,000 females.HPV DNA testing was most effective in reducing the cumulative risk of cervical cancer,saving life years and QALYs and gaining benefits.The CERs of HPV DNA testing every three and five years,and LBC every three years were considered to be very cost-effective if they were below China's GDP per capita.The CERs of HPV+LBC were considered to be cost-effective if they were below three times GDP per capita.The incremental cost-effectiveness analysis showed that HPV DNA testing every three and five years,LBC every three years and HPV+LBC every five years were dominant strategies.Conclusions:The findings of this study indicated that HPV DNA testing every five years or LBC every three years should be recommended in urban China.

Evaluation of triage strategies for high-risk human papillomavirus-positive women in cervical cancer screening:A multicenter randomized controlled trial in different resource settings in China

Objective:We aimed to evaluate the effectiveness of different triage strategies for high-risk human papillomavirus(hrHPV)-positive women in primary healthcare settings in China.Methods:This study was undertaken in 11 rural and 9 urban sites.Women aged 35-64 years old were enrolled.HrHPV-positive women were randomly allocated to liquid-based cytology(LBC),visual inspection with acetic acid and Lugol’s iodine(VIA/VILI)(rural only)triage,or directly referred to colposcopy(direct COLP).At 24 months,hrHPV testing,LBC and VIA/VILI were conducted for combined screening.Results:In rural sites,1,949 hrHPV-positive women were analyzed.A total of 852,218 and 480 women were randomly assigned to direct COLP,LBC and VIA/VILI.At baseline,colposcopy referral rates of LBC or VIA/VILI triage could be reduced by 70%-80%.LBC(n=3 and n=7)or VIA/VILI(n=8 and n=26)could significantly decrease the number of colposcopies needed to detect one cervical intraepithelial neoplasia(CIN)2 or worse and CIN3+compared with direct COLP(n=14 and n=23).For the 24-month cumulative detection rate of CIN2+,VIA/VILI triage was 0.50-fold compared with LBC triage and 0.46-fold with the direct COLP.When stratified by age,baseline LBC triage+performed best(P<0.001),peaking among women aged 35-44 years(Ptrend=0.002).In urban sites,1,728 women were hrHPV genotyping test positive.A total of 408,571 and 568women were randomly assigned to direct COLP for HPV16/18+,direct COLP for other hrHPV subtypes+,and LBC triage for other hrHPV subtypes+.LBC(n=12 and n=31)significantly decreased the number of colposcopies needed to detect one CIN2+and CIN3+compared with direct COLP(n=14 and n=44).HPV16/18+increased the 24-month cumulative detection rate of CIN2+(17.89%,P<0.001).Conclusions:LBC triage for hrHPV-positive women in rural settings and direct COLP for HPV16/18+women and LBC triage for other hrHPV subtype+women in urban settings might be feasible strategies.

Value of multi-quadrants biopsy:Pooled analysis of 11 population-based cervical cancer screening studies

Objective:The accuracy of colposcopy-guided biopsy is key to the success of colposcopic triage in cervical cancer screening programs.However,there is no widely adopted biopsy guideline up to date.Our study aimed to determine whether multi-quadrants biopsy improves the yield of cervical lesions.Methods:Eleven population-based cervical cancer screening studies were conducted in China.Cytology,highrisk human papillomavirus(hrHPV)testing and visual inspection were performed for primary screening.Females positive on one or more tests were referred for colposcopy and biopsy.The proportion of detected cervical intraepithelial neoplasia(CIN)2+and yields by quadrant lesion-targeted biopsy or 4-quadrant random biopsy were compared.Results:Among 4,923 females included,1,606 had quadrant lesion-targeted biopsy,and 3,317 had 4-quadrant random biopsy.The cumulative CIN2+yield increased from 0.10 for only one quadrant-targeted biopsy to 0.21,0.34,and 0.58 for at most two,three and four quadrants targeted biopsies.Among hrHPV positive females with high-grade squamous intraepithelial lesion(HSIL)+cytology,the cumulative CIN2+yield of a second targeted biopsy in another quadrant was significantly increased(P<0.05).Among hrHPV-negative females,the yield of 4-quadrant random biopsies was 0.005,and the yield by lesion-targeted biopsies was 0.017.For hrHPV positive females who had 4-quadrant random biopsy,the additional CIN2+yield for HSIL+,low-grade squamous intraepithelial lesion(LSIL)cytology,or abnormal visual inspection via acetic acid and Lugol’s iodine(VIA/VILI)were 0.46,0.11,0.14.Conclusions:A 4-quadrant random biopsy is recommended only for hrHPV positive females with HSIL cytology,and is acceptable if hrHPV positive with LSIL cytology or with abnormal VIA/VILI.Our findings add evidences for an objective and practical biopsy standard to guide colposcopy in cervical cancer screening programs in low-and middle-income countries.

Development and validation of a predictive model for endocervical curettage in patients referred for colposcopy:A multicenter retrospective diagnostic study in China

Objective:This study aimed to develop a nomogram that can predict occult high-grade squamous intraepithelial lesions or worse(HSIL+)and determine the need for endocervical curettage(ECC)in patients referred for colposcopy.Methods:This retrospective multicenter study included 4,149 patients who were referred to any one of six tertiary hospitals in China for colposcopy between January 2020 and November 2021 because of abnormal screening results.ECC data were extracted from the medical records.Univariate and multivariate logistic regression analyses were performed to identify factors that could predict HSIL+on ECC.Patients were randomly assigned to a training set or to an internal validation set for performance and comparability testing.The model was externally validated and tested in patients from two additional hospitals.The nomogram was assessed in terms of discrimination and calibration and subjected to decision curve analysis.Results:HSIL+was found on ECC in 38.8%(n=388)of cases.Our predictive nomogram included age group,cytology,human papillomavirus(HPV)status,visibility of the cervix and colposcopic impression.The nomogram had good overall discrimination,which was internally validated[area under the receiver-operator characteristic(AUC),0.839;95%confidence interval(95%CI),0.773-0.904].In terms of external validation,the AUC was 0.843(95%CI,0.773-0.912)for the consecutive sample and 0.843(95%CI,0.783-0.902)for the comparative sample.Calibration analysis suggested good consistency between predicted and observed probabilities.Decision curve analysis suggested this nomogram would be clinically useful with almost the entire range of threshold probabilities.Conclusions:This internally and externally validated nomogram can be easily applied and incorporates multiple clinically relevant variables that can be used to identify patients with occult HSIL+who need ECC.

Guidelines for cervical cancer screening in China

In response to the incidence of cervical intraepithelial neoplasia and cervical cancer in China and global screening strategies,a collaborative effort was undertaken by seven Chinese medical associations to develop this guideline for cervical cancer screening.The guideline recommends high-risk human papillomavirus(hr-HPV)testing as the preferred method for primary screening,which should have been approved by authoritative institutions and clinically validated for primary screening.In areas without access to HPV testing,cytology can be used as an alternative.However,it is recommended to replace cytology with HPV-based screening as conditions permit.Cotesting(HPV testing in combination with cytology)is recommended for areas with sufficient medical resources,opportunistic screening populations,and partial special populations.The guideline recommends that individuals with a cervix initiate cervical cancer screening at the age 25 years and undergo HPV testing alone or cotesting every five years,or cytology alone every three years.Women over the age of 65 who have had documented adequate negative prior screening in the past may terminate screening.Corresponding screening programs are proposed for different special populations.The development of these guidelines is an important step in the effort to eliminate cervical cancer in China.

Preventive Oncology International:A brief history of HPV self-collected vaginal specimens for cervical cancer screening

Since 1998,Preventive Oncology International,Inc.(POI)has been at the forefront of studying human papillomavirus(HPV)self-collection for cervical cancer screening,with a significant focus in China.Through multiple clinical trials over the past 25 years,POI has explored various aspects related to self-collection methodologies.In 2004–2006,POI established that self-collection could be equivalent to direct endocervical samples.Subsequently,a large randomized trial involving 10,000 patients in 2010 further confirmed that self-collected vaginal specimens,tested for high-risk HPV(hrHPV)using a PCR-based assay with high analytic sensitivity,could effectively replace endocervical specimens with minimal loss of sensitivity and a slight decrease in specificity.Throughout the years,POI's research has encompassed several crucial topics,including patient acceptance,the development of new cost-effective,simpler,and faster assays,exploring different collection devices,devising efficient methods of specimen transport,and implementing population-based screening systems.The findings strongly support the integration of self-collection methodologies into cervical cancer control programs worldwide,particularly in medically underserved regions.As HPV self-collection continues to evolve,ongoing research and innovations are expected to play a pivotal role in achieving the global mission of combating cervical cancer.

我国加速消除子宫颈癌的挑战与机遇

子宫颈癌是全球女性常见的恶性肿瘤。2018年,WHO总干事向全球发出了消除子宫颈癌的动员令。我国的子宫颈癌人群防治工作累积了大量的实践经验,并取得一定成效。面对2030年“90%-70%-90%”的阶段性目标,我国仍有不同程度的挑战和机遇。人乳头状瘤病毒(HPV)疫苗在国内得以应用,部分省市已开展适龄人群接种,90%适龄女性接种疫苗的阶段性目标的实现较为乐观,应密切关注国际上HPV疫苗接种的研究进展;子宫颈癌人群筛查技术已取得突破性进展,但我国存在人口基数大、资源不足等困难,70%适龄女性接受高效检测方法筛查的目标存在较大困难,应尽早推广应用新技术,快速提高筛查服务能力及其均质化;我国子宫颈病变的治疗水平不断进步,且随着总体经济发展、基本医疗保险高覆盖、医保政策优化等,预计90%确诊子宫颈病变的妇女得到治疗的阶段性目标能够实现,目前应开展全国性治疗数据的收集。我国实现消除子宫颈癌的战略目标任重而道远。

Programmable endonuclease combined with isothermal polymerase amplification to selectively enrich for rare mutant allele fractions

Liquid biopsy is a highly promising method for non-invasive detection of tumor-associated nucleic acid fragments in body fluids but is challenged by the low abundance of nucleic acids of clinical interest and their sequence homology with the vast background of nucleic acids from healthy cells.Recently,programmable endonucleases such as clustered regularly interspaced short palindromic repeats(CRISPR)associated protein(Cas)and prokaryotic Argonautes have been successfully used to remove background nucleic acids and enrich mutant allele fractions,enabling their detection with deep next generation sequencing(NGS).However,the enrichment level achievable with these assays is limited by futile binding events and off-target cleavage.To overcome these shortcomings,we conceived a new assay(Programmable Enzyme-Assisted Selective Exponential Amplification,PASEA)that combines the cleavage of wild type alleles with concurrent polymerase amplification.While PASEA increases the numbers of both wild type and mutant alleles,the numbers of mutant alleles increase at much greater rates,allowing PASEA to achieve an unprecedented level of selective enrichment of targeted alleles.By combining CRISPR-Cas9 based cleavage with recombinase polymerase amplification,we converted samples with0.01%somatic mutant allele fractions(MAFs)to products with 70%MAFs in a single step within 20 min,enabling inexpensive,rapid genotyping with such as Sanger sequencers.Furthermore,PASEA's extraordinary efficiency facilitates sensitive real-time detection of somatic mutant alleles at the point of care with custom designed Exo-RPA probes.Real-time PASEA'performance was proved equivalent to clinical amplification refractory mutation system(ARMS)-PCR and NGS when testing over hundred cancer patients'samples.This strategy has the potential to reduce the cost and time of cancer screening and genotyping,and to enable targeted therapies in resource-limited settings.