宫颈癌筛查文献汇报HPV和TCT培训课件.ppt

1、宫颈癌筛查文献汇报HPV和TCT 移行带位置的变动主要取决于柱状上皮生长能力的移行带位置的变动主要取决于柱状上皮生长能力的优势，而上皮的生长受激素的影响。优势，而上皮的生长受激素的影响。在年轻妇女可见鳞柱交界的部位多位于解剖学外口在年轻妇女可见鳞柱交界的部位多位于解剖学外口以下，绝经后妇女，移行带内移，通常在子宫颈的以下，绝经后妇女，移行带内移，通常在子宫颈的高处。高处。2宫颈癌筛查文献汇报HPV和TCT3宫颈癌筛查文献汇报HPV和TCT 柱状上皮转化为鳞状上皮存在两种不同转化机制即柱状上皮转化为鳞状上皮存在两种不同转化机制即鳞状上皮化生和鳞状上皮化生。鳞状上皮化生和鳞状上皮化生。鳞状上皮化鳞

2、状上皮化是指成熟的鳞状上皮直接向邻近的柱是指成熟的鳞状上皮直接向邻近的柱状上皮内生长，是成熟的鳞状上皮保护层取代子宫颈状上皮内生长，是成熟的鳞状上皮保护层取代子宫颈管细胞。管细胞。鳞状上皮化生鳞状上皮化生是指从子宫颈管基层膜上面具有改是指从子宫颈管基层膜上面具有改向功能的储备细胞细胞增生而来向功能的储备细胞细胞增生而来。4宫颈癌筛查文献汇报HPV和TCT 这些细胞一旦受到刺激开始分层和分化，最这些细胞一旦受到刺激开始分层和分化，最后分化为成熟的鳞状上皮，根据鳞状上皮化生过程后分化为成熟的鳞状上皮，根据鳞状上皮化生过程的不同阶层分为：储备细胞增生、未成熟磷化、成的不同阶层分为：储备细胞增生、未成

3、熟磷化、成熟磷化。熟磷化。5宫颈癌筛查文献汇报HPV和TCT三三、宫颈病变的概念、宫颈病变的概念宫颈病变宫颈病变(Cervicallesions)：是一个尚未限定的、比较泛化的概念，指在：是一个尚未限定的、比较泛化的概念，指在宫颈区域发生的各种病变，包括宫颈区域发生的各种病变，包括(以及癌前病变以及癌前病变)、等等。6宫颈癌筛查文献汇报HPV和TCTCompany Logo临床上将宫颈病变限定在临床上将宫颈病变限定在和和(CervicalIntraepithelialNeoplasia，对宫颈病变进行正确处理及采用合适的管理方法是对宫颈病变进行正确处理及采用合适的管理方法是宫颈癌防治体系中关键

4、的组成部分。宫颈癌防治体系中关键的组成部分。不适当的处理可能增加宫颈癌的发病风险，抑或过不适当的处理可能增加宫颈癌的发病风险，抑或过度处理导致不必要的并发症发生和医疗资源的浪费。度处理导致不必要的并发症发生和医疗资源的浪费。7宫颈癌筛查文献汇报HPV和TCT不同诊断术语的含义不同诊断术语的含义组织学诊断术语，按病变细胞涉及上皮层次分组织学诊断术语，按病变细胞涉及上皮层次分为为、级。级。细胞学细胞学TBS分类诊断术语，按细胞的异型性改分类诊断术语，按细胞的异型性改变分为低度鳞状上皮内病变（变分为低度鳞状上皮内病变（LSIL）和高度鳞）和高度鳞状上皮内病变（状上皮内病变（HSIL）8宫颈癌筛查文献

5、汇报HPV和TCT细胞学细胞学阴道镜阴道镜组织病理学组织病理学由于中国国情，对宫颈癌筛查因地区、经济条件、由于中国国情，对宫颈癌筛查因地区、经济条件、医疗资源等差异而采用不同手段，如：细胞学检测、医疗资源等差异而采用不同手段，如：细胞学检测、裸眼醋酸染色检查裸眼醋酸染色检查(VIN)(VIN)及复方碘染及复方碘染(VILI)(VILI)检查，高检查，高危型危型HPVDNAHPVDNA检查、肉眼观察高度怀疑宫颈浸润癌等，检查、肉眼观察高度怀疑宫颈浸润癌等，这些筛查结果异常者，需转诊阴道镜检查和诊断，这些筛查结果异常者，需转诊阴道镜检查和诊断，并在阴道镜指导下完成组织病理学检查诊断，即并在阴道镜指

6、导下完成组织病理学检查诊断，即“三阶梯三阶梯”的检查诊断。的检查诊断。9宫颈癌筛查文献汇报HPV和TCT五、阴道镜检查指征10宫颈癌筛查文献汇报HPV和TCT11宫颈癌筛查文献汇报HPV和TCT12宫颈癌筛查文献汇报HPV和TCT13宫颈癌筛查文献汇报HPV和TCTJuly3,201814宫颈癌筛查文献汇报HPV和TCTquestion Does cervical cancer screening using primaryprimary cervical human papillomavirus(HPV)cervical human papillomavirus(HPV)testing te

7、sting compared with cytologycytology result in a lower likelihood of cervical intraepithelial neoplasia grade 3 or worse(CIN3+)at 48 months?15宫颈癌筛查文献汇报HPV和TCTImportance There is limited information about the relative effectiveness of cervical cancer screening with primary human papillomavirus(HPV)pr

8、imary human papillomavirus(HPV)testing alone testing alone compared with cytologycytology in North American populations.Objective To evaluate histologically confirmed cumulative incident cervical intraepithelial neoplasia(CIN)grade 3 or worse(CIN3+)(CIN)grade 3 or worse(CIN3+)detected up to and incl

9、uding 48 monthsup to and including 48 months by primary HPV testing alone primary HPV testing alone(intervention)or liquid-based cytology(control).(intervention)or liquid-based cytology(control).16宫颈癌筛查文献汇报HPV和TCTMethods The primary objective of this study was to evaluate primary HPV testing for cer

10、vical cancer screening in an organized program setting.Participants Inclusion criteria were women in British Columbia,Canada,with a personal health number,aged 25 to 65 years who had not had a Papanicolaou test in the previous 12 months,were not pregnant,were not HIV positive or receiving immunosupp

11、ressive therapy,and had no history of CIN2+in the past 5 years;did not have invasive cervical cancer;or did not have total hysterectomy.Women who met inclusion criteria and were patients of 224 collaborating clinicians in Metro Vancouver and Greater Victoria were invited to participate.17宫颈癌筛查文献汇报HP

12、V和TCTInterventions Participants randomized to HPV testing alone(intervention HPV testing alone(intervention group)group)with negativenegative test results were recalled at 48 months 48 months for exit with HPV and LBC testing.Participants randomized to LBC testing(control group)LBC testing(control g

13、roup)with negativenegative test results were asked to return at 24 months 24 months for repeat testing with LBC in accordance with the cervical cancer screening guidelines in British Columbia.If LBC results were negative at this 24-month24-month screen,participants were asked to return at 48 months

14、48 months for exit with HPV and LBC testing.19宫颈癌筛查文献汇报HPV和TCTIntervention Group Primary HPV testing was followed by reflex LBC in women with positive HPV positive HPV test results.At baseline,if HPV positive and LBC negativenegative,women were recalled in 12 months 12 months for HPV and LBC testing

15、.At 12 months,if women were either HPV or LBC positivepositive(atypical squamous cells of undetermined significance ASCUS),they were referred for colposcopycolposcopy.If both HPV and LBC negativenegative at 12 months,they were recommended for exit screen at 48 screen at 48 monthsmonths.If the baseli

16、ne reflex LBC result was greater than or equal to ASCUS,they were referred for immediate colposcopy immediate colposcopy and management.20宫颈癌筛查文献汇报HPV和TCTControl Group Primary LBC testing was followed by reflex HPV testing for women with ASCUS.If ASCUS and HPV positivepositive at baseline,women were

17、 referred for immediate colposcopycolposcopy.Women with ASCUS and HPV-negativenegative baseline results were recalled for LBC again at 12 months 12 months and were referred for colposcopy if their LBC result was greater than or equal to ASCUS.Women with baseline LBC low-grade squamous intraepithelia

18、l lesions or greater results were referred for colposcopy and colposcopy and managementmanagement.21宫颈癌筛查文献汇报HPV和TCTSafety Group Primary HPV testing was followed by reflex LBC in women with positive HPV test results,and they received the same management as the intervention group.However,in the safet

19、y group,HPV-negative women were recalled for exit screening with LBC at 24 months.The safety group was closed December 31,2010,when the planned sample size for this group was achieved.Intervention and Control Group Exit Screening Exit screening for both the intervention and control groups occurred 4

20、8 months after baseline screening and consisted of HPV testing and LBC(exit co-testing).22宫颈癌筛查文献汇报HPV和TCTprocedures Complete a demographic and behavioral questionnaire After 2010,women completed an abbreviated survey pelvic examination HPV testing was performed with the Hybrid Capture 2 High Risk H

21、PV DNA test(Qiagen),which detects high-risk HPV types 16,18,31,33,35,39,45,51,52,56,58,59,and 68.To confirm specimen adequacy,461 sequential ThinPrep specimens with valid HC2 results(34 HC2 positive and 427 negative)were tested with an in-house beta-globin polymerase chain reaction test and all were

22、 positive.As part of the trial protocol,samples with no visible cell pellet after conversion were rejected as inadequate.LBC slides were prepared using the ThinPrep 2000(Hologic)processor and smears were screened manually by program cytotechnologists.Abnormal cytology test results were referred to a

23、 cytopathologist for final interpretation and reporting.23宫颈癌筛查文献汇报HPV和TCT The main trial objective was to compare the rates of cervical intraepithelial neoplasia(CIN)grade 3 or greater(CIN3+)48 months after baseline screening with primary HPV vs LBC.Detailed trial methods and results have been prev

24、iously described.As outlined in Figure 1,round 1 refers to the baseline screen and any 12-month follow-up results in both the intervention and control groups.The 24-month screen round refers only to women in the control group because the intervention group did not receive 24-month screening,and this

25、 24-month screen round included 24-month screen results and 36-month follow-up results.The 48-month exit round refers to 48-month exit screening results(plus 24-month results for the control group)and associated outcomes for both the intervention and control groups 24宫颈癌筛查文献汇报HPV和TCT?25宫颈癌筛查文献汇报HPV和

26、TCTTrial Outcomes Primary end pointsPrimary end points：Rates of CIN3+at 48 months in the intervention and control groups.Secondary trial endSecondary trial end included in this analysisincluded in this analysis：rates of CIN2+at 48 months,the threshold for colposcopy referral and further evaluation,a

27、nd evaluation of the impact of primary HPV testing on colposcopy services through evaluation of colposcopy referral rates in each group.Other secondary end points not included not included in this analysis：histologically confirmed CIN2+detected at 2 years in both the control and safety groups;cleara

28、nce of HPV infection in women who were baseline HPV positive measured at 24 and 48 months;detection of histologically confirmed CIN3+in HPV-positive women who received 12-month retesting measured at 24 months in the safety group;and total estimated cost per woman screened and total estimated cost pe

29、r quality-adjusted life-year gained for each technology measured at 48 months.All intervention and control group women who did not have a CIN2+lesion detected during the trial or otherwise became ineligible(eg,hysterectomy,moved out of province)were invited for the 48-month exit screening.Women who

30、were negative on both LBC and HPV co-testing at 48 months were deemed negative for CIN2+.Women who were either LBC of greater than or equal to ASCUS or HPV positive at 48 months were referred for colposcopy and biopsied to determine their status as CIN3+,CIN2+,less than or equal to CIN1,or normal.26

31、宫颈癌筛查文献汇报HPV和TCTResults Primary End Points Primary End Points Among baseline HPV or LBC-negative women,rates of CIN3+at 48 months were significantly higher across all age groups in the control compared with the intervention group(Table 2).Cumulative incidence curves show that women who were HPV nega

32、tive at baseline had a significantly lower risk of CIN3+at 48 months compared with cytology-negative women.Secondary End Points Secondary End Points In the first round of screening,significantly more CIN2+cases were detected in the intervention group(HPV tested)compared with the control group.Cumula

33、tive CIN2+incidence curves show no significantly different disease detection across trial groups.In the intervention group,cumulative incidence was higher earlier in the trial at 18 and 42 months compared with the control group.In this trial,all women in the intervention and control groups had the s

34、ame intervention at the 48-month exit(HPV and cytology co-testing).By the end of trial follow-up(72 months),incidence was similar across both groups.27宫颈癌筛查文献汇报HPV和TCT?28宫颈癌筛查文献汇报HPV和TCT Among 19 009 women who were randomized(meanage,45 years10th-90th percentile,30-59),16 374(8296 86.9%in the interv

35、ention group and 8078 85.4%in the control group)completed the study.At 48 months,significantly fewer CIN3+and CIN2+significantly fewer CIN3+and CIN2+were detected in the intervention vs control group.29宫颈癌筛查文献汇报HPV和TCTDiscussion In this trial,by 48 months,among women screened for cervical cancer wit

36、h HPV testing without cytology,there were significantly fewer CIN3+and CIN2+cases compared with women who were screened with cytology alone at baseline.Women who were HPV negative at baseline were significantly less likely to have CIN3+and CIN2+at 48 months compared with women who were cytology nega

37、tive at baseline.These results have demonstrated that primary HPV testing detects cervical neoplasia earlier and more accurately than cytology.Although cervical screening guidelines from a number of organizations have recommended primary HPV testing based on the natural history of cervical cancer,cr

38、oss-sectional studies,18 studies where HPV-based screening was part of a screening group,or where studies ultimately evolved into primary HPV evaluations,none of these studies were designed specifically to examine HPV testing as the primary screening modality.This trial,which compares primary HPV te

39、sting vs LBC with standardized triage and colposcopy follow-up,found primary HPV testing detected significantly more CIN3+and CIN2+cases in the first round and significantly reduced CIN3+and CIN2+rates 48 months later.This trial also confirmed that women who were HPV negative at baseline have lower

40、rates of CIN2+at 48 months than cytology-negative women at baseline.Previous studies found the benefit of HPV and cytology co-testing was based primarily on the contribution of HPV,21 which this trial now prospectively validates.Further analyses modeling the cost-effectiveness of HPV primary screeni

41、ng using parameters from this study will be carried out to assess the potential economic effect of moving to HPV-based screening 30宫颈癌筛查文献汇报HPV和TCTConclusions Among women undergoing cervical cancer screening,the use of primary HPV testing compared with cytology testing resulted in a significantly lower likelihood of CIN3+at 48 months.Further research is needed to understand long-term clinical outcomes as well as cost-effectiveness.31宫颈癌筛查文献汇报HPV和TCT32宫颈癌筛查文献汇报HPV和TCT