宫颈癌筛查文献汇报HPV与TCT.ppt

1、内容回顾,一、转化区 二、鳞状上皮化生 三、宫颈病变的概念 四、三阶梯检查 五、阴道镜检查指征,一、转化区(移行带),原始鳞柱交界与新生鳞柱交界的宫颈段。 原始鳞状上皮 原始柱状上皮 原始鳞柱交界（OSCJ） 新的鳞柱交界（NSCJ） 转化区（TZ） 正常转化区,一、转化区(移行带),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。 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，通常在子宫颈的高处。,一、转化区(移行带),移行带是CIN和宫颈Ca的好发部位，因此细胞学检查必须包括这一部位，阴道镜检查的原则之一就是要了解移行带的情况。,二、

2、鳞状上皮化生,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管细胞。 鳞状上皮化生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。,二、鳞状上皮化生,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的不同阶层分为：储备细胞增生、未成熟磷化、成熟磷化。,三、宫颈病变的概念,广义：宫颈病变(Cervicallesions)：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，包括炎症、损伤、肿瘤(以及癌前病变)、畸形和子宫内膜异

3、位症等 。,Company Logo,狭义：临床上将宫颈病变限定在宫颈细胞学异常和宫颈上皮内瘤变(CervicalIntraepithelialNeoplasia，CIN)。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，抑或过度处理导致不必要的并发症发生和医疗资源的浪费。,不同诊断术语的含义,子宫颈上皮内瘤变（Cervical Intraepithelial Neoplasia，CIN）：组织学诊断术语，按病变细胞涉及上皮层次分为、级。子宫颈鳞状上皮内病变（Squamous intraepithelial Lesion，SIL

4、）： 细胞学TBS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（LSIL）和高度鳞状上皮内病变（HSIL）,四、宫颈病变三阶梯检查,细胞学阴道镜组织病理学 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、裸眼醋酸染色检查(VIN)及复方碘染(VILI)检查，高危型HPVDNA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，并在阴道镜指导下完成组织病理学检查诊断，即“三阶梯”的检查诊断。,五、阴道镜检查指征,1、宫颈细胞学检查结果异常 （1）不典型鳞状上皮细胞(ASC-US)； （2）不典型鳞状上皮细胞-不除外高

5、度鳞状上 皮内病变（ASC-H）； （3）低度鳞状上皮内病变（LSIL）； （4）高度鳞状上皮内病变（HSIL）； （5）鳞状细胞癌（SCC）；,（6）不典型腺上皮细胞（AGC）； （7）腺原位癌（AIS）； （8）腺癌； （9）巴氏分级标准中巴氏b级以上的结果； （10）高危型HPV检测结果阳性（需注明hpv检测方法，如：hc-2法、hpv基因分型法特别是16、18型阳性、PCR法）,2、裸眼醋酸染色或复方碘染色后肉眼观察（via/vili）结果异常。 3、裸眼直观为宫颈溃疡、肿块或可疑宫颈浸润癌。 4、可疑病变处指导性活检,5、宫颈锥切前确定病变范围 6、宫颈尖锐湿疣 7、慢性宫颈炎长期治

6、疗无效 8、阴道和外阴病变：阴道和外阴上皮内瘤样变、早期阴道癌、阴道腺病、梅毒、结核、尖锐湿疣等,July 3, 2018,question,Does cervical cancer screening using primary cervical human papillomavirus (HPV) testing compared with cytology result in a lower likelihood of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) at 48 months?,Importance,

7、There is limited information about the relative effectiveness of cervical cancer screening with primary human papillomavirus (HPV) testing alone compared with cytology in North American populations.,Objective,To evaluate histologically confirmed cumulative incident cervical intraepithelial neoplasia

8、 (CIN) grade 3 or worse (CIN3+) detected up to and including 48 months by primary HPV testing alone (intervention) or liquid-based cytology (control).,Methods,The primary objective of this study was to evaluate primary HPV testing for cervical cancer screening in an organized program setting.,Partic

9、ipants,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 immunosuppressive therapy, and had no history of CIN2+ in the past

10、 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.,Randomization,Women were randomly assigned 1:1:1 to 1 of 3 (int

11、ervention, control, or safety) groups between January 2008 and December 31, 2010. Starting January 1, 2011, women were assigned 1:1 to the intervention or control when the safety group was closed. Women and clinicians were blinded to group assignment until 24 months or if the baseline screen results

12、 were positive and required follow-up. The primary analysis for this study focuses on the intervention and control groups.,Interventions,Participants randomized to HPV testing alone (intervention group) with negative test results were recalled at 48 months for exit with HPV and LBC testing. Particip

13、ants randomized to LBC testing (control group) with negative test results were asked to return at 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-month screen, participants were asked to re

14、turn at 48 months for exit with HPV and LBC testing.,Intervention Group,Primary HPV testing was followed by reflex LBC in women with positive HPV test results. At baseline, if HPV positive and LBC negative, women were recalled in 12 months for HPV and LBC testing. At 12 months, if women were either

15、HPV or LBC positive (atypical squamous cells of undetermined significance ASCUS), they were referred for colposcopy. If both HPV and LBC negative at 12 months, they were recommended for exit screen at 48 months. If the baseline reflex LBC result was greater than or equal to ASCUS, they were referred

16、 for immediate colposcopy and management.,Control Group,Primary LBC testing was followed by reflex HPV testing for women with ASCUS. If ASCUS and HPV positive at baseline, women were referred for immediate colposcopy. Women with ASCUS and HPV-negative baseline results were recalled for LBC again at

17、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 intraepithelial lesions or greater results were referred for colposcopy and management.,Safety Group,Primary HPV testing was followed by reflex LBC in women w

18、ith positive HPV test results, and they received the same management as the intervention group. However, in the safety 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 achi

19、eved.,Intervention and Control Group Exit Screening,Exit screening for both the intervention and control groups occurred 48 months after baseline screening and consisted of HPV testing and LBC (exit co-testing).,procedures,Complete a demographic and behavioral questionnaire After 2010, women complet

20、ed an abbreviated survey pelvic examination HPV testing was performed with the Hybrid Capture 2 High Risk HPV 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 re

21、sults (34 HC2 positive and 427 negative) were tested with an in-house beta-globin polymerase chain reaction test and all were 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 (H

22、ologic) processor and smears were screened manually by program cytotechnologists. Abnormal cytology test results were referred to a cytopathologist for final interpretation and reporting.,The main trial objective was to compare the rates of cervical intraepithelial neoplasia (CIN) grade 3 or greater

23、 (CIN3+) 48 months after baseline screening with primary HPV vs LBC. Detailed trial methods and results have been previously 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 r

24、ound refers only to women in the control group because the intervention group did not receive 24-month screening, and this 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 f

25、or the control group) and associated outcomes for both the intervention and control groups,Trial Outcomes,Primary end points：Rates of CIN3+ at 48 months in the intervention and control groups. Secondary trial end included in this analysis：rates of CIN2+ at 48 months, the threshold for colposcopy ref

26、erral and further evaluation, and 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 in this analysis：histologically confirmed CIN2+detected at 2 years in both the control and s

27、afety groups; clearance 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

28、total estimated cost per 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-m

29、onth exit screening. Women who 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

30、than or equal to CIN1, or normal.,Results,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 n

31、egative at baseline had a significantly lower risk of CIN3+ at 48 months compared with cytology-negative women. 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. Cumulative CIN2+

32、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 same in

33、tervention 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.,Among 19 009 women who were randomized(meanage, 45 years10th-90th percentile, 30-59), 16 374 (8296 86.9% in the intervention group and 8078 85.4% in the

34、 control group) completed the study. At 48 months, significantly fewer CIN3+ and CIN2+ were detected in the intervention vs control group.,Discussion,In this trial, by 48 months, among women screened for cervical cancer with HPV testing without cytology, there were significantly fewer CIN3+ and CIN2

35、+ 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 negative at baseline. These results have demonstrated that primary HPV test

36、ing 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, cross- sectional studies,18 studies where HPV-based screening was part

37、 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 testing vs LBC with standardized triage and colposcopy follow-up,

38、 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 rates of CIN2+ at 48 months than cytology-negative women

39、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 screening using parameters from this study will be carried o

40、ut to assess the potential economic effect of moving to HPV-based screening,Conclusions,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.,THANK YOU!,