宮頸癌篩查文獻(xiàn)匯報HPV和TCT培訓(xùn)課件

1、宮頸癌篩查文獻(xiàn)匯報HPV和TCT宮頸癌篩查文獻(xiàn)匯報HPV和TCT一、轉(zhuǎn)化區(qū)(移行帶)移行帶位置的變動主要取決于柱狀上皮生長能力的優(yōu)勢，而上皮的生長受激素的影響。在年輕婦女可見鱗柱交界的部位多位于解剖學(xué)外口以下，絕經(jīng)后婦女，移行帶內(nèi)移，通常在子宮頸的高處。2宮頸癌篩查文獻(xiàn)匯報HPV和TCT一、轉(zhuǎn)化區(qū)(移行帶)移行帶位置的變動主要取決于柱狀上皮生長能一、轉(zhuǎn)化區(qū)(移行帶) 移行帶是CIN和宮頸Ca的好發(fā)部位，因此細(xì)胞學(xué)檢查必須包括這一部位，陰道鏡檢查的原則之一就是要了解移行帶的情況。3宮頸癌篩查文獻(xiàn)匯報HPV和TCT一、轉(zhuǎn)化區(qū)(移行帶) 移行帶是CIN和宮頸Ca的好發(fā)二、鱗狀上皮化生 柱狀上皮轉(zhuǎn)化為

2、鱗狀上皮存在兩種不同轉(zhuǎn)化機(jī)制即鱗狀上皮化生和鱗狀上皮化生。鱗狀上皮化是指成熟的鱗狀上皮直接向鄰近的柱狀上皮內(nèi)生長，是成熟的鱗狀上皮保護(hù)層取代子宮頸管細(xì)胞。鱗狀上皮化生是指從子宮頸管基層膜上面具有改向功能的儲備細(xì)胞細(xì)胞增生而來。4宮頸癌篩查文獻(xiàn)匯報HPV和TCT二、鱗狀上皮化生 柱狀上皮轉(zhuǎn)化為鱗二、鱗狀上皮化生 這些細(xì)胞一旦受到刺激開始分層和分化，最后分化為成熟的鱗狀上皮，根據(jù)鱗狀上皮化生過程的不同階層分為：儲備細(xì)胞增生、未成熟磷化、成熟磷化。5宮頸癌篩查文獻(xiàn)匯報HPV和TCT二、鱗狀上皮化生 這些細(xì)胞一旦受到刺激開始分三、宮頸病變的概念廣義：宮頸病變(Cervicallesions)：是一個尚

3、未限定的、比較泛化的概念，指在宮頸區(qū)域發(fā)生的各種病變，包括炎癥、損傷、腫瘤(以及癌前病變)、畸形和子宮內(nèi)膜異位癥等 。6宮頸癌篩查文獻(xiàn)匯報HPV和TCT三、宮頸病變的概念廣義：宮頸病變(CervicallesioCompany Logo 狹義：臨床上將宮頸病變限定在宮頸細(xì)胞學(xué)異常和宮頸上皮內(nèi)瘤變(CervicalIntraepithelialNeoplasia，CIN)。 對宮頸病變進(jìn)行正確處理及采用合適的管理方法是宮頸癌防治體系中關(guān)鍵的組成部分。 不適當(dāng)?shù)奶幚砜赡茉黾訉m頸癌的發(fā)病風(fēng)險，抑或過度處理導(dǎo)致不必要的并發(fā)癥發(fā)生和醫(yī)療資源的浪費。 7宮頸癌篩查文獻(xiàn)匯報HPV和TCTCompany Lo

4、go 狹義：臨床上將宮頸病變限定在宮頸細(xì)不同診斷術(shù)語的含義子宮頸上皮內(nèi)瘤變（Cervical Intraepithelial Neoplasia，CIN）： 組織學(xué)診斷術(shù)語，按病變細(xì)胞涉及上皮層次分為、級。子宮頸鱗狀上皮內(nèi)病變（Squamous intraepithelial Lesion，SIL）： 細(xì)胞學(xué)TBS分類診斷術(shù)語，按細(xì)胞的異型性改變分為低度鱗狀上皮內(nèi)病變（LSIL）和高度鱗狀上皮內(nèi)病變（HSIL） 8宮頸癌篩查文獻(xiàn)匯報HPV和TCT不同診斷術(shù)語的含義子宮頸上皮內(nèi)瘤變（Cervical Int四、宮頸病變?nèi)A梯檢查細(xì)胞學(xué)陰道鏡組織病理學(xué)由于中國國情，對宮頸癌篩查因地區(qū)、經(jīng)濟(jì)條件、醫(yī)

5、療資源等差異而采用不同手段，如：細(xì)胞學(xué)檢測、裸眼醋酸染色檢查(VIN)及復(fù)方碘染(VILI)檢查，高危型HPVDNA檢查、肉眼觀察高度懷疑宮頸浸潤癌等，這些篩查結(jié)果異常者，需轉(zhuǎn)診陰道鏡檢查和診斷，并在陰道鏡指導(dǎo)下完成組織病理學(xué)檢查診斷，即“三階梯”的檢查診斷。9宮頸癌篩查文獻(xiàn)匯報HPV和TCT四、宮頸病變?nèi)A梯檢查細(xì)胞學(xué)陰道鏡組織病理學(xué)9宮頸癌五、陰道鏡檢查指征1、宮頸細(xì)胞學(xué)檢查結(jié)果異常（1）不典型鱗狀上皮細(xì)胞(ASC-US)；（2）不典型鱗狀上皮細(xì)胞-不除外高度鱗狀上 皮內(nèi)病變（ASC-H）； （3）低度鱗狀上皮內(nèi)病變（LSIL）；（4）高度鱗狀上皮內(nèi)病變（HSIL）；（5）鱗狀細(xì)胞癌（SC

6、C）；10宮頸癌篩查文獻(xiàn)匯報HPV和TCT五、陰道鏡檢查指征1、宮頸細(xì)胞學(xué)檢查結(jié)果異常10宮頸癌篩查文（6）不典型腺上皮細(xì)胞（AGC）；（7）腺原位癌（AIS）；（8）腺癌；（9）巴氏分級標(biāo)準(zhǔn)中巴氏b級以上的結(jié)果；（10）高危型HPV檢測結(jié)果陽性（需注明hpv檢測方法，如：hc-2法、hpv基因分型法特別是16、18型陽性、PCR法） 11宮頸癌篩查文獻(xiàn)匯報HPV和TCT（6）不典型腺上皮細(xì)胞（AGC）；11宮頸癌篩查文獻(xiàn)匯報HP2、裸眼醋酸染色或復(fù)方碘染色后肉眼觀 察（via/vili）結(jié)果異常。3、裸眼直觀為宮頸潰瘍、腫塊或可疑宮 頸浸潤癌。4、可疑病變處指導(dǎo)性活檢12宮頸癌篩查文獻(xiàn)匯報H

7、PV和TCT2、裸眼醋酸染色或復(fù)方碘染色后肉眼觀12宮頸癌篩查文獻(xiàn)匯報H5、宮頸錐切前確定病變范圍6、宮頸尖銳濕疣7、慢性宮頸炎長期治療無效8、陰道和外陰病變：陰道和外陰上皮內(nèi)瘤樣變、早期陰道癌、陰道腺病、梅毒、結(jié)核、尖銳濕疣等13宮頸癌篩查文獻(xiàn)匯報HPV和TCT5、宮頸錐切前確定病變范圍13宮頸癌篩查文獻(xiàn)匯報HPV和TCJuly3,201814宮頸癌篩查文獻(xiàn)匯報HPV和TCTJuly3,201814宮頸癌篩查文獻(xiàn)匯報HPV和TCTquestionDoes cervical cancer screening using primary cervical human papillomavirus

8、 (HPV) testing compared with cytology result in a lower likelihood of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) at 48 months? 15宮頸癌篩查文獻(xiàn)匯報HPV和TCTquestionDoes cervical cancer sImportance There is limited information about the relative effectiveness of cervical cancer screening with p

9、rimary human papillomavirus (HPV) testing alone compared with cytology in North American populations. Objective To evaluate histologically confirmed cumulative incident cervical intraepithelial neoplasia (CIN) grade 3 or worse (CIN3+) detected up to and including 48 months by primary HPV testing alo

10、ne (intervention) or liquid-based cytology (control). 16宮頸癌篩查文獻(xiàn)匯報HPV和TCTImportance There is limited inMethods The primary objective of this study was to evaluate primary HPV testing for cervical cancer screening in an organized program setting. Participants Inclusion criteria were women in British C

11、olumbia, 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 5 years; did not have invasive cervical cancer;

12、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宮頸癌篩查文獻(xiàn)匯報HPV和TCTMethods The primary objective宮頸癌篩查文獻(xiàn)匯報HPV和TCT培訓(xùn)課件Interventions Participants randomized to HPV

13、testing alone (intervention group) with negative test results were recalled at 48 months for exit with HPV and LBC testing. Participants 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

14、cancer screening guidelines in British Columbia. If LBC results were negative at this 24-month screen, participants were asked to return at 48 months for exit with HPV and LBC testing. 19宮頸癌篩查文獻(xiàn)匯報HPV和TCTInterventions Participants rIntervention GroupPrimary HPV testing was followed by reflex LBC in w

15、omen 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 HPV or LBC positive (atypical squamous cells of undetermined significance ASCUS), they were referred for colposcopy. If bot

16、h 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 for immediate colposcopy and management. 20宮頸癌篩查文獻(xiàn)匯報HPV和TCTIntervention GroupPrimary HPV Control GroupPrimary LBC testing

17、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 12 months and were referred for colposcopy if their LBC result was greater t

18、han or equal to ASCUS. Women with baseline LBC low-grade squamous intraepithelial lesions or greater results were referred for colposcopy and management. 21宮頸癌篩查文獻(xiàn)匯報HPV和TCTControl GroupPrimary LBC testiSafety Group Primary HPV testing was followed by reflex LBC in women with positive HPV test result

19、s, 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 achieved.Intervention and Contro

20、l 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). 22宮頸癌篩查文獻(xiàn)匯報HPV和TCTSafety Group Primary HPV testiproceduresComplete a demographic and behavioral questionnaire After 2

21、010, women completed an abbreviated survey pelvic examinationHPV 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

22、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 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

23、 ThinPrep 2000 (Hologic) processor and smears were screened manually by program cytotechnologists. Abnormal cytology test results were referred to a cytopathologist for final interpretation and reporting. 23宮頸癌篩查文獻(xiàn)匯報HPV和TCTproceduresComplete a demographThe main trial objective was to compare the rat

24、es 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 previously described. As outlined in Figure 1, round 1 refers to the baseline screen and any 12-month follow-up results i

25、n 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 24-month screen round included 24-month screen results and 36-month follow-up results. The 48-month exit round r

26、efers 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宮頸癌篩查文獻(xiàn)匯報HPV和TCTThe main trial objective was t25宮頸癌篩查文獻(xiàn)匯報HPV和TCT25宮頸癌篩查文獻(xiàn)匯報HPV和TCTTrial Outcomes Primary end points：Rates of CIN3+ at 48 month

27、s in the intervention and control groups.Secondary trial end included in this analysis：rates of CIN2+ at 48 months, the threshold for colposcopy referral and further evaluation, and evaluation of the impact of primary HPV testing on colposcopy services through evaluation of colposcopy referral rates

28、 in each group. Other secondary end points not included in this analysis：histologically confirmed CIN2+detected at 2 years in both the control and safety groups; clearance of HPV infection in women who were baseline HPV positive measured at 24 and 48 months; detection of histologically confirmed CIN

29、3+ 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 per quality-adjusted life- year gained for each technology measured at 48 months. All intervention and control group women who did

30、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 were negative on both LBC and HPV co-testing at 48 months were deemed negative for CIN2+. Women who were either LBC of gr

31、eater 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宮頸癌篩查文獻(xiàn)匯報HPV和TCTTrial Outcomes Primary end poiResults Primary End Points Among baseline HPV or LBC-negative women, r

32、ates 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 negative at baseline had a significantly lower risk of CIN3+ at 48 months compared with cytology-negative

33、 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+ incidence curves show no significantly different disease detection across trial groups. In the interventi

34、on 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 intervention at the 48-month exit (HPV and cytology co-testing). By the end of trial follow-up (72 months),

35、 incidence was similar across both groups. 27宮頸癌篩查文獻(xiàn)匯報HPV和TCTResults Primary End Points 228宮頸癌篩查文獻(xiàn)匯報HPV和TCT28宮頸癌篩查文獻(xiàn)匯報HPV和TCTAmong 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 control group) complet

36、ed the study. At 48 months, significantly fewer CIN3+ and CIN2+ were detected in the intervention vs control group. 29宮頸癌篩查文獻(xiàn)匯報HPV和TCTAmong 19 009 women who were raDiscussion In this trial, by 48 months, among women screened for cervical cancer with HPV testing without cytology, there were significa

37、ntly 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 negative at baseline. These results have demonstra

38、ted 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, cross- 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 specifical