組別：第五組 指導老師：楊煦星 報告者：4A0H0051楊舒婷 4A0H0053周侑樺 Cervical-Cancer Screening with Human Papillomavirus and Cytologic Cotesting 組別：第五組 指導老師：楊煦星 報告者：4A0H0051楊舒婷 4A0H0053周侑樺

子宮頸癌成因 1.多重性伴侶 2.初次性交的年齡早 3.抽菸 4.和有子宮頸癌伴侶的發生性關係

子宮頸癌成因 子宮頸癌發生時，先會出現子宮頸癌的前期病變，叫做子宮頸上皮內瘤。子宮頸癌的成因就是引起子宮頸上皮內瘤的元兇。 類乳突病毒中，有些是屬於高危險致癌型的病毒，有些是屬於低危險型病毒。一般而言，可能導致子宮頸癌的人類乳突病毒是屬於高危險致癌型的病毒。

當受到人類乳突病毒的感染後，子宮頸的上皮細胞會因為病毒基因的作用形成子宮頸上皮內瘤。 依據病變的程度，可分為第1級、第2級、第3級的子宮頸上皮內瘤。第1級的子宮頸上皮內瘤歸類為低度麟狀上皮內病變，第2級和第3級的子宮頸上皮內贅瘤歸類為高度麟狀上皮內病變。高度病變進一步的惡化發展，就變成了子宮頸癌。

Pap smear 所謂抹片篩檢是以抹片棒(spatula)或子宮頸刷(brush)等器具，採集外子宮頸之上皮細胞，目前為採集到子宮頸鱗狀上皮與柱狀上皮交界處，取樣後之細胞將其固定在玻片上，再利用帕氏染色後透過顯微鏡檢查是否有可疑性的癌細胞存在。

The Clinical Problem Cervical cancer is the third leading type of cancer in women worldwide. There are approximately 530,000 new cases and 275,000 associateddeaths annually. The disease burden is highest in resource-poor countries, where more than 80% of cases occur. Nevertheless,approximately 4000 women die from cervical cancer each year in the United States.

The Clinical Problem HPV-16 is the mostcarcinogenic type,accounting for half of cervical-cancer cases.HPV-18, which is implicated in many cases of endocervical adenocarcinoma,is the second most carcinogenic type,accounting for approximately 15% of all cervical cancers.

The Clinical Problem 第16型HPV造成的子宮頸癌多為表皮細胞癌，而第18型造成的多為腺癌，雖然18型的感染率不如16型那麼高，但18型的致癌率比16型還要高，且腺癌比表皮細胞癌更容易轉移。

偵測HPV-DNA及第16、18型分型的臨床意義

人類乳突病毒

人類乳突病毒

The Clinical Problem Cervical cancer screening in the United States should not start until the age of 21 years, since adolescents are at extremely low risk for cervical cancer but have high rates of transient HPV infections and associated minor cytologic abnormalities.

The risk of cervical precancer and cancer is very low in the years after a negative HPV test. For women in the United States who are 30 years of age or older cotesting with HPV and cytologic tests every 5 years is an accepted alternative to cytologic testing alone every 3 years.

感染的時間越長，風險也愈增加。總而言之，HPV感染大多是暫時性的，大約12~24個月，而免疫力降低的人較可能會持續感染，最後子宮頸發生病變或轉變成侵犯性子宮頸癌的機會將很高。

Strategies and Evidence Low-grade Squamous Intraepithelial Lesion：若抹片檢查為LSIL，陰道鏡為最適當的檢查。其他代替方案為每3-6個月重複的抹片檢查或檢測HPV。LSIL 病灶有相當比例會恢復為正常。 若無立即colposcopy而3-6個月重複抹片的結果還是ASCUS，或仍有LSIL或HSIL，則應立即接受colposcopy。

High-grade Squamous intraepithelial Lesions：所有HSIL婦女應立即接受colposcopy。

HPV在30歲以下的女性族群非常常見，然而子宮頸癌在這個年齡層卻非常少見。 只有在於抹片出現一種稱為ASCUS的異常，有一半的人會同時存在有人類乳突病毒的感染，藉由人HPV檢查可以得知ASCUS是來自人類乳突病毒感染，還是有其他原因，例如發炎所引起。

colposcopy 做陰道鏡檢查時，子宮頸先塗上4%的醋酸，再透過一個放大10—16倍的顯微鏡觀察細胞顏色及微血管形狀的變化，在變化最顯著的地方切片確認是否有侵襲性疾病或是發炎。

陰道鏡檢查與切片確認是CIN1的婦女，因為大多數的病變會自然消失且沒有肯定的治療方法，所以可以在6個月後做第二次抹片，如果連續二年陰道鏡切片是CIN2，則應做一個局部子宮頸的治療。第二次的抹片報告是HSIL時則需更進一步的陰道鏡診斷，若第二次抹片報告是正常時則回到一年一次的常規篩檢。

Cost-Effectiveness of Various Screening Strategies There has been insufficient comparison of the cost-effectiveness of various screening options (in particular, cytologic and HPV cotesting vs. HPV testing alone). The addition of cytologic testing to HPV testing is much more expensive than HPV testing alone .

Among the women involved in the Kaiser Permanente Northern California study, the 5-year risk of CIN 3 or cancer after negative cotests was estimated to be 0.16%, which was not meaningfully lower than the risk after a negative HPV test alone (0.17%).

It is unclear whether U. S It is unclear whether U.S. clinicians and women who are accustomed to more frequent Pap tests will accept the extended screening interval warranted by more sensitive screening.

If cotesting were performed at more frequent intervals, new tests with positive results in women with previously negative test results would most likely represent incident HPV infections, with a low associated risk of HSIL or cancer.

management of Positive Screening Cotests Less than 10% of women will have a positive screening result on cotesting. The various combinations of positive cytologic categories and HPV test results are associated with different risks of HSIL or cancer.

management of Positive Screening Cotests Management options include continued regular screening, increased surveillance (shorter screening intervals), or colposcopic assessment, depending on the risk.

management of Positive Screening Cotests For high-risk combinations (e.g., cytologic HSIL, regardless of the HPV test result), immediate colposcopy is warranted. The associated 5-year risks of histologic HSIL (approximated by data for CIN 2 and CIN 3) and cancer and the currently recommended management are shown in Table 2.

However, randomized trials of various management options have not been conducted, and many recommendations are based on observational data or expert opinion.

management of Positive Screening Cotests Intensified surveillance is recommended, but the best timing for repeat testing is uncertain; longer intervals allow a higher proportion of infections to clear but result in a greater, though still small, risk of cancer.

management of Positive Screening Cotests The most recent guidelines recommend repeat cotesting in 1 year, with referral for colposcopy if cytologic testing is positive or if HPV testing remains positive, suggesting persistent infection.

management of Positive Screening Cotests An alternative is genotyping DNA or RNA specifically for HPV-16 and HPV-18, with immediate colposcopy if either of these highest-risk types is found and repeat cotesting in 1 year if neither type is found. This is currently the only recommended use of genotyping to determine individual HPV types.

Biomarkers have also been proposed to help identify women who are at particularly high risk for HSIL and cervical cancer and require colposcopy. One proposed biomarker measured in a cytologic specimen is p16.

非典型性細胞抹片 (ASCUS )是目前最常見的異常細胞抹片結果（佔細胞抹片檢查結果約5％），是臨床診斷具爭議的個案病例。 在ASC-US的細胞抹片檢測結果，有一半的婦女有陰性結果但是有致癌HPV。

針對上述結果，可能是因為檢查結果細胞抹片呈現陰性、HPV呈現陽性。 根據細胞抹片、HPV陽性的30歲以上女性進行HPV16/18基因分型檢測（見下圖），以及時發現細胞抹片正常結果中存在的CIN癌前病變高危人群

30歲以上，細胞抹片陰性、HPV陽性的女性如何進行管理 每一年重覆聯合檢測 HPV的DNA分型 細胞學陰性和 HPV檢測陰性 不明確或HPV檢測陽性 HPV16或18陽性 HPV16或18陰性 陰道鏡檢查 每一年重覆聯合檢測 三年重覆聯合檢驗 根據ASCCP指南進行管理 根據ASCCP指南進行管理

2011年，美國癌症協會與其他組織一起，制定了預防和發現早期子宮頸癌的篩檢方法。

　　含有細胞學的檢查在台灣是每三年一次的間隔時間,而在美國則是每五年一次的檢查標準,且被判定這些時間間隔的檢查標準可以有效的減少子宮頸癌發生率及死亡率。

在2013年, ASCCP發表更新的篩檢方針來管理異常的子宮頸結果。 例如：接種了 HPV 疫苗的婦女和未注射過的婦女一樣，也都必須做子宮頸癌檢查。

Conclusions and Recommendations

對於30歲以上的女性,我們會建議HPV和細胞抹片的聯合測試檢查比單獨細胞學檢查要來的安全。

聯合測試檢查可以提高靈敏度,如果兩個結果都是陰性的,結果的可信度也比較有保證 絕大多數女性接受檢查都會有正常的結果，並於5年重複篩查。

疫　　苗 預防重於治療，疫苗接種可以預防疾病之產生，HPV疫苗現階段都是預防性疫苗， 是類病毒微粒之基因重組疫苗，含有病毒蛋白，但不含病毒 DNA ，能讓身體產生免疫反應，但不會引發疾病。 　　

目前子宮頸癌的預防性疫苗共有兩種，一種是屬於默克藥廠所發展的疫苗稱之為 Gardasil(台灣名稱為嘉喜) ，而另一種則是由葛蘭素藥廠所研發的疫苗稱之為 Cervirax (台灣名稱為保蓓)。

參考文獻 子宮頸癌應如何治療，其治癒率如何？台灣癌症基金會http://www.canceraway.org.tw/page.asp?IDno=556http://www.canceraway.org.tw/page.asp?IDno=556 臺北榮民總醫院婦女醫學部http://wd.vghtpe.gov.tw/obgy/i_site.jsp?id=6051 人類乳突狀病毒與子宮頸癌-醫學檢驗百科http://www.accuspeedy.com.tw/L01_library_1/410_PCR/101_HPV_cervix_cancer.htm

康健雜誌http://m.commonhealth.com.tw/article/article.action?nid=69981 ASCCP 2013年版子宮頸癌篩查指南http://www.360doc.com/content/15/0207/17/19660925_447045989.shtml 林新醫院-衛教知識平台http://www.lshosp.com.tw/wei/Folder/Obstetrics_Gynecology/OG_008.htm

謝謝各位聆聽 The end