Y Hpc TP. Ho Chi Minh * Tap 20 * So 1 * 2016 Tong Quan
XET NGHIEM TAM SOAT UNG THU" CO TLT CUNG KIEN THL/C CAP NHAT VE PHl/ONG DIEN Y HOC CHU^G CU"
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Tir thap nien 50 ciia the ky tnroc, nho phat minh cua Papanicolaou, viec tam soat img thu CO tir cung (UTCTC) bang phet te' bao co tu cung (gQi tat la PAP) ra doi, danh daii su khai sinh ciia nganh te bao hoc. TCr do deh nay, hang trieu phu nii tren the gioi da duoc cihi song nho phuong phap tam soat ung thu co tCr cung dua tren te'bao nay. Tai Hoa Ky, neu ti le moi mac ciia ung thu co tii cung vao nhung nam 1940 vao khoang 32,6/100.000 dan thi Men nay chi la 8,1/100.000 dan*". Tai Thanh Pho' Ho Chi Minh, theo so lieu ciia berth vien Ung Buou ti le moi mac ciia UTCTC naml997 la 26,8/100.000 dan thi hien nay ti IS nay chi khoang 16/100.000 dan.
Da hon niia theky trdi qua, ti IS bi img thu CO tir cung da giam nhieu, tuy nhien cd mgt Ihuc te'dang lo ngai la du co chuong trinh tich cue tam soat UTCTC thi can benh nay van la mot nguyen nhan quan trong gay benh suat va tir sua't 6 phu nii. Theo so lieu cua Hpi Ung Thu Hoa Ky (American Cancer Society), vao thdi diem 2010, moi nam d My cd khoang 12.000 ngudi mdi mac UTCTC va khoang 4.000 chet VI can benh nayi*'. Ngoai ra, moi nam tai Hoa K^ con cd deh 500.000 phu nii bi rUiixng ton thuong hen ung thu co tir cung miic do nang: loan san trung binh va nang. Benh nhan lai la nhiing ngucri co dugc xet nghiem PAP dinh ky. Vi sao v3y?
Da cd nhieu nghien ciiu chiing minh rang do nhay ciia PAP chi khoang 50%, cao lam la 70%, nghia la am tinh gia tu 30-50% nen moi cd nhiing benh nhan tuy van dugc sang loc ma van khong phat hien ra b$nh. N 5 luc lam tang
Trdn Thj Loi*
do chinh xac a i a PAP la mot van de ma cac nha te'bao hoc khong ngiing nghien ciiu.
PAP quy udc (conventional) vdi cac nhugc diem:
Khi phe't benh pham len lam kinh, chi khoang 20% te' bao thu thap dugc phet len lam, cd deh khoang 80% cac te' bao thu dugc van con dinh tren que Ayre hoac choi te'bao bi bd di, trong so dd cd the con nhung te bao di d?ng.
Phei: thii cong khieh cac te'bao chong chat len nhau, co lan mau, chat nhay khieh ket qua dpc lam kem chinh xac.
PAP nhiing dich (liquid- based) la mot tie'n bp vugt b$c a i a nganh te' bao hpc: thu thap dugc toan bp benh pham va xii ly bang may giup te' bao dugc trai mdng, quan sat ro hon.
Do dd PAP nhiing dich co dp nhay cao hon, cd ihedeh75%P).
Tuy nhien, ca PAP quy uoc va PAP nhiing dich deu tiiy thuoc vao nhieu yeu to chu quan nhu: tir viec lay benh pham, co' dinh, bao quan, deh nhupm va dpc lam, vi vay dp nhay ciing chua cao lam.
Nham bii trii tinh kem nhay, va vi ung thu CO tir cung la mot benh tieh trien cham qua nhieu nam thang, PAP dugc lap lai thudng xuyen, moi hai hoac moi ba nam tiiy timg noi, va n h u v|y, chucng trinh tam soat ung thu co tu cung trd thanh la mpt ganh nang quoc gia ca ve phuang dien tai chinh ciing n h u viec to chiic tham kham phu khoa<^-*J. Dd la ly do vi sao nhieu quoc gia khong thuc hien noi chucmg trinh tam soat ung thu co tii cung.
* Bo Mon Sire Khde Sinh Sin, Khoa Y, DHQG, TP.HCM
Tdc gia liin Igc: GS.TS. Tran Thj Lgi DT: 0913678064 Email: [email protected] S ^ Phu Khoa
Tong Quan Y Hpc TP. H 6 Chi Minh * Tap 20 * So 1 » 2016
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Hinh 1: Quy trinh chudn bi PAP quy udc (Nguon hinh: tdi lieu tham khao sd7).
Nam 2001, hai tac gii MH. Stoler, M.
Schiffman da dang tren tap chi JAMA nghien cihi "Interobsever Reprodudbihty of Cervical Cj^logic and Histologic h\terpretations"(*>
nham xac dinh dp tin cay ciia PAP nhiing dich. Nghien cuu thuc hien trgn 4948 lam PAP nhiing djch da dugc dgc bdi mgt nhdm cac nha te bao hpc, ke^ qua dugc giii bi m$t va nhiing Iam tr&n dugc dua cho mpt nhdm nha te' bao hpc khac dpc Igi. Ca hai nhdm deu la nhiing chuyen gia ve te* bao hpc. K^t qua nghien ciiu cho thay su phii hgp v& ke't qua cua hai nhdm: khdng ton thuong ac tinh la:
78%, ASCUS: 43%, LSIL: 68%, HSIL: 47%. Dieu dang chii y la su thong nha't ve ke^ qua HSIL giua hai nhom chuyen gia chi la 47% cang cho thay dp tin cgy thSp den miic nguy hiem cua PAP va cung giai thich dugc vi sao d My c6 nhimg phu nii van tam soat ung thu c6 tit cung djnh ky ma van bi ung thu c6 tir cung deh giai doan xam lah. Tir do PAP dugc xem la mpt cong cy rat khong hoan h i o d^ tim soat ung thu CO tu cung, dugc vi nhu mOt vi^n kim cuong bi khuyet
Hinh 2: Quy trinh chudn b( PAP nhiing djch
N H I J N G 1 H A Y D 6 I T R 0 N G CAC P H C O N G PHAPTAM SOAT UNG THU*C6 TID'CUNG Ph^t hi^n moi lien he gjua HPV va ung thu CO tur cung
Hinh 3: Harald Zur Hausm Nam 1976, Harald Zur Hansen, mpt nhk vims hpc (virologist) cong bo gia thuyfit Human Papillomavirus (HPV) cd the la nguyen nhan quan trpng gay ra ung thu co ttr cung, va d^n nhiing nSm 1983-84 6ng xdc dinh dugc dd la hai typ HPV 16,18. Phdt minh niy giiip ong vinh dif nh$n dugc mpt niia giii|
Nobel ve Y Hgc nam 2008, mpt niia giai Nobel • trao cho Luc Montagnier va Frangoise Barrd-
220 Chuy@n De Siic Khde Sinh S i n - Ba M e Tre Em
Y Hgc TP. H o Chi Minh * T|lp 20 * So 1 * 2016 Tong Quan
Sinoussi la nhiing nha bac hgc tim ra HIV.
Phat minh a i a Hausen md ra mdt ky nguyen mdi trong chioi luge du phdng ung thu co tit cung vdi d u phdng cap 1: vac xin HPV, va d u phong ca'p 2: tam soat ung thu co tir cung bang DNA HPV.
T£r khoang 10 nam qua, song song vdi su ma't dan vi tri chii luc trong trong tam scat ung thu CO tir cung a i a PAP, la su xuat hien cua xet nghiem tim DNA HPV trong dich am dao, CO tii cung. Tren thi tnrong deh nay da co rat nhieu loai xet nghiem tam soat nhiem HPV, tir loai chi don ttiuan phat Men cd nhiem HVP deh nhiing loai phat hien dugc cac typ nguy CO cao gay ung thu co tir cung. Do nhgy ciia cdc xet nghiim tim DNA HPV lin t&i 90-95%,, vd dimt ddng chit y la do co the phdt hiin nhiem HPV tru&c khi co nhdng bHu him bdi thu&ng tren tebdo, nhieng doi tugng nhiem HPV se dugc theo ddi chat che nha do se dugc chan dodn vd diiu tri benh s&m han'*K
Chuyen doi t u CO-Test thanh HPV D N A nguy CO cao
Theo Hudng Dan DSng Thugn thang 3 nam 2012 ciia Co Quan Phong Benh Hoa Ky (United States Preventive Services Task Force) ket hgp vdi Hpi Ung Thu Hoa Ky (American Cancer Society), Hpi Soi Co Tir Cung va Benh Hgc Co Tii Cung (American Society for Colposcopy and Cervical Pathology), Hoi Benh Hgc Lam Sang Hoa Ky (American Society for Clinical Pathology)'^' da cong bo ban hudng dan dong thuan: khong lam soat ung thu CO tii cung cho ph^ nir dudi 21 tu6i bai ke tien sis sinh hoat tinh dtic**'. Phu nu tir 21 - 29 tuoi Iam PAP mdi 3 nam. Tir 30 - 65 tuoi Iam co-testing: PAP ket hgp DNA HPV.
Trong nhdm chi lam PAP don thuan, neu ket qua la ASCUS thi s e t h i r them HPV DNA.
Cach thii nay bi chi trich vi PAP cd do nhay tlia'p, vay se co nhung trudng hgp bi nhiem HPV ma PAP binh thudng, nhu vay phai (hir HPV trudc mdi hgp Iy, vi dg nhay cua HPV
len deh 95%. De diuye't phuc viec hraxc hien y tudng lam xet nghiem HPV DNA trudc, ve phuong d i | n y hpc chiing cii, nghien cihi ATHENA (Addressing the Need for Advanced HPV Diagnostics), mpt thu nghiem lam sang tie'n ciiu, da tnmg tam da dugc thuc hien tai Hoa Ky tir thang 5/2008 den fliang 8/2009. ATHENAi^ dugc hd trg mgt phan bdi Roche Molecular System, hen hanh qua 2 giai doan: cat ngang va theo doi tie'n ciiu trong 3 nam tren 47.208 phy nii tir 21 tuoi trd len, nham 3 muc tieu:
- Xac dinh tinh hieu qua a i a cobas HPV test nhu mgt xet nghiem tam soat khi ket qua PAP la ASCUS.
- Xac dinh tinh hieu qua cua cobas HPV test n h u mpt x ^ nghiem tham gia them khi ket qua PAP la khong ton thuong ac tinh.
- Danh gia tinh hieu qua ciia cobas HPV test nhu mpt xet nghiem tam soat ung thu co tir cung dau tay cho phu nii tir 25 tuoi trd len.
[Cobas HPV test: test PCR phat hien DNA HPV cac t ) ^ nguy co cao: 16, 18 rieng va chung cho 12 t^p khac (31,33,35,39,45,51,52, 56,58,59,66,68)].
Sau 3 nam theo ddi, trong s6 nhiing phu nii cd PAP(-) khi mdi tham gia vao nghien ciiu ATHENA, ti le mdi mac cong ddn (cumulative incidence ratio: CIR) bi ton thuong >CIN3 la 0,74%. Trong so nhiing phu nir cd HPV(-) khi mdi tham gia vao nghien ciiu ATHENA, sau 3 nam, CIR bi td'n thuang >CIN3 chi cd 0,34%.
Ket qua nay cd nghia la nhd sii d\mg xet nghiem HPV co dp nhay cao ma sau 3 nam, ti le phu nii bi bi ton thuang >CIN3 chi bang Vi ti le nay d nhung phu nii theo doi bang PAP.
Phan tich chi tiet hon ti le mdi mac cong don cua nhiing phu nir bi ton thuang co tii cung >CIN3 theo t ^ HPV cho thSy:
- CIR cua ton thuong S CIN3 d phii nii cd HPV 16 va hogc 18 (+): 21,16% (KTC 95%:
18,39-24,01).
San Phv Khoa 221
Tong Quan Y Hoc TP. Ho Chi Minh * Tap 20 * So 1 * 2016
- CIR ctia tdn thuang > CIN3 d phu nii cd HPV cac typ khac (+): 5,4% (KTC 95%: 4,5-6,4).
Rijkaart va cong su, nam 2012 tai Netherland ciing co ket qua: CIR a i a ton thuong >CIN3 d phu nu cd HPV 16 va hoac 18 (+) la 21,6% trong khi ket qua nay cua nhiing phu nu HPV cac typ khac (+) la 6,6%.
Til nhirng bang chimg day thuyet phuc ciia nghien ciru ATHENA va cac nghien ciiu khac, ngay 24 thang 4 nam 2014, FDA duyet cobas HPV test la xet nghiem dau tay dupe sir dung dan dpc trong tam soat ung thu co tir cung cho phu nii tir 25 tuoi trd len. Xet nghiem dau tay cobas HPV test chua dupe ke't hop vao Hudng Dan Dong Thuan tam soat ung thu co ttr cung tuy nhien mpt so' noi da ap dung cobas HPV test la xet nghiem dau tay.
Ngay 8/1/2015, Hpi Soi Cd Tii Cung va Benh Hpc Co Tir Cung (American Society for Colposcopy and Cervical Pathology: ASCCP), va Hpi Ung Thu Phu Khoa (Society of Gynecologic Oncology: SCO) dua ra Hudng Dan Lam Sang Tam Thdi (Interim Clinical Guidance)'^':
- XN dau tay tam soat ung thu co' tir cung HPV nguy co cao (cobas®HPV Test) cho nhiing phu nii bat dau tir 25 tuoi duoc xem nhu thay the'phuong phap hien nay cua Hoa Ky dua tren te'bao.
Nhung phu nii HPV(-) se duoc xet nghiem lai sau it nhat 3 nam.
- HPV(+) vdi typ 16 hoac 18 se duoc Soi Co Tu Cung.
- HPV(+) vdi 12 typ nguy ca cao khac se dugc Iam PAP.
KETLUAN
Nhiing xet nghiem tarn soat ung thu co tir cung dang cd nhieu thay doi nhd su tieh bp
vugt bac cua khoa hoc ky thuat. Viec xet nghiem DNA HPV nhiing typ nguy co cao dugc FDA duyet lam xet nghiem dau tay trong tam soat ung thu co tii cung cho nhirng phu nii tir 25 tuoi trd len la mpt budc chuyen quan trpng nham cung cap cho nhiing nha lam sang mot cong cu dang tm cay hon te'bao hpc trong viec phat hien sdm va theo doi chat che nhiing phu nii cd nguy co bi ung thu co tirJ cung tir trudc khi cd nhiing bieu hien bat thuang tren te bao. Hy vgng nhd each tam soat nay ma benh suat va tir suat cita ung \hn CO tir cung se giam thieu dang ke. Tuy nhien de ket luan chac chan ve Ipi ich ciia xet nghiem dau tay nay, van cdn nhieu nghien' a i u can dugc tie'p tuc thuc hien.
TAILDEUTHAMKHAO
1 American Cancer Society (2011) What are the kef, statistics about cervical cancer? Available ab Htlp/AVww.Cancer-Org/Cancer/CervicalCancer/DelailEd guideAndex. Accesed March 13. 2010Cerlers for Disease Control and Prevention Morbid. Mortal. Weekly Rep.
October 14,2011/ 60(40), 1382-1384 a 2 Department of Health (2011), UK, Annua! HPV V a c d J
Coverage in England in 2010/2011. 1 3 H u h WK. Au!t KA. et al (2015) Use ot p n m a r y high riskj
h u m a n papillomavirus testing for cervical canca screening I n t e n m clinical guidance Gynecol Qncol, 136(2);178-82.
4 H u m p h r i e s C (2012). T e s t n g times. Nahire OUTLOOK H U M A N PAPILLOMAVIRUS, 30 August 2012/Vol488/Issue N o 7413. S8-S9
5 h t t p //www.thinprep com/hcp/thinprep, rfifference<bevon d conventional p a p html
6 Stoler MH, Schiffman M (2001). Interobserver r e p r o d u a b i l i t y of cervical cytologic and histologii:
interpretations, realistic estimates from the ASCUS-LSIL Triage Shidy lAMA 285(11) 1500-5.
7 W n g h t TC, Stoler M H , Behrens CM, et al (2012). Tti ATHENA h u m a n papillomavirus study: design. methwS and baseline results A m J Obstet Gynecol,206:46el-ll. ^
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