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1 e l n i j i O A þ t ý m O i g in h c s Identifiction nd Genotyping of High-Risk HPV in Cevicl Swps with Rel-Time PCR in Women Attending Blikesi Univesity Hospitl Blıkesi Ünivesitesi Hstnesine Bşvun Kdınld Yüksek Riskli HPV Tipleinin Sevikl Swp Önekleinde Rel Time PCR ile Belilenmesi ve Tiplendiilmesi Re l Blıkeside HPV Pevelnsı ve Tiplei / HR-HPV Pevelnce nd Types in Blikesi Mine Islimye Tskin 1, Etn Adli 1, Tevfik Yvuz 2, Coskun Cuce 3, Mehmet Unlu 2 1Deptment of Obstetics nd Gynecology, 2 Deptment of Micobiology, 3 Deptment of Public Helth, Blikesi Univesity Fculty of Medicine, Blikesi, Tukey Özet Onkojenik humn ppillom vius tiplei (HPV) yüksek ond sevikl knse gelişim iski ile bebedi ve bu çlışm Blıkesi ilindeki kdınld yüksek iskli HPV tipleinin (HR-HPV) pevelnsının ştıılmsı için düzenlenmişti. 204 kdın hstnın sevikl öneklei sevikl sitolojik değelendime ve Xpet HPV PCR testi ile HR-HPV tipleinin belilenmesi için toplnmıştı. HR-HPV pevelnsı ve sitolojik sonuçl ile ilişkisi ve epidemiyolojik veile SPSS pogmı ile değelendiilmişti. HR-HPV sıklığı %5.4 bulunmuştu (204 hstnın 13 ü). Anoml sevikl sitolojili kdınld HR-HPV pozitifliğinin noml sitolojili kdınl göe dh yüksek olduğu sptnmıştı (%3.2 vs. %46.7) (p<0.01). İlk cinsel ilişki yşı ve botuslın syısı ile HR-HPV pozitifliği koele iken (p<0.05); yş, seksüel ptne syısı y d kullnıln kontseptif metot HR-HPV pozitifliği ile koele bulunmmıştı. Çlışmmızın sonuçlı göstemişti ki bizim popülsyonumuz için HPV 16 ve 18 dışındki yüksek iskli tiple en yüksek on ship sptnmıştı. HR-HPV, ASCUS, LSIL, HSIL için sısıyl %16.7, %80, %50 pozitif sptnmıştı. Sonuç olk bizim bölgemizde HR-HPV sıklığı %5.4 bulunmuştu. Dh büyük hst guplı ile ypıln clışmll yeni tm metotlının ve ikinci jenesyon HPV şılının geliştiilmesinin mümkün olcğı düşünülmektedi. Anht Kelimele HPV; HR-HPV Tiplei; Sevicl Knse; PCR Abstct As oncogenic types of humn ppillom vius (HPV) e ssocited with highe isk of cevicl cnce, this study ws undetken to investigte highisk humn ppillom vius (HR-HPV) pevlence mong Tukish women in Blikesi. Cevicl smples wee collected fom 204 women fo cytologicl sceening nd HR-HPV testing by Xpet HPV PCR test. HR-HPV pevlence nd its eltion with cytologicl esults nd epidemiologic dt wee nlyzed by SPSS. The pevlence of HR-HPV ws 5.4% (13 of the 204 women). Women with bnoml cytologicl sceening esults hd significntly highe isk of HR-HPV positivity comped with women with noml cytologicl esults (3.2% vs. 46.7%) (p<0.01). Age t fist sexul intecouse nd numbe of botions wee coelted with HR-HPV positivity (p<0.05), but thee ws no ssocition with ge, numbe of sexul ptnes, o contception methods. We found tht othe HPV types pt fom HPV type 16 nd 18 e the most common types in ou popultion. HR-HPV ws positive in 16.7%, 80%, nd 50% of the ASCUS, LSIL, nd HSIL, espectively. The pevlence of cevicl HR-HPV infection is 5.4% in ou popultion. Futhe studies with lge smple sizes e needed fo the development of new sceening sttegies nd second genetion HPV vccines. Keywods HPV; HR-HPV Types; Cevicl Cnce; PCR DOI: /JCAM.3783 Received: Accepted: Published Online: Coesponding Autho: Mine Islimye Tskin, Deptment of Obstetics nd Gynecology, Blikesi Univesity School of Medicine, 10145, Çğış Kmpüsü, Blıkesi, Tukey. T.: /4550 F.: E-Mil: minetskin1302@yhoo.com.t Jounl of Clinicl nd Anlyticl Medicine 1

2 Blıkeside HPV Pevelnsı ve Tiplei / HR-HPV Pevelnce nd Types in Blikesi Intoduction Cevicl cnce is the thid most common cnce mong women woldwide. Appoximtely 75-80% of cevicl cnce cses e seen in developing counties, whee efficient cevicl sceening is insufficient [1]. In Tukey, cevicl cnce is the 8th most common femle cnce, with n ge stnddized incidence te of 4.2 in 100,000 nd ge stnddized motlity te of 1.6 in 100,000 [2]. All cevicl cnces e consideed elted to oncogenic humn ppillomvius (HPV) infection. HPV infection is the most common sexully tnsmitted infection woldwide. HPV types e divided into two goups ccoding to thei neoplstic potentil. Types tht cuse low gde cevicl lesions nd genitl wts, minly HPV 6 nd 11, e clled low isk HPV types, while those tht cuse cevicl cnce e clled high isk HPV (HR-HPV) types [3]. Among the HR-HPV types, HPV genotypes 16 nd 18 e ssocited with ppoximtely 71% of ll cses of cevicl cnce, nd HPV genotype 45 is ssocited with ppoximtely 6% of dditionl cses of cevicl cnce [4]. HPV 16 is solely esponsible fo one hlf of cevicl cnces. Multiple HPV-type infections constitute moe thn qute of infections [5,6]. Thee e moe thn 100 types of HPV, with moe thn 30 nogenitl types nd ppoximtely 15 of these e oncogenic [6]. E6/E7 oncogenes of HR-HPV DNA integte in cevicl cells, led to cell cycle modifictions tht suppot conditions fvoble to HPV vil epliction. Thus, HPV vil genome integtion into the host DNA nd E6/E7 oncopotein expession coelte with the development of cevicl lesions. So to detect the E6/E7 oncopotein expessed ely in cevicl cells hve n impotnt ole [7]. The idel HPV test cn be flexibly integted esily into most envionments nd enble physicins to effectively isk sttify ptients bsed on cytology nd HR-HPV. Futhe, pid compehensive HPV esults tht include integted high isk HPV 16 nd HPV 18 testing sttegies suppot qulity decision mking fo colposcopy efel [8]. The pevlence of HPV infection diffes fom egion to egion. Diffeent HPV pevlences hve been epoted mong Tukish women. Becuse of the close eltionship between HR-HPV nd cevicl cnce, the im of the pesent study ws to investigte the pevlence of HR-HPV with genotyping using the Xpet HPV test (Cepheid, USA) in women in Blikesi who pesented to the gynecology outptient clinic of univesity hospitl, nd to coelte this to Pp sme esults nd isk fctos. Mteil nd Method This etospective study ws ppoved by the locl Ethicl Committee of Blikesi Univesity. With 95% confidence intevl fo detecting vege 10% HPV positivity, 204 women wee included in the study popultion. The study goup included 204 women who wee subjected to cevicl HPV-DNA testing with simultneous cevicl Pp sme t the outptient clinic of Blikesi Univesity Fculty of Medicine between Septembe 2014 nd Apil Dt wee collected fom ptients files nd the compute-bsed dt ecod system. Women with dignosis of invsive o peinvsive cevicl cnce nd women who hd neve hd sexul intecouse wee excluded. Women dmitted fo outine gynecologic exmintions o gynecologic complints wee included. Smples wee obtined duing gynecologic exmintions nd tnsfeed using liquid bsed medium to the micobiology lbotoy dily. Fo the Pp test, the conventionl cevicl sme technique ws used. Specimens wee fixed in lcohol nd the Bethesd system ws used to clssify the esults [9]. HPV identifiction nd typing wee done by the Xpet HPV genotyping test (Cepheid, USA). Xpet HPV includes egents fo the simultneous detection of thiteen high isk HPV (HR-HPV) types (HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, nd 68) nd one possible HR-HPV type (HPV66), humn efeence gene (HMBS = Hydoxymethylbilne synthse), nd n intenl Pobe Check Contol (PCC). The 14 tgeted HPV types e detemined in five fluoescent chnnels: 1. HPV 16, 2. HPV18 nd HPV 45 ( HPV18/45 ), 3. HPV 31, 33, 35, 52, nd 58, 4. HPV 51 nd HPV 59, nd 5. HPV 39, 56, 66, nd 68. The humn efeence gene (fluoescent chnnel 6) veifies specimen dequcy. The PCC veifies egent ehydtion, PCR tube-filling in the ctidge, pobe integity, nd dye stbility. In totl, the ssy utilizes six fluoescent chnnels fo the detection of individul types of HPV, goups of HPV, nd the humn efeence gene. Ech fluoescent chnnel hs its own cutoff pmetes fo tget detection/vlidity. If sufficient signl is detected by the humn efeence gene (i.e. the smple hs sufficient cellulity), the ssy esults e epoted s n ovell positive if ny type of tgeted HPV is detected, but dditionlly, HPV 16, nd HPV 18/45, nd collectively the othe high-isk HPV types detected by the ssy e epoted specificlly s positive o negtive. Test esults fo Xpet wee ctegoized ccoding to pioi cnce isk: HPV16 positive, else HPV16 negtive nd HPV 18/45 positive, else HPV16 nd HPV18/45 negtive nd positive fo othe HR-HPV types, else HR-HPV negtive. Clinicl dt (ge, ge of menche, numbe of deliveies, contceptive method, smoking sttus, ge t fist sexul intecouse, numbe of sexul ptnes, nd histoy of genitl wts nd pelvic inflmmtoy disese) wee ecoded. SPSS vesion 11.5 (SPSS Inc., Chicgo, IL, USA) ws used to mnge the dt nd to pefom the sttisticl nlyses. The chi-sque test ws used to compe the te of HR-HPV infection nd bnoml cytology in diffeent goups of ptients. The esults wee consideed sttisticlly significnt if the p vlue ws < Results The men ge of the ptients ws 40.1± Thei esons fo pesenting to the gynecology clinic e summized in tble 1. Out of the 204 pticipnts, 13 (6.4%) wee HR-HPV positive nd 191 (93.6%) wee negtive. Among the 13 HR-HPV positive women, HPV 16 ws detected in 3 (1.5%); othe HR-HPV types wee detected in 10 women (4.9%) by the Xpet HPV genotyping test. We did not detect HPV 18 in ou study goup (Tble 2). Cevicl cytologicl sceening esults of the entie goup showed 92.6% women with noml cytology, 2.9% women with typicl squmous cells of undetemined significnce (ASCUS), 0.5% women with typicl squmous cell not excluding high gde lesion (ASC-H), 2.5% women with low-gde squmous intepithelil lesions (LSIL), 1% women with high-gde squmous intepithelil lesions (HSIL), nd 0.5% women with squmous cell ccinom (tble 3). Futhemoe, HR-HPV ws positive in 46.7% of women with 2 Jounl of Clinicl nd Anlyticl Medicine

3 Blıkeside HPV Pevelnsı ve Tiplei / HR-HPV Pevelnce nd Types in Blikesi Tble 1. Resons fo ppliction to hospitl Abnoml bleeding 27,9 Pelvic pin 22,5 Contol 11,8 Infetility 16,7 Vginl dischge 6,4 Pevious bnoml PAP sme esult 5,9 Vulvodyni 2,9 Oligo/Amenohe 1,5 Uiny incontinnce 1,5 Condylom 1,5 Hisutism 0,5 Menpousl symptoms 0,5 Tble 2. Distibutions of HR-HPV types in the specimens. HR-HPV Type n In ll women (n=204) HPV type ,5 23,1 HPV type Othe HR-HPV types 10 4,9 76,9 HPV Negtive ,6 Tble 3. Pp sme esults fo pticipnts. cytologic bnomlities nd in 3.2% of women without ny cytologic bnomlity. Women with bnoml cytologicl sceening esults hd significntly highe isk of HR-HPV positivity comped with women with noml cytologicl esults (3.2% vs. 46.7%) (p<0.01). The distibutions in the cytologiclly noml women of most common HPV types wee s follows: HPV 16 (0.55%), HPV 18 (0%), nd othe HR-HPV types (HPV 31, 33, 35, 52, 58, 51, 59, 39, 56, 66, 68) (2.65%). The most common HPV types in the cytologiclly bnoml women wee HPV 16 (13.4%) nd othe HR-HPV types (33.3%) (Tble 4). HR-HPV ws positive in 16.7%, 80%, nd 50% of the ASCUS, LSIL, nd HSIL, espectively. One womn whose sme esult showed ASC-H ws negtive fo HR-HPV nd one womn whose sme esult showed squmous cell ccinom ws positive fo HR- HPV (Tble 5). Age t fist sexul intecouse nd numbe of botions wee found to be coelted with HR-HPV positivity (p<0.05) mong % n % In HR-HPV (+) women (n=13) Benign cytology ,6 ASCUS 6 2,9 LSIL 5 2,5 HSIL 2 1,0 ASC-H 1,5 Squmous cell ccinom 1,5 Tble 4. Distubitions of HPV types with noml nd bnoml cytology. HR-HPV type HR-HPV types in ll positive women (n=13) Noml cytology (n = 189) Abnoml cytology (n = 15) 16 23,1 % 0,55 % 13,4 % 18 0 % 0 % 0 % Othe HR-HPV types 76,9 % 2,65 % 33,3 % Totl 100 % 3,2 % 46,7 % 0,000 p Tble 5. HR-HPV esults in diffeent cytology. PAP test SAYI (n) HR-HPV (+) % HR-HPV (- ) % P vlue Benign cytology 189 3,2 96,8 0,000 ASCUS 6 16,7 83,3 LSIL 5 80,0 20,0 HSIL 2 50,0 50,0 ASC-H 1 0,0 100,0 Squmous cell ccinom 1 100,0 0,0 the pmetes investigted. The men ge t fist sexul intecouse ws 21.31±7.5 fo HR-HPV positive women nd 23.46±4.10 fo HR-HPV negtive women. Compison of the contceptive methods in HR-HPV positive nd negtive women eveled tht the sttisticl nlyses did not detect ny inteeltion between the contceptive method nd HR-HPV positivity in ou study (Tble 6). Abnoml cevicl cytology ws seen in 53.8% of HR-HPV positive cses nd in 4.2% of HR-HPV negtive cses. Tble 6. Reltions between epidemiologicl fetues nd HPV infection. Vibles HR-HPV(+) HR-HPV(-) P vlue Age 39,62±7,87 40,1±10,30 0,629 Smoking 5( %41,7) 47 (%25,1) 0,306 Gvid 2,33±1,56 2,14±1,80 0,570 Pity 1,42±1,00 1,59±1,39 0,728 Volunty Abotions 0,75±1,22 0,18±0,72 0,000 Age t fist sexul intecouse 21,31±7,5 23,46±4,10 0,017 Numbe of sexul ptne 1,23±0,44 1,08±0,32 0,08 Histoy of PID 0 (%0) 42(%22) 0,075 Histoy of condylom 2(%15,4) 9(%4,7) 0,150 Contceptives Homonl 1(%16,7) 7(%7,5) 0,405 Intuteine device 3(%37,5) 22(%20,4) 0,367 Condom 2(%28,6) 38(%30,6) 1,000 Coitus inteuptus 1(%16,7) 27(%23,9) 1,000 Discussion The pevlence of HR-HPV in the genel popultion vies depending on the study cohot nd othe isk fctos. Sevel studies bout genotype distibution in diffeent egions of Tukey nd HPV pevlence hve been epoted. Howeve, ccoding to ou eview of the litetue, thee e no dt bout ou esticted egion, Blikesi in Tukey. Thee e lso limited dt bout HR-HPV pevlence in Tukey, which leds to high isk of cevicl neoplsi. Accoding to ou esults, HR-HPV pevlence ws 5.4% in ou egion. High-isk o oncogenic HPV types cn cuse cetin cnces, including nogenitl nd oophyngel cnces, in both men nd women. Among HPV-elted cnces, cevicl cnce is unique becuse it ws found tht HPV my be detected by PCR in vitully ll cevicl cnce ptients elted to pesistent infection with HPV [10]. Afte detecting the HPV-DNA with PCR, cevicl HPV-DNA detection sceening policies becme impotnt nd studies wee executed fo developing HPV vccines [11], becuse decesing the fequency of cevicl cnce equies peventing, dignosing, nd teting HPV infection. 3 Jounl of Clinicl nd Anlyticl Medicine

4 Blıkeside HPV Pevelnsı ve Tiplei / HR-HPV Pevelnce nd Types in Blikesi Detection of the pevlent HPV genotypes in cetin es of the wold hs become vitlly impotnt due thei diffeent oncogenic potentil. In study published by Snjose et l. [12], ovell HPV pevlence in women with noml cevicl cytology ws epoted to be 10.4% on vege, nging fom 6.2% to 31.6%. In Tukey, studies hve epoted lowe pevlences fo ovell HPV thn the woldwide ovell HPV pevlence stted by Snjose et l. [13-16]. On the othe hnd, thee e lso highe tes fo ovell HPV positivity in Tukey nging between 16.5% nd 25.7% [17-22]. Cohot studies show tht pesistent HR-HPV infections led to high isk fo cevicl neoplsi. Due to this close eltionship, we identified HR-HPV by Xpet HPV genotyping test in ou study. Accoding to ou esults, HR-HPV positivity ws 5.4%. In Tukey, simil lowe tes hve been epoted peviously. Ozcn et l. studied 501 women nd epoted 4.2% positivity fo HR-HPV by testing with hybid cptue 2 [23]. Akcli et l. [16] used PCR nd found tht HR-HPV positivity ws 5%, simil to ou esults. Een et l. [20] studied HPV positivity in Istnbul they found 12% positivity te fo HR-HPV. The HR-HPV pevlence te diffes fom egion to egion: it ws epoted s 7.5% in Euope [24], 31.2% in sttes of the fome Soviet Union [25], nd 13% in Russi [26]. Rtes epoted fom Tukey e lowe thn those of othe egions. HR-HPV positivity is significnt isk fcto fo bnoml cytologicl findings ccoding to ou esults. HR-HPV positivity in women with bnoml Pp smes ws 46.7% in this study. Howeve, pevious epot lso fom Tukey found HR-HPV pevlence to be 62.8% by PCR in 35 ptients with bnoml cytology evluted with liquid-bsed cytologicl sceening [27]. In nothe study fom Tukey, HR-HPV positivity in women with bnoml cytology ws 19% [23]. In study fom Izmi, locted in westen Tukey nd djcent to Blikesi, HPV positivity ws epoted to be 32.1% women with noml cytology efeed fo cevicl cnce sceening. When the smes with pthologicl cytology wee included, HPV positivity incesed to 38.9%. HR-HPV positivity ws 74.3% in women with noml cytology. These tes e highe thn ous. We detected HR-HPV in 3.2% of women with noml cytology. This diffeence cn be ttibuted to the lck of isk fctos fo HPV infection in ou study goup, becuse smoking hbit, numbe of sexul ptnes, nd histoy of sexully tnsmitted diseses wee ssocited with HPV infection [28]. The low incidence of HPV infection hs been thought to be due to the low numbe of sexul ptnes becuse of eligious beliefs, nd socil nd cultul ules [17]. Although pevious epots mention n incese in HPV pevlence with ol contceptive use nd decese with bie method use, we did not obseve n ssocition between HR- HPV positivity nd contceptive method [19,23,29]. Moeove, ge, smoking, histoy of PID nd condylom, nd numbe of sexul ptnes wee lso not ssocited with HR-HPV pevlence. Fctos ffecting HR-HPV positivity wee the numbe of volunty botions nd ge t fist sexul intecouse in ou study (Tble 6). In the litetue, HPV pevlence ws epoted to be coelted with the numbe of biths. Ksp et l. [28] epoted positive coeltion, while Demi et l. [19] epoted negtive coeltion. Howeve, ccoding to ou eview of the litetue, thee e no dt bout botions. We showed tht the isk of HR-HPV incesed with the numbe of botions. This is pobbly becuse of cevicl tum cused by multiple tum due to ecuent pegnncy temintions. Accoding to some studies, HPV type 16 is the most fequent type in cevicl typicl chnges [12, 16, 17, 19, 21]. We found multiple HR-HPV types including HPV 31, 33, 35, 39, 51, 52, 56, 58, 59, 66, nd 68 s the most fequent type, t te of 2.65%, followed by type 16, t te of 0.5%. Howeve, othe pevlence studies fom Kysei epot HPV type 18 s the most fequent type [30]. We did not detect HPV 18 in ou specimens. Een et l. [20] nd Akcli et l. [16] lso detected vey low HPV 18 tes in Tukey. In study fom Mesin, HPV type 66 ws the most common [31]. Distibution of individul HPV genotypes vies coss geogphic es nd ethnic goups. These diffeences in HPV types mong egions ought to be consideed when vccines e developed. Multiple HR-HPV ws the most common type in ou study. Nielssen et l. [32] found tht the isk of hving multiple HR-HPV types incesed with the numbe of sexul ptnes, but we did not detect coeltion. Akcli et l. [16] showed significntly high te of multiple HPV infection in women with single ptnes, like in ou study. The Intentionl Biologicl Study on Cevicl Cnce study goup stted tht 92.9% of tumos on vege contined HPV- DNA, with nge of % [33]. Shifh et l. [34] detected high-isk HPV-DNA in 95% of ptients with bnoml cevicl cytology, in 100% of ptients with cevicl cnce, nd in 92% of cevicl intepithelil lesions. Ksp et l. [28] epoted HPV-DNA in 78.3% of women with cevicl cnce nd 76.9% of women with HGSIL. Abnoml cevicl cytology ws obseved in 30% of HPV-DNA positive cses nd in 5.4% of HPV-DNA negtive cses; 73.9% of thei ptients with cevicl cnce nd 71.2% of those with ASCUS, ASCH, LGSIL, nd HGSIL wee high-isk HPV-DNA positive cses. In ou study, bnoml cevicl cytology ws obseved in 53.8% of HR-HPV positive cses nd in 4.2% of HR-HPV negtive cses. HR-HPV ws positive in 16.7%, 80%, nd 50% of the ASCUS, LSIL, nd HSIL, espectively. One womn with ASC-H ws negtive fo HR-HPV nd one womn whose sme esult showed squmous cell ccinom ws positive fo HR-HPV. HPV detection methods ely on the detection of vil nucleic cids in the infected tissue becuse HPV cnnot be cultued. The most commonly used tests e bsed on diect hybidiztion o DNA-bsed mplifiction techniques. Among DNA tests, Hybid Cptue-II is widely used ssy. The nlyticl sensitivity of Hybid Cptue-II is lowe thn PCR. Coss-ectivity esulting in flse-negtive nd flse-positive esults e its mjo limittions. PCR is cuently the most sensitive detection technique [20,35,36]. Becuse of this, Xpet HPV genotyping test (Cepheid, USA) which is PCR technique ws used fo the detection nd typing HPV in the pesent study. Conclusion Accoding to ou esults, 7.4% of ptients hd bnoml cevicl cytology nd 5.4% of ll ptients hd HR-HPV infection. HPV 16 nd 18 wee lso not detected s the most common types in ou popultion. Futhe studies with lge goups will shed moe light egding the pevlence of the diffeent HPV types 4 Jounl of Clinicl nd Anlyticl Medicine

5 Blıkeside HPV Pevelnsı ve Tiplei / HR-HPV Pevelnce nd Types in Blikesi in ou egion nd guide locl vccintion pogms. Competing inteests The uthos decle tht they hve no competing inteests. Refeences 1. Pkin DM, By F, Fely J, Pisni P. Globl cnce sttistics. CA Cnce J Clin 2005;55: Fely J, Shin HR, By F, Fomn D, Mthes C, Pkin DM. Estimtes of woldwide buden of cnce in 2008: GLOBOCAN Int J Cnce 2010;127: Munoz N, Bosch FX, de Snjosé, Heeo R, Cstellsgué X, Shh KV, et l. Epidemiologic clssifiction of humn ppillomvius types ssocited with cevicl cnce. N Eng J Med 2003;348: de SnJose S, Quint WG, Alemny L, Geets DT, Klustemeie JE, Lloves B, et l. Humn ppillomvius genotype ttibution in invsive cevicl cnce: etospective coss-sectionl woldwide study. Lncet Oncol 2010;11: Schiffmn M, Cstle PE. Humn ppillomvius: epidemiology nd public helth. Ach Pthol Lb Med 2003;127: Bosch FX, Loincz A, Munoz N, Meije CJ, Shh KV. The cusl eltion between HPV nd cevicl cnce. J Clin Pthol 2002;55: Scheue ME, Toloeo-Lun G, Adle-Stothz. Humn ppillomvius infection: biology, epidemiology, nd peventio. Intentionl Jounl of Gynecologicl Cnce 2005;15: Cox JT, Cstle PE, Behens CM, Shm A, Wight TC J, Cuzick J, et l. Compison of cevicl cnce sceening sttegies incopoting diffeent combintions of cytology, HPV testing, nd genotyping fo HPV 16/18: esults fom the ATHENA HPV study. Am J Obstet Gynecol 2013;208:184.e Solomon D, Dvey D, Kumn R, Moity A, O Conno D, Pey M, et l. The 2001 Bethesd System: teminology fo epoting esults of cevicl cytology. JAMA 2002;287: Wlboomes JM, Jcobs MV, Mnos MM, Bosch FX, Kumme JA, Shh KV, et l. Humn ppillomvius is necessy cuse of invsive cevicl cnce woldwide. J Pthol 1999;189: Koutsky LA, Ault KA, Wheele CM, Bown DR, B E, Alvez FB, et l. A contolled til of humn ppillomvius type 16 vccine. N Engl J Med 2002;347: de Snjose S, Diz M, Cstellsgue X, Cliffod G, Buni L, Munoz N, et l. Woldwide pevlence nd genotype distibution of cevicl humn ppillomvius DNA in women with noml cytology: met-nlysis. Lncet Infect Dis 2007;7: Inl MM, Köse S, Yildiim Y, Ozdemi Y, Töz E, Etopçu K, et l. The eltionship between humn ppillomvius infection nd cevicl intepithelil neoplsi in Tukish women. Int J Gynecol Cnce 2007;17: Tunce ZS, Bsn M, Ustcelebi S, Mocn-Kuzey G. High-isk humn ppillom vius (HPV) infection detemined by Hybid Cptue II ssy in Tukish univesity hospitl outptient clinic. Gynecol Obstet Repod Med 2006;12: Ozcelik B, Sein IS, Gokhmetoglu S, Bsbug M, Eez R. Humn ppillomvius fequency of women t low isk of developing cevicl cnce: peliminy study fom Tukish univesity hospitl. Eu J Gynecol Oncol 2003;24: Akcli S, Goke A, Ecemis T, Kndiloglu AR, Snlidg T. Humn ppillom vius fequency nd genotype distibution in Tukish popultion. Asin Pc J Cnce Pev 2013;14(1): Dusun P, Senge SS, Asln H, Kuşçu E, Ayhn A. Humn ppillomvius (HPV) pevlence nd types mong Tukish women t gynecology outptient unit. BMC Infect Dis 2009;30;9: Dusun P, Ayhn A, Mutlu L, Çğl M, Hbel A, Güngö T, et l. HPV types in Tukey: multicente hospitl bsed evlution of 6388 ptients in Tukish gynecologic oncology goup centes. Tuk Ptoloji Deg 2013;29(3): Demi ET, Ceyhn M, Simsek M, Gunduz T, Alie S, Aytc R, et l. The pevlence of diffeent HPV types in Tukish women with noml Pp sme. J Med Viol 2012;84(8): Een F, Eenus M, Bs E, Ahiskli R, Yoldemi T. Pevlence of HPV infection by cytologic dignosis nd HPV DNA extction nd pevlence of the HPV genotypes detected in ubn Tukish women. Int J Gynecol Obstet 2010;109(3): Yuce K, Pin A, Slmn MC, Alp A, Syl B, Dogn S, et l. Detection nd genotyping of cevicl HPV with simultneous cevicl cytology in Tukish women: hospitl-bsed study. Ach Gynecol Obstet 2012;286(1): Tunce ZS, Boyz G, Shin N, Alp A. Distibution of humn ppillomvius types in Tukish women. Eu J Gynecol Oncol 2012;33(2): Ozcn ES, Tşkin S, Otç F. High-isk humn ppillom vius pevlence nd its eltion with bnoml cevicl cytology mong Tukish women. J Obstet Gynecol 2011;31(7): Leinonen M, Kotniemi-Tlonen L, Anttil A, Dyb T, Tkknen J, Nieminen P. Pevlence of oncogenic humn ppillomvius infection in n ognised sceening popultion in Finlnd. Intentionl Jounl of Cnce 2008;123: Kulml SMA, Shblov IP, Petovitchev N, Syjnen KJ, Gyllensten UB, Syjnen SM nd the NIS Study Goup. Pevlence of the most common high-isk HPV genotypes mong women in thee new independent sttes of the fome Soviet Union. Jounl of Medicl Viology 2007;79: Shipitsyn E, Zolotovekhy E, Kuevd D, Nsonov V, Romnyuk T, Khchtuyn A, et l. Pevlence of high-isk humn ppillomvius types nd cevicl squmous intepithelil lesions in women ove 30 yes of ge in St. Petesbug, Russi. Cnce Epidemiology 2011;35: Egüny K, Misilioglu M, Pin F, Tunce ZS, Tunce S, Ust çelebi S. Humn ppillom vius DNA in cevicl smples with cytologicl bnomlities nd typing of the vius. Mikobiyoloji Bülteni 2007;41: Ksp B, Yetiml H, Keklik A, Yildiz A, Cukuov K, Soylu F. Pevlence nd isk fctos fo humn ppillomvius DNA in cevicl cytology. Eu J Obstet Gynecol Repod Biol 2011;159(1): Klsson R, Jonsson M, Edlund K, Evnde M, Gustvsson A, Bode n E, et l. Lifetime numbe of ptnes s the only independent isk fcto fo humn ppillomvius infection: A popultion-bsed study. Sex Tnsm Dis 1995;22: Eoglu C, Kesli R, Eyilmz MA, Unlu Y, Gonenc O, Celik C. Seviks knsei için iski oln kdınld HPV tiplendimesi HPV sıklığının isk fktölei ve sevikl smel ilişkisi. Nobel Med 2011;7: Tezcn S, Ozgu D, Ulge M, Asln G, Guses I, Sein MS, et l. Humn ppillomvius genotype distibution nd E6/E7 oncogene expession in Tukish women with cevicl cytologicl findings. Asin Pc J Cnce Pev 2014;15(9): Nielsen A, Kje S, Munk C, Iftne T. Type-specific HPV infection nd multiple HPV types: pevlence nd isk fcto pofile in nely younge nd olde Dnish women. Sex Tnsm Dis 2008;35(3): Bosch FX, Mnos MM, Munoz N, Shemn M, Jnsen AM, Peto J, et l. Pevlence of humn ppillomvius in cevicl cnce: woldwide pespective Intentionl biologicl study on cevicl cnce (IBSCC) Study Goup. J Ntl Cnce Inst 1995;87: Shifh NA, Seeni A, Nuismh MI, Clence-Ko CH, Htt AZ, Ho NP, et l. Pevlence of humn ppillomvius in bnoml cevicl smes in Mlysin ptients. Asin Pc J Cnce Pev 2009;10(2): Lie AK, Kistensen G. Humn ppillomvius E6/E7 mrna testing s pedictive mke fo cevicl ccinom. Expet Rev Mol Dign 2008;8: Cstle PE, Schiffmn M, Buk RD, Wcholde S, Hildesheim A, Heeo R, et l. Resticted coss-ectivity of hybid cptue 2 with nononcogenic humn ppillomvius types. Cnce Epidemiol Biomkes Pev 2002;11: How to cite this ticle: Tskin M.İ, Adli E, Yvuz T, Cuce C, Unlu M. Identifiction nd Genotyping of High- Risk HPV in Cevicl Swps with Rel-Time PCR in Women Attending Blikesi Univesity Hospitl. J Clin Anl Med 2015; DOI: /JCAM Jounl of Clinicl nd Anlyticl Medicine