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1 대한요로생식기감염학회지 : 제 5 권제 2 호 2010년 10월 Korean J UTII Vol. 5, No. 2, October 2010 종설 회음부및요도사마귀 인제대학교의과대학비뇨기과학교실 이건철 조인래 [Abstract] Genital and Urethral Warts Keon Cheol Lee, In Rae Cho From the Department of Urology, Inje University, Ilsan Paik Hospital, Goyang, Korea External genital warts are one of the most common sexually transmitted infections (STI) which appear as typical skin growing lesions in the perigenital and perianal regions. The causative organisms are low-risk human paillomavirus (HPV), mostly types 6, 11. Physical examination assisted with bright light and magnification is usually enough for diagnosis, but biopsy is needed in cases that are refractory to treatment or exhibit atypical lesion appearance. Genital warts are benign and resolves spontaneously in some patients and removal of lesions do not guarantee elimination of all organisms or confer protection from recurrence. Treatment is consisted of diverse drug application locally and surgical therapy. Urethral warts are uncommon presentation of HPV and could be treated by endoscopic surgery accompanied by intraurethral instillation of medications. Vaccination for HPV is promising up to 4 years and can be an important strategy against HPV, but have to be proven with additional long-term results. (Korean J UTII 2010;5: ) Key Words: Warts, Human papillomavirus 서 론 성기사마귀 (genital warts) 는인간유두종바이러스 (human papilloma virus; HPV) 의감염에의한흔한 교신저자 : 조인래, 인제대학교의과대학비뇨기과학교실경기고양시일산서구대화동 2240 번지우 Tel: , Fax: ircho@paik.ac.kr Received: September 7, 2010 Accepted: September 29, 2010 성매개질환 (sexually transmitted infection; STI) 으로성기와항문주위에발생하는표피의양성증식으로첨규콘딜롬 (condyloma accuminatum) 이라고도불린다. 젊은연령에서호발하나모든연령군에서발생할수있다. 양성질환으로자연소실되는경향을보이기도하나, 1-4 이질환으로인한이환율은상당하며주요한건강문제로사회경제적부담을크게야기하는질병이다. 5 성인인구의 70% 는일생동안적어도한번이상의 HPV 감염을겪는다고한다 세의성적으로활동적인여성의 50 60% 가 HPV 감염에노출되지만실제 10 15% 에서만성기 사마귀에이환된다. HPV의아형은각각다른질환 151

2 152 대한요로생식기감염학회지 : 제 5 권제 2 호 2010 년 10 월 을야기하는데성기사마귀는저위험도 HPV DNA에의해야기되며주로 6형과 11형이대부분을차지한다. 고위험도 HPV DNA로분류되는 HPV 16형과 18형은상피내암과항문, 생식기부위의암을야기한다 Winer 등 12 의연구에의하면 HPV 6/11형을무증상으로갖고있는여성을 1년동안추적관찰하면 57% 에서성기사마귀가발현된다고하며 HPV 16/18형을무증상으로갖고있는여성을 1년간관찰해도성기사마귀가발생하지않아 16/18형은성기사마귀로진행되지않는다고볼수있다. Insinga 등 13 은 HPV 6/11형의평균잠복기는 0.7년이라고추정하였지만보고자에따라변화폭이크다. HPV의자연경과에대하여보다많은사실들이밝혀지고있다. 치료없이도일부환자에서병변이자연소실되기도하고병변제거후에도바이러스가여전히남아있으며결핵균의경우와비슷하게동면 (dormant) 상태로잠복하여있다가면역저하시급격하게활성화되는가능성도제시되고있다 본글에서는성기사마귀의진단, 치료및예방적측면을살펴보고최근관심이증폭되고있는예방백신에대한내용을정리하였다. 본론 I. 진단치료시작전정확한진단은필수이다. 성기사마귀는특징적인피부병변을보이는데꽃양배추 (cauliflower) 양상이잘알려져있지만편평하거나 dome-shape, keratotic 또는 pedunculated 양상도있을수있다. 단독으로나타날수도있으나대개는다발성으로나타나며군 (cluster) 을형성할수도있고판 (plaque) 모양을띌수도있다 형태학적특징을이해하는것은성기사마귀와비슷한양상을보이는다른질환들과의감별진단에필수적이다. 성기사마귀는성기, 항문주변이외에다른부위에도드물지만나타날수있고성적행위에의한다. 자궁에발생한성기사마귀의경우다른부위와달리 Papanicolaou (Pap) test를치료전반드시시행하여야한다. 성기사마귀는밝은조명과확대경을이용하여직접시진 (inspection) 으 로진단할수있으며 26 남성요도구와주상와부위는이경 (otoscope) 이나작은 spreader 등을활용하여관찰할수있다. 27 전형적인양상을보이는성기사마귀에대하여조직검사를시행할필요는없다. 조직검사는감별진단을위하여시행되는데다음과같은경우에행해진다. 표준치료에반응하지않거나오히려악화되는경우, 환자가면역저하되어있는경우, 병변에색소침착이있거나주변조직에유착되어단단히고정된경우, 출혈, 경결, 궤양성변화를보일때등이다. 26,28 이외에도 Bowen씨병이나 bowenoid papulosis, giant condyloma의경우시행된다. 보다전문적진단법인 acetowhite test나 virus-typing assay 등은일차적으로시행되지는않으며선별된환자에서적용될수있다. 29 이외에핵산에대한분자생물학적진단법도통상적으로는적용되지않는다. 성기사마귀는양성질환이지만장기간방치하여공격적으로성장하여거대한크기로자랄수있으며이를 giant condyloma (Buschke-Lowenstein tumor) 라고부른다. 이경우심한위생문제뿐아니라양성콘딜롬이비정형상피세포혹은편평세포암병소와섞여서나타날수도있는등악성병변의혼재를염두에두어야한다. 따라서광범위한외과적절제술을시행하게되는데술후피부이식이필요한경우가많다. 30,31 다른감별해야할질환으로는매독병변인 condyloma latum, 흔한국소색소침착피부병변인지루성각화증 (seborrheic keratosis), poxvirus 에의해야기되고면역저하환자에서흔히나타나는전염성연속종 (molluscum contagiosum), 진피내모반 (intradermal nevus), 남성성기의 corona에정상적으로나타나며치료가필요없는 angiofibroma인 pearly penile papule이있다. Bowen씨병은표피에국한된편평세포암으로드물게침습적으로되는질환으로성기사마귀와감별해야하며 32 HPV 저위험아형및고위험아형과의연관성이보고되기도하였다. 33,34 Bowenoid papulosis 또한종종성기사마귀양상으로나타나기도하나조직검사에서국한된편평세포암으로확인되며여성에서는 vulvar intraepithelial neoplasia (VIN) 으로나타나기도한다 Bowenoid papulosis에서도저위험및고위험아형의 HPV가검출되었다. 38

3 이건철외 : 회음부및요도사마귀 153 II. 치료다른성매개전염성질환과달리성기사마귀에대하여는잘갖춰진치료알고리즘을갖고있지못하다. 임상양상과맞물려단순하고이해하기쉬운치료지침을확립하지못하고다양한치료법들이사용되고있고어느한치료방법이다른치료법들보다뚜렷하게우수하다고말할수없다. 명쾌하고도이상적인단일치료지침을갖고있지못한주된이유는성기사마귀의치료에대하여불확실한부분들이많기때문이다. 주로바이러스를완전히제거할수없다는것과설령완전히제거할수있다하더라도바이러스제거가재발방지를보장할수없다는이유때문이다. 40 이러한치료의불확실성으로인해예방백신에거는기대는클수밖에없다. 성기사마귀의치료는가시적인모든병변을제거하는데있다. 현재사용되는구체적인치료법을살펴보면환자가직접몸에바르게되는자가치료법으로는 imiquimod 5% 크림이나 podophyllotoxin 0.5% 용액또는겔이있다. 치료접근성은좋지만치료의순응도와환자가신체적조건상시술가능한지가선행조건이다. 치료자에의해행해지는외래치료법에는 bi- 혹은 tri-chloroacetic acid (BCA or TCA) 80 90%, podophyllin 10 25% 등의약물요법이있다. 수술적요법으로는액화질소등의매질을이용하여냉동프로브를사용하여병변을냉동시키는냉동치료법과그외전기소작술, 레이저를사용한절제술, 외과적절제술등을사용할수있다 성기사마귀가면역저하된경우호발하므로면역촉진제를투여하여재발율을낮추었다는보고도있다 환자자가국소치료 1) Podophyllotoxin/podofilox (Condylox) Podofilox는조직괴사를유도하여사마귀를치료하는분열저지성 (antimitotic) 약제로분류된다. 적정농도와투여간격등을찾기위한다양한시도들이 있었지만 % 농도로 3 일연속, 일일 2 회투여 를 2 4 회반복하는 regimen 이흔히사용된다. 52,53 원형물질인 podophyllin과달리 podofilox젤과용액은최기성 (mutagenic) 물질인 quercetin과 kaempherol이없다. 54 Podofilox의치료효과에대하여는보고가오래전부터있어왔는데대략 4 6주치료에 45 77% 의치료율을나타내고있다. 53,55-57 부작용으로는국소염증과자극으로피부미란, 작열감, 통증, 소양증등이있을수있다. 재발은 4 38% 로다양하게보고되며 53,58 임신중안전성은확립되지않았다. 2) Imiquimod/imidazoquinolinamine (Aldara) Imiquimod는면역조정제로그자체로항바이러스작용을나타내지는않으나대식세포로하여금 cytokine (IL-2나 IFN-alpha) 을분비하도록유도하는약제로 in vivo 실험에서세포분해작용과임파구증식을촉진시킨다 Imiquimod는비교적최근의치료법이지만많은분석이이루어졌다. 5% cream 형태가가장효과적으로알려져있으며성기사마귀의치료로미식약청허가를받았으며, 16주이내에 37 54% 의치료율을나타낸다. 63,64 투여방법은주 3회취침시자가도포하고아침에비누와물로씻어내며 16주까지반복한다. 부작용으로는홍반이발생할수있고이외일반적피부부작용은타약제와대동소이하다. 재발률은 13 19% 정도이며임신시안전성은확립되지않았으므로치료중피임이권유된다. 2. 치료자에의한국소치료 1) Podophyllin resin Podophyllin은 podofilox와같이국소조직괴사를유도하여성기사마귀를치료하는분열저지성약제로서가장오래된성기사마귀치료제중하나이다. 전신흡수를막기위해 benzoin을첨가하여 10 25% 현탁액으로사용하며 10mm 2 이상의넓은면적에는사용하지않는다. Podophyllin의효과는 podofilox, 냉동치료, 전기소작, 병변내 interferon 주입등과많이비교되었는데효과에서는동등하다고보고되었으나부작용면에서골수억제, 간기능장애, 신경학적이상, 정신과적부작용, 오심, 구토, 설사, 급성복통등의매우다양한부작용들을나타냈다 이러한부작용은치료면적이넓거나전신흡수가잘될만한부

4 154 대한요로생식기감염학회지 : 제 5 권제 2 호 2010 년 10 월 위의병변치료에주로나타났다. 가용한타약제의개발과맞물려이러한높고다양한부작용때문에 podophyllin은치료제로선택되지않는추세이다. 치료후재발률은 23 65% 정도이며최기 (mutagenic) 물질인 quercetin과 kaempherol을함유하고있어임신중안전하지않으므로치료중피임이필수적이다. 2) BCA/TCA Trichloroacetic acid는 chemical peeling으로활용되기도하는약제로피부와점막을부식시켜서성기사마귀를치료하는약제이다. 피부를통해흡수되지않는장점이있으며 85 95% 농도를사용한다. 효과는 63 70% 로보고되나냉동치료와의비교에서우위에있음이입증되지않았다. 치료시인접정상피부로흘러들어손상을줄수있으며국소통증, 피부궤양등이부작용으로보고되었고임신중레이저와병용치료로시도되었으나치료환자중일부에서요로를설치해야했거나양막파열및조기출산등의부작용이나타났다 수술적치료성기사마귀를직접적으로절제하거나파괴하는방법으로적절히치료되면파괴및창상의범위는진피상부에까지만국한된다. 1) 외과적절제 (Surgical excision) 메스나 curettage, 가위등을이용하여사마귀를제거하는치료로시술 1년후 19 29% 에서재발되었고, 76,77 podophyllin 보다는우수하지만레이저치료와는동등한효과를나타낸다. 76,77 2) 전기소작 (Electrosurgery) 시술 3 6주후 61 94% 의치료성공률을보였고근육내 interferon 주사보다는 3배, 피하 interferon 주사보다는 6배보다효과적이었다. 79,80 Podophyllin과냉동치료를전기소작과비교했을때치료직후에는전기소작이우수하였으나 3개월시점에서는비슷한효과를나타냈다. 80 재발율은 14 22% 정도로보고된다. 81 3) 냉동치료 (Cryotherapy) 액화질소를사용하여병변부위를동결-해동을반복시키는 cryotherapy는치료후병변부위가탈락하고이후염증반응후재생되는과정을거친다. 치료 3개월후 40%, 6개월후 27% 정도의치료율을보이며재발률은 6개월시점에 38 73% 로다양하게보고된다. 82,83 4) 레이저치료 (Laser therapy) 다른치료에비해별도의장비를갖추어야하는레이저치료는단독효과로보고된경우보다레이저치료후다른부가적치료를병용한보고가많다. 시술후 3 18개월관찰시 23 52% 의치료율과 60 77% 의재발률이보고된다. 84,85 III. 예방흡연은성기사마귀의발생을높이는것으로알려졌는데북유럽의대단위역학연구에서흡연은성기사마귀의발생을증가시키고용량증가적으로흡연량에따라위험도가증가한다고보고한바있다. 86 이는흡연의면역저하효과에의한다고추정된다. 평생동안의성배우자의수가많을수록성기사마귀의이환율이높다고확인된바있으며 5년이상의장기간의경구피임제복용, 다빈도임신, 다른 STI의존재, 불충분한상태나면역억제상태등도성기사마귀의높은이환율과연관된위험인자로알려져있다. 이외에도어린나이의성관계경험과유전적감수성도위험인자로알려져있으며이러한위험인자를조절하는것이예방의한방법이될수있다. 87 콘돔의사용에관하여는콘돔이 HPV의전염을막는다고명확히말할수는없으나다른공동위험인자들을막는효과도부가되므로 HPV 예방에일정부분도움이된다고할수있다. 특히, 새로운성파트너와의관계가있을경우콘돔이추천된다. 88 임산부가성기사마귀를가지고있을경우아이에게 HPV 가수직감염되는것을막기위해제왕절개술을하는것은추천되지않는다. 제왕절개술이 HPV의수직감염을막는데효과적이라고입증된바없으며

5 이건철외 : 회음부및요도사마귀 155 산도를병변이막는상황이아니라면제왕절개술이시행될필요는없다. HPV 예방백신 : 감염성질환에대한가장효과적인치료법이라할수있는예방백신은 HPV에대하여비교적최근에시도되기시작하였는데 HPV 6, 11, 16, 18형에대한 4가예방백신 (HPV4) 이 Gardasil TM 이라는이름으로 Merck (MSD) 사에의해상품화되었고 2009년 10월남성의성기사마귀에대하여미식약청의허가를받았다. 대상남성은 9세에서 26세로 HPV 6, 11형에의한성기사마귀의발생을감소시키는목적으로허가받았으나모든남성에서일괄적으로사용하는것은권고하지않았으므로선별된남성에서접종되어져야한다. 89 여성에서의사용허가는이보다더일찍받았으며국내에서도 2007년 9 26 세의여성에서질, 외성기, 자궁경부의전암병변, 암, 성기사마귀등의예방에 HPV4의국내식약청의허가가있었다. 87 여성에서는 11 12세에모든여성을대상으로접종하며이후 13 26세에 catch-up 접종을하게된다. 성기사마귀의아형과는상관없지만 HPV 16/18형만을표적으로하는 Cervarix TM 는 2가예방백신으로 GlaxoSmithKline (GSK) 사에서생산하고있다. 90 무작위대조군연구인대규모 3상연구에서두예방백신모두내약성과효과에서우수한결과를보여주었다. 91 그러나추적관찰기간이 4년밖에되지않아장기간예방효과가지속될지가관심사이며이는결국면역체계가장기기억을하느냐는문제로귀결된다. HPV 예방백신의효과는 % 로예방접종시점에해당아형에대한감염이없다면 HPV 에의한질환들을예방할수있다고보여현재까지는매우고무적이나진행중인장기간연구들의결과또한기다려봐야할것이다. IV. 요도내성기사마귀 (Urethral warts) 성기사마귀는주로외성기나항문주위에호발하나드물게요도를침범하기도한다. 95 피부에나타나는병변과마찬가지로대개조직검사없이진단이가능하며치료에반응이없거나요도암의감별진단이필요한경우에한해병리조직검사를시행한다. 92 요도내성기사마귀의경우대개외요도구나요도주 상와 (fossa navicularis) 에호발하나근위부의요도나방광에서도동반되어나타날수있다. 93 요도내성기사마귀의증상은혈뇨, 요도출혈, 빈뇨, 절박뇨및요도분비물등이있으며특별한자각증상없이외요도구의종물이발견되거나외성기의성기사마귀에대한진단과정에서요도내시경에의해확인되는경우도있다. 94 요도내성기사마귀의진단및치료를위해요도내시경은필수적인검사이다. Kaplinsky 등 95 은외성기나외요도구에성기사마귀가발견되는경우모든환자에서요도내다른병소를확인하기위해요도내시경을시행할것을주장하였다. 그러나 Dretler와 Klein 96 은요도내시경을시행함으로써원위부의병변을근위부의요도로전파시킬가능성이있기때문에모든원위부의병변이완전히제거된후에시행할것을주장하기도하였다. 요도내성기사마귀의치료는국소요법과수술적요법으로구분할수있다. 먼저국소요법을살펴보면 Dretler와 Klein 96 은 20명중 19명에서 5% 5-FU 연고를요도내주입하여치료에성공하였다고보고하였다. Wein 등 97 도 4주동안 11명의환자에게사용한결과 10명에서완전관해를보였다고하였으며잠재적병소까지파괴하는 5-FU의효과로인해요도내시경에의한병변의전파가없다고추정하였다. 그러나이러한약물의요도내주입과더불어외과적절제나전기소작등의처치가추가로필요한경우가있었고피부나요도자극으로인한부작용또한있었다. 국내보고로는 Kim 등 98 이 5% 5-FU용액을 holmium YAG 레이저와병용한치료를 7명의환자에서보고하였는데치료도중추적에실패했던 1 명외에재발이나합병증이없었고국소마취하에시행가능함으로요도내성기사마귀의효과적인치료선택이라고보고하였다. 요도내성기사마귀의치료로과거에는외과적절제, 전기소작또는냉동치료등이많이시행되어왔으나재발률이높고요도점막의손상으로인해추적관찰시요도협착이문제가되었다. 이에요도손상의가능성이적은레이저를치료에이용하게되었고 CO 2 레이저나 Nd-YAG 레이저를이용하여치료한결과들이보고되어왔다. 13명의환자에서 Nd-YAG 레이저를이용한 Kim 등 99 의보고에서는 12명에서재발되지않았다고하였

6 156 대한요로생식기감염학회지 : 제 5 권제 2 호 2010 년 10 월 다. 수술적치료는눈에보이는병변만을제거할수있는데가시적인병변만을치료하는것의단점에대하여 Schneede 등 100 은직접적인비교를하여반박하였는데요도내성기사마귀환자 43명에서근위부요도내에도병변이있는지를알기위해일반요도경검사와 photodynamic 요법을활용한형광요도경을비교하였다. 그에따르면일반요도경검사상단지 8명에서만성기사마귀가발견되었으나 0.1% 5-ALA를주입하고 1시간후시행한 photodynamic 요도경검사에서 13명의환자에서추가로병변을관찰할수있었고모두병리조직검사나분자생물학진단으로확진되었다고하였다. 따라서요도내성기사마귀의수술적치료법으로레이저의활용은고무적이며요도내약물주입등의부가적치료는재발성경향을보이는환자에서선별적으로행하는것이효과적인치료전략이라할수있을것이다. 결론성기사마귀 ( 첨규콘딜롬 ) 는인간유두종바이러스 (HPV) 중저위험아형군 ( 대부분 6, 11형 ) 에의해발생하는성매개전염병으로외성기와항문주위의특징적외형을나타내는피부병변을보인다. 밝은빛과확대경을이용한시진으로진단할수있으며치료저항성이나비전형적병변등선별된증례에서조직검사가필요한경우가있다. 치료법은약물의병변내국소도포와수술적요법등다양하나타치료에비해뚜렷하게우수한단일치료법은없다. 성기사마귀가양성질환으로자연소실을보이기도하고치료에의해바이러스가박멸되지않는다는회의, 그리고완벽한치료라할지라도재발을보장할수없다는점은 HPV와성기사마귀의자연경과에대한많은연구와고찰을요구하고있다. 치료에대한이러한난해성으로인해예방백신에거는기대는더크다. 생식기암을유발하는고위험아형군 (16, 18형 ) 에대해서뿐아니라성기사마귀에대한백신효과도현재까지는매우고무적이고보다장기적인결과들이보고되고있다. 따라서광범위하게접종이이루어진다면성기사마귀의유병률을현저히낮출것으로기대해본다. REFEENCES 1. Moscicki AB, Shiboski S, Broering J, Powell K, Clayton L, Jay N, et al. The natural history of human papillomavirus infection as measured by repeated DNA testing in adolescent and young women. J Pediatr 1998;132: Ho GY, Bierman R, Beardsley L, Chang CJ, Burk RD. Natural history of cervicovaginal papillomavirus infection in young women. N Engl J Med 1998;338: Franco EL, Villa LL, Sobrinho JP, Prado JM, Rousseau MC, Désy M, et al. Epidemiology of acquisition and clearance of cervical human papillomavirus infection in women from a high-risk area for cervical cancer. J Infect Dis 1999;180: Evander M, Edlund K, Gustafsson A, Jonsson M, Karlsson R, Rylander E, et al. Human papillomavirus infection is transient in young women: a population-based cohort study. J Infect Dis 1995;171: Lacey CJ, Lowndes CM, Shah KV. Chapter 4: burden and management of non-cancerous HPV-related conditions: HPV-6/11 disease. Vaccine 2006;24:S3/ Koutsky LA, Galloway DA, Holmes KK. Epidemiology of genital human papillomavirus infection. Epidemiol Rev 1988;10: Broomall EM, Reynolds SM, Jacobson RM. Epidemiology, clinical manifestations, and recent advances in vaccination against human papillomavirus. Postgrad Med 2010;122: Gross G, Ikenberg H, Gissmann L, Hagedorn M. Papillomavirus infection of the anogenital region: correlation between histology, clinical picture, and virus type. Proposal of a new nomenclature. J Invest Dermatol 1985;85: Ault KA. Epidemiology and natural history of human papillomavirus infections in the female genital tract. Infect Dis Obstet Gynecol 2006;2006 (suppl 40470): Lacey CJ. Therapy for genital human papillomavirus-related disease. J Clin Virol 2005;32:S82-S Lacey CJ, Lowndes CM, Shah KV. Chapter 4: burden and management of non-cancerous HPV-related conditions: HPV-6/11 disease. Vaccine 2006;24:S3/35-41

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