{"id":5111,"date":"2023-03-17T08:43:05","date_gmt":"2023-03-17T08:43:05","guid":{"rendered":"https:\/\/www.eurocytology.eu\/course\/4-pathogenese-des-zervixkarzinoms\/"},"modified":"2023-04-26T07:39:11","modified_gmt":"2023-04-26T07:39:11","slug":"4-pathogenese-des-zervixkarzinoms","status":"publish","type":"course","link":"https:\/\/www.eurocytology.eu\/de\/course\/zervixzytologie-auf-dem-laufenden-2016\/4-pathogenese-des-zervixkarzinoms\/","title":{"rendered":"4. Pathogenese des Zervixkarzinoms"},"content":{"rendered":"<div data-object_id=\"5111\" class=\"cbxwpbkmarkwrap cbxwpbkmarkwrap_guest cbxwpbkmarkwrap_user_cat cbxwpbkmarkwrap-course \"><a  data-redirect-url=\"https:\/\/www.eurocytology.eu\/de\/wp-json\/wp\/v2\/course\/5111\/\"  data-display-label=\"1\" data-show-count=\"1\" data-bookmark-label=\"Bookmark\"  data-bookmarked-label=\"Bookmarked\"  data-loggedin=\"0\" data-type=\"course\" data-object_id=\"5111\" class=\"cbxwpbkmarktrig  cbxwpbkmarktrig-button-addto\" title=\"Bookmark This\" href=\"#\"><span class=\"cbxwpbkmarktrig-label\" >Bookmark (<i class=\"cbxwpbkmarktrig-count\">0<\/i>)<\/span><\/a> <div  data-type=\"course\" data-object_id=\"5111\" class=\"cbxwpbkmarkguestwrap\" id=\"cbxwpbkmarkguestwrap-5111\"><div class=\"cbxwpbkmarkguest-message\"><a href=\"#\" class=\"cbxwpbkmarkguesttrig_close\"><\/a><h3 class=\"cbxwpbookmark-title cbxwpbookmark-title-login\">Please login to bookmark<\/h3><form name=\"loginform\" id=\"loginform\" action=\"https:\/\/www.eurocytology.eu\/wp-login.php\" method=\"post\"><p class=\"login-username\">\n\t\t\t\t<label for=\"user_login\">Benutzername oder E-Mail-Adresse<\/label>\n\t\t\t\t<input type=\"text\" name=\"log\" id=\"user_login\" autocomplete=\"username\" class=\"input\" value=\"\" size=\"20\" \/>\n\t\t\t<\/p><p class=\"login-password\">\n\t\t\t\t<label for=\"user_pass\">Passwort<\/label>\n\t\t\t\t<input type=\"password\" name=\"pwd\" id=\"user_pass\" autocomplete=\"current-password\" spellcheck=\"false\" class=\"input\" value=\"\" size=\"20\" \/>\n\t\t\t<\/p><p class=\"login-remember\"><label><input name=\"rememberme\" type=\"checkbox\" id=\"rememberme\" value=\"forever\" \/> Angemeldet bleiben<\/label><\/p><p class=\"login-submit\">\n\t\t\t\t<input type=\"submit\" name=\"wp-submit\" id=\"wp-submit\" class=\"button button-primary\" value=\"Anmelden\" \/>\n\t\t\t\t<input type=\"hidden\" name=\"redirect_to\" value=\"https:\/\/www.eurocytology.eu\/de\/wp-json\/wp\/v2\/course\/5111\/\" \/>\n\t\t\t<\/p><\/form><p class=\"cbxwpbookmark-guest-register\">No account yet? <a href=\"https:\/\/www.eurocytology.eu\/de\/register\/?redirect_to=https%3A%2F%2Fwww.eurocytology.eu%2Fde%2Fwp-json%2Fwp%2Fv2%2Fcourse%2F5111%2F\">Register<\/a><\/p><\/div><\/div><\/div><h4>CIN und Plattenepithelkarzinom<\/h4>\n<p>Es gilt als anerkannt, dass dem invasiven Plattenepithelkarzinom, welches den h\u00e4ufigsten histologischen Typ des Zervixkarzinoms darstellt, ein pr\u00e4invasives Krankheitsstadium vorangeht, in welchem sich die abnormen Zellen \u00fcber das Epithel ausbreiten. Dabei wird das normale Plattenepithel der Zervix durch abnormes Epithel neoplastischer Zellen ersetzt. Dieses nicht-invasive Krankheitsstadium wird als zervikale intraepitheliale Neoplasie bezeichnet (CIN) und steht unmittelbar in Zusammenhang mit einer vorangegangenen Infektion und Integration von HPV (siehe Kapitel 3).<\/p>\n<p>The development of CIN involves a progression from early changes (CIN1) involving the deeper layers of the epithelium to full thickness involvement at its most severe (CIN3) equating to carcinoma in situ (Figure 4.1).&nbsp;&nbsp;<\/p>\n<figure><a data-toggle=\"modal\" href=\"#modal-container-2\"><img fetchpriority=\"high\" decoding=\"async\" alt=\"\" height=\"682\" src=\"http:\/\/lnx.eurocytology.eu\/sites\/default\/files\/styles\/max\/public\/images\/2204_1427301614.png?itok=dmTNaryO\" width=\"1187\" \/><\/a><figcaption>Abbildung 4.1. Schematische Darstellung der Entwicklung einer CIN&nbsp;(aus&nbsp; Abbildung 1 in Kelloff &amp; Sigman 2007)<\/figcaption><\/figure>\n<p>&nbsp;<\/p>\n<table border=\"3\" cellpadding=\"0\" cellspacing=\"0\" style=\"width:500px;\">\n<tbody>\n<tr>\n<td>\n<ul>\n<li>CIN1, CIN2 and CIN3 have increasing risk of progression to invasion and decreasing likelihood of natural regression<\/li>\n<li>The three-tier concept of CIN has to be modified by the understanding that CIN1 usually represents reversible infection with human papillomavirus (HPV)&nbsp;<\/li>\n<\/ul>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<p>&nbsp;<\/p>\n<p>Figure 4.2 (a-c).&nbsp; CIN1<\/p>\n<h4>FIGURE<\/h4>\n<p>(a) CIN1 in a cervical biopsy; (b) LSIL in a Pap smear; (c) LSIL with koilocytosis (see Figures 9c-2a and 9c-3b in Chapter 9c and scanned slides linked to that chapter).<\/p>\n<p>CIN1 bzw. Koilozytose einer HPV-Infektion bildet sich f\u00fcr gew\u00f6hnlich innerhalb von 9-12 Monaten spontan wieder zur\u00fcck. Es gibt jedoch zahlreiche Follow-up Studien, die sehr unterschiedliche Progressionsrisiken zu CIN2-3 und f\u00fcr eine \u00e4u\u00dferst kleine Minderheit der Patientinnen eine resultierende Gefahr f\u00fcr ein invasives Karzinom zeigen (Ost\u00f6r 1993; Holowaty 1999; Bansal et al. 2008).&nbsp;<\/p>\n<p>Eine gro\u00df angelegte retrospektive Follow-up Studie von Holowaty et al. zur leichten, m\u00e4\u00dfigen und schweren Dysplasie konnte belegen, dass sich der Gro\u00dfteil der F\u00e4lle einer leichten Dysplasie (62.2%) und m\u00e4\u00dfigen Dysplasie (53.7%) zur\u00fcckbildet (Endpunkt: zwei negative Abstriche innerhalb von 2 Jahren) w\u00e4hrend das Progressionsverhalten zu einer m\u00e4\u00dfigen Dysplasie oder h\u00f6hergradigen L\u00e4sion (CIN2+) ca. 25% innerhalb von 5 Jahren betr\u00e4gt, was sich auch mit den Ergebnissen anderer Studien deckt.<\/p>\n<p>A large retrospective follow-up study of mild, moderate and severe dysplasia by Holowaty et al. showed that the majority of cases of mild (62.2%) and moderate dysplasia (53.7%) regressed (two negative smears within 2 years) while progression to moderate dysplasia or worse was approximately 25% within 5 years, which is consistent with other studies.&nbsp;&nbsp;<\/p>\n<table border=\"3\" cellpadding=\"1\" cellspacing=\"1\" style=\"width: 500px;\">\n<tbody>\n<tr>\n<td>\n<h3>Progression der leichten Dysplasie (vgl. Holowaty et al.)<\/h3>\n<p>&nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp;<strong>Moderate<\/strong>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; <strong>Severe<\/strong>+<\/p>\n<p><strong>Innerhalb von 2 Jahren<\/strong>&nbsp;&nbsp;&nbsp; &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; 11.1%&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; 2.1%<\/p>\n<p><strong>M\u00e4\u00dfige Dysplasie<\/strong>&nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; 20.4%&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; 5.5%<\/p>\n<p><strong>Schwere Dysplasie<\/strong>&nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; 28.8%&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; 9.9%<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<p>&nbsp;<\/p>\n<p><strong>Likelihood of progression<\/strong> depends on persistence of HPV, its integration into the host genome and its type (Jaisamrarn et al. 2013).&nbsp;<\/p>\n<ul>\n<li>HPV16 and 33 have the highest risk of progression to CIN3<\/li>\n<li>HPV16 and 31 to have the least likelihood of regression<\/li>\n<\/ul>\n<p><span style=\"color: inherit; font-family: inherit; font-size: 20px; font-weight: 700; line-height: 1.1;\">High-grade CIN<\/span><\/p>\n<p><strong>CIN2 and CIN3<\/strong> are managed as \u2018high-grade\u2019 CIN and usually treated by excision or ablation when diagnosed at colposcopy.<\/p>\n<p><strong>CIN2<\/strong> is an intermediate lesion and there is evidence from the ALTS trial that around 40% resolves spontaneously but was less likely to do so when HPV16-related (Castle et al. 2009). &nbsp;The retrospective study by Holowaty et al. (1999) showed that the majority of moderate dysplasia regressed dysplasia regressed (53.7%) while progression was more likely than for mild dysplasia.<\/p>\n<table border=\"3\" cellpadding=\"1\" cellspacing=\"1\" style=\"width: 357px;\">\n<tbody>\n<tr>\n<td style=\"width: 348px;\">\n<h3>Progression of moderate dysplasia (from Holowaty et al.)<\/h3>\n<p>&nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp;<strong>Severe+<\/strong><\/p>\n<p><strong>Within 2 years<\/strong>&nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp;16.3%<\/p>\n<p><strong>Within 5 years<\/strong>&nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp;25.1%<\/p>\n<p><strong>Within 10 years &nbsp;<\/strong>&nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; &nbsp; 32.0%<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<p>&nbsp;<\/p>\n<p>Die kumulative statistische Progressionsrate der m\u00e4\u00dfigen Dysplasie (1.2) zum invasiven Karzinom bezogen auf 100 Frauen innerhalb von 5 Jahren, liegt zahlenm\u00e4\u00dfig zwischen der leichten Dysplasie (0.4) und der schweren Dysplasie (3.9) (kompletter Datensatz einschl. Konfidenzintervallen vgl. Holowaty&nbsp;<em>et al<\/em>. 1999)<\/p>\n<p><strong>CIN2&nbsp;ist charakterisiert durch Kernatypien mit erh\u00f6hter Mitoserate ausgedehnt auf die basalen 2\/3 des Epithels. Eine Koilozytose ist kaum bis nicht vorhanden.&nbsp;<\/strong><\/p>\n<p><strong>Figure 4.3 (a-b).&nbsp; CIN2 (moderate dysplasia): intermediate risk of progression&nbsp;<\/strong><\/p>\n<h4>FIGURE<\/h4>\n<p>(a) HSIL, favour CIN2, on a LLETZ; (b) HSIL (favour CIN2) (see Figure 9c-7b and scanned slides linked to Chapter 9c)<\/p>\n<p>In view of its intermediate position between CIN1 and CIN3 in terms of risk of progression and the clinical importance of deciding whether CIN2 should be managed as a high-grade precancerous lesion, immunohistochemistry using the cyclin-dependent kinase inhibitor p16<sup>INK4A<\/sup> is now recommended in the US to improve consistency of diagnosis and define high-grade CIN (Galgano <em>et al<\/em>. 2010; Darragh <em>et al<\/em>. 2012). &nbsp;<\/p>\n<table border=\"3\" cellpadding=\"1\" cellspacing=\"1\" style=\"width: 500px;\">\n<tbody>\n<tr>\n<td>\n<h4>P16INK4A&nbsp;F\u00e4rbung hilft in der Unterscheidung einer CIN2 zu<\/h4>\n<ul>\n<li>CIN1 in unreifer Metaplasie<\/li>\n<li>Benignen Zellbildern wie unreife Metaplasie, atrophe Metaplasie und Regeneratepithel<\/li>\n<\/ul>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<figure>&nbsp;<\/figure>\n<p>CIN3&nbsp;ist charakterisiert durch Kernatypien, die die gesamte Epitheldicke betreffen, mit erh\u00f6hter Mitoserate in allen Schichten.&nbsp;&nbsp; CIN3 (and severe dysplasia) equates to carcinoma in situ, which term is seldom used nowadays.<\/p>\n<p>&nbsp;<\/p>\n<p>Risk of progression is highest for CIN3 and inter-observer variation is considerably less than for CIN1 or CIN2 (Stoler et al. 2001).&nbsp; Microinvasive carcinoma is almost always seen in a background of widespread CIN3 further demonstrating its malignant potential.&nbsp; The exact risk is difficult to calculate because most CIN3\/carcinoma in situ is treated when diagnosed. &nbsp;<\/p>\n<p><strong>Figure 4.4 (a-c). CIN3 and occult cancer<\/strong><\/p>\n<figure><a data-toggle=\"modal\" href=\"#modal-container-2\"><img decoding=\"async\" alt=\"\" height=\"1079\" src=\"http:\/\/lnx.eurocytology.eu\/sites\/default\/files\/styles\/max\/public\/images\/2208_1427301883.png?itok=YotbPrWj\" width=\"1440\" \/><\/a><figcaption>(a) Focus of early stromal invasion;<\/figcaption><\/figure>\n<figure><a data-toggle=\"modal\" href=\"#modal-container-2\"><img decoding=\"async\" alt=\"\" height=\"1411\" src=\"http:\/\/lnx.eurocytology.eu\/sites\/default\/files\/styles\/max\/public\/images\/2209_1427301934.png?itok=VxNV0b9N\" width=\"1440\" \/><\/a><figcaption>(b) cytology showing HSIL (favour CIN3) from the same case<\/figcaption><\/figure>\n<figure><a data-toggle=\"modal\" href=\"#modal-container-2\"><img loading=\"lazy\" decoding=\"async\" alt=\"\" height=\"500\" src=\"http:\/\/lnx.eurocytology.eu\/sites\/default\/files\/styles\/max\/public\/images\/2210_1427301981.png?itok=6GzI_g2e\" width=\"848\" \/><\/a><figcaption>(c) stage IA carcinoma (microinvasive) developing in widespread CIN3.<\/figcaption><\/figure>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<div data-object_id=\"5111\" class=\"cbxwpbkmarkwrap cbxwpbkmarkwrap_guest cbxwpbkmarkwrap_user_cat cbxwpbkmarkwrap-course \"><a  data-redirect-url=\"https:\/\/www.eurocytology.eu\/de\/wp-json\/wp\/v2\/course\/5111\/\"  data-display-label=\"1\" data-show-count=\"1\" data-bookmark-label=\"Bookmark\"  data-bookmarked-label=\"Bookmarked\"  data-loggedin=\"0\" data-type=\"course\" data-object_id=\"5111\" class=\"cbxwpbkmarktrig  cbxwpbkmarktrig-button-addto\" title=\"Bookmark This\" href=\"#\"><span class=\"cbxwpbkmarktrig-label\" >Bookmark (<i class=\"cbxwpbkmarktrig-count\">0<\/i>)<\/span><\/a> <div  data-type=\"course\" data-object_id=\"5111\" class=\"cbxwpbkmarkguestwrap\" id=\"cbxwpbkmarkguestwrap-5111\"><div class=\"cbxwpbkmarkguest-message\"><a href=\"#\" class=\"cbxwpbkmarkguesttrig_close\"><\/a><h3 class=\"cbxwpbookmark-title cbxwpbookmark-title-login\">Please login to bookmark<\/h3><form name=\"loginform\" id=\"loginform\" action=\"https:\/\/www.eurocytology.eu\/wp-login.php\" method=\"post\"><p class=\"login-username\">\n\t\t\t\t<label for=\"user_login\">Benutzername oder E-Mail-Adresse<\/label>\n\t\t\t\t<input type=\"text\" name=\"log\" id=\"user_login\" autocomplete=\"username\" class=\"input\" value=\"\" size=\"20\" \/>\n\t\t\t<\/p><p class=\"login-password\">\n\t\t\t\t<label for=\"user_pass\">Passwort<\/label>\n\t\t\t\t<input type=\"password\" name=\"pwd\" id=\"user_pass\" autocomplete=\"current-password\" spellcheck=\"false\" class=\"input\" value=\"\" size=\"20\" \/>\n\t\t\t<\/p><p class=\"login-remember\"><label><input name=\"rememberme\" type=\"checkbox\" id=\"rememberme\" value=\"forever\" \/> Angemeldet bleiben<\/label><\/p><p class=\"login-submit\">\n\t\t\t\t<input type=\"submit\" name=\"wp-submit\" id=\"wp-submit\" class=\"button button-primary\" value=\"Anmelden\" \/>\n\t\t\t\t<input type=\"hidden\" name=\"redirect_to\" value=\"https:\/\/www.eurocytology.eu\/de\/wp-json\/wp\/v2\/course\/5111\/\" \/>\n\t\t\t<\/p><\/form><p class=\"cbxwpbookmark-guest-register\">No account yet? <a href=\"https:\/\/www.eurocytology.eu\/de\/register\/?redirect_to=https%3A%2F%2Fwww.eurocytology.eu%2Fde%2Fwp-json%2Fwp%2Fv2%2Fcourse%2F5111%2F\">Register<\/a><\/p><\/div><\/div><\/div><p>CIN und Plattenepithelkarzinom Es gilt als anerkannt, dass dem invasiven Plattenepithelkarzinom, welches den h\u00e4ufigsten histologischen Typ des Zervixkarzinoms darstellt, ein pr\u00e4invasives Krankheitsstadium vorangeht, in welchem sich die abnormen Zellen \u00fcber das Epithel ausbreiten. Dabei wird das normale Plattenepithel der Zervix durch abnormes Epithel neoplastischer Zellen ersetzt. Dieses nicht-invasive Krankheitsstadium wird als zervikale intraepitheliale Neoplasie bezeichnet [&hellip;]<\/p>\n","protected":false},"featured_media":0,"parent":5099,"menu_order":0,"template":"","meta":[],"tags":[],"course_area":[120],"authors":[],"class_list":["post-5111","course","type-course","status-publish","hentry","course_area-zervixzytologie"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v22.6 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>4. 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