Απνηειέζκαηα παξαθνινύζεζεο γπλαηθώλ κε CIN2 ελδνεπηζειηαθέο αιινηώζεηο ηξαρήινπ πνπ δελ ππνβιήζεθαλ ζε ζεξαπεία. Γηεξεύλεζε ηνπ ξόινπ (ζρεηηθώλ κε ηνλ HPV) βηνδεηθηώλ. M Kyrgiou, K Papakonstantinou, P Abrol, S.Gkritzeli, G Valasoulis, M Cowen, SM Stasinou, N Tsagkas, ME Anaforidou, P Karakitsos, M. Nasioutziki, D Lyons, A. Loufopoulos, E Paraskevaidis, The HeCPA Group. Σζάγθαο Νηθόιανο Δηδηθεπόκελνο Ιαηξόο Μ/Γ Π.Γ.Ν.ΙΩΑΝΝΙΝΩΝ
HG SIL: 33-40% regress Östör Int J Gyn Pathol 1993 CIN2: 54% spontaneously regress 12m Ho 2011 Severity of the lesion Regression Persistence Progression to CIN3 CIN2 - LSIL: 74% spontaneously regress Discacciati 2011 % Hg cytology, % regression in <30yrs Insinga RP 2004 Expectant Mx CIN2: safe Castel 2009; Fuchs 2007 No immediate Tx in young women with CIN2 Progression to invasive cancer CIN1 60% 30% 10% 1% CIN2 40% 40% 20% 5% CIN3 33% <55% - >12% Am Guidelines Wright 2007
Why should we be cautious with young women? a.high regression rates of CIN1 and CIN2 b.to avoid damage of the cervix, if unnecessary, that can impair future Cx Anatomy Cx Function (e.g. Pregnancy)
Gestation (Weeks) Dose Effect 12 24 28 32 37 2006 Kyrgiou 2008 Arbyn Overall prematurity Severe & extreme PD Perinatal mortality 2014 Kyrgiou BMJ 2 nd trimester miscarriages=early pregnancy losses
ΚΟΠΟ - ΜΕΘΟΔΟΛΟΓΙΑ Προοπτική δηαγλσζηηθή κειέηε παξαηήξεζεο (αλαδξνκηθή αλάιπζε απνηειεζκάησλ) θνπόο: Δθηίκεζε απνηειεζκάησλ ζε κε κε ζεξαπεπζείζεο CIN2 αιινηώζεηο & πξνγλσζηηθή αμία ησλ βηνδεηθηώλ. Πιεζπζκόο: Γπλαίθεο κε CIN2 αιινηώζεηο πνπ δελ ζεξαπεύζεθαλ. Υξνληθή πεξίνδνο: 1 νο /2009 12 νο /2011 (4-7 έηε FU) πλεξγαδόκελα Κέληξα: -Παλ/θν Ννζνθνκείν Ισαλλίλσλ -QCCH Hammersmith Hospital -St Mary s Hospital London
Flowchart CIN2 (103) LBC (40%) HPV DNA NASBA Flow cytometry p16 Colposcopy (103) CIN 2 untreated N = 96 Women that conceived N = 3 Women that declined Tx N = 4 Rpt cytology + colposcopy +/- PBs Treatment if indicated PBs at end of FU <CIN2 (2) CIN2+ (29) Outcomes: Progression Persistence Regression rates
Results Total Population: 103 Hospital Cytology Colposcopy Punch Biopsies BLN % Mild % Mod % Sev % HSIL % LSIL % HSIL % CIN 2 % CIN 3 % N/A St Mary s (n=42) 30 (71) 3 (7) 8 (19) 30 (71) 12 (29) 42 (100) QCCH (n=19 ) 6 (32) 4 (21) 6 (32) 3 (16) 14 (74) 5 (26) 15 (79) 4 (21) UOI (n=42) 3 (7) 10 (24) 29 (69) 18 (43) 24 (57) 38 (91) 1 (9) Total (n=103) 39 (38) 17 (17) 14 (16) 3 (3) 29 (28) 62 (60) 41 (40) 95 (92) 1 (1) 4 (4)
Invasion 0% 0% 0% 0% CIN 3 2% 2% 3% 0% CIN 2 25% 5% 0% 0% CIN 1 18% 10% 4% 0% 71% HPV 13% 6% 13% 6% Normal 19% 28% 57% 55% Tx 23% 9% 4% 0% 29% DNA 7% 10% 13% 42% 18% FU 6 m 12 m 18 m 24 m
Treatment Histology St Mary s (n=14) QCCH (n=6) UOI (n=11) Total (n=31) CIN 3 4/14 1/6 2/2 7/31 (23%) LLETZ CIN 2 9/14 4/6 9/11 22/31(70%) CIN 1 1/14 1/6 0/11 2/31 (7%) Likelihood of regression increased: - Age (<30y v >30y, 75% v 43%) - LSIL cytology (LSIL v HSIL, 82% v 39%) - LSIL or normal colposcopy (LSIL/N v HSIL, 68% v 52%) - Size of lesion 1 vs >1 quadrant (UOI) (<1 v >1, 78% v 43%) - HPV not 16 (UOI) (HPV not 16 v 16, 84% v 48%)
HPV-related biomarkers Results Single and combinations tests Primary triage: high sensitivity detect women at high-risk of progression Next challenge : high specificity detect women at low-risk of progression
Accuracy of single tests S 1 0,9 0,8 0,7 0,6 0,5 0,4 0,3 0,2 0,1 0 X optimum test NASBA p16 Biomarker Flow HR HPV DNA HPV 16/18 HPV 16 0 0,2 0,4 0,6 0,8 1-Sp Biomarker
Test Sensitivity Specificity hrhpv DNA or - 94% 67% NASBA 94% 65% p16 94% 60% Flow 90% 59%
Test Sensitivity Specificity HPV 16 44% 92% HPV 16 AND p16 21% 96% HR HPV AND NASBA 50% 96% HR HPV AND p16 73% 90% NASBA AND p16 65% 96%
CIN2 Sensitivity hrhpv DNA Negative Positive Specificity - HPV16 and p16 or - HR HPV and NASBA or - NASBA and P16 Negative Positive Surveillance 6 m Surveillance 6m Treatment
12 parameters Age Smoking Cytology Colposcopy + + Scoring System HPV DNA test HPV DNA typing NASBA P16 Flow cytometry Viral load (1pg) Microspectroscopy mrna E6/E7 / Histology TZ (Gold standard) PRECISION IN MEDICINE, special interest: GYNECOLOGIC ONCOLOGY, APRIL 2016 IN PRESS
ΤΜΠΕΡΑΜΑΣΑ Τςειά πνζνζηά ππνζηξνθήο CIN2 (έσο 70%) Παξάγνληεο: ειηθία, θπη/γία, θνιπνζθόπεζε, κέγεζνο αιινίσζεο, HPV16 CIN2 = Γηθνξνύκελε δηάγλσζε (CIN1/CIN3) ΠΛΔΟΝΔΚΣΗΜΑΣΑ ΒΙΟΓΔΙΚΣΩΝ - Έγθαηξε αλίρλεπζε CIN1/CIN3 πνπ αξρηθά ηαμηλνκήζεθαλ σο CIN2 - Αλαγλώξηζε αιινηώζεσλ κε ηάζε επηδείλσζεο - Μείσζε Σx ΙΟΡΡΟΠΊΑ: θόζηνο/ππεξζεξαπεία/ ειηθία/γνληκόηεηα ΠΡΟΟΥΗ: Γηαθπγή δηεζεηηθήο λόζνπ!!!
ONGOING STUDY 1 ST PRIZE BSCCP 2014 1 Ο ΒΡΑΒΕΙΟ, ΤΝΕΔΡΙΟ ΜΑΙΕΤΣΙΚΗ ΓΤΝΑΙΚΟΛΟΓΙΑ, ΒΟΛΟ 2015
12 +, parameters Age Smoking Sexual history Cytology Colposcopy + + Scoring System HPV DNA test HPV DNA typing NASBA P16 Flow cytometry Viral load (1pg) Microspectroscopy mrna E6/E7 / Histology TZ (Gold standard) Weight of Parameters
Accuracy of single tests S 1 0,9 0,8 0,7 0,6 0,5 0,4 0,3 0,2 0,1 0 X optimum test NASBA p16 Biomarker Flow HR HPV DNA HPV 16/18 HPV 16 0 0,2 0,4 0,6 0,8 1-Sp Biomarker