Gebärmutterhals - Krebsabstrich
1941 Zytologie
Papanicolaou
Gebärmutterhalskrebs 1983 - 2002 Österreich
-
200
400
600
800
>50a
<50a
ÖSTAT 2006
Zytoscreening Europa
0
10
20
30
40
50
60
70
80
90
GB NL D
Teilnahmerate %
Zervixca Inz 100 000 FJ
CIS Austria 1983-2002
0
200
400
600
800
1000
1200
n
<50a
>50a
21
22
23
24
25
26
27
28
1984 1989 1994 1999 2004
Alter beim 1sten Kind
KONTROVERSE SCREENING GEBÄRMUTTERHALSKREBS ?
URSACHE - HPV
1976
Humane Papillomaviren
Harald zur Hausen
HPV - Epidemiologie
20a 30a 40a 50a 60a 70a 80a 90a
CIS
SCC
HPV
HPV-Prävalenz
0%
5%
10%
15%
20%
25%
30%
35%
HPV %
<20 21-
30
31-
40
41-
50
51-
60
>60 all
Alter
HPV all
HPV HR
(Clavel et al. 1999)
Nahezu 100% „lifetime risk“ für HPV Infektion !
Ziel
• Häufigkeit CxCa
• Sterblichkeit CxCa
• Identifikation der Vorstufen
• Lebensqualität
• Reproduktion
Pap vs. HPV testing
Screening USA
Screening - Industrieländer
SCREENING FOR CERVICAL CANCER
CLINICAL SUMMARY OF U.S. PREVENTIVE SERVICES TASK FORCE RECOMMENDATION
Population
Women ages 21 to 65 Women ages 30 to 65 Women
younger than age 21
Women older than age 65 who have had adequate prior
screening and are not high risk
Women after hysterectomy with removal of the cervix and with no history of high-grade precancer or
cervical cancer
Women younger than age 30
Recommendation
Screen with cytology (Pap smear) every 3
years. Grade: A
Screen with cytology every 3 years or
co-testing (cytology/HPV testing)
every 5 years Grade: A
Do not screen. Grade: D
Do not screen. Grade: D
Do not screen. Grade: D
Do not screen with HPV testing (alone or
with cytology) Grade: D
Risk Assessment Human papillomavirus (HPV) infection is associated with nearly all cases of cervical cancer. Other factors that put a woman at increased risk of cervical cancer include HIV
infection, a compromised immune system, in utero exposure to diethylstilbestrol, and previous treatment of a high-grade precancerous lesion or cervical cancer.
Screening Tests and Interval
Screening women ages 21 to 65 years every 3 years with cytology provides a reasonable balance between benefits and harms. Screening with cytology more often than every 3 years confers little additional benefit, with large increases in harms.
HPV testing combined with cytology (co-testing) every 5 years in women ages 30 to 65 years offers a comparable balance of benefits and harms, and is therefore a reasonable alternative for women in this age group who would prefer to extend the screening interval.
Timing of Screening
Screening earlier than age 21 years, regardless of sexual history, leads to more harms than benefits. Clinicians and patients should base the decision to end screening on whether the patient meets the criteria for adequate prior testing and appropriate follow-up, per established guidelines.
Interventions Screening aims to identify high-grade precancerous cervical lesions to prevent development of cervical cancer and early-stage asymptomatic invasive cervical cancer.
High-grade lesions may be treated with ablative and excisional therapies, including cryotherapy, laser ablation, loop excision, and cold knife conization. Early-stage cervical cancer may be treated with surgery (hysterectomy) or chemoradiation.
Balance of Benefits and Harms
The benefits of screening with cytology
every 3 years substantially outweigh
the harms.
The benefits of screening with co-testing (cytology/HPV testing) every 5 years outweigh
the harms.
The harms of screening earlier than age 21 years
outweigh the benefits.
The benefits of screening after age 65 years do not outweigh the potential harms.
The harms of screening after hysterectomy
outweigh the benefits.
The potential harms of screening with HPV testing (alone or with
cytology) outweigh the potential benefits.
Other Relevant USPSTF Recommendations
The USPSTF has made recommendations on screening for breast cancer and ovarian cancer, as well as genetic risk assessment and BRCA mutation testing for breast and ovarian cancer susceptibility. These recommendations are available at http://www.uspreventiveservicestaskforce.org/.
For a summary of the evidence systematically reviewed in making this recommendation, the full recommendation statement, and supporting documents, please go to http://www.uspreventiveservicestaskforce.org/.
• 21 – 30a
• eine Probenentnahme
• Thin Prep Cytology
• Kolpo
• 1 – 5 Jahre Intervall
Gebärmutterhalskrebs Targeted Screening
• 30 – 65
• eine Probenentnahme
• HPV Screening
• Thin Prep Cytology
• Kolpo
• 1 – 5 Jahre Intervall
Gebärmutterhalskrebs Targeted Screening
HPV assoziierte Karzinome
Über 100 mio
sicher
hocheffizient
HPV Impfung 2006-2013
• Ab Februar 2014
• 4.Schulstufe
• Alle Kinder
• 2 Dosen Schema
• Bundesbeschaffungsbehörde
HPV Impfprogramm
Frauenheilkunde Innsbruck
Screening – Ovarialkarzinom
Frauenheilkunde Innsbruck
Tumor markers elevated in epithelial
ovarian carcinoma
• CA 125
• HE 4
• Polymorphic epithelial mucins eg
HMFG1&2 and CA15-3
• EA
• CASA
• CSF1, MCSF
• CA 72.4
• CEA
• CA 19.9
• Kallikrein 6 and 10
• D-Dimer
• Galactosyl transferase
• Placental alkaline phosphatase
• Urine B core fragment of HCG
• Tissue polypeptide antigen (TPA)
• Tumour associated trypsin inhibitor (TATI)
• Lipid associated sialic acid (LASA)
• Proteomics
• Interleukin-6 and -7
• Soluble FAS
• Vascular Endothelial Growth factor
(VEGF)
• Anti-p53-antibodies
Frauenheilkunde InnsbruckSarojini et al, Journal of Oncology 2012
Clinical trials (currently active or completed) for evaluating novel biomarkers
of ovarian cancer
Early Detection Biomarkers for Ovarian Cancer
• Nur in ca. 50% der Frühstadien erhöht
• 20- 35% der Ovarialkarzinome keine CA 125 Expression
• Guter Verlaufsmarker, diagnostisch bedingt einsetzbar
• Beeinflussung durch benigne Zustände
– Endometriose
– Entzündungen
– Lebererkrankungen
– Herzerkrankungen
– menstrueller Zyklus
– Aszites
CA 125
Frauenheilkunde InnsbruckBuys et al, JAMA 2011
Ovarian Cancer Cumulative Cases and Deaths
Effect of Screening on Ovarian Cancer Mortality
Frauenheilkunde InnsbruckBuys et al, JAMA 2011
Major Complications Associated With Diagnostic Evaluation for
Ovarian Cancer
Effect of Screening on Ovarian Cancer Mortality
Frauenheilkunde InnsbruckMoyer et al, Annals of Internal Medicine 2012
SCREENING FOR OVARIAN CANCER
CLINICAL SUMMARY OF U.S. PREVENTIVE SERVICES TASK FORCE
RECOMMENDATION
Do not screen for ovarian cancer
• Derzeit keine Empfehlung zum organisierten Screening
• Mehr Karzinome diagnostiziert
• ABER kein deutlich besseres Überleben
• Kompromittierung von Gesunden
• Bei familiärem Ovarialkarzinom (BRCA1/2, Lynchsyndrom) kein Screening sondern OP!
• bei symptomatischen Patientinnen: CA-125/Sono
TVS + Serologie Screening Ovarialkarzinom
• Potentielle frühere Diagnose
• Medizinisch und gesundheitsökonomisch nicht sinnvoll
• Keine Verringerung der Mortalität
• Große Zahl unnötiger invasiver Eingriffe
Gebärmutterkrebs TVS Screening AGO Uterus der DGGG 2012
MG-Screening: NO!
Screening minor effect in mortality
Mortality reduction mainly due to treatment
Overdiagnosis
No justification for MG screening
Jorgensen et al. Radiology 2011
MG-Screening: YES!
Screening: more lives saved than harm
2 to 2.5 lives saved for every overdiagnosed case
Provide information about pros and cons for MG screening
Women have to decide if they want to participate
MG screening leads to mortality reduction
Kopans et al. Radiology 2011
Duffy et al. J Med Screen 2011
Mortality reduction by MG- Screening according to WHO
0,00%
0,02%
0,04%
0,06%
0,08%
0,10%
0,12%
30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74
AGE
NO Screening
Screening
Mammographie Screening ab 2014
• dezentrales Programm
• qualifizierten Radiologen
• über 2000 Untersuchungen
• Doppelbefundung
• Ultraschall
• Einladung alle 2 Jahre
• 40-75 flexibel
Frauenheilkunde Innsbruck
WHO Public Health Paper 1968
„Zehn Gebote“ für einen Screening Test
1. Die Zielkrankheit sollte ein bedeutendes Problem der öffentlichen Gesundheit sein
2. Es sollte dafür eine anerkannte Behandlung geben
3. Möglichkeiten für diagnostische Abklärungen und Therapie sollten verfügbar sein
4. Die Zielkrankheit sollte ein erkennbares Latenz- oder Frühstadium haben
5. Eine anwendbare Filteruntersuchung sollte vorhanden sein
6. Diese sollte von der Bevölkerung akzeptiert werden können
7. Der natürliche Verlauf der Krankheit (von latent zu manifest) sollte in ausreichendem
Masse bekannt und verstanden sein
8. Es sollte einen allgemein akzeptierten (und wissenschaftlich begründeten)
Behandlungsplan für die Zielkrankheit geben
9. Die Kosten für Früherkennung und Behandlung sollten als Ganzes abgewogen
werden (economically balanced)
10. Die Identifikation von kranken Personen sollte ein fortlaufender Prozess und keine
einmalige Aktion sein
Ökonomie Bürokratie
Politik Gesellschaft und Grundhaltung
Qualität Fachkompetenz
Sozialisierung Weltanschauung
Eigenverantwortung Grundhaltung
Lebensplanung
Aspekte
• einmal jährlich gynäkologische Untersuchung
• Abstrich
• Ultraschall
• einmal monatlich Selbstuntersuchung der Brust
• Mammographiescreening
• HPV Impfung
EMPFEHLUNG