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