adenocarcinoma della cervice e problematiche di screening ... · with at least a negative smear •...
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Adenocarcinoma della cervice e problematiche di screening:
trend di incidenza
Convegno Nazionale GISCi Sorrento: 2005
Marco Zappa, Carmen Beatrix Visioli
Centro per lo Studio e la Prevenzione Oncologica (CSPO) – Florence, Italy
Several studies have reported an increasing proportion of adenocarcinomas relative to squamous
Schwartz, Weiss US Am J Epidemiol, 1986Eide Norway JNCI, 1987Bergstrom et al Sweden Br J Cancer, 1999Antilla A et al Finland Int J Cancer 1999 Sasieni et al UK BMJ 1999Alfsen et al Norway Cancer 2000Smith US Gynecol Oncol 2001Liu et al Canada Int J Gynecol Cancer 2001Bulk et al The Netherlands Int J Cancer 2004Visioli et al Italy Cancer Detec Prev 2004
Trends in age adjusted incidence rates of squamous cell and adeno carcinoma of the cervix uteri in Sweden, 1958-1995
Bergstrom et al Br J Cancer 1999, modify
Analisi per istotipi (ICD0-2M) da Berg 1994, modificata
• K. Squamoso : 8050-8089, 8120-8139• Adenocarcinoma e adenosquamoso: 8140-
8149, 8160-8169, 8190-8229, 8260-8339, 8350-8560, 8570-8579, 8940-8949
• Altro: 8000-8049, 8090-8119, 8150-8159, 8170-8189, 8230-8259, 8340-8349, 8561-8569, 8580-8939, 8950-9989
Methods• EAPC Estimated annual percent change. The EAPCs are calculated by fitting a least
squares regression line to the natural logarithm of the rates using the calendar year as a regressor variable. Testing the hypothesis that the EAPC is equal to zero is equivalent to testing the hypothesis that the regression parameter of the calendar year is equal to zero.
Trends in age adjusted incidence rates of squamous cell carcinoma of the cervix uteri in ITALY, 1986-1997
EAPC -1.72, p=0.012
ITrends in age adjusted incidence rates of adeno carcinoma of the cervix uteri in ITALY, 1986-1997
EAPC= +2.0, p=0.11
Cervical carcinomas Incidence Trend (EAPC)ITALY 1986-1997 by age and hystologyin red Statistycal significant values
Age Squamous AdenoK
other Total
20-39 +0.60 +3.70 -7.48 -0.15
40-59 -1.53 +2.47 -3.80 -1.34
60+ -3.38 +0.01 -7.06 -3.26
Source: AIRT
Figure2: Age and cohort effects estimated from data for England 1971-87Age effect is for a cohort born in 1924. Relative incidence of cohort effect is relative to that in the 1924 cohort. Lifetime risk is calculated from mortality rates in 1994.9
Sasieni P, Adams J. The Lancet 2001; 357: 14
Estimated Annual Percent Change (EAPC) by histologic subtype of invasive cervical cancer, ITALY 1986-1997in red Statistycal significant values
Center Squamous Adenok Other Total
Firenze - 2.0% +6.2% -0.2% - 0.7%
Genova +0.7% +5.5% -1.5% +1.4%
Modena +3.7% -1.5% nc +1.3%
Parma - 4.3% +4.7 nc -4.5%
Ragusa - 7.8% +4.7% nc -6.4%
Romagna - 2.8% +0.5% +9.9% -1.7%
Torino -2.0% +2.5% -13.4% -2.6%
Varese -2.5% +5.4% nc -2.2%
Veneto +0.1% -0.4% -5.3% -0.9%
Trends in age-adjusted* incidence rates of cancer of cervix uteri by histologic subtype in RTT, 1985-2001
(3-years moving averages)
012345678
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
Year
Log
age-
adju
sted
* ra
tes
per
100,
000
wom
en
*european population
Squamous
Adenocarcinomas and adenosquamous
Data from Tuscany Cancer Registry (RTT, population about 600,000 women)
EAPC=+4.6; 95%CI +1.5;+7.7
EAPC=-2.0, 95%CI -3.7, - 0.3
Trends in age-adjusted* incidence rates of adenok of cervix uteri in RTT, 1985-2001
(3-years moving averages)
0
0.5
1
1.5
219
85
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
Year
Log
age-
adju
sted
* ra
tes
per
100,
000
wom
en
*european population
Adenocarcinomas and adenosquamous
Data from Tuscany Cancer Registry (RTT, population about 600,000 women)
EAPC=+4.6; 95%CI +1.5;+7.7
Trends in age-specific incidence of adenocarcinoma of the cervix in five registries with available data 1971-97Open circles=3-year running averages of actual rates. Continuous curves are rates predicyted from age-cohort model fitted to data from England 1971-87.
Sasieni P, Adams J. The Lancet 2001; 357: 1490-93
Estimated Annual Percent Change (EAPC) by histologic subtype of invasive cervical cancer,
Tuscany Cancer Registry 1985-2001
Age Adenok Squamous Other Total
25-54 +8.9%(+3.3,+14.8)
+0.8%(-2.1,+3.7)
NV +1.5%(-1.2,+4.3)
55+ +1.5%(-3.2,+6.3)
-4.8%(-6.5-3.1)
-7.9%(-13,-2)
-4.1%(-5.8-2.5)
All Ages +4.6%(+1.5,+7.7)
-2.0%(-3.7, 0.)
-4.3(-9.1,+0.8)
-1.4(2.8, +0.1)
Trends in age-adjusted* incidence rates of adenok of cervix uteri in Australia, 1985-1999source:Australia Institute of Health and Welfare
• 1987-89 = 2.3*100000
• 1997-99 = 1.6*100000
Ratio between Adenocarcinoma –Adenosquamous and Squamous cell
Carcinoma• Area del RTT• 1985-88:
• 1997-2000:
• SEER - USA• 1985-88:
• 1997-2000
8.9% Adenok
20.9% Adenok
18,7% Adenok
26.3% Adenok
• Increasing incidence trends of Invasive adenocarcinomas of uterine cervix
despite Pap test screening
Efficacy of pap test by histologic subtypeCase-control studies
Squamous Adenocarcinoma(95% IC) (95% IC)
Herrero,1992 OR=0.40 (0.3-0. 5) OR=0.50 (0.3-0. 8)
Mitchell, 1995 - OR=0.62 (0.4-1. 1)
Sato, 1996 OR=0.14 (0.1-0.3) OR=0.45 (0.1-3.7)
Case-Control Study:Cytological Screening Protection for Adenocarcinomas in
Florence- Zappa, Visioli, Ciatto , Iossa , Sasieni Br J Cancer 2004
Materials and Methods• cases: 208 women <70 years with fully invasive cervical
carcinoma incident between 1994 and 1999 in RTT area• controls: 832 women random selected from the general
population (same area) matched by year of birth• criteria of inclusion: resident at least 5 years in the
screening area, alive at the index date, nohysterectomized before the index date
• screening history: all Pap tests archived at CSPO,excluded smears taken within 12 months before theindex date (excluded women with symptoms)
• statistical analysis: conditional logistic analysis (STATA)
Odds Ratios (OR) of developing invasive cervical cancer byscreening history (time since last Pap test), adjusted for civilstatus and birth place Zappa et al Br J Cancer 2004,modify
Histologic type (OR 95% CI)Time sincelast test*(years)
squamous Adk andadksquamous
All cases
<3 0.15 (0.07-0.30) 0.65 (0.26-1.65) 0.25 (0.15-0.42)
3-<6 0.20 (0.10-0.39) 0.99 (0.43-2.29) 0.34 (0.21-0.56)
>= 6 0.56 (0.36-0.87) 0.54 (0.24-1.23) 0.56 (0.38-0.82)
Neverscreened
1.0 1.0 1.0
* excluding tests in the year before test
Zappa et al Br J Cancer 2004, modify
Odds Ratios (OR) of developing invasive cervical cancer by screening history (time since last Pap test) and by age group, adjusted for civil status and birth place
<40years
Histologic type (OR 95% CI)
Timesince lasttest*(years)
squamous Adenocarcinomaandadenosquamous
All cases
<3 0.16 (0.03-0.77) 0.76 (0.18-3.11) 0.35 (0.13-0.95)
3-<6 0.45 (0.14-1.48) 1.24 (0.26-5.86) 0.63 (0.26-1.52)
>= 6 0.68 (0.23-2.01) 1.03 (0.25-4.25) 0.83 (0.37-1.86)
Neverscreened
1.0 1.0 1.0
* excluding tests in the year before test
Zappa et al Br J Cancer 2004, modify
Odds Ratios (OR) of developing invasive cervical cancer by screening history (time since last Pap test) and by age group, adjusted for civil status and birth place
>=40years
Histologic type (OR 95% CI)
Timesince lasttest*(years)
squamous Adenocarcinomaandadenosquamous
All cases
<3 0.15 (0.07-0.33) 0.56 (0.16-2.01) 0.22 (0.12-0.42)
3-<6 0.14 (0.06-0.33) 0.78 (0.27-2.28) 0.26 (0.14-0.48)
>= 6 0.53 (0.32-0.88) 0.42 (0.14-1.24) 0.48 (0.31-0.74)
Neverscreened
1.0 1.0 1.0
* excluding tests in the year before test
Materials and Methods• cases: 127 women <70 years with fully invasive cervical
adenocarcinoma incident between 1987 and 2001 inVictoria Region (Australia) with at least a negative smear
• controls: 508 women random selected from registrydatabase (same area) matched by year of birth (+/-2)with at least a negative smear
• screening history: all Pap tests archived SPO, excludedsmears taken within 6 months before the index date(excluded women with symptoms)
• statistical analysis: conditional logistic analysis (STATA)
Improvement in protection agains AdenoCarcinoma of the cervix resulting from Partecipation in Cervical screeningMitchell et al Cancer 2003; pp 336-41
Percent reduction in the Cumulative Incidence of Invasive Adenok in women (age 20-70) with different frequencies of screeningMitchell et al cancer 2003
Interval Between screening (yr)
Relative Protection
95% CI Reduction in cumulative incidence
1 2.85 1.6-5.2 65%
2 1.38 0.8-2.5 46%
3 1.12 0.5-2.3 34%
Conclusions• Adenocarcinoma of the cervix is a rare disease
• Incidence rates of cervical adenocarcinomas areincreasing among younger women, whereas rates ofsquamous cancers are decreasing in the older age-groups.
• In recent time this trend seems to became flat: thereasons are unclear
• The conventional Pap smear screening is less effectivein preventing adenocarcinomas than squamouscancers.