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.