NEGRI, EVA

PARAZZINI, FABIO

VECCHIA, CARLO LA

RERO DOC Digital Library

International Journal of EpidemiologyC International Epktemiotogical Association 1992Vol. 21, No. 5Printed in Great BritainLetters to the EditorUse of Intrauterine Device and Risk of Invasive Cervical CancerFrom FABIO PARAZZINI,*-' CARLO LA VECCHIA*•* AND EVA NEGRI*Sir—We have read with interest the paper of Lassise etal. recently published by the IJE on the relation bet-ween use of intrauterine devices (IUD) and risk of in-vasive cervical cancer.' That study, conducted in fivemetropolitan areas in the US on 481 cases and 801general population controls, showed a nonsignificantreduced risk of invasive cervical cancer associated withcopper IUD use (relative risk [RR] 0.6, 95% con-fidence interval [CI] : 0.3-1.2), but not with inert IUDuse (RR 1.1, 95% CI : 0.9-1.7). To offer further dataon this issue we would like to add the following.The study by Lassise et al. is well conducted;however, there is considerable uncertainty about therelation between IUD use and risk of invasive and intra-epithelial cervical cancer, with other reports showingan increased risk of cervical cancer in ever IUDusers.2"4 We have analysed data collected in a case-control study conducted in North Italy,3 an areacharacterized by a low prevalence of IUD use. A totalof 720 histologically confirmed invasive cervical cancercases (median age 52, range 22-74) and 820 controls(median age 54, range 20-74) in hospital for acute,non-hormonal or gynaecological conditions (27%traumas, 33% non-traumatic orthopaedic disorders,15% acute surgical conditions and 25% other miscel-laneous conditions) were interviewed.RR estimates and the corresponding 95% CI of in-vasive cancer in relation to IUD use were computedusing multiple logistic regression. Included in theregression were terms for age, education, parity,smoking, age at first intercourse, lifetime numbeT ofsexual partners, contraceptive use, number of Papsmears and years since last Pap smear.The main results are shown in Table 1. A total of 20(2.8%) cases and 38 (4.6%) controls had ever used anIUD, for a crude RR of 0.6 (95% CI : 0.3-1.0). Therewas no evidence of a duration-risk relationship, thecrude RR estimates being 0.6 in women reporting a use* Istituto di Rkerche Farmacologiche 'Mario Negri', via Eritrea 62,20157 Milan, Italy.* II Clinica Ostetrico Ginecologica, University of Milan, 20100 Milan,Italy.* Institute of Social Preventive Medicine, University of Lausanne1005, Lausanne, Switzerland.lasting 3 years or less and 0.7 for more than 3 years.Likewise no relation emerged with time since last use.TABLE 1 Distribution of 720 cervical cancer cases and 820 controls,and corresponding relative risk, according to IUD use (Milan, Italy)IUD useNoYesCervicalcancer70Oc20Controls78238Duration of use (yean)>3Tune since<5>59111818last use (years)1182490.60.60.70.51.0RR (95ft CI)aCrudel d(0.3-1.0)(0.3-1.2)(0.3-1.4)(0.3-1.0)(0.4-2.6)MLVbl d0.6 (0.3-1.1)0.5 (0.2-1.3)0.6 (0.3-1.5)0.6 (0.2-1.4)0.7 (0.3-1.6)a RR = relative risk. CI •= confidence interval.Multivariate estimates adjusted for age, education, parity, smoking,age at first intercourse, number of sexual partners, oral contraceptiveuse, number of Pap smears and years since last Pap smear.c In some cases the sum does not add up to the total because of missingvalues.d Reference category.These results offer some support to the suggestionthat IUD use may reduce the risk of invasive cervicalcancer and are, therefore, at least in part supportive ofthe paper by Lassise et al.1 The estimated RR washowever of borderline statistical significance (possiblyfor the small number of users) and no trend in risk wasfound with duration of use.The protective effect of IUD use has been discussedby Lassise et al.' on the basis of an effect of copper indecreasing enzyme production and synthesis of DNAand carbohydrate, mucopolysaccharide metabolism.However, we were not able in our study to analyseseparately the effects of copper or inert IUD. It ispossible that stronger protection exists from copperIUD use. In any case these results do not support adirect relationship between invasive cervical cancerand IUD use.1030LETTERS TO THE EDITOR 1031ACKNOWLEDGEMENTSThis work was conducted within the framework of theCNR (Italian National Research Council) AppliedProject 'Oncology' (Contract 87.01544.44) and 'Pre-vention and Control of Disease Factors' (Contract91.00285. PGF1), and with the contributions of theItalian Association for Cancer Research and theItalian League Against Tumours, Milan, Italy.REFERENCES1 Lassise D L, Savitz D A, Hamman R F et al. Invasive cervical cancerand intrauterine device use. Int J Epidemiol 1991; 20: 863-70.2 Pincus G, Garcia C R. Studies on vaginal, cervical and uterinehistology. Metabolism 1965; 14: 344-47.3 Jones M C, Buschmann B O, Dowling E A. The prevalence ofactinomycetes-like organisms found in cervico-vaginal smearsof 300 IUD wearers. Ada Cytol 1979; 23: 282-86.4 Engineer A D, Misra J S, Tandon P. Long-term cytologk studiesof copper-IUD users. Ada Cytol 1981; 25: 550-56.3 Parazzini F, La Vecchia C, Negri Eetal. Oral contraceptive use andinvasive cervical cancer. Int J Epidemiol 1990; 15: 259-63.Effects of Environment and Passive Smoking on the RespiratoryHealth of ChildrenFrom C M WONG AND D J SPIEGELHALTERSir—We refer to an article by Francesco Forastiereet al.'In the study described in the article, two pollutedareas were chosen and were compared with a controlarea in order to evaluate the effects of air pollution onthe respiratory health of schoolchildren. Seventeenschools in the areas were randomly selected and all the3092 children in the required grades were recruited. Inthe data analyses, logistic regressions were used toobtain the odds ratios for the two polluted areas andfor parental smoking, with adjustments for variouspotential confounding factors. However, no accountwas taken of the between subject correlation producedas a result of sampling from the schools instead offrom the individual subjects.A basic requirement for a valid logistic regressionanalysis is the assumption of independence betweenindividual observations. Unless adjustments are madeby some means, the effect of ignoring the lack ofindependence will be underestimation of the standarderror and hence a narrower confidence interval (CI)being used erroneously in the analysis. In Table 3 ofthe article, the odds ratios with 95% CI for theeight respiratory symptoms in the industrial area(Civitavecchia) and the urban area (Rome) werereported. In both areas, three symptoms were found tohave 95% CI greater than one, but with lower limitsall below 1.06. Had the correlation been taken intoaccount, it is likely that these CI would not haveexcluded 1.00.Biostatistics Unit, Medical Research Council, Institute of PublicHealth, University Forvie Site, Robinson Way, Cambridge CB2 2SR,UK.Techniques for dealing with such dependence arebecoming increasingly available. Williams' method ofadjustment by means of an iterative reweighted pro-cedure2 is described in Collett3 with provision of aGLIM macro. However this method only works ongrouped data and on the assumption that the degreeof correlation is uniform among the subunits of thesample. In practice, random effects modellingmethods can be used to take account of the extravariation due to between subject correlation. Somecomputational procedures are available in thestatistical package EGRET.4 Multilevel modellingtechniques5 can also be used to explain the sources ofthe extra variation using the statistical package ML3.6Skinner et al.7 contains a good discussion of the issues,and describes other approaches in analysing complexsurvey data.REFERENCES1 Forastiere F, Corbo G M, Michelozzi P et al. Effects of environ-ment and passive smoking on the respiratory health ofchildren. Int J Epidemiol 1992; 21: 66-73.2 Williams D A. Extra-binomial variation in logistic linear models.Applied Statistics 1982; 31: 144-48.3 Collett D. Modelling Binary Data. London: Chapman & Hall,1st edn. 1991.4 EGRET reference manual. Statistics & Epidemiology ResearchCorp and Cytel Software Corp, 1985-89.3 Goldstein H. Multilevel mixed linear model analysis using iterativegeneralized least squares. Biometrika 1986; 73: 43-56.6 Prosser R, Rasbash J and Goldstein H. ML3 software for three-level analysis users' guide for v.2. London: Institute of Educa-tion, University of London, 1991.7 Skinner C J, Holt D and Smith T M F (eds). Analysis of ComplexSurveys. New York: John Wiley & Sons, 1989.

Use of Intrauterine Device and Risk of Invasive Cervical Cancer

Abstract

Similar works

Full text

Available Versions

RERO DOC Digital Library