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Incidence
Theincidencerate(IR)isdefinedasthenumberofnewcasesofdiseaseinapopulation
withinaspecifiedtimeperiod:
IR=Newcases/Person-time
The fact that time is a component of the denominator should help clinicians avoid the
misapplication of this term to prevalence—anothermeasure of disease occurrence that
includesbotholdandnewcasesexistingatasinglepointintime.
CancerIncidenceandMortality
Cancerincidenceormortalityisusuallystatedascases(ordeaths)per100,000people
peryear,orascasesper100,000person-years.Incidenceormortalityismeasuredina
specificpopulationoveraspecificperiod.For example,countryorstatecancerregistries
countthenumber of new cancer cases diagnosedorcancerdeaths among residents over a
yearanddividethatfigurebycensusestimatesofthetotalpopulationintheregion.
CrudeIncidenceorMortality
Crudeincidenceormortalityisthetotalnumberofnewcancers(ordeaths)thatoccur
overaspecifiedtimeintheentirepopulation.
Age-SpecificIncidenceorMortality
Age-specific incidence (or mortality) is the number of new cancers (or deaths) that
occuroveraspecifiedtimeamongindividualsofaparticularagegroupdividedbythe
totalpopulation in thatsameagegroup. Age-specificincidenceormortalityratesare
thebestwayto describe the occurrence of cancerin a population and arecommonly
graphedin5-or10-yeargroups.Annualage-specificincidenceandmortalitycurvesforthe
common malignant gynecologic cancers in the United States based on all women in the
Surveillance, Epidemiology, and End Results (SEER) program for 2006 to 2016 are
shown in Figures 7.1Aand B (3). Invasive cervical cancer shows a gradual rise and
plateauafter40yearsofageat approximately15 casesper 100,000women-years.These
ratesdonotincludeinsitucervicalintraepithelialneoplasia(CIN).Thevastmajorityofthese
casesareseenbetweentheagesof20and50years,withapeakoccurrenceofapproximately
200casesper100,000womenperyearatages25to29.
Figure 7.1 A: Age-specific incidence curves for the gynecologic cancers in women in the
UnitedStates,1992–2016.B: Age-specificmortalitycurves for the gynecologic cancers
inwomenin theUnitedStates,1990–2016. Endometrialcancersarecancers ofthecorpus
uteri including sarcomas. (Modified from Howlader N, Noone AM, Krapcho M, et al., eds.
SEER Cancer Statistics Review, 1975–2016, National Cancer Institute. Bethesda, MD.
Available at https://seer.cancer.gov/csr/1975_2016/, based on November 2018 SEER data
submission,postedtotheSEERwebsite,April2019.)
Endometrial cancer rises during the perimenopause and peaks at approximately 90
casesper100,000women-yearsafter60yearsofage.Dramaticchangesintheincidenceof
endometrial cancer have occurred over the past decades, with a sharp increase in the late
1970sand1980sassociatedwith useofunopposedestrogenfor menopause,then adecline
withuse andtypeof menopausalhormones toamore recentincrease thatlikelycorrelates
withincreasingtrendsinobesity(4).
Ovariancancerdisplaysanincreaseduringtheperimenopauseandpeaksafter70years
ofageatapproximately50casesper100,000women-years.Mortalityandincidenceratesof
ovarian cancer in the United States have declined in recent decades (5). Although
improvements in survival may account for some of the decline in the mortality (6), this
wouldnotexplainchangesinincidencewhichhavedeclinedinparalleltomortalityandhave
beenattributedtotheincreaseinoralcontraceptiveuse(7).Morerecentdeclinesinovarian
cancerincidence atthe same timethat ratesoffallopian tubecancer haveincreasedwould
suggestashiftinpathologists’assignmentofprimarysites(8).
Table7.1LifetimeRiskofAcquiringorDyingfromGynecologicCancersinWhiteandBlackU.S.
Women
a
CumulativeIncidenceorMortality
Cumulativeincidence(ormortality)maybethoughtofastheproportionofpeoplewho
develop disease (or die from it) during some period of observation. Cumulative
“incidence”is technicallya misnomer becauseit doesnotcontain timein thedenominator
but,rather,isexpressedasapercentage.
Thecumulativeincidence(CI)maybecrudelyapproximatedfromage-specificIRsby
thefollowingformula:
whereIRiistheage-specificratefortheiagestratumand∆Tiisthesizeoftheageinterval
oftheistratum(usually5years).
Cumulative incidence, summed over the age range 0 to 85 years, yields the “lifetime
risk”forcanceroccurrenceordeath.LifetimerisksthatawomanintheUnitedStateswill
haveordiefromcancerofthecervix,corpus,orovaryareshowninTable7.1and confirm
that a U.S. woman has a greater risk of developing cancer of the corpus than cervical or
ovariancancer,butahigherriskofdyingfromovariancancerthancervicalandendometrial
cancerscombined.
Age-AdjustedIncidenceorMortality
Age-adjustedincidence(AAI)ormortalityisobtainedbysummingweightedaverages
oftheincidenceormortalityratesforeachagestratum.Theweightisderivedfromthe
agedistributionofastandardpopulation:
whereIRiistheIRintheiagestratum,andWiisthenumberofpeopleintheistratuminthe
standardpopulation.
Age-adjustedratesarebetterthancruderatesforsummarizingincidenceormortality
when comparing cancer occurrence among populations that may differ in their age
structure.An“old”populationwouldhaveahighercrudeincidenceofovariancanceranda
lower crude incidence of carcinoma in situ of the cervix than a “young” population, even
though both populations might have identical age-specific incidences for each disease.
Cancerratesadjustedtothe“worldpopulationstandard”areshowninTable7.2.
Worldwide, cervical cancer is the most prevalent of the gynecologic cancers and is
secondonly to breast cancerinoverall occurrence. Cervical cancer is most frequent in
southernAfricaandCentralAmericaandleastfrequentinNorthAmericaandpartsofAsia.
EndometrialcancerismostfrequentinNorthAmericaandleastfrequentinAfricaandAsia.
OvariancancerismostfrequentinnorthernEuropeandleastfrequentinAfricaandAsia.
Prevalence
Prevalence(P)istheproportionofpeoplewhohaveaparticulardiseaseorconditionat
aspecifiedtime.Prevalence can becalculatedby multiplying incidencetimesthe average
durationofdisease:
Prevalence=Incidence×Averagedurationofdisease
Morecommonly,prevalenceisderivedfromcross-sectionalstudiesinwhichthenumber
ofindividualsalivewithaparticularconditionisidentifiedfromasurveyandstatedas
apercentageofthetotalnumberofpeoplewhorespondedtothesurvey.Otherexamples
ofstudiesthatyieldprevalencedataarethosebasedonautopsyfindingsandscreeningtests.
Thefrequencyofpreviouslyunidentifiedcancersfoundinaseriesofautopsiesyieldsdataon
the prevalence of occult cancer. The first application of a screening test in a previously
unscreenedpopulationyieldstheprevalenceofpreclinicaldisease.
CancerSurvival
Whentheproportionof patients surviving cancer is plotted against time, the pattern
oftenfitsanexponentialfunction,meaningthattherateofdeathisconstantovertime,
whichcan be demonstrated by plottingthelogarithm of the probability ofsurvivalagainst
timeanddemonstratingastraightline.Summarymeasuresforasurvivalcurvecommonly
includemediansurvivaltime,orthepointatwhich50%ofthepatientshavedied,and
theprobabilityofsurvivalat1,2,and5years.
Table7.2Age-AdjustedIncidenceRatefortheGynecologicCancersinComparisonwithOtherMajor
CancersinWomenin2018
a
RelativeSurvival
Relativesurvivalisdefinedastheratiooftheobservedsurvivalforthepatientgroupto
the survival expected for a population with similar demographic characteristics.
RelativesurvivalforU.S.womendiagnosedbetween2000and2014isshowninFigure7.2
for the major gynecologic cancers and reveals that survival is best after diagnosis of
endometrialcancer,worstafterovariancancer,andintermediateaftercervicalcancer.FiveyearrelativesurvivalisshowninTable7.3bytypeandstageofgynecologiccancerforU.S.
women.Stage at presentation and 5-yearsurvivalaremost favorable for endometrial
cancerandleastfavorableforovariancancer.Ingeneral,blackstendtobediagnosedat
moreadvanced stages and have poorersurvivalcomparedwithwhites, especially for
endometrialandcervicalcancers.
EtiologicStudies
Indistinctiontodescriptivestudies,etiologicstudiesexaminetherelationshipbetween
cancer occurrence and survival and personal factors such as diet and reproductive
history. This relationshipisoften described by the epidemiologic parameters, relative
risk,andattributablerisk.
RelativeRisk(RR)istheriskofdiseaseordeathinapopulationexposedtosomefactor
ofinterestdividedbytheriskinthosenotexposed.Absenceofassociationisindicatedby
anRRof1(nullvalue);anumbergreaterthan1mayindicatethatexposureincreasestherisk
ofdiseaseandanumberlessthan1thatexposuredecreasestheriskofdisease.
Attributableriskistheriskofdiseaseordeathinapopulationexposedtosomefactorof
interestminustheriskinthosenotexposed.Thenullvalueis0;anumbergreaterthan0
may indicate that exposure increases the risk of disease and a number less than 0 that
exposuredecreasestherisk.
Case–ControlStudy
Inacase–controlstudy,diseasedandnondiseasedpopulationsareselected,andexisting
orpast characteristics(exposures)areassessed to determine the possible relationship
betweenexposureanddisease.Theinvestigatorstartswithdiseasedcasesandthenselectsa
sampleofnondiseasedcontrolswhoarerepresentativeoftheunderlyingpopulationthatgave
risetothe cases and are then studied to determine whethertheyhada particular exposure
(beforetheillness).
Figure7.2Relativesurvival for invasive cancers of the cervix, corpus,andovariesfor
womendiagnosedintheUnitedStates,2000–2014.Endometrialcancersarecancersofthe
corpusuteriincludingsarcomas.(ModifiedfromHowladerN, NooneAM,KrapchoM, etal.,
eds. SEER Cancer Statistics Review, 1975–2016, National Cancer Institute. Bethesda, MD.
https://seer.cancer.gov/csr/1975_2016/, based on November 2018 SEER data submission,
postedtotheSEERwebsite,April2019.)
Table7.3StageatDiagnosisfortheGynecologicCancersand5-YearSurvivalforU.S.Women
a
Figure7.3Case–controlstudy design. (ModifiedfromHowlader N, Noone AM, Krapcho
M,MillerD,BrestA, YuM,RuhlJ,TatalovichZ, Mariotto A, LewisDR,ChenHS,Feuer
EJ,CroninKA(eds). SEERCancerStatisticsReview,1975–2016,NationalCancerInstitute.
Bethesda,MD, https://seer.cancer.gov/csr/1975_2016/,basedonNovember2018 SEER data
submission,postedtotheSEERwebsite,April2019).
OddsRatio
Theoddsthatthecaseswereexposed(a/b)arecomparedwiththeoddsthatthecontrol
subjectswereexposed(c/d)inameasurecalledtheoddsratio(Fig.7.3).Itapproximates
theRR. If an entire population could be characterized by its exposure and disease status,
then the exposure odds ratio would be mathematically identical to the RR obtained in a
cohortstudy.Becauseit is feasibleto study onlysubsets of casesand control subjects,the
exposureoddsratiointhesampledpopulationapproximatestheRR,aslongasthecasesand
control subjects actually sampled were not preferentially selected on the basis of their
exposurestatus.
CohortStudies
Inacohortstudy,thegroupstobestudiedaredefinedbycharacteristics(orexposures)
thatoccurbeforethediseaseofinterest,andthe studygroupsarefollowedtoobserve
the risk of disease in the cohorts. The investigator starts with exposed and nonexposed
individuals who are monitored over time to identify the number of diseased cases that
develop.Theinitialsizeofthecohortandthenumberofyearscohortmembersarestudied
determinetheperson-timecontributedbythecohorts.
Theinvestigatorcalculatestheratesofdiseaseinexposedandunexposedsubjectsand
determines the RR or attributable risk. The ability to calculate attributable risk, the
amountofdiseasepossiblyduetotheexposure,representsanadvantageofcohortovercase–
control studies (although attributable risk can be estimated by a term called the etiologic
fractionincase-controlstudies)(4,9).
Forrareexposures, aninvestigatormay usethegeneral populationasthe unexposedgroup
andcalculateaparameterequivalenttotheRRthatisknownasthestandardizedmorbidity
ratio(Fig.7.4).
StandardizedMorbidityorMortalityRatio
The standardized morbidity or mortality ratio (SMR) is the observed number of
exposedcohortmembersinwhomdiseasedeveloped,dividedbythenumberexpectedif
generalpopulationdiseaserateshadprevailedinthecohort.
Cohortstudiesarefurtherdistinguishedbywhentheexposureandoutcomeoccurredorwill
occurinrelationtowhentheinvestigatorbeganthestudy.
RetrospectiveCohortStudy
In a retrospective cohort study, the exposures and outcomes have already occurred
whenthestudyisbegun.Forexample,studiesofsecondcancersaftertherapeuticradiation
are based on review of medical records and death certificates of women irradiated for
cervicalcancerdecadesearlier,allowingassessmentofbothexposureandoutcomeafterthey
haveoccurred.
ProspectiveCohortStudy
Inaprospectivecohort study,enrollment is restrictedtothosewhohavenothadthe
outcomeofinterestandtherelevantexposuremayormaynothaveoccurredwhenthe
study began. After the cohort is selected, the investigator must wait for the disease or
outcometoappearinthecohortmembers.TheNurses’HealthStudyisagoodexampleofa
prospectivecohortstudy(10).
ClinicalTrial
A clinical trial is a special type of prospectivecohort study in which the investigator
assigns a therapy or preventive agent in a randomized fashion to minimize the
possibility of bias accounting for different outcomes subsequently observed between
treatmentcohorts.Obviously,suchstudiescannotbeusedtoassessaharmfuleffectofan
exposureexceptasmightoccurasanunintendedsideeffectofthetherapy.Clinicaltrialsare
the only satisfactory way to assess the effect of different cancer therapies on disease