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CervicalCancerScreeningMethods

CervicalCancerScreeningMethods
HumphreyMisiri1,2 (hmisiriatgmaildotcom)
1 DepartmentofBiostatistics,InstituteofBasicMedicalSciences,UniversityofOslo,Oslo,Norway.2 DepartmentofCommunityHealth,
CollegeofMedicine,PrivateBag360,Chichiri.Blantyre3.Malawi
DOI //dx.doi.org/10.13070/rs.en.1.591
Date 20140304
Citeas Research20141:591
License CCBY

Abstract

Cervicalcancerisoneofthedeadliestcancersamongwomenintheworld.Routinescreeninghelps
detectprecancerouslesionsinwomen.Severallaboratorybaseddiagnostictestshavebeeninuseforquitea
long time. The performance of these screening methods has been assessed. This article summarizes the
evaluationstudiesforthescreeningmethodsfrom2006tillnow.

Introduction
Cervicalcancerisacommongynaecologicalcancer.Humanpapillomavirusinfectionisoneofthemostsignificant
riskfactors.InMalawi,cervicalcancerisoneoftheleadingcancersandcausesofdeathamongwomen[1].
Therearetwomaintypesofcancerofthecervix,thecommonestofwhichissquamouscancerofthecervix.Like
allothercancers,cervicalcancerisprogressiveandsocanbepreventedifdetectedearly.Mostpremalignantand
malignant changes of the uterine cervix take place at the squamocolumnar junction, the transitional zone. The
cells involved are the ectocervical squamous cells, squamous metaplastic cells and endocervical columnar cells.
Invasivesquamouscervicalcancerisusuallyprecededbyanasymptoticpreinvasivestageofthediseasewhere
the precancerous cells are confined to the epithelium of the cervix. This precancerous stage is called cervical
intraepithelial neoplasia (CIN). If precancerous lesions are diagnosed and treated, there is strong evidence that
invasivecancercanbeprevented.Evidenceexistsofthebenefitsofscreeninginreducingtheincidenceofcervival
cancer[2][3][4].Cervical cancer is caused by the human papilloma virus (HPV). More than 230 types of HPV
havebeendiscoveredbecauseofadvancesinDNAtesting[5].However,notallHPVvarietiescausecancer.
There are several tests for screening women for cervical cancer. This report attempts to provide an up to date
overviewoftheperformanceofsomescreeningmethodscurrentlyinuse.Thereviewspanstheperiodbetween
2006and2013inclusive.
Screeningmethods
The methods for screening women for cervical cancer are cytology tests, cervicography, HPV DNA tests, visual
inspectionwithaceticacidorLugolssolution(VIAorVILI),colposcopicandBiopsy.
Cytologytests

During cytology procedures, a cell sample is taken from the womans cervix, and subjected to one of two
procedures:Papsmeartest,orliquidbasedcytologytest.
Papsmeartest

Thecellsampleissmearedontoaglassslideandstained.Acytologistthenexaminestheslideforabnormalcells
underaconventionallightmicroscope.
ResultsofthePapsmeartest
Two most commonly used classification system for Pap smear tests are cervical intraepithelial neoplasia (CIN)
gradingandBethesdaclassificationsystem.Table1liststhedescriptionofresultsforPapsmeartest,CINgrading
anditscorrespondingBethesdaclassification[6].
InterpretationofPapsmearresults
Description

CINGrading

Bethesda
System

Normal

Normal

Normal

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Atypia,Reactiveor
Neoplastic

Atypia

ASCUS

HPV

HPV

Lowgrade
SIL

AtypiawithHPV

Atypia,condylatomatous,atypiaand
koilocyticatypia

Lowgrade
SIL

MildDysplasia

CINI

Lowgrade
SIL

ModerateDysplasia

CINII

Highgrade
SIL

Severedysplasia

CINIII

Highgrade
SIL

Carcinomainsitu

CIS

Highgrade
SIL

Pap smear test examines the cervical

cells at the intraepithelial layer. The
testresultcanbenormal,orabnormal
or if the results are unclear, ASCUS.
Another test is usually needed to
establish a definitive diagnosis in the
case of ASCUS [2]. Early changes in
shape and size of the intraepithelial
cells are called lowgrade squamous
intraepithelial lesions (LSILs) [2].
These are regarded as mild cell
abnormalities. These changes can

also be classified as CIN1. In some

cases, there are evident changes in
the intraepithelial cells such that the
Table1.DescriptionofresultsfromaPapsmeartestandclassificationof
abnormalities of the cells are severe.
squamouscellabnormalities.Source://www.oncolink.org/types/article1.cfm?
id=6028.
Thechangesinshapeandsizeofthe
intraepithelial cells are so great that
thecellslookcompletelydifferentfromnormalcells.Theselesionsarecalledhighgradesquamousintraepithelial
lesions(HSILs)[2].Theseprecancerouslesionshaveaveryhighlikelihoodofprogressingtocanceriftheyarenot
treated. HSILs can be CINI, CINII, depending on whether the lesions exhibit signs of moderate or severe
dysplasia and carcinoma in situ (CIS). When test results are not normal, other tests like the HPV test and
colposcopic examination can also be used as followup procedures. The gold standard for cervical screening
methodsisabiopsy.Theroutineuseoffollowuptestslikethecolposcopicexaminationisadvisableonlyifthere
are suspicions of cervical cancer otherwise this may lead to increased costs if screening is conducted on a
massive scale [7]. The main advantage of conventional cytology is its high specificity. However, it has a low
specificity.Mucusorbloodcanmakeslidesunreadable,therebyresultinginabignumberofASCUScases.
Invasivecancer

Invasive
cancer

Invasivecancer

Liquidbasedcytologytest(LBC)

During liquidbased cytology tests, a cervical cell sample is placed into a liquid solution, which acts as a
preservative.Alaboratoryinstrumentthenremovesexcessblood,mucous,andinflammatorycellsandspreadsa
thin layer of cells onto a glass slide. The cells are stained and examined under a microscope. Automated
technologycanalsobeusedtoevaluatetheslide[8].Thesensitivityofsuchautomaticproceduresisconsidered
to be inferior to the sensitivity of manual examination. The grading or classification of results from a LBC test is
similar to that described for the Pap smear. The LBC is deemed more convenient. The quality of the sample of
cellstendstobehigher,andslidesareoftenclearer,leadingtoaccurateassessmentsoftheslides.Thetestisstill
subjectivesincetheratingoftheslidedependsontheexaminers.
Colposcopy

A colposcopy, a type of microscope with low power, is used to examine a woman's cervix. A colposcopic
examinationisconductedasafollowuptestwhentheresultofaPapsmearorLBCtestisabnormal.Aceticacid
orLugolssolutionisappliedonthebirthcanalorcervixusingaswabtohelpvisualization.Thistestisusuallyused
asareferenceonitsownorwithbiopsy.
Visualaidedinspectionofthecervix

The practice of looking at a cervix in order to detect cervical cancer disease in its early stages is called down
staging or unaided visual inspection (VI). Before 1987, this was one of the methods for detecting diseases in
women [9]. From 1987 to date, dilute acetic acid (35%) or Lugols iodone is applied to the cervix to help
inspection.ThemethodiscalledVisualInspectionwithAceticAcid(VIA)orVisualInspectionwithLugolssolution
(VILI), depending one which solution is used. The reference standard for assessing the performance of VIA is
colposcopy with directed biopsy. In some cases, a handheld device like a magnifying glass is used in VIA. The
performanceofVIAorVILIdependsontrainingofpersonnelandtypeoflightsource.TheresultsofVIAorVILI
areclassifiedasinTable2.
A
more
detailed
classification of the
resultsisinTable3.

Description

VIA
has
many
advantages. The test

Normal

Possible
Characteristics
threshholds
A

Normallookingcervix:nowhitelesion,smooth,uniform,featureless
Atypicalcervix:ectopion,polyp,cervicitis,inflammation,Nabothian
cysts

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isrelativelysimpleand
no specialized skills
are
required.
Paramedics
and
health workers after
simple training can
perform it. VIA is
cheap,
does
not
require
special
infrastructure, causes

Classification

Indeterminate +

Severeinflammationorcervicitissothatcervixcannotbe
adequatelyassessedforacetowhitelesion

Illdefined
lesion

Palewhitelesion(acetowhitelesion),poorlycircumscribedand
faintlyacetowhiteFocal,smallpunctuatedareasofacetowhitening
usuallyinvolvingthetransformationzone

Definite
lesion

Densewhitelesionwithsharpborderoneborderabuttingthe
squamocolumnarjunction

Suspicious
cancer

CervicalulcerorgrowthcauliflowerlikegrowthorulcerFungation
mass

Table2.Classificationofresultsofvisualinspectionwithaceticacid.:negative+:positive.Source:
IARC.2005.

Appearanceofthecervix

Smooth,pink
Clearmucoidsecretion
Normal

Centralholeexternalos
Nulliparoursround
Multiparousslitorcriciate
Cervixinpostmenopausalwomenisatrophic
Hypertrophy
Rednessorcongestion
Irregularsurface

no discomfort, and requires

only 2 3 minutes. It does not
need transport or special
personnel. Consequently, it
can be used even at rural
hospitals.
The
major
limitations of VIA are that the
testisunreliableforscreening
postmenopausal women and
has a lower specificity
compared to that of the Pap
test.Ithasahighrateoffalse
positives.
Cervicography

Distortion

This method was invented in

1981 [10]. To perform
Abnormal
cervicography, acetic acid
Cervicalpolyps(withsmoothsurface)
(5%) is applied to the cervix
Abnormaldischarge:foulsmelling,dirty/greenish,
andaspecialisedcamerawith
cheesywhite,bloodstained
a fixed focal length and
Nabothianfollicles
internallightsourceisusedto
Prolapseduterus
takepicturesofthecervix.The
photographs
are
called
Erosionthatbleedsontouchorfriable
Suspiciousof
cervigrams. These pictures
malignancy
are similar to what is seen
Growth,withanirregularsurfaceorfriable
during
colposcopy.
The
photographs are interpreted
Table3.Classificationofresultsofvisualinspectionwithaceticacid
by specially trained people.
TheresultsofcervicographyareclassifiedaccordingtotheclassificationshowninTable4.
Simpleerosions(donotbleedontouch)

Cervicography benefits from

the advances in photography
technology.Itisrelativelyeasy
to take clear pictures of the
cervix. However, the method
can produce blurry or dark
photographswithoutadequate
lighting.
Besides,
cervicography
is
also
subjective
TheHPVtest

Classification Description
Negative

Nodefinitelesionisvisible

Atypical1(A1)

Alesioninsidethetransformationzoneisvisiblebasedonthelesion's
siteandmorphology,thelesionispresentlyconsideredtobeofdoubtful
significance

Alesionoutsidethetransformationzoneisvisiblebasedonthelesions
Atypical2(A2): siteandmorphology,thelesionispresentlyconsideredtobeofdoubtful
significance
Technically
defective

Thecervigramslideisnotadequateforevaluation"koilocytic"atypia

Table4.Classificationofresultsofcervicography.Source:IARC,2005

This method detects the

presence of DNA or RNA from carcinogenic HPV types 16 and 18 in cervical cells. There are two main
approaches: polymerase chain reaction method (PCR) and hybrid capture method (HC) [5]. Many DNAbased
HPVtestsarevariationsofthePCRorHCtests.ExamplesofHPVtestsaredigeneHCIIassay[3],HybridCapture
II(HCII),careHPVtest[11],HybridCapture((R))2(HC2)[12],CervistaHPVtestandRocheAMPLICOR[13].The
HPVtestisdeemedeffective[14].
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More than 200 types of HPV have been discovered [5]. These HPV types are classified as low or high risk
according to whether they are associated with low or high grade lesions respectively [5]. Research has
documentedaspectrumofHPVtypeswithknownproportionofcervicalcancerstheycause[15]. Table 5 shows
someHPVtypesandcorrespondingattributablefractions.

HPVType

Percentageofcervical
cancerscaused

Cumulative
total

HPV16

54.6

54.6

HPV18

15.8

70.4

HPV33

4.4

74.8

HPV45

3.7

78.5

HPV31

3.5

82

HPV58

3.4

85.4

HPV52

2.5

87.9

HPV35

1.8

89.7

HPV59

1.1

90.8

HPV56

0.8

92.2

HPV51

0.7

92.9

HPV39

0.7

93.6

HPV73

0.5

94.1

HPV68

0.5

94.6

HPV82

0.2

94.8

Notype
identified

5.2

100

Table5.Proportionofcervicalcancerscausedbythe
carcinogenicHPVtypes.Source:Schiffmanetal(2007)

One advantage of the HPV test is the availability of

many varieties. All HPV tests are very sensitive and
objective.Thesamplesmustbefreeofcontamination
andDNAsequencingmustbeaccurate.
Methods
Published studies assessing the performance of
VIA,VILI,LBC, Pap test, HPV test and cervicography
were identified from PUBMED database. Of our
interest were studies conducted between 2006 and
2013 inclusive which had colposcopy or biopsy as a
referencediagnosis.ThekeywordsusedinPUBMED
search were cervicography, visual aided
inspection, pap smear,evaluation, HPV test,
liquidbasedcytology,colposcopy,andbiopsy.
Results
Among the 152 evaluation studies we identified, only
25studiesweredeemedofhighqualitytobeincluded
in this review. The excluded studies were either of
poor quality, or descriptive but theoretical, or without
extractable information about the performance of
screening tests. A good number of excluded studies
had statistics but the key indices of diagnostic
performance like sensitivity and specificity were

missing.Table6liststhedataonthe25studies.

Method

Lesion
threshhold

SE*

SP*

HRHPV

CIN2+

95.3

56.1 63.3 93.8

Pap

CIN2+

82.4

92.5 89.7 86.8

Colposcopy/biopsy HC2

CIN2+

77.8

79.4 20.4 98.1

Colposcopy/biopsy HPVDNA

HSIL

96.0

92.9 96.0 92.9

Pap

CIN2+

40.0

97.0

HPVDNA

CIN2+

93.0

89.2

CIN2+

82.5

93.6 52.4 98.4

CIN2+

87.5

93.2 52.2 98.9

CIN2+

77.5

87.3 34.1 97.9

14.8

95.4

CIN2+

100.0 69.1

GP5+/+6and
Physician
HPV

CIN2+

98.0

48.1

SelfHPVand
SPF(10)
DEIALiPA

CIN2+

95.9

42.9

HPVProofer

CIN2+

78.1

75.5

HCII

CIN2+

95.8

39.6

Pap

HSIL+

93.3

83.5

HCII

HSIL+

93.3

90.8

mRNAtest

CIN2+

72.0

73.0 39.0

Study

Samplesize Age

Reference

Maetal(2010)

192

Colposcopy/biopsy

Chengetal
(2013)

424

Wangetal(2011) 97

LazcanoPonce
etal(2013)

50159

2070

Colposcopy/biopsy SelfHPV
Physician
HPV

Bhattaetal(2009) 546
BomfimHyppolito
1292
etal(2006)

Geraertsetal
(2013)

30+

Colposcopy/biopsy Pap
Pap

Colposcopy/biopsy Digital
cervicography

Colposcopy/biopsy

Ratnamet
al(2010)

1551

Colposcopy/biopsy

Kumaret
al(2007)

133

Colposcopy/biopsy

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PPV NPV

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Benevoloetal
(2011)

Szarewskietal
(2012)

Maoetal(2007)

Bhattaetal
(2007)

CervicalCancerScreeningMethods
464

1099

319

100

Balasubramanian
1981
etal(2009)

Colposcopy/biopsy
LBC
BDHPV

CIN2+
CIN2+

58.0
95.0

99.0 93.0
24.2

HCII

CIN2+

96.3

19.5 37.4

AbbottReal
time

CIN2+

93.3

27.3 38.2

Aptima

CIN2+

95.3

28.8 39.3

CIN2+

74.1

70.8 55.4

CINtec
p16(INK4a)

CIN2+

85.7

54.7 49.1

cytology

CIN2+

Papat
colposcopy

mild
dyskaryosis 88.9
orworse

PreTectHPV
Colposcopy/biopsy Proofer

35.4

Colposcopy/biopsy p16(INK4a)
ELISA(conc> CIN3
or=8units/ml)

83.0

46.9

Colposcopy/biopsy

VIA

HSIL+

100.0 55.3

HPV

HSIL+

85.7

89.7

Pap

HSIL+

50.0

98.9

VIAthenHPV

HSIL+

85.7

95.4

50.9

90.4

58.1

p16(INK4a)
ELISA(>or=8
pg/mLcut
Median
Colposcopy/biopsy point)
23
HCII

Monsonegoetal
(2006)

Belinsonet
al(2012)

Jiangetal(2011)

Wentzensenet
al(2012)

10000

246

625

Colposcopy/biopsy

Colposcopy/biopsy

Mean
38.9

2536

<30

89.3

100.0 69.2

LSIL

45.5

HSIL+

76.5

Colposcopy/biopsy

Colposcopy/biopsy

858

Cancer

88.8

Pap

ASCUS+

94.5

30.0

HCII

ASCUS+

90.0

54.3

HCII&Pap

ASCUS
LSIL

66.7

41.3

HPV
CIN3+
Cervista(PCR)

70.9

Pysician
collected

CIN3+

95.0

MALDI
TOF(PCR)

CIN3+

(SelfCollected
CIN3+
cells)

94.3

Pysician
collected

CIN3+

94.3

highriskHPV
DNAtest

CIN2+

79.8 86.5 96.0

highriskHPV
DNAtest

CIN3+

91.3

98.7

highriskHPV
DNAtest

LSIL

90.0

highriskHPV
DNAtest

HSIL+

100.0

p16/Ki67

93.2

46.1

Colposcopy/biopsy p16/Ki67

97.2

60.0

CIN3

90.6

48.6

CIN3+

98.9

31.5

Glucyte

CIN2+

86.9

49.2

ThinPrep

CIN2+

81.9

61.6

p16/Ki67
Cuzicket
al(2010)

59.1 50.7

90.0

urine/cervix
HPV(PCR)
100

Immunoassay CIN3

Pap

Daponteetal
(2006)

Colposcopy/biopsy Abbott
LBC

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Alaghehbandan
etal(2013)

Fletcheret
al(2011)

Josietal(2013)

Angstetraetal
(2009)

Wentzesenetal
(2007)

CervicalCancerScreeningMethods
331

28

1128

528

245

Colposcopy/biopsy SurePath

Colposcopy/biopsy

Colposcopy/biopsy

Colposcopy/biopsy

CIN2+

83.7

66.9

Glucyte

HSIL+

40.5

93.8

ThinPrep

HSIL+

20.5

99.1

SurePath

HSIL+

54.7

94.3

ProExC

CIN2+

100.0 87.0

VIA

ASCUS

83.6

88.8

VILI

ASCUS

89.1

89.3

Pap

ASCUS

63.3

94.5

HPVtest

ASCUS

94.6

77.4

LBC

HSIL

89.1

83.1

Pap

HSIL

88.6

84.7

LBC

ASCUS+

86.6

53.8

Pap

ASCUS+

87.0

56.4

LBC(p16INK4)

ASCUS&
LSIL

96.0

83.0

LBC(p16INK4) ASCUS

95.0

84.0

LBC(p16INK4) LSIL

100.0 81.0

Table6.TheperformanceofVIA/VILI,LBC,Pap,HPVtestandcervicographyindifferentstudies.

Conventionalcytology,digitalcervicography,andVIA/VILIwerewithoutanyvariants.Liquidbasedcytologyhadthe
followingvariants:p16INK4immunoassay,ThinPrep,SurepathandGlucyte.HPVtesthadthebiggestnumberof
varieties,someofwhichwere:ProExc,HCII,Abbott,highriskHPVtest,Cervista,MALDITOF,SPF(10)DeIALiPA,
GP5+/6+HRHPV,Abbott, BDHPV,PreTect,ProofermRNA,Aptima and CINtec. HPV tests and LBC were the most
commontestsinevaluationstudies.Thestudiesinthisreviewhavevariablesamplesizes.ThePaptesthadhigh
specificity.HPVtests,cervicography,andVIAweresensitivetests.WhenCINclassificationwasusedtodescribe
lesion thresholds, it was found that LBC tests which used Glucyte and ThinPrep were very sensitive, unlike LBC
tests which used Surepath. HPV tests were more sensitive in detecting lesions. For all screening tests, the CIN
classification is associated with very high values of sensitivity. The Bethesda classification is associated with few
butunusuallylowsensitivityvalues.
Discussion
Thisreviewshowsthatthesensitivityofatestisaffectedbythesettings,anyvariationofatestused,thecutofffor
diagnosis (lesion threshold) and the sample size. The study also indicates that different varieties of HPV have
differentsensitivitiesandspecificities.VIA/VILIareverysensitivetests.ThePaptesthasamodestsensitivitybuta
veryhighspecificitywhereasdigitalcervicographyhasaveryhighsensitivity.
Screeningtestswith100%specificityorsensitivityarealwaysrareornonexistent.Thesettingisoneofthefactors
which can affect the choice and performance of screening tests. That may explain why all the tests bar
cervicographyhaddifferentsensitivitiesindifferentstudiesconductedindifferentsettings.Forinstance,availability
ofwelltrainedpersonnel,theequipmentordevicesorreagents,andtheconditionorqualityofavailabledevicesor
reagentsvaryfromplacetoplace.Allthesecanaffecttheperformanceofascreeningtestinonewayoranother.
Different tests may also be preferred in different localities depending on different reasons. Therefore, it is
advisabletoconductanevaluationstudycomparingtheperformanceofseveralscreeningmethods.Themethod
whichiscosteffectiveandperformsbetterinthatparticularlocationshouldbeadoptedforuseasthemethodof
choice.
DuringPapsmeartests,VIAorVILIandLBCtests,theslidesorphotographsareevaluated.Twopeoplereading
thesameslidecanarriveattwodifferentconclusions.Methodswhereforexampleprecancerouslesionsaretobe
detectedbyassessingapictureofthecervixorbylookingatacervixsmearedwithaceticacidarealsoproneto
subjectivitybecausedifferentpeoplelookingatthesamepictureorstainedcervixmayseedifferentthings.Some
ofthereasons[16]ofthesubjectivitywhichmaycontributetouncertaintywhenscreeningforcervicalcancerare
lackofadequateexperienceonthepartoftherater,poortrainingoftherater,differencesinthescalesofrating
used, poor quality of fixation of slides (in Pap smears), imprecise classification rules, an overelaborate
classificationscale,ratermisunderstandingoftheclassificationrules.
Uncertaintyinscreeningleadstofalsepositivesandfalsenegatives.Followuptestsarerecommendediftheresult
is that the woman has abnormal results. The recommended gold standard for cervical cancer screening is an
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invasive biopsy. Colposcopy is also a noninvasive reference test. All the studies selected for this review had
colposcopyorbiopsyasthegoldstandard.
ThefindingsinthisstudyshowthatLBCandconventionalcytologyaremoderatelysensitivetests.Infact,thereis
noconsensusonwhichofthetwocytologytests(PapsmearandLBC)ismoresensitiveorspecificthantheother.
A metaanalysis of prospective studies [17] comparing cytologic diagnosis and sample adequacy of liquidbased
cervicalcytologicsmearstudyandconventionalPapanicolaousmearsfoundthattheThinPreptesthadimproved
sample adequacy and improved diagnosis of lowgrade and highgrade squamous intraepithelial lesions. The
samestudyfoundthattherewasnodifferenceintherateofatypicalcellsofundeterminedsignificancediagnosis
betweenThinPrepandconventionalsmeargroups.Anotherstudy[4]comparedaliquidbased(ThinPrep)cytology
test and a conventional Pap smear as method for the detection of CIN ICIN II lesions found conflicting results.
Liquidbased cytology test had better sensitivity than a Pap smear test. Besides, the agreement between the
diagnosisoftheliquidbasedtestandhistologywashigherfortheliquidbasedtestthanthePapsmeartest.Other
studies reported that the liquid based cytology test showed no significant difference in sensitivity to conventional
cytology [4] [18]. Over all, the liquidbased test is convenient because a HPV DNA test can also be conducted
using the same sample. Besides, LBC produces clear slides which can be easily read and so the proportion of
ASCUSislowerthanforthePapsmeartest.
VIAperformedbetterthanconventionalcytologyinatleast2studies.Infact,thereisevidencetosuggestthatVIA
hasahighersensitivityindetectingCINIIorworselesionsthanaPapsmeartest.ABrazillianstudy[19]foundthat
VIA had the best performance in detecting CINII or worse lesions, HC II had the highest sensitivity and the Pap
smearwasthemostspecifictest.
Onefindingofcervicographyhadaveryhighsensitivity.Whencervicographywasfirstusedin1981,ithadapoor
performance. Cervicography is know to perform marginally better that LBC for the detection of invasive cervical
cancer but is not recommended for postmenopausal women [20]. However, cervicography has a moderately
higher sensitivity and a very high specificity in the special case of highgrade squamous intraepithelial lesions
(HSILs).
TheHPVtestshadhighsensitivitiesindifferentstudies.Thistestisknowntoperformbetterthancytologybased
tests [22] [23] and VIA. The HPV test can be performed on a sample of cervical cells collected by a physician
(PhysicianHPVtest)orbythewomanherself(SelfHPVtest).OurfindingsshowthatthesensitivitiesofSelfHPV
testscomparedfavourablywellwiththosephysicianHPVtests.Infact,astudyreportedthatthesensitivityofthe
SelfHPVtestcomparesfavourablywiththatoftheLBCandissuperiortothesensitivityofVIA[24].Thephysician
HPVtestperformsslightlybetterthantheSelfHPVtestalthoughthemarginisnarrow.VIAandVILIarereputedto
beslightlymoresensitivebutlessspecificthanPap[25].
ThefactthattheSelfHPVtestperformswellisagooddevelopmentbecauseitimpliesthatwomenwillbesaved
from the shame of having to undress before doctors and nurses. Obviously, screening for cervical cancer is a
procedure which can be interpreted as a violation of sexual modesty as the subject to be screened has to be
partiallyundressedinwhichcasethegenitalregionisexposed.
Limitation
The search for evaluation studies was conducted on Medline only. Other databases like EMBASE were not
searchedbecauseoflimitedinternetconnectivity.
Conclusions
HPV test, VIA/VILI and LBC are very sensitive tests which can be used in a screening program. However the
performance of HPV tests varies from setting to setting. A screening method should be selected based its
performanceandcosteffectivenessinaparticularsetting.Acombinationofcosteffectivescreeningtestscanalso
beadoptedifthemethodsareofhighperformance.
Acknowledgements
IamthankfultoNUFUforsponsoringmeduringlate2013whenIstartedworkingonthispaper.
References
1.MisiriH,DzamalalaC,EdrissA,ParkinMD,BrayF:CancerincidenceinMalawi:TimetrendsinBlantyre19962005and
predictionsupto2015.GlobalAdvancedResearchJournalofMedicineandMedicalSciences2012,1(6):14451153.
2.PapandHPVTesting.Availablefrom:

www.cancer.gov/cancertopics/factsheet/detection/PapHPVtesting

https://www.labome.org/research/CervicalCancerScreeningMethods.html

7/8

11/28/2016

CervicalCancerScreeningMethods

3.MandelblattJ,LawrenceW,WomackS,JacobsonD,YiB,HwangY,etal.BenefitsandcostsofusingHPVtestingtoscreenfor
cervicalcancer.JAMA.2002287:237281 pubmed
4.ZhuJ,NormanI,ElfgrenK,GaberiV,HagmarB,HjerpeA,etal.AcomparisonofliquidbasedcytologyandPapsmearasa
screeningmethodforcervicalcancer.OncolRep.200718:15760 pubmed
5.CarvalhoN,DelCastilloD,PeroneC,JanurioJ,MeloV,BrasileiroFilhoG.ComparisonofHPVgenotypingbytypespecificPCR
andsequencing.MemInstOswaldoCruz.2010105:738 pubmed
6.ColposcopicExamination(patientoriented.Availablefrom:

www.oncolink.org/types/article1.cfm?id=6028

7.SherrisJ,WittetS,KleineA,SellorsJ,LucianiS,SankaranarayananR,etal.Evidencebased,alternativecervicalcancerscreening
approachesinlowresourcesettings.IntPerspectSexReprodHealth.200935:14754 pubmed publisher
8.KitchenerH,BlanksR,DunnG,GunnL,DesaiM,AlbrowR,etal.Automationassistedversusmanualreadingofcervicalcytology
(MAVARIC):arandomisedcontrolledtrial.LancetOncol.201112:5664 pubmed publisher
9.IARC:Cervicalcancerscreening.Lyon,France:IARCPress2005.
10.StaflA.Cervicography:anewmethodforcervicalcancerdetection.AmJObstetGynecol.1981139:81525

pubmed

11.QiaoY,SellorsJ,EderP,BaoY,LimJ,ZhaoF,etal.AnewHPVDNAtestforcervicalcancerscreeningindevelopingregions:a
crosssectionalstudyofclinicalaccuracyinruralChina.LancetOncol.20089:92936 pubmed
12.CuzickJ,ArbynM,SankaranarayananR,TsuV,RoncoG,MayrandM,etal.Overviewofhumanpapillomavirusbasedandother
noveloptionsforcervicalcancerscreeningindevelopedanddevelopingcountries.Vaccine.200826:K2941 pubmed publisher
13.MonsonegoJ,BohbotJ,PolliniG,KrawecC,VincentC,MerignarguesI,etal.PerformanceoftheRocheAMPLICORhuman
papillomavirus(HPV)testinpredictionofcervicalintraepithelialneoplasia(CIN)inwomenwithabnormalPAPsmear.Gynecol
Oncol.200599:1608 pubmed
14.LongattoFilhoA,ErzenM,BrancaM,RoteliMartinsC,NaudP,DerchainS,etal.Humanpapillomavirustestingasanoptional
screeningtoolinlowresourcesettingsofLatinAmerica:experiencefromtheLatinAmericanScreeningstudy.IntJGynecol
Cancer.200616:95562 pubmed
15.SchiffmanM,CastleP,JeronimoJ,RodriguezA,WacholderS.Humanpapillomavirusandcervicalcancer.Lancet.2007370:890
907 pubmed
16.MisiriH:Impactofinterobservervariabilityontheconfidenceinterval/reliabilityofthecytologicalreportingofpapsmears.MSc
Thesis.Hasselt:HasseltUniversity1998.
17.BernsteinS,SanchezRamosL,NdubisiB.LiquidbasedcervicalcytologicsmearstudyandconventionalPapanicolaousmears:a
metaanalysisofprospectivestudiescomparingcytologicdiagnosisandsampleadequacy.AmJObstetGynecol.2001185:30817
pubmed

18.RoncoG,CuzickJ,PierottiP,CariaggiM,DallaPalmaP,NaldoniC,etal.Accuracyofliquidbasedversusconventionalcytology:
overallresultsofnewtechnologiesforcervicalcancerscreening:randomisedcontrolledtrial.BMJ.2007335:28 pubmed
19.BraganaJ,DerchainS,SarianL,MessiasdaSilvaS,LabatteS,ZeferinoL.Aidedvisualinspectionwithaceticacid(VIA)andHPV
detectionasoptionalscreeningtoolsforcervicalcanceranditsprecursorlesions.ClinExpObstetGynecol.200532:2259 pubmed
20.SchneiderD,HerreroR,BrattiC,GreenbergM,HildesheimA,ShermanM,etal.Cervicographyscreeningforcervicalcancer
among8460womeninahighriskpopulation.AmJObstetGynecol.1999180:2908 pubmed
21.SzarewskiA,CuzickJ,EdwardsR,ButlerB,SingerA.Theuseofcervicographyinaprimaryscreeningservice.BrJObstet
Gynaecol.199198:3137 pubmed
22.KinneyW,StolerM,CastleP.Specialcommentary:patientsafetyandthenextgenerationofHPVDNAtests.AmJClinPathol.
2010134:1939 pubmed
23.CuzickJ,ClavelC,PetryK,MeijerC,HoyerH,RatnamS,etal.OverviewoftheEuropeanandNorthAmericanstudiesonHPV
testinginprimarycervicalcancerscreening.IntJCancer.2006119:1095101 pubmed
24.ZhaoF,LewkowitzA,ChenF,LinM,HuS,ZhangX,etal.PooledanalysisofaselfsamplingHPVDNATestasacervicalcancer
primaryscreeningmethod.JNatlCancerInst.2012104:17888 pubmed publisher
25.SangwaLugomaG,MahmudS,NasrS,LiarasJ,KayembeP,TozinR,etal.Visualinspectionasacervicalcancerscreening
methodinaprimaryhealthcaresettinginAfrica.IntJCancer.2006119:138995 pubmed
ISSN:23341009

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