Cervical human papillomavirus infection and persistence: a clinic-based study in the countryside from South Brazil

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ww w . e l s e v i e r . c o m / l o c a t e / b j i d

The

Brazilian

Journal

of

INFECTIOUS

DISEASES

Original

article

Cervical

human

papillomavirus

infection

and

persistence:

a

clinic-based

study

in

the

countryside

from

South

Brazil

Janaina

Coser

a,b

,

Thaís

da

Rocha

Boeira

b,∗

,

Jonas

Michel

Wolf

b

,

Kamila

Cerbaro

a

,

Daniel

Simon

b

_,

_Vagner

_Ricardo

_Lunge

a

a_Curso_de_Biomedicina,_Universidade_de_Cruz_Alta_(UNICRUZ),_Cruz_Alta,_RS,_Brazil

b_Programa_de_{Pós-Graduac¸ão}_em_Biologia_Celular_e_Molecular_Aplicada_à_Saúde,_Universidade_Luterana_do_Brasil_(ULBRA),_Canoas,_RS,

Brazil

a

r

t

i

c

l

e

i

n

f

o

Articlehistory:

Received4August2015 Accepted14October2015 Availableonline17December2015

Keywords: HPVprevalence HPVpersistence Cervicalcancer Epidemiology

a

b

s

t

r

a

c

t

Humanpapillomavirus(HPV)infectioniscommoninsexuallyactivewomenandviral per-sistencemaycauseintraepitheliallesionsandeventuallyprogresstocervicalcancer(CC). ThepresentstudyaimedtoinvestigateepidemiologicalfactorsrelatedtoHPVinfection andtoevaluateviralpersistenceandCCprecursorlesionsfrequenciesinwomenfroma cityinthecountrysideofSouthBrazil.Threehundredwomenwererecruitedfroma pri-marypublichealthcareclinic.The patientswereinterviewedandunderwentsampling withcervicalbrushesforHPV-DNAdetection/typingbyaPCR-basedassayandcytological analysisbyPapsmeartest.HPVwasdetectedin47(15.7%)women.HPVinfectionwas sig-nificantlyassociatedwithyoungage(<30years)andlowsocio-economicstatus.Seventeen (5.7%)womenpresentedcytologicalabnormalities,threeofthemwithprecursorCC intraep-itheliallesions.Asubgroupof79womenhadbeenpreviouslyanalyzedandthirteen(16.4%) werepersistentlyinfected,twowithprecursorCCintraepitheliallesionsandhigh-riskHPV typesinfection(bothofthemwithoutcervicalabnormalitiesinthefirstexam).In conclu-sion,HPVinfectionwasassociatedwithyoungage(<30years)andlowfamilyincome;viral persistencewaslow(16.4%)butrelatedtoCCprecursorlesions;andHPV-DNAhighrisk typesdetectionwouldhelptoscreenCCinthepopulation.

Introduction

Human papillomavirus (HPV) is one of the most common causes ofsexually transmitted diseases in the worldwide.

∗ _{Corresponding}_author_at:_Laboratório_de_Diagnóstico_Molecular,_Universidade_Luterana_do_Brasil,_92425-900_Canoas,_RS,_Brazil.

E-mailaddress:thaisboeira@gmail.com(T.d.R.Boeira).

Ithastheabilitytoinfectepithelial andmayresist asymp-tomatic or cause a variety of diseases, including cancer.1

HPV infection is usually transient and most people elimi-nate the virus from the body with the effective action of the immune system after5.1–15.4 months.2 _However,_HPV

http://dx.doi.org/10.1016/j.bjid.2015.10.008

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persistencecancausebenignlesions,knownaswarts(in dif-ferentparts ofthebody), orlow/highgradeintra-epithelial lesions(LSIL/HSIL)thatcanprogresstocancer,mainlyinthe uterinecervix.3 _Further,_HPV_persistence _and _consequently

cervicalcancer (CC)dependsonotherfactors,suchasage, high parity,smoking,long-termuse ofcontraceptives, sex-ualbehaviorandco-infectionwithothersexuallytransmitted infectiousagents.4

HPV prevalence ranges from 13.7% to 54.3% according to the studied population and geographic area in Brazil reviewed by.5 _However, _main _{epidemiological} _studies _have

beenperformedinthecapitalsandmetropolitancities.These studies demonstrated that HPV infection was associated withmultiplesexualpartners6_;_young_age,_more_lifetime_sex

partners and abnormal vaginal flora7 _and _non-stable

sex-ualpartners.8_HPV_persistence_also_presented_frequencies_as

differentas19.2%inPorto Alegre(Rio GrandedoSulstate) and 59.6% in Ouro Preto (Minas Gerais state)in two stud-ies performed in primary public health care clinics from Brazil.9,10

Thisstudy aimedto investigateepidemiological aspects associatedwithHPVinfectionandtoevaluateHPVpersistence inwomenfromthecityofCruzAltaandsurroundingsmall localities.ThiscountrysideregionislocatedintheNorthof theRioGrandedoSul(thesouthernmoststateinBrazil)and itismorethan300kmawayfromtherespectivecapitalcity (PortoAlegre).

Methodology

Studypopulationandsamplecollection

Across-sectionalstudywasconductedwith300womenwho acceptedtoparticipateinthe studywhileattendingforCC screeninginaprimarypublichealthcareclinic(Centerfor WomenandChildren)inthecityofCruzAlta(RioGrandedo SulState,Brazil)fromJanuary2012toApril2013. Epidemiologi-calinformations(socio-demographic,behavioral,andclinical) wereobtainedfromastandardizedindividualquestionnaire thatwasadministeredbyatrainedinterviewerinaprivate room. The research projectwas approved by the Research EthicsCommitteeoftheUniversityofCruzAlta(ProtocolNo. 078.0.417-09).

After each participant gave informed consent, cervical samples were collected from all participants for HPV-DNA testing and cytologicalanalysis. Clinicalsamples were col-lected by scraping the ectocervix and endocervix of each patientwithanendocervicalbrush,smearedonaglassslide (thatwasfixedimmediatelywithpolyethyleneglycolfor cyto-logical examination) and after stored in a buffer solution (EDTApH8.00.01M,SDS0.03M),andstoredat−20◦_C_until

analysis.

Womenalsoenrolled inapreviousreport11 _or _with_two

visitsinthisstudy(minimumintervaloftwelvemonths)were identifiedtoevaluateHPVpersistence.Atotalof79 (26.3%) womenattendedthesecriteria(57evaluatedintheprevious studyand22analyzedtwiceinthisstudy)andcomposeda subgrouptoinvestigateHPVpersistence.

The clinical management of the patients was in accor-dance with the “Brazilian classificationforcervical reports andrecommendedprocedures:recommendationsforhealth professionals”.12_This_protocol_do_not_establish_HPV_testing_in

theroutinescreening,soresultsofHPVtypeswerenotused inthemanagementofthepatients.

HPV-DNAdetectionandtyping

HPV-DNA testing was performed by nested polymerase chainreaction(nested-PCR)andrestrictionfragmentlength polymorphism(RFLP)aspreviouslydescribed.13_Samples

pre-senting insufficientDNA for HPV typing were classified as inconclusive. Resultswere interpreted by twoindependent analystsandHPVtypeswereclassifiedintohigh-risk(HR)and low-risk(LR).14

Cytologicalanalysis

The cytological analysis was performed by conventional Pap smear test evaluated by two independent cytologists (conflictingresultsweresubmittedtoathirdevaluation).Cell abnormalitieswereclassifiedaccordingtotheBethesda Sys-tem2001.15_Basically,_it_classifies_the_modified_cells_into_nine

categories(fivetosquamousandfourtoglandularcells):(1) squamouscellcarcinoma,(2)high-gradesquamous intraep-itheliallesion(HSIL),(3)low-gradesquamousintraepithelial lesion(LSIL),(4)atypicalsquamouscellsofundetermined sig-nificance (ASC-US),(5)atypical squamouscells thatcannot excludeHSIL (ASC-H),(6) adenocarcinoma, (7)endocervical adenocarcinomainsitu,(8)atypicalglandularcells(AG),and (9)atypicalglandularcellsnototherwisespecified(AG-NOS). Normalcellsweredefinedasnegativeforintraepitheliallesion andmalignancy(NILM).

HPVpersistence

Womenwith twoevaluationswere classified into four cat-egoriesaccordingtotheHPVinfectionstatus:(1)persistent infection:HPV-DNApositiveinbothassessments;(2) conver-sion:HPV-DNAnegativeinthefirstvisitandHPV-DNApositive inthe follow-up;(3) elimination(clearance):HPV-DNA pos-itive onlyinthefirst evaluation;(4) withoutHPVinfection: HPV-DNAnegativeinbothvisits.

Statisticalanalysis

DataanalysiswasconductedusingtheSPSSversion17.0 soft-ware (SPSS Inc., USA). Association between HPV infection statusandothervariableswasdeterminedwiththechi-square test. Multivariate modelswere conductedusing amodified Poissonregression16_to_test_the_independent_associations_of

HPVinfectionwithsocio-demographic,behavioraland clin-icalcharacteristics.Associations thatpresentedvaluesofp

between 0.05 and 0.15 in bivariate analysis were regarded as havingborderline significanceand were included inthe modelingofconfoundingfactors.Allpvaluespresentedare two-tailedandthevaluesofp<0.05wereconsidered statisti-callysignificant.

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Table1–Analysisofsocio-demographiccharacteristicsinwomenaccordingtoHPVstatus.

Variables Overall(n=300) WithoutHPV(n=253) WithHPV(n=47) p-Valuea

Age(years) 0.003 ≤19 28(9.3) 19(7.5) 9(19.1) 20–29 56(18.7) 41(16.2) 15(31.9) 30–39 59(19.7) 50(19.8) 9(19.1) 40–49 60(20.0) 57(22.5) 3(6.4) 50–59 59(19.7) 53(20.9) 6(12.8) ≥60 38(12.7) 33(13.0) 5(10.6) Schoolingb _0.247

Elementaryorlowereducation 178(60.8) 153(62.2) 25(53.2)

Mediumorhighereducation 115(39.2) 93(37.8) 22(46.8)

Totalhouseholdincome(inBrazilianminimummonthlywage) <0.001

≤1 126(42.0) 93(36.8) 33(70.2)

2–3 162(54.0) 151(59.7) 11(23.4)

>3 12(4.0) 9(3.6) 3(6.4)

Maritalstatusb _0.014

Marriedorstableunion 56(56.6) 54(60.7) 2(20.0)

Single/divorced/widowed 43(43.4) 35(39.3) 8(80.0)

Childrenb _0.016

Yes 232(78.1) 203(80.6) 29(64.4)

No 65(21.9) 49(19.4) 16(35.6)

Dataarereportedasnumberwithpercentinparentheses.

a

2testwasusedtocomparebetweenparticipants.

b _Total_do_not_coincides_due_to_the_lack_of_data.

Results

Ofthe300womenevaluatedinthestudy,HPVwasdetectedin 47(15.7%).Ofthesepositivesamples,26(55.3%)hadsingleand 10(21.3%)multipleHPVtypeinfections(itwasnotpossibleto determinethetypeintheremaining11positivesamples).A totalof23viraltypeswereidentified;including15(65.2%)HR and8(34.8%)LR.TypesHRmostfrequentswere16(n=6),31 (n=4),45(n=4)and56(n=3).OtherHRtypeswere18,35,39, 52,53,58,59,68,70,73and82.TypesLRmostfrequentswere 6and81(n=3;each).OtherLRtypeswere11,42,44,55,64and 84.

HPVpositivewomenwereyounger(33.9±17.0years)than the HPV negative ones (41.8±14.7 years; p<0.001). Other socio-demographiccharacteristicssignificantlyassociatedto HPVinfectionwere:tohaveatotalhouseholdincomelower than oneBrazilian minimummonthly wage (p<0.001), not to be married (p=0.014) and to have children (p=0.016) (Table1).

Consistentcondomusewassignificantlyassociatedtothe HPVinfection(p<0.001).Otherbehavioralcharacteristics(age atfirstintercourse,numberoflifetimesexualpartners, smok-ingand contraceptiveoraluse)didnotpresent association withHPVdetection(Table2).

Regardingclinical aspects,HPVinfection wasassociated totheoccurrenceofcellabnormalitiesinthePapsmeartest (p<0.001). Further,HPVwas morefrequentin womenthat underwentaPaptestinthelasttwelvemonthsthaninthe otherones(p=0.031).Historyofsexuallytransmitteddiseases andconcurrentvaginalinfectionwerenotassociatedtoHPV infection.

All theaboveepidemiologicalvariableswithastatistical significanceinthechi-squaretestweresubmittedtothe mul-tivariateanalysis(exceptingmaritalstatusthatpresenteda high number ofmissed data and the expected occurrence ofcell abnormalitiesinthe PapsmeartestinHPVpositive women).HPVinfectionwasassociatedtothetotalhousehold income lower than one Brazilianminimum monthly wage (p=0.001),youngage(<30yearsold;p=0.028)anduseof con-dominallrelations(p=0.023)(Table3).

Inthecytologicalanalysis,mostwomendidnotpresent cellabnormalities(n=279;93%),243(87.1%)withoutHPVand 36(12.9%)withHPV.Seventeen(5.7%)womenpresentedcells alterations,fourteen(4.7%)ofthemonlywithatypicalcells, one(0.3%)withLSIL andtwo(0.7%) withHSIL.Thepatient withLSILwasinfectedbyHRtype45,whilethewomenwith HSILwereinfectedwiththeHRtype16andLRtype16plus 6 (mixedinfection).Four samples presentedunsatisfactory cytologyresultscausedbycontaminationwithbloodcells,pus andmucusinover75%ofthesmear(Table4).

Inthesubgroupof79womenwithtwovisits,46women (58.2%)showednoHPVinfectioninbothassessments.Almost allofthem(n=44;95.7%)hadnormalPapsmeartestonboth visits,buttwo(4.3%)presentedatypicalresults(oneASC-US andanotherASC-USplusAG-NOS,bothinthesecondvisit). Eighteen(22.8%)womeneliminatedHPVinfection,presenting normalcellsinbothPapsmeartests.Onlytwo(2.6%)women showedconversiontoanHPV-DNApositivestatus,but with-out cytological alterations. The remaining thirteen (16.4%) womenhadpersistentHPVinfection,mostofthemwithan HRtypeinthebaselinetest(n=11;84.6%).Allthesewomen presentednormalPapsmearinthefirstvisitandten(76.9%) hadthissameresultinthesecondexam,whilethree(23.1%)

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Table2–AnalysisofbehavioralandclinicalcharacteristicsinwomenaccordingtoHPVstatus.

Variables Overall(n=300) WithoutHPV(n=253) WithHPV(n=47) p-Value*

Ageatfirstintercourse 0.248

<18 175(58.3) 144(56.9) 31(66.0)

≥18 125(41.7) 109(43.1) 16(34.0)

Lifetimesexpartners 0.147

1 144(48.0) 126(49.8) 18(38.3)

≥2 156(52.0) 127(50.2) 29(61.7)

Smoking 0.674

Yes 39(13.0) 32(12.6) 7(14.9)

No 261(87.0) 221(87.4) 40(85.1)

Contraceptiveoraluse 0.259

Yes 106(35.3) 86(34.0) 20(42.6) No 194(64.7) 167(66.0) 27(57.4) Condomuse <0.001 Yes 92(30.7) 67(26.5) 25(53.2) No 208(69.3) 186(73.5) 22(46.8) HistoryofSTD 0.275 Yes 48(16.0) 43(17.0) 5(10.6) No 252(84.0) 210(83.0) 42(89.4)

Concurrentvaginalinfection 0.977

Yes 57(19.0) 48(19.0) 9(19.1)

No 243(81.0) 205(81.0) 38(80.9)

LastPaptest 0.031

Firsttime 37(12.3) 27(10.7) 10(21.3) ≤1year 150(50.0) 124(49.0) 26(55.3) ≥2years 113(37.7) 102(40.3) 11(23.4) Paptest <0.001 Normal 279(94.3) 243(96.1) 36(76.6) Abnormal 17(5.6) 6(2.3) 11(23.4) Unsatisfactorysample 4(1.4) 4(1.6) 0(0.0)

∗

2testwasusedtocomparebetweenparticipants.

Table3–MultivariateanalysisofriskfactorstoHPVinfectioninwomeninSouthBrazil(n=300).

Variable PRadjusted CI(95%) p-Value

Age 0.028

≥30years 1 –

<30years 2.00 1.08–3.72

Totalhouseholdincome 0.001

>1Brazilianminimummonthlywage 1 –

≤1Brazilianminimummonthlywage 2.74 1.55–4.86

Havechildren 0.438

Yes 1 –

No 1.28 0.68–2.42

Lifetimesexualpartner 0.262

1partner 1 –

≥2partner 1.36 0.80–2.31

Useofcondominallsexualrelations 0.023

No 1 –

Yes 1.87 1.09–3.22

FirstPaptest 0.761

No 1 –

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Table4–CytologicaldiagnosisaccordingtothepresenceofHPVinfection.

Cytologicaldiagnosis WithoutHPV(N=253) WithHPV(N=47) Allwomen(N=300)

NILM 243(96.0) 36(76.6)a ₂₇₉_(93.0) ASC-US 4(1.6) 6(12.8)b ₁₀_(3.3) ASC-H 1(0.4) 1(2.1)c ₂_(0.7) ASC-H+AG 0(0.0) 1(2.1) 1(0.3) LSIL 0(0.0) 1(2.1)d ₁_(0.3) HSIL 0(0.0) 2(4.3)e ₂_(0.7) AG-NOS 1(0.4) 0(0.0) 1(0.3) Unsatisfactorysample 4(1.6) 0(0.0) 4(1.4)

Dataarereportedasnumberwithpercentinparentheses.NILM:negativeforintraepitheliallesionandmalignancy;ASC-US:atypicalsquamous cellsofundeterminedsignificance;ASC-H:atypicalsquamouscells,cannotexcludehigh-gradelesion;LSIL:low-gradesquamousintraepithelial lesion;HSIL:high-gradesquamousintraepitheliallesion;AG:atypicalglandularcells;AG-NOS:atypicalglandularcellsnototherwisespecified.

a _Includes_sixteen_cases_of_infection_single_by_HPV_types_high_risk:₁₆₍₃_cases),₃₁_and₅₃₍₂_cases_each),_35,_45,_58,_70,₇₃_and₈₂₍₁_case_each)

andthreecasesofinfectionmultiplebyHPVtypes52and68;31and45;55and56;alsoincludessevencasesofinfectionsinglebyonlyHPV typeslow-risk:6,11,42,44,64,and84(1caseeach)andonecaseinfectionmultiplebyHPVtypes6and81.

b _Includes_four_cases_of_infection_single_by_HPV_types_high_risk:_31,_52,_56,₅₉_and_two_cases_of_infection_multiple_by_HPV_types₁₆_and_35;₃₉

and81.

c _Include_infection_single_by_HPV_type_18. d _Include_infection_single_by_HPV_type_45.

e _Include_one_infection_single_by_HPV_type₁₆_and_one_infection_multiple_by_HPV₆_and_16.

presentedcellsabnormalities.OneofthesewomenhadAG associatedtoapersistentinfectionwithHRtype45,another presentedLSILassociatedtomixedinfectionsofHRtypesin bothvisits(18plus33inthefirsttestand16plus18inthe secondone) andthe lastonepresentedHSIL withamixed infection ofHRtype 52 and73 in thefirst visit and single infectionwithHRtype52inthefollow-up(Table5).

Discussion

The present work is a cross-sectional study with women attendedinapublichealthserviceinacity fromthe coun-trysidefromSouthBrazil.Inthisregion,HPVinfectionwas associatedwithfoursocio-demographical(youngage, mari-talstatus,parityandtotalhouseholdincome),onebehavioral (consistentcondomuse)andtwoclinical(cellalterationsin thePaptestperformedinthepresentstudyandpreviousPap testinginaperiodofoneyear)aspects.

Young age is a classical independent factor associated to HPV infection and it is well reported in the scientific literature.8,17,18_It_is_related_to_the_more_intense_sexual_activity

inthisage(thatfavorstheinfection)aswellastoan anatom-icalcharacteristicoftheyoungwomen(cervicalectopy)that

exposesthecolumnarepitheliumintheectocervix,makingit morevulnerabletopathogeninfections.19,20

It was also observed a significant higher proportion of single,divorcedorwidowedthanmarriedwomenwithHPV infectioninthebivariateanalysis.Howeverthisvariablewas notincludedinthemultivariateanalysisbecausethelimited dataavailable(n=99,lessthanonethirdofthetotalsample population).Otherstudies havealsofoundthisassociation, probablybecauseunmarriedwomenhaveahigherrisk behav-iorthantheseoneslivingwithastablepartner.21–23

Furthermore,itwasfoundasignificantlyhigherproportion ofHPVinfectedwomenwithchildrenthanthosewithout chil-dreninthebivariateanalysis.Howeverthisassociationwas notsignificantinthemultivariateanalysis.Intheliterature, somestudies founda positiveassociation10,24,25 _while

oth-ersreportednosignificantrelationbetweenparityandHPV infection.6,26

Interestingly, total household income of less than one minimum Brazilian monthly wage (that means low socio-economystatus)wasstronglyandsignificantlyassociatedto HPVinfection inthebivariateand eveninthe multivariate analyses wage (p=0.001). Similar findings were reportedin othercountries27,28_and_also_in_the_Northeastern_from_Brazil.29

AnotherstudyalsoreportedthatHPVwasmorefrequentin

Table5–CourseofHPVinfectionandclassificationofviraltypeinwomenfromSouthBrazil.

Courseofinfection Alla_(N₌₇₉₎ _HPV_baseline_(N₌₃₃₎

High-risk(N=19) OnlyLoworindeterminate risk(N=14)

Persistence 13(16.4) 9(47.3) 4(28.5)

Clearance 18(22.8) 8(42.2) 10(71.5)

Conversion 2(2.6) 2(10.5) 0(0.0)

NoHPV 46(58.2) – –

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publichealthservicesthaninprivateclinics,highlightingthe roleofthesocioeconomicstatusinHPVinfection.30_As_a_global

context,povertyorinsufficientincomeisasocialdeterminant forincreasedvulnerabilityofwomenandcaneitherinfluence theadoptionofpreventivemeasuresagainstsexually trans-mitteddiseasesorreducetheaccesstoinformationandhealth services.31 _This_reinforces_the_need_for_the_development_of

preventionandcontrolprogramsinlow-incomepopulations. Several sexual behaviors have been associated to HPV infectioninotherBrazilianreports.6,8,32,33_In_the_present_study,

HPV infection was surprisingly associated with consistent condomuse. Condomoffers goodprotectionagainst infec-tions,but HPVcan be transmittedby contactwith genital areas not covered by this preservative.34 _Previous _studies

havereportedaprotectiveeffectofcondomsinpreventing HPVinfection,butwithoutstatisticalsignificance.35,36_In

addi-tion,misuseorproblemswithcondoms(breakage,slippage or incomplete use with delayed placement, early removal andevenreuse)arefactorsthatmayofferlessprotection,as reportedpreviously.37_Condom_use_may_also_have_been_more

reportedthaneffectivelydoneinthepractice,consideringthat theuseissociallydesirable.34_Finally,_women_with_new_and/or

multiplesexualpartnersusecondomsmorefrequentlythan thosewhoonlyhaveoneregularpartnerandcouldberelated toahigherriskbehavioraspreviouslyreported.34,38

Ontheotherhand,itwasnotobservedassociationbetween HPVinfectionandthenumberoflifetimesexualpartners,age atfirstintercourseand historyofsexually transmitted dis-easeandotherconcomitantgenital infectiondemonstrated inpreviousstudies.6,32_Another_study_conducted_in_the_South

BrazildidnotfindassociationofthesecharacteristicsandHPV infection.39

In the cytological analysis, a lowpercentage of women withoutHPVinfection(4.1%)hadabnormalPapsmearwhile ahigherfrequencyofwomenwithHPVinfection(23.4%) pre-sentedatypicalcellsand/orLSIL/HSILasexpected.Regardless ofthedegreeofthelesion,allofthempresentedHRHPVtypes. Infact,normalcytologypredominatesamongwomenwithout HPVinfection,asshowninpreviousstudiesinBrazil7,26,40_and

eveninothercountries.17,41

HPVpersistenceinthispopulationwas16.4%.Further, per-sistentHRHPVtypesinfectionwasassociatedwithabnormal Papsmearinthreepatients(oneAG,oneHSILandoneLSIL). ThefrequencyofAGislow,rangingfrom0.05%to2.1%,but thiscytologicalabnormalityhasclinicalsignificance(several casesprogresstoCC).42 _On_contrast,_LSIL_and _HSIL_are

rel-ativelycommon,accountingfor31%and9.7%(respectively), amongwomenwithcytologicalabnormalcervicalcells.43_In

thissituation,HPV-DNAtestwouldbeusefultomonitorthe occurrenceofcervicallesionsinwomen.43–45

PapsmeartestisaneffectivemethodadoptedfortheCC screeningandshouldbeperformedonceayearineachwoman aged25–64.43 _This_procedure_{significantly}_reduced_the

inci-dence ofcervical cancer in Brazil in the last five decades. Howeverseveral newCC patientshavebeen detectedeach yearandthisdiseaseisstilloneofthemaincausesofdeath inwomen.43_There_is_consistent_evidence_on_the_performance

of HPV-DNA testing combined with cytological analysis to detectcervicallesionswithmoreaccuracy.Somecountriesin EuropeandNorthAmericahaveadoptedHPV-DNAtestingin

clinicalpractice.ThelatestCCscreeningguidelinesofseveral internationalhealthinstitutionsrecommendedtheadoption ofcytologyandHPV-DNAtestingforanywoman.46,47

How-ever, HPV-DNA testingin combinationwith cytologyisnot routinelyperformedinthepublicclinicsinBrazil.The intro-duction ofHPV-DNAtesting couldhelp inthescreeningof precursorlesionsandintheeffectiveCCcontrol.43,46,48,49

Screening programs forcervical lesions in womenhave beenimplementedinthelastdecadesinBrazil.Suchefforts aimtodetectcancerprecursorlesionsandtoprovideearly treatmentforthepatients,reducingtheincidenceofuterine cervicalcancerinwomen.Thepresentstudywasconducted inoneofthispublicprimaryhealthcareserviceslocatedina medium-sizecityfromtheSouthofBrazil.Althoughwomenof onlyonecitywereincludedinthestudy,themajorityofthem isoflowsocioeconomicstatus,representingwomenattended bythehealthpublicservicesinothercitiesandregionsofthe country.Inthis sense,the datareportedherecontributeto abetterunderstandingoftheHPVepidemiologyandwillbe helpfultodefinepublichealthpoliciesinBrazil.

Inconclusion,the resultsofthisstudyindicate thatage lowerthan30yearsandlowfamilysocioeconomicstatusare associatedtoHPVinfectioninwomenfromthecountryside ofSouthBrazil.Further,itwasdetectedaprevalenceofHPV infectionof15.7%andarelativelylowHPVpersistence(16.4%), stronglyrelatedtoCCprecursorlesions.HPV-DNAhighrisk typesdetectionwouldhelptoscreenCCinthepopulation.

Conflicts

of

interest

Theauthorsdeclarenoconflictsofinterest.

Acknowledgments

TheauthorsthankthestaffoftheCenterforWomen’sHealth in Cruz Alta/RS and patients for their collaboration. We alsothankthetechniciansoftheUniversidadedeCruzAlta (CytopathologyLaboratory),UniversidadeLuteranadoBrasil (MolecularDiagnosticsLaboratory)whoperformedtechnical support and Simbios Biotecnologia for the partial finan-cialsupport.ThisworkwasalsosupportedbyFundac¸ãode AmparoàPesquisadoEstadodoRioGrandedoSul(FAPERGS; Grant1265-2551/13-4).

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