cervical cancer screening in developing countries ppt

Cervical screening is acknow ‘edged a currently the most effective approach for eervial cancer control However, in many countries, including most middle-income developing, ‘countries, th

CERVICAL CANCER SCREENING

WHO Library Cataloguing-in-Publiation Data

‘Cervical cancer screening in developing counties: report ofa WHO consultation,

1.Cervix neoplasms ~ diagnosis 2 Diagnostic techniques, Obstetrical and gynaecological ~ utization

43 Natonal health programmes organization and administration 4, Guidelines 5 Developing cosntses Ismx92 41545720 (NLM/LC clsieaton: WP 480)

(© World Health Organization 2002

Al ight reserved Publications ofthe Word Heakt Organization can be obtained rom Marketing and

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Pring in France

TABLE OF CONTENTS

1_Epidemiologcl Status Cervical Cancer 3

2 Programme Organization 5

‘Then elements fr ceil rl rir“ 8

Fundamental components ese an nganued programme Lt

Cytology Screening in Middlencome Counties 13,

Cervical ology sa eerie screening est 13

‘Theva of cervical enolog aa seenng tet 13

shat in

‘programmes 20°

‘The srengiy ofthe conensonal ceva ploy tet 20

“The implarions of dierent methods of ampling_ 22

‘The mpliations of iterent methndsof see reading_23

Visual Inspection with Acstc Aci Application VIA 35

‘Aleimative Approach to Cytology Screening in Low-income Counties 25

'5_HPV Tessin Cenc Screening Programmes; Possible ole in Mddlencome Counties 39

avon fring HPV cei inser arecning_ 40

HV recog ots: erent mete for seeing, 41

——.-

Sample prepation / and

HIV eng sper: deelopmens othe nea Bước 45

(ses of HPV esting in erening 46

Nan story ss and ease cond i

HV tes in primary screening programmes 49

[ARCH toting and HEV types esingprfrmance inseeening 49 Impacto HEY sara an age on perfomance of HPV DNA 50

HV in qual condo aged sercring programines 54

Recommendations on th designs of cus on HIV fesing fr ceri sceing 56 Advamags and disantages of HP test insrecning 88

Conchioas on HPV esting 58

6_OveralCondusion 61

Appendix: Epidemiological sues in the Evaluation of

‘Altematve Serening Tests 63

“Teas se in the diagnos and manage of minimal cervical abnormalities 63

Appendix 2: List of participants 65

References 69

PREFACE

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+ Toi pty ao aoa WHO whit pares

The meeting was organized in thece modules, and a chaiperson was appointed for cach, Dr Anthony Miller chaired the moxdsle on cytology screening, Dr Rengaswamy Sankaranarayanan the modle on vst inspec tion with acetic ail application (VIA) and Dr Xavier Bosc che module on human papilloma virus (HPV) screening 1 am extremely gateil to each

‘oF these distinguished sient for contributing so much oftheir time and expertise

For each module, key participants were chosen on the bass of their ree=

‘ognized expertise in the subject matter ‘These participants conteibuted actively to the considerations oftheir ypeciaized subject matter, but were also able to attend the meetings ofthe other modules if they chose to-do S50 Atte conclusion ofthe discussions on each topic the main con

were reported and discussed jointly by all meeting participants during the final session ofthe consultation Subsequent discussions whieh continued

for several months after the consulotion helped to lai criti keUes in

Pre cạnh module Again, my thanks to each of che participants inthe meeting

whose names ate listed in Appendix 2

Te resulting report ofthis consltation aims to provide policy makers With the evidence hase upon which to found dessions about the establish

‘meat or moxification of existing cervical cancer screening programmes It also gies insight into types of screening for which there is currently ins cient evidence on which to base a screening programme I signals to policy iakers areas that will be of importance inthe Future, including potential promising screening tests ch as VIA, which are the subject of current trials these tals yield postive results these tests may provide elective alterna tives to corent screening systems

‘Cervical cancer isa important public health problem, and a priority con

«em for the WHO Programme on Cancer Conteo.Inits recent publication fon National Cancer Control Programmes (WHO, 2002) WHO recom: mend carly detection policies for countries with various level of resources,

‘Special emphasis given to the need to develop peogrammes that have a systemic approach, age well integrated into the exiting health system and take into account he socal, cultural and economic context

WHO will continue to monitor progress in the area of cervical cancer sreening and make evidence-based recommendations about screening tests However, the undersing tuth is tha respective of how good a screening testis if will have no impact tnles introdaced as part of a well planned and implemented screening programme, Te will always remain important Yor WHO and its Member States to work together to ensure that these 9s tems function effectively so thatthe iesaving potential of cervical cancer screening can benefit women and their fms in ll parts of the world

EXECUTIVE SUMMARY

WV crusty eraser ens ipeeetnty 2am cea ea

«erin women, In is the second most common cancer in women worldwide but the commonest in developing counties Cervical screening is acknow

‘edged a currently the most effective approach for eervial cancer control However, in many countries, including most middle-income developing,

‘countries, the existing programmes af fling to achieve a major impact

PROGRAMME ORGANIZATION

‘Central tothe success of any screening programme isthe functioning of that programme in its emery The requirements include the ability ofa peo~ _gramme to ensure high eves of coverage ofthe target population, to offer high quality, caring services, to develop and monitor good referral systems that ensure good patient follow-up and to ensure tha the patiemts receive appropriate, acceptable and caring treatment in the context of informed

‘women with an abnormality attend for diagnosis and teatment must be put

in place, Systems to manage the abnormalities and follow-up those treated will ako be required, while the programme will require monitoring an eval tation Leadership, management sis, attention to linkages at all eves of the programme, and budgeting skills are eset

Bar CYTOLOGY SCREENING IN MIDDLE-INCOME COUNTRIES

It is generally agreed that cytology screening for cancer of the cervix has

‘been effective in reducing the incidence and mortality from the disease in _many developed countries Irs the organised programmes that have shown the greatest effect, while using less resources than the unorganised pro: grammes There i general agreement that high quality cytology ia highly specific screening es, with estimates ofthe order of 98-99%, There i es agreement on the sensitivity of the test, cross-sectional studies have sug gested sensitivity in the order of 50% in some circumstances However, studies that have been able to asses sensitivity longitudinally have proce estimates that approximate 10 75%

The essential elements for successful cytology screening include:

‘+ teaining of the relevant health care professionals, including smear takers, smear readers (cytoteshnologists), cytopathologst, colposcopists and programme managers,

‘+ an agreed decision on the priority age group to be screened (intial 35-54),

adequately taken an ied smears, cficient and high quality laboratory services, thar should preferably be semlized,

quality control of cytology reading,

8 means to rapidly: transport smears to the laboratory,

‘8 mechanism to inform the women screened of the recults ofthe rst in an understandable form,

4 mechanism to ens For management and treatment,

‘+ an accepted definition of an abnormality to be treated, ie high grade lesions,

that women with at abnormal test result attend

8 mechanism to follow-up treated women,

8 decision on the frequency of subsequent screens,

| mechanism to invize women with negative smears for subsequent

ements thar interfere with the development of suecessful cytology scteening programmes inclide oxerrclanse upon maternal and child health services for screening, a8 women in thelr taget group are generally too young, opportunistic rather than organised screening, and low coverage

‘of the target group Setting coo low a threshold for referal for colposcopy,

ie over-treating non-progressve disease, will lead 10 reduced cost effec

“The major advantages oF cytology sereening, are the considerable expert

cence accrued worldwide in is use, and thar it isso fir the only established

sercening test for cervical cancer precursors that has been showen go reduce

the incidence and mortality of the disease, However, eytology has hits

tions, it incompatible with some women's belies and it impossible

to abolish the disease with screening, It is important that women are not

«coerced into screening, nor given an oxeroptimistc view ofits potenti

"Now developments in cytology, sch a lguid-based cytology and auto

mated reading have advantages, but are currently out of reach of most

programmes

Research into means to improve programme efficiency in middle income

sonntdeslsa hgh prioriey

VISUAL INSPECTION WITH ACETIC ACID (VIA) AS AN

ALTERNATIVE APPROACH TO CYTOLOGY SCREENING

IN LOW-INCOME COUNTRIES

“The techniol and financial constrsints of iplementing cytology-based

screening programmes in developing counties have led tothe investigation

‘of screening rests based on visual examination of the uterine cervis Among,

those tests, isl inspection with 3-85 acetic acid (VIA) appears to Fall the

Ise criteria ofa satnfctory screening test VIA inolves non-magnitid vis-

ualzation of uterine cervix soaked with 3-5% acetic ac

The results of est accuracy in eros sectional study settings indicate that

the sensitivity of VIA to detect high rade precancerous lesions anges from

.66-96 % (median 84%); the specifiy varie fom 64-98% (median 82%)

the postive predictive value ranged from 10-208 and the negative predic-

tive vale ranged from 92-97%, However, all reported suis,

sured from verification biss, Despite biferent std sti

providers, study protocols and definitions of postive fests, the estimates of VIA sen"

sitivity cluster around a mean value of 76%, In most of the studies where

«tology and VIA have been proved under the same conditions, the sen

sitivity of VIA was found to be similar to that of eytologs, whereas its

specificity was consistently lower,

‘A.wide range of personnel ranging from doctors, nurses and other allied

health workers to non-medical personnel hos been involved inthe admins

tration and reporting of VIA rests The most common form of reporting

involved negative and positive categories The emerging consensus is that

well-defined, demarcated, densely opaque acetowhit lesions located in the

transformation zone (TZ) close to the squamocolumnar junction should

line postive VIA test, The criteria fora negative test have included one

Beenie

Bar for more of no acetowhite lesions, fhinti-detined translucent acetowhite

lesions, endocervical polyps, nabothian ests, dot-like azetowshite lesions and

4 prominent squamocolumnar junction

To date, the investigation of women with a positive VIA has fallawed sim: ike principles co those ofeytology-posiive women, In varus setting, five

‘options have been offered:

+ Referral for colposcopy with histological sampling an treatment based

‘on the histological findings, + Referral for colposcopy with histological sampling and treatment given on the basis of the colpossopie diagnonis (with retrospective access to histo logical diggnosis

+ Reteral for magnified visna inspection (VIAM) with histological sam pling and immecate treatment with cryotherapy:

+ Reterral for colposcopy and treatment on the basis of the colposcopic logos;

+ Referral for immediate treatment with cryotherapy on the basis oF a posi tive VIA test

All of the above approaches ate still being, evaluated in terms of safer, acceptability to women, feasibility and effectiveness in eradicating pr-inva sive cervical disease

In most ofthe reported study setting, training in the administration and reporting of VIA has been carried out in sessions lasting 3 days to 2 weeks, sscompanied by written manuals A learning period has been recognized following the training sessions In both reported and unreported studies,

‘vith investigations/treatment, consistent estimates of accuracy, eit to

be offered in low resource settings and the possibilty of rapid caning of providers

Tanherro arch in addressing method for improving speciity reducing false posit, quality’ contro, tests to be vse to follow-up women who have been treated and competency and evaluation of skills of screeners and

‘other health personnel involed in screening programs is essential The ef

«acy al cost fletiveness of VIA-based population sereening programmes

in reducing the incidence of, and mortality from, cervial canger x not

known and remains to be established, 26 do the long term complications

and salty of overtreatment in the context ofa VIA screening programme

Further information from ongoing studies regarding VIA's longitudinal

(programme) sensitivity, efiacy in reducing incidence/morality Irom ver

vical cancer, its cost-efectiveness and safety will be useful in formulating

public health polices to guide the organization of VIA-based mass popula

tion: based screening programmes in developing countries and to reorganize

ology sereening pro-

programmes in counties with current ineficient eV

‘grammes

HPV TESTS IN CERVICAL CANCER SCREENING PROGRAMMES: POSSIBLE ROLE

IN MIDDLE-INCOME COUNTRIES

‘Molecular and epidemiological studies have unequivocally shown that

the vast majority of cervical cancer cases workdwice are cated by persistent

lnlsstions with some high-risk types of the human papillomavirus fil

From the perspective of defining preventive strategies, the HPV'ataiburable

Faction shoul be considered t0 be 100%,

‘Current HPV testing systems are able to detect the presence of veal

markers (HPV-DNA in exfoliated vervial cells) in close to 100% of invasive

<ervical cancer specimens, 75 t0 90% of precusor lesions (ISIE / CINI,

‘CIN2/3, HSL) and in 50% of borderline sytology lesions (ASCUS)

‘Commercially svailable, FDA approved, testing systems can be ranserred

te laboratory settings with some level of sophisticated technology which are

‘generally found in middle-income countries

In triage studies (investigations ofthe minor abnormalities detected by

«xtology) an! in screening studies (when both eytology and HPV tests

jointly performed) the cross-sectional sensitivity of the HPV test to detect

HEIL or more advanced lesions sat lasts good a cytology la most studies,

the reported sensitty ofthe HIPV tests some 10% higher than cytology,

Triage studies, including large randomized conteolled trials, have shown

thar reduction in the number of Visits and relerals to colposcopy /biopsy

‘an be achieved with HPV tess

‘One ofthe strongest gains ofthe combination of HPV tests an! cytology

lis in the very high negative predictive value (Le 5978), Mgjor savings to

the health systems may derive from substantially increasing the duration

‘of the interval betwcen screens without losses insensitivity for bigh-grade

imaepithelal lesions

“The advantages of HPV tess as compared to cytology ae

Beenie

Bar «The objectivity of the tes resulting in very low inter- andl inea-observer

saris

"The possibilty of almost complete automation ofthe proses, This should

‘ensure high throughput a standard level of quality

“Built-in quality contol procedures,

‘Opportunities forse sampling for HIPV DNA in some populations with limitadons in health care cilities andl manpower, albeit with some los of semidlin

+ The high sensitivity of the HPV DNA test to identify HLL in women aged 30 and above

Gains in effectiveness could be achieved by incresing the length of the imersal between screens and reducing the rol number of hfetime screens required

“The disulvantages of HEV DNA testing ate Cost

“Dependence on reagents cusrently produced by only a single commercial manofacturer

“The requirement fora molecular diagnostic borstory

Its low specificity in younger women and populations with significant rates of HIV seropositivity

+ Furthermore, since HPV DNA testing, like eytology, is not a test that prosides results atthe time of the visit oF soon afterward, many of the tradidonal barriers to cytological sctcening have not been eliminated, CCost-beneft analyses of HPV testing are underway: Modeling, based upon results from South fia, suggests that VIA or HIPV DNA teats may offer ttrsctive alternatives ro cytology based screening programmes

In comntres with established cytology-based screening programmes, TIDY tests are an alternative to repeat cptology in the presence of abnormal evtology In countries without established cytology-based sereening pro: game, bụt with the necessary Iaboratory flies, HPV tests could be evaluated for primary screening, Appropriate tris are strongly encouraged,

+ to develop a status report on visual inspection with acetic aid (VIA) and human papilloma virus (HPV) DNA testing with attention 10 their eff

‘acy’ and effectiveness in detecting cervical neoplasia in diferent resource sertings;

* to identify esearch issues in relation to sereening with VIA and HPV test, ing, that neod to be addressed for adequate policy development,

For the purpose ofthis report, the generic term “middle-income counties”

‘embraces a variety of developing countries, some having limited se to

«ytology-based screening activities Typically, these have low population

‘coverage of screening, predominance of clinical serves for women pre- senting with symptoms, absence of pre-established calls for seeening to

‘women in pre-defined age groups, insufiient quality control of eytology and limited follow-up of women with postive smears, In many connties

Uhis is associated with limited agvess to treatment, especialy Hor pressn-

<erous lesions, Programmes tend to be decentralized and only partially Funded, and organized to mect immediate needs eather thon longterm Follow-up and management In these populations, combinations of health

«are stems with private and public practice, eiferent modes of reimburse- ment for services and predominance of case fnding activites rend to occu There ae ths ma

of ether starting dé mave screening programmes or considerably reorgan iaing existing ones,

diferent scenarios that may have in common the need

EPIDEMIOLOGICAL STATUS OF

CERVICAL CANCER

Worldwide, cervical cancer comprises approximately 12% of all cancers in women, I is the second most common cancer in women worldwide, but the commonest in developing countries, Annual global estimates around the year 2000 are for 470 600 new cases and 283.400 deaths from cerial cancer Annually (2) Fighty percent ofthese cases occu in developing countries

In most countries in North America and Weston Europe, the incidence

‘of cervical cancer has been faling, although recently at 4 much slower rate (2) In many’ developing countries, however, cancer ofthe cers has

‘hanged litle in incidence, except foe these counties that have achieved the demographic (epidemiological) transition with increasing affluence fiom industialization In such countries, chere has been a fll in incidence

‘of cancer ofthe veri al 3 rise in nelle in eancer of the breast, sin ile to-changes that oecurted in North America and Western Europe in the

‘arly par of the last century Many of the counties that have been shrough this transition are in the “middle-income” category

Ths een estimated thatthe number of prevalent cervical cancer eases diagnosed inthe previous five years was around 1-401 400 in the year 2000

«compared with 3860 300 for breast cancer, with 1064000 and 1522000

‘of these oscurring in developing countries, respectively (2) Thos although breast cancers increasing i importance in many’ developing counties, cet vical cancer remains a major cause of morbidity and mortal

Dats a

cervis and, with some notable exceptions, tend to show declines (3) This

walabe internationally on trends and incidence of sancer of the

is true for narly all registtes inthe Americas, Asia, Australasia and Hawai, and Europe The reductions have been quite suiking in Havaii, Denmark, Finland, Sweden, Japan, and more recent in the Maoris of New Zealand but ake in Cai, Colombia and Puerto Rico, In Calis Colombia, serening programmes have heen operational, and a case-conteo study confirmed that screened women had a reduced risk of disease (4) However since overall coverage does not sufficiently explain all of this ineence reduction, much

‘oF it may reflect epidemiological transition Reductions have been quite small recently in many counties with low incidence in the ealy 1960's including Canada, many parts ofthe United States, and the Caucasian pop ladon of New Zealand, In Finland there has ben some recent increase i

incidence, but notin mortality, in women aged 25-54 (5)

* to offer high quality, caring services

+ t0 develop and monilor good

Fallow-ups

ral stems that ensure good patient + to ensure thatthe patienseeceive appropriate, acceptable and caring man- agement in the contest of informed consent

Programmes need to be loslly appropriate an those designing the overall progeamme need to be ava ofthe multiple barviess thar women may expe- rience in accessing services (e.g physical access, economis considerations, control over decision-making at the household level, access to informs tion et.) and attempt decrease such burirs Mest fests use in cervical screening are uncomfortable and potentially embarrassing, as they tequice a

‘ginal examination with a speculum, Adequate training of health care pro viders on the serening programme itself technical skills in relation t0 the sereening technique eter ste reatment protocols, quality control of the sefcening rest, etc are esential ro setting up or eeorganizing screening programmes The rype of screening tests subordinate to the need to have these systems in place and functioning wel Furthermore, these systems are required, respective of which method of sreening is used,

Drage

One «cervical cancerin the county (6) hing, and a decision made afer a determination ofthe clave priority of

‘In many midlle income developing countries cericl screening exists in some form of other, often asoxiated with maternal or cil health ser ices, and/or asa component of private health care foraluent women AS already indicated, such programmes tend to be ineffective, as adequate cov

‘erage doesnot extend to the majority of women at high risk of the disease Moreover, they ate decentralized and only parvally nded Ineeasing in such counties, low-ingome and middle-income families are struggling to provide the monies necessary for long-term care However, it i unlikely

‘that simply providing fads for dhe expansion of sueh efforts wil enable the programme to he successful Experience in the United Kingdom confiems that a radical reorganization ofthe programme i required, with appropriate incentives to ensure that relevant health care providers participate (7) In several other Western European countries with liberal health care systems, screening is often performed on an opportunistic basis, characterized by

‘overscrecning of those a lw risk in conjunction with wnder screening of certain social groups at igh ris, and heterogencous quality of screening It isotien impossible to document eflectivenessofsrcening hecatse ofack of adequate monitoring (8),

The political will to proceed, with support and fi

the Ministry of Health Jing from Although programmes can intially be based on support from external slonors, they will never become selF sustaining without a political dec sion to support the programme and maintain it with governmental Funding ater the external support ends Further, without political support, it may bbe extremely dificult to cape with varons internal or sometimes external, pressures to change decisions taken with regard o the programme

An adequate health care infrastructure Iris impossible to organize serening programmes inthe absence ofa health

«ate system that is capable of providing the diagnostic and treatment services inseparable from screening It important to ensure that the introduc: tion of screening des not adversely alfect other important health services,

“Therefore, implementation of cervical screening should be planned! so that, itis consistent with the developing heath cate infastructure ofthe county Developing a cervical screening programme can fasilitate the improved fimetioning of health care sytem I should, therefore, be ndertaken in

4 manner that is integrated with existing services so as to improve health

system functioning Health care ystems can be relormed, but the appro-

pate advice must be given, Adequatelytsined managers that have the kil

Ise to sce the interrelated aspects of setting up a programme and address

‘each are often lacking within health systems, The most profound need is

support for the management functions to enable screening to be under-

taken

Definition of the target population

e other

Te target population should be defined in tems of age Rarely a

parameters appropriate, though the epidemiology of the disease in the

‘country will guide the decision-making process (9) Iti importanc that

decisions of age are taken on the basis of age-related incidence rates of

invasive cervical cancer and not om the percentage distribution by age of

<linially detested cases of ancer in the counts

Education of the target population,

Te has een well documented that professional and public education, som

bined with the availabilty of reatment for early stages of invasive cancer of

the servi, had an important eect in reducing the morbidity and mortage

from the disease, long before screening programmes were introduced (10)

Facation is thus a base measuee that will contribute to early diagnenis of

the disease, and upon which sercening must be based,

It is important that the educational programmes be designed For the

‘culture of the country, and that they observe the myths that tend to be

prevalent aboot cancer In some cultures men will ako need information

Women should not be coerced into screening, nor should they be given

‘over optimistic messages concerning benefits, Thos, women should vider

stand that a negative test, though encouraging, does not guarantee absence

‘of disease now or in the Tanase, nel conversely, that a positive test dss not

mean cance, but the nee for further iavestigation, Education throug the

media will be only partially effective, Education wil also be necessary atthe

time of administering srecning tests or roersing women for diagnosis Such

‘education must be administered by individuals who can achieve personal

Ineraction with subjects, and should be interactive, not simply passive,

A means to identify the target population

Te ideal means ia population register, but tis will ofen be unavailable, or

ingeessble to the screening programme, oven i present, Other means are

‘often Found to exis and be accesible, however, providing data protection

Praga Opanization

‘working in the community, or utlzing contacts women make with the health ate system for other purposes, if none ofthe other approaches are possible

Tn many countries twill be nesessiry to ene thatthe womans personal heath concerns ave taken care of to ensure her collaboration with sreening,

Training of relevant health care professionals There are many types of health care professionals shar will require taining, For administration of the screening test these tend to be specific t0 the test tht will be used and are discussed further in the sections that follow However, forall tests, adequately trained professionals will be required for the disgnosis and treatment of the detected abnormalities,

Initiating programmes by screening current health staffas the fist step

my increase empathy in service providers From a managerial point of iw method of ongoing monitoring that tracks issues sch as privacy, respect Interactions, informed consent, ec would be important in reinforcing their

«centrality to service provision and to sustaining respectil caring service pro vision Method of engaging service users in monitoring the quality of care are an option that has proved use io other programmes and should also

he investigated (21) Means must be introslced to Fislitate problem solving and team lestning

‘The problem is often to change the entrenched practices of physicians, mi Wives and other profesionals who had been involved with screening, in spite of scarce financial resources, ‘The methodology requires a combina tion ofthe problem identification and solving approach and a variant of the problem-based approach to meslcal education

The main areas of intervention are personal (consistency, optimism, flex ibility, good interpersonal relations and quality), and collective focus on

“achieving” specific objectives in a systemic overvicw cttical mas, team work, elicient use of resources, a projet planned with creative input From the lca team, and quality information that is propel circulated,

“The process includes + Definition ofthe problem asa quantified dserepancy between an actual and

a dese sivation with the best available information anal/or estimate,

+ General options for solving the problem defined

* Analysis of the options tor solving the problem,

* Choice ofthe best solutions in light ofthe relevant criteria

* Design of strategies 10 implement he solutions

+ Implementation ofthe solution

+ Reslew and modification ofthe solution in light of experience

+ Evaluation of the rel

‘A defined referral system for women with an abnormality

and a mechanism to ensure women with an abnormality

attend for diagnosis and treatment Iris essential to ensure that women with a defined abnormality receive

appropriate diagnostic tests, and if confirmed to have lesion that requires

treatment, receive the relevant therapy There should be no financial barier

tosuch releral and attendance Health cae practitioners Working atthe pri-

mary level should understand the proces

‘Several studies have identified poor communication and feedback ss

tems between clinic and laboratory staf and beticen screening centres and

treatment faites, Secondary and rersary levels of care do no see them

selves as part ofa system They se litle value in reporting patent outcome

and primary sare sites may have dificulty making appointments for patent

Follow-up, This ia barrie that patents are often lle to negotiate on their

‘own, Frequently, patients referred to secondary level cate sites who have

abnormal results are subjected toa repeat Pap smear anl are asked to turn

‘agin once that rest salable

All this s compounded by poor information and monitoring ssstems Fa

many centes its not possible to link data and thus track ia patent has pre-

sented for and received care This again leads to de-motivated primary ca

stoff and inadequate patient follow-up

Patient management guidelines Tes important that protocols ae developed for primary cate stafFon how

to Intespret and act on screening test results, Thee absence can lead to

inadequate action and the rk that patients who require either repeat rests

‘or investigation and definitive treatment will be overlooked, I also results

in significant costs to the healthcare services and indivival women when

women ave unnecessarily requested to present fora tepeat tes

Cryotherapy loop electrosurgical excision procedure (LEED), laser abla

tion al cold knife coniation of the cervix are diferent standard therapeutic

‘options forthe treatment of precancerous lesions and most ofthese can be

Praga Opanization

Drage

One provided as outpatient procedures, Ir has now been established that all of the standard outpatient treatments for dysplasia under colposcopis guid

ance are highly effective and ate associated with low rates of complications

No significant diffrences in overall lure and complication rates between these diferent reatment modalities have been observed in randomized clin ical tials in developed countries (12-17)

I is imperative that adequate resources be Mentiied and invested t0 establish a certain minimum ingiasteucture in terms of diagnostic (col poscopy, histopathology) and treatment (cryosurgery, LEED, cold knife

‘excision procedures) foils in health services before decisions on imple menting sreening programmes ate taker

Follow-up of patients

‘Systems to routinely follow-up patients must bein ple, Such systems may

‘be absent because ofthe poor introhicton ofthe screening programmes, i pare because funding for heath serves is decreasing and patient follow-up for any disease isnot seen as a prorty Supervisors must be encouraged to see ths as part of system to improve quality of cae

A means to identify failures of the programme,

eg invasive cancer

If the programme is set within an area with an existing population-based acer registry, invasive cancers wll be identified by linking the sreening le with the cancer registry Ifa reistry doesnot exist, means should be found oset upa reise’ ofalleaes oF invasive cervical cancer, however dsgynosed,

to specifically serve the programme With both approaches, artemps should

‘be made to distinguish cases diagnosed a a result of srcening (oft micro invasive or early stage) from those that are clinically diggnosed, the trae failures of che programme However, in addition, it shoul be decermined whether che latter cases have heen previously sctcened, and thus ae fil

‘ures of the screening process, or were never screened, being fires of the recruitment proces

T's important 1 revognize thar even when a screening programme is well,

‘organized, there will continue to be adequately screened women with true negative sles en review who develop cervical cancer, One reson could be thatthe lesion did not exfoliate, another that the particular malignancy pro

‘essed 100 rapidly for detection by seeening Thus some invasive cancers

in the sereened population should be expected although onganization will censure they are minimized The population being invited for screening sbould also he aware ofthis and advised to report symptoms when they osc

Strategies for evaluation have been proposed (6.1819) Eventually, the

succes ofthe programme wil be determined by reduction in the incidence

‘of invasive cancer I excellent coverage with screening is achieved, incidence

willl within 10 years of stating the programme Several intemediste

‘endpoints can be proposed to monitor the programme

However, care must to taken to not over-rely on the process and impact

measures, unless it can be documented that the women who enter the pre

‘gramme include those at high rsk ofthe disease

FUNDAMENTAL COMPONENTS ESSENTIAL

FOR AN ORGANIZED PROGRAMME

Leadership fective leadership is citcal The leader should have characteristics, exper

‘ence and qualifications similar to those defined far National Cancer Comtrol

Programmes coordinators (6)

‘Management of all phases of the programme is ako critical, Progeammes

‘offen fal because an important component has filed (for example, failure

to ensure women with an abnormality attend for diagnosis and trostment)

Pregame Opanization

"

Drage

One Managers require training, so that they understand the requirements for clfective programmes,

Attention to, and linkages between, all programme levels

the level

‘of recruitment, the level ofthe laboratory, the level of colposcopy, the level

‘of treatment, the level of follow-up, The organization of the programme should ensure adequate linkages between these diferent levels, and ensure

Thee are several diferent “levels” ina programme For exampl

that each level understands what happens at the next, and there is adequate

‘communication between them, The objective is to ensure that women pro ceed from one level to the next (iPsecessary), without the woman having to take the initiative with her hited understanding of the proces

Budgeting Each component ofthe programme requites realistic budgeting The process should be conducted in collaboration with experts inthe Ministry of Health

“They will need speci information on the needs for each component ofthe programme A detailed flowchart wil facilitate this proces

CYTOLOGY SCREENING IN

MIDDLE-INCOME COUNTRIES

CERVICAL CYTOLOGY AS AN EFFECTIVE SCREENING TEST Even though the efficacy of cytology screening has never been proven through randomized tral, it fs generally agreed that it has been effective

in reducing the incidence of and morality from the disease in developed countries (20-24) It isthe organized programmes that have shown the sgeatest effect, while using fewer resources than the unorganized pro-

‘grammes (23,25), However, in all countries that contemplate introducing sereeaing, this should be set within the context of National Cancer Consrol Programme (NCCP) planning (6),and with fl attention to programmatic issues 26)

Data from the WHO cancer mortaliyclats bank confirm major reduetions

in cervix cancer morality in the Nordic counties that initiated organized programmes in the 1960s, and in Canada and the US where major efforts were made t0 encourage screening in the 1960s, though as yet organized programmes are notin place in North America, In the United Kingdom 3 major effort was begun in 1988 to initiate organized progsammes, and 3 significant reduction in cervix cancer mortality now being seen (27) The flare of opportunistic screening in Norway and the UK before 1988 is

‘exemplied by the contest erween Norway and Finland and berween the

UK and North America in the 1980s and 1990s, In contss, in most devel-

‘oping countries seeening appears to have had litle or no effect (28,20) with the exception of the programme in Chile (30)

‘THE VALIDITY OF CERVICAL CYTOLOGY

AS A SCREENING TEST There is general ageeement that high quality cytology is a highly spesiic screening test, with estimates ofthe order of 95-99%, Recently, controversy has arisen over whether cytology is sciently sensitive largely because of

‘rossectonal studies conducted in diffrent setings, meta-analyses of Sev~

‘eral studies (31-33) and comparisons made with VIA and HV testing (see later sections) Estimates of extology sensitivity of the onder of 30% or even

Chap

Chmie

less have been made However, several of these studies evaluated cytology

<crosssectonaly as a disgnostc test, rather than asa screening test

Sensitivity i defined as the ability ofa screening test to detect all those With the dsease in the detestable pee-inical phase in the screened pop

‘lation, atthe time the test administered I is usual in measuring the sensitivity ofa screening test for cancer to regard the disease a the cancer itself, However, in the context of s test designed to detest precunsors of

a disease, the fae negatives that tly matter may be dificult ro deter tine This reflects the fict that as the extent to wich precursors destined

10 progress to invasive cervical cancer were missed by screening cannot be dletermined in a erosssectiona study, but requires profonged follow-up and evaluation (ie a longitudinal study) This basic principle (34), was

«endorsed i a recent WHO consultation on the principles of screening (38), and therefore was not reconsidered in the present consultation, The recent -meti-analyses assed semsitiity of cytology cros-sectionally, and with Few

‘exceptions, inchded stadies tha suffered from veeiation bias (36), which

‘crs when only those who test positive ae submitted tothe gold standard test (often colposcopy with histalogclly confirmed diagnoses), such that fuse negatives to the screening test were simply not identified, Such a design cantor distinguish herween those precursor lesions destined to regress and those destined to progress Its the later that need to be considered in et _mating sensitivity relevan to programme planning, lis ent

thatthe sensitivity of tests that identity diferent spectra of precursors may

be very diferent with regard to the proportion of potentially progressive lesions fond, Only fe studies have asessed sensitivity of cytology lon sstedinally, using cancer as the endpoint All were conducted several years ago in developed counties with high quality laboratories and produced est ates of sensi ranging from 0% to 90% (37,38)

—-

In many cytology laboratories in developing countries, itis probable that the sensitivity achieved i substantially les: chan in these published reports (37,38) Poor sensitivity in the laboratory’ will be compounded ifadequate mars ate not taken, as there are wo components of false negatives, that saused by poor smeartaking, and that caused by laboritory (pracessing/ reader) error (37) Cytology ako ses fron relatively low reproduibiity (39-41), To reduce the impact ofthese deficiencies, there are many esental clements for succesful cytology based Serening programmes

‘THE ESSENTIAL ELEMENTS FOR SUCCESSFUL CYTOLOGY SCREENING PROGRAMMES

In addition to the esential elements common to ll programmes summs

rized cai, there are additional elements requited for success cervical Gtr

Commir

‘Training of relevant health care professionals,

Tere are many ypes of health care professionals that will cguin tining:

The smear-takers (primary care practitioners or nurses) These indivi

als must be techy competent and capable of achieving good rapport

Attention should be given to the assembly of the project team All eam

members must be able to work well together A dysfunctional team is

unlikely to sueceed

‘Sigaificant political issues usually must be resolved dusing team assembly,

The following team components should be clearly defined up oat, with

the understning that changes may be made in team composition as the

programme evolves:

1) Insticution(s) and individuals who will be in charge of organized com

munity outreach and Pap smear colestion,

2) Ineviduals who wil be in charge of contacting women with abnormal

test results should be specially designated

3) Insticution(s) and individuals who will be in charge of the centralized

ejtology laboratory;

3) Centralization faclittes quality control efforts, reduces overhead costs,

sss in tracking the sereened population, and catalyses ineoduetion

‘of improved technologies and procedures

by Ie ease, politically, to centralize merging laboratory serves than

to centralize pre-existing laboratory services

4) Insiution(s) and individuals to whom women with abnormal cytology

test results will be referced

5) Institution(s) and individuals who will be in charge of the centralized

pathology laboratory to evaluate biopsy specimens (should be the same

Laboratory to which smears are sent for examination)

Chap

Mia come

Chmie

‘An agreed decision on the priority age group to be screened

"The priority age group to be seeened shoul be defined by the age-related incidence of imasive cancer ofthe servi in the country, not on the basis of the percentage distbtion by age of clinically detected cases of cancer in the county In most counties it will be found that the majonty of smears are being performed on young, women, who are at low risk of presenting With invasive cancer within the next 5 years Almost invariably it will be sletermined tha the priority age group for intl screening are women age 38-54 years

“The most important screen isthe Fist, and priaity mst be given to

‘ensuring that as high a proportion of the target population as possible is screened once belore attention is diverted to recaling women for subse

— Adequately taken and fixed smears and their preparation Inadequate collection of cellslar matesal from the transformation zone and inadequate preparation ization and processing of the smear are major

‘causes of false negative results 42-4),

An extended tip spatula (45), the combination of the Ayre spatula and endocervical brush and Cervex brush spatulis (46,47) allow adequate co! lection of the target zone for preparation of conventional smears The use of the Ayre spatula or cotton tip applicator alone should be avoided (464849)

“The speed of fixation is very important (the time between spread of

‘material on the ghss and Fixation should be minimized to a few secon), Fisation with alcoho has been shown infield circumstances t be adequate, (Commercial fixative sprays are a akernative, bt ate more expensive Smeartakers need sufficient training Several illustrated guidelines a available and are very’ useful tool, (50452)

‘The laboratory should introduce a mechanism ro monitor the propor tion of inadequate smears submitted by the individual smear takers, Those wvth >10% inadequate smears should undergo hands-on retraining in smear taking,

Efficient and high quality laboratory services

"Hinh quality laboratory services ate essential to elective cytology steening, [iis possible to solve transport problems, the greater the centralization of such services the more ecient the laborstory will be In small counties, this could imply a single central (national) laboratory, In lage countries,

several regional laboratories will be eequieed Is any ease, a minimum

throughput will be required to ensure adequate quality and eficiency, This

minimum bạc been variously defined as 15-25,000 smears per annum (20,

26), of a work load justiing the employment of atleast three technolơ-

“is, ho can cach be expected to examine approximately 80 smears in an

hour day The average time required forthe interpretation of a one-slide

‘gynaecological smear by an experienced cytotechnologis is estimated to be

approximately 6 minutes (5 minutes for reading and I minute for reporting

and handling) (53)

Small laboratories tend to use or interpret reporting systems inconsst

cently Reports sent to clnis ate not well derstood by sina st, wich

may explain why so many women ate requested fo Feturn for an unnecessary

repeat smear Quality contol in laboratories aso varies with some having

ization of ab

‘outstanding systems and others having none at all, Compa

‘oratories i not standard and some laboratories use a paper-based system

‘only There is often no linking berween cytology and histology reports

making quality control a problem

Quality control of cytology reading Quality conteol programmes must be intcoduced in all ytology laboratories

A 10% fll esereening of negative smears is ineffective and isnot recom:

mended Rapid re-reading of 100% of negative desis elective ($4), but

may be outside the reach of low resourced progsammes, Careful evala-

tion of detection rates by the smear reader and special evaliation of those

swith mates ont of fine with expectation may help to ent poor performers

‘Continous programmes of retaining ae ideal, Patsipation of the labor

ratory in an external quality conttol programme, such as that organized by

the Pan-American Health Organization (PAHO) for many Latin American

«countries (REDPAC (Panamerican Network of Cytology) sone option for

Iaege laboratories,

‘A means to rapidly transport smears to the laboratory

Delay in transportation of smears should be avoided as fr as posible, Pare

(of the budget for the programme should be dedicted fo the cost of tans-

porting specimens

A mechanism to inform the screened women of the test

results in an understandable form Women must be informed of the results oftheir test in a Form they can

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7

‘A mechanism to ensure that women with an abnormal test

result attend for management and treatment {In many programmes in middle-income countries, those with an abnormality

‘commonly fil to return to the clinic for management, This is a general problem forall programmes that require referral for subsequent gnosis and treatment (as distinct from a test and treat policy as discussed below for VIA) Practical see and teat polices for eytology have not yet been slessed The basic esponsibility For ensuring such referal resides atthe pri nary cate level, rather than at the level of the indivi woman, A special

«ade of health Visitors whose responsibilty it to ensure thar women with abnormal rest results do attend for diagnosis and management may have t0

be appointed, An evalvation of the cost-effectiveness of iferent screening polices in South Africa identified fire to attend for investigation and

"ueatment of abnormalities 35 a major factor in reducing the cost-efective: ness of extology (35)

Trained (licensed) colposcopists

In most middle-income countries, colposcopists will either already be avail able, or can be trained A licensing (taining and certification) system is desirable, and cael ongoing evaluation oftheir performance should be an incegral part ofthe progtamme

An accepted definition of an abnormality There has been considerable confusion on the type of abnommality sought ia cervical screening The intial programmes in developed countries concen: trated on eletestion of carcinoma inst, laterdyplsia was ented, bu this vas usualy observed by repeat smears, Only recently have changes in obs sation systems resled in ation following wiht used tobe labelled as typisal (orChss2) smears, orborderlneabnonmalitis classed inthe Bethesda system ssatypial squamous cell of undetermined significance (ASCUS) (50) new

‘ersion ofthe Bethesda system has recently been devised, with ovo ASCUS: type designations: ASC-US (same as before) and ASC-H (cannot exchide high-grade squamous intraepithelial sion (HSIL)) (57)

Tn the USA, the adoption of the Bethesda ystem dramatically increased

the proportion of smears with cytological abnormalities that appeared to Cleo require clinial atention, The new terminology increased the overall pro- Screens portion of low-grade lesions by combining the original mill dysplasia Bae tare category with cytological abnormalities consistent with koilocytotic at Gane pias into the low-grade squamous inespithelial lesion (LS) designation

Shortly afer the adoption ofthe Bethesda classification it was estimated

that ASCUS and LSIL comprised 94% of al Psp smears and up to 12.5% of

smears in certain ethnic groups (58) As cytopathology laboratories gained

‘experience with the classification, a decreas in the proportion of ASCUS

(ome 45%) and ISIL (some 28) smears occurred (59)

“There is currently agreement that cytology indicative of high-grade

lesions (CIN TE-HTT of moderate and severe dtsplasia pls carcinoma sate

‘or HSIL in the Bethesda syste) should engender immediate eeferal for

colposcopy: Lowarade etology (LSHL or ASCUS), under circumstances

‘where women can be fellow with rege tology, should beso manage

and only refered for colposcopy if epeat smears at 6-month intervals show

‘evidence of cytologic progression (26) As the lange majority’ of low-grade

lesions resolve spontancoush (37,6361), there is no urgent need for teat

ment The programme must provide specific guidelines on this ise

‘A mechanism to follow-up treated women

“There are appreciable flares of treatment, 5 that Fllow-up (asa minima

with a eepear smear, bur if possible with colposcopy), should be ensured,

“Those with high-grade abnormalities should be followed anally fr at least

5 years before they are retumed to rtne srecning,

Decision on frequency of subsequent screens

“The previous WHO revemmendation was that when 80% of women aged

35-40 year have heen screened once, screening frequency should increase

to 10-yeaely and then S-yearly for women aged 30-60 yeas, ae resources

permit (22) To date, data are not avilable that suggest that these ree

‘ommendations be revised, However, om the basis of modeling diferent

approaches, it has been suggested that other intervals may be appropriate

(uch as five-yearly screening from the age of 38 for a total of three tests

ina lifetime) (55) However, increasing the frequency of sreening, and

‘extending serening to younger age groups, does not compensate for del

ences in laboratory’ quality or of population coverage

“There has been some enim of the estimates mad by the International

Agency for Research on Cancer (IARC) Working Group on Ci

Screening (38), which ate used to justly relatively infrequent screening

esvical Cancer

9

in Finland based on 5-year eytology screening for those age 85-59 (3)

‘A mechanism to invite women with negative smears

for a subsequent smear

‘Whatever the decision on the frequency’ of repeating screening (sce above),

it will be necessary to actively invite women to retum for screening when their next smear is duc The appropriate mechanism will wsually involve 3 similar mechanism to that use to invite women for thee frst smear

ELEMENTS THAT INTERFERE WITH THE DEVELOPMENT

OF SUCCESSFUL CERVICAL SCREENING PROGRAMMES

"The converse of the essential elements discussed above ate the most critical

in terms of fires of programmes However, there are some elements that

“may require sect attention in some countries, (Over-reliance on reproductive health services for screening,

i most middle-income counties, screening will aleady bein place but may

he largely restricted othe maternal and cid health services (reproductive health), Unfortanatels, women screened in sich services tend to assume there is no need for screening alter they have completed their attendance, and no mechanism is putin ple for screening older women A major role forthe new of revitalized programme will be reallocating resources ro ensire thatthe target group for the programme is serene

Opportunistic screening Opportunistic (spontaneous) sreening will often be ongoing, There is ev dence that such scecening is fr les efficient and effective (han organized programmes while costing more, because those screened tend to beat low

rk forthe disease (25) Resllocation of thee resources to the organized programme will often save mone,

Low coverage of the target group with screening

Throughout this report low coverage has been identified as the most critica

reason for lure of cervical screening, Evidence presented atthe consulta~

tion from the National Progsamme in Costa Ria shows thatthe previous

reports that high screening coverage in that country produced no reduc-

tion in incidence ofthe disease, were flawed, These reports were based on 3

ful process of estimating coverage sul that smears were counted rather

than individuals entering the programme, and they eli not account for the

fact that many women had repeat smears, Coverage must, therelore, be

measured on the basis of inividals reervited into the programme, rather

than smears performed,

Setting too low a threshold for referral for colposcopy, ie

‘over-treating non-progressive disease

As the lage majority oflow grade lesions regress (37,6061), policy based

‘on referral for colposcopy of eytology reported as low-grade (or ASCUS)

will increase cous, yet have minimal impact on the seas The programe

should be capable of racing and following women who are seteened, Thus

it showld be posible to follow these women by repest cytology every 6

‘months unt its posible to determine whether there iscjtologial evidence

‘of disease progression

THE STRENGTHS OF THE CONVENTIONAL

CERVICAL CYTOLOGY TEST Cervical extology is known to reduce cervical cancer incense and mor

tality, porticlary in organized programmes, thowgh in North America and

some countries in Europe benefit was obtained with excesive opportunistic

screening In addition, the test has te Following strengths:

+ Decades of experience in its se

+ High specific

* Lesions identified ae easy t0 teat

* Relatively low cost

* Qualified manpower and laboratory resources exist in most counts,

However, there are limitations of the test, These include:

* The test is embarrassing and i dificult to comprehend in many euhurss,

+ Requires esined personnel

* Smear adequacy not intrinsically obvious

Gtr Commir

2

Chap

Chmie

‘eis necessary to recall women for further tests ifthe smear is inadequate,

‘or for evaluation if an abnormality i suspected + In most laboratories only moderate sensitivity is achieved and reproxiue ibslty is poor

“+ Cytology is unable to distinguish progressive disease fom that destined t0 regres This is true for both reported low-grade and high grade lesions, with the probability of progresion being much lower for low grade abnormalities (37,6801)

Cytology may be less effective in older women, Tis reflects reduced

‘exfoliation of lstons in such women, and the fist that the transforma tion zone tends to: mote to the endocervical canal, However, if women have been adequately screened over the age ange 35-54 and have never had aa absiormal smear, they are at low risk of disease and screening can stop

+ Cervical sereening using estology requires considerable management

‘effort and coordination because of the number of different agencies involved, This can prove expensive

+ eis impossible to abolish the disease by screening, There will always be

‘ses of invasive cancer that osc despite screening because the biology

‘of the diseae in thar individual resulted in a progression that was too rapid for timely detection to result in effective treatment In addition, no programme can guarantee 100% coverage or tol effectiveness of the sereening process Thus programmes are likely to reach an ieredcible minimum of invasive cancer in the population served, that will peobably

be ofthe level 10-20% of the insidence inthe absence of screening Its important tha this s understood by pariipants in the programme, and

by these who fund snd support the programme

THE IMPLICATIONS OF DIFFERENT METHODS

OF SAMPLING Liguil-bosed cytology is curently too expensive for most developing cou tries, In adliton, itis important to recognize that liguid-based cytology does not compensate for an inadequate smear being taken ‘Thus at present, liguid-based eyrology needs to be further evaluated as to its viability in slexcloping counties

However, experience fn is use in developed countries suggests i has 2 umber of advantages over conventional cytology, and in some circum stances these advantages could result in an overall cost-fletiveness ofthe process being improved, even though the test ite fs more expensive The advantages of liquic-based cytology are that it

+ Produces a uniform ayer of cells, representative of those present i the

+ Has the potential to:

~ Improve sensitivity

~ Improve specitcty

= Increase throughput in the laborstory

However, iquid-basedeytology has a numberof additional requirements or

will quite readjustment of existing programmes, These inchi

* Reersining of smear takers

# Transport and storage of ils by different approaches,

+ Reenining of evtotechnologis

+ Purchase of new equipment

* Review of quality assurance schemes asthe tangets change (the expected

rhumbers and ranges will change)

Nevertheless, experience in the UK and USA suggests thar the learning

«curve is bref, and that technologists who are trained for the fst time on

Tiguid-based cytology perform better, and more apy reach an adequate

level of expertise, than these previously trained t examine conventional

smears For those taking smears a course of 2-3 days duration i sulin,

THE IMPLICATIONS OF DIFFERENT METHODS

OF SMEAR READING + Smears ean be read by’ specially trained ly worker,

*+ Smear reading isa good occupation for some dsabled workers

+ Computer assisted reading shows promise in improving sensitivity and

possibly spesitcty, but the costs too high for most developing countries

2 present Furthermore, in such countries, maintenance of auromated

seaders wil require arention

‘THE CIRCUMSTANCES WHEN CERVICAL SCREENING

PROGRAMMES SHOULD BE RECOMMENDED

* Cervical cancer contol is judged © be a suicently high prionty as part

‘of National Cancer Control Programme

+ The essential elements discussed earlier 3 cin place, oF can be proved,

ani intended tht they be sustained in the count

+ The politcal and profesional will for the relevant changes has been

scoured

Gtr Commir

2

in the country, and these should be successfully completed (in tems ofthe process and impact measures previously defined) before the programme is cestnded to the whole country

RESEARCH ISSUES ON CERVICAL SCREENING PROGRAMMES IN DEVELOPING COUNTRIES + Determine culturally relevant ways to secure an educated target popu

ing in each counery:

+ Eoluate different approaches to manage programmes and improve their performance

+ Determine whether vertical (top down) or horizontal organization is

‘optimal foe the country Determine optimal ages for niating and stopping Sreenine, Determine the required period of intensive follow-up For those treated for high-grade lesions,

RESEARCH ISSUES ON CERVICAL CYTOLOGY

IN DEVELOPING COUNTRIES + Conduct a detailed evaluation of smeartaking devices

+ Longitudinally determine the sensitivity of smear testing in developing + Evaluate the nee! for repeat smears after the fist smear ~ by age

+ Evaluate the merits of liguid-bosed ss, conventional eytology with study

“designs that permit measurement of sensisity and specific + Develop laboratory quality control strategies that are gelevant 0 the needs of the country

+ Develop a cytology clasifieation system that is more relevant to the natural history of the disease, and the needs for a system that concen trates management resources on the CIN II component of high-grade lesions,

VISUAL INSPECTION WITH AceTIC AcID

AppLicaTion (VIA) AS AN ALTERNATIVE

APPROACH TO CYTOLOGY SCREENING

In Low-INCOME CouNTRIES

Even though eytology’ screening may be feasible in middle-income coun-

tries, there are technical, human resource and financial constrains in

implementing sich peogrammes in low-income countries In view of this,

ltcrnative methods based on visa examination of the cervix have beet

investigated forthe coorvol of cervical cance in low resource settings (6

67) ‘The visual methods of screening include unaided vsual inspection of

the cervix (‘downstaging’), visual inspection with 3-5% acetic acid (VIA)

(synonyss direct vital inspection (DVI), erviconcopy, aed vil inspec-

tion), VIA with low-level magnification (VIAMM),cervicography, and visual

inspection with Lugo!’ iodine (VILI) Downstaging has been shown to be

inaccurate in detecting disease, particulaty cervical pre-cancers (64), and is

not farther considered inthis port

Among the visual inspection approaches, VIA has heen more widely inves

tigated for its performance characteristic (accuricy in detecting cervical

neoplasia, in various sextings, by ferent providers VIA involves naked

‘eye examination ofthe 3-58 acetic acid sabe uterine cervix without any

magnification, usually by nurses and other paramedic health workers, with

illumination provided by a bright light source, such a6 a halogen lamp A

positive texts the detection of well defined, dll azetonhite lesions on the

ervik, The objective of VIA isto detect acetowhite lesions leading 10 the

‘early disgnosis of high-grase cervical inteaepithelal ncoplasa and eal pee-

<inisal, asymptomatic invasive cancer major advantage with VIA is thats

isa teal-time srcening test a8 the ovtsome is known immetstely afc the

administration of the fst, 0 that further investigations treatment can be

planned and cared out during the same viết

Historically, before the advent of Pap smears and routine cytology based

screening programmes, health care providers relied on inspection of the

sersix t0 detect abnormalities After the 1950s, when cytology’ smears

became the standard for cervical sreening, the colposcope (initially devel-

‘oped in the 1930s) began to be used increasingly to further investigate

sereen-postive women and to dlrect biopsies in order to confim screening

findings Eventually, VIA was explored as an adjunct 10 the Pap smear to

decrease the falbe negative rate of cytology and for more efficient ident

Fcation of women for solposcopic triage These studies, and the need for

4 suitable slternative for cervical cytology led to the investigation of the

2

TEST CHARACTERISTICS AND CURRENT LEVEL

OF EVIDENCE FOR VIA AS AN ALTERNATIVE

SCREENING APPROACH

“The basi step in asesing the uty of a sereening test isthe determination ofits est characteristics in tems of sensitiiy speicity and predictive values,

‘Consistently lene sensitivisy and specify ofa given test preclide it further

«valuation for eeducing incidence and/or mortality from a given disease

A summary of ke cross-sectional studies adresing the test characteristics

of VIA ispresemted in Table 1 Otiaviano and 1a Torte (68) examined 2400

‘women using VIA and the colposcope VIA detested abnormalities in 98.4%

‘of patints asesed colposcopically as having an abnormal transformation zone and it correctly ientiied 98.9% of normal eases, Ina study involving

148 women attending health clinics, the reported ods ratio fora postive sytology was 6,6 if the VIA test vs aso positive (09) In a study among,

2827 women, Slawson etal (70) demonstrated that VIA might be help in reducing referrals for colpossopy Van Leet al (71) found! that VIA resulted inan additional 15% of CIN cases being identified among cycology-negaive

‘women, but 40% of women with positive VIA underwent unnecessary col pscopy (ibe positives) Frisch etal (72) found that combining a negative

«ytology and negative VIA test resulted ina negative preitve value (NPV)

‘of 91% — greater than that obtained for eyology alone, but with some loss

in positive predictive value (PPV) These studies demonstrated the poter tial value of VIA asa viable sreening approach, but did ot establish its test

“qualities sa primary sereening method

‘Cecchini et al (73) provided evidence on the ascuraey of VIA, VIA was more sensitive than eytology, but less specific, Additionally, screening, sequently vsing VIA was more cost-effective than with cervicography, Subsequently, six published studies on VIA as a primary screening rodality have been carried out in developing counties In the study by

“Meegevand et al (74) in South Alfiea, VIA and extology were performed

in mobile unit equipped to provess smears on site In that setting, VIA