Colposcopy versus Pap smear for cervical cancer screening in high-risk women: a tertiary care centre study

Title of theproject COLPOSCOPY VERSUS PAP SMEAR FOR CERVICAL CANCERSCREENING IN HIGH RISK TRIBAL WOMEN  AHOSPITAL BASED STUDY Aim To compare the accuracy of colposcopy using Swedescore and Pap smear for the detection of premalignant and malignant lesions ofthe cervix taking histopathology as gold standard  in high risk tribal women Objectives Primary To compare the accuracy of Swede score aidedcolposcopy and Pap smear taking histopathology as reference standard in highrisk tribal women Secondary To estimate the prevalence of premalignant andmalignant cervical lesions in high risk tribal women Justification for study Exfoliative cytology HRHPV DNA test and visualinspection tests have been widely used as primary screening tests of cancercervix Colposcopy has till now been used to guide the biopsy site The womenwith abnormal exfoliative cytology report and positive HRHPV test are referredfor colposcopy However it has been observed that women with chronic cervicallesions are reported false negative on papanicoloau smear which is the mostwidely available and used screening test till date  Colposcopy using swede score is very accurateinvestigation which detects HGL and malignant lesions with about 95 100sensitivity in the background of inflammatory changes specificity 80 88  So colposcopy should be done in allsymptomatic patients with chronic cervical lesions like chronic cervicitiserosion endocervicitis lacerations polyps and leukoplakia Pap smear can bemasked by inflammation in chronic cervicitis making colposcopy a better choice for cervical cancer screening in thesecases of unhealthy cervix These lesions have been observed to harbourpremalignant lesions even when a Pap smear is negative  Also there is scarcity of information anddearth of literature related to cervical cancer screening and prevalence inindigenous women In todays world of advancement colposcopy if used judiciouslycan accurately screen and treat premalignant lesions of the cervix at the samesetting for cervical cancer control in underprevilaged indigenous areas Scope of the Project Cervical cancer is one of the leading cause ofmorbidity and mortality in women especially in the developing countries despitebeing a preventable disease Early detection and diagnosis is the mainstay ofcervical cancer control Exfoliative cytology is the most commonly usedscreening method till date The women with abnormal test are referred forcolposcopy However it has been observed that chronic cervical lesionsharbouring premalignant lesions are likely to be missed by Pap test and arereported false negative In chronic inflammatory lesions Pap smear can be maskedby underlying inflammation making colposcopy a better choice The false negativerate of Pap smear had been reported as low as 2 earlier but as high as 47 in recent times So colposcopy should be usedfor screening these cervices so that premalignant lesions are not missed in thebackground of inflammation If null hypothesis is refuted the use of colposcopyas a primary screening tool in women at high risk of cancer cervix would beproven and utilized with improved portable technology telemedicine andartificial intelligence Also the treatment of abnormal cervices in the samesetting facilitates expedited management and better patient satisfaction andovercomes the attrition risk This would be helpful for cervical cancer controlin underprevilaged region as in this study This is synchronous with the WHOglobal strategy to accelerate the elimination of cervical cancer as a publichealth problem Details of procedure and methodology proposed to be Studypopulation The study willbe conducted in 150 high risk women aged 21 to65 years attending gynecologyoutpatient department of AIIMS Deoghar Deoghar is one of the six districts ofSanthal Pargana in Jharkhand with population of over 6 million Women having twoor more risk factors of the following and at least one of the followingexamination finding will be classified as highrisk and would be included in the study In history Complain of postcoital bleeding Complain of postmenopausal bleeding Complain of persistent discharge per vaginum On examination  cervicalerosion  laceration polyp leukoplakia chronic cervicitis Study setting This will be a hospital based study on tribal womenvisiting gynecology out patient department in All India Institute of MedicalSciences Deoghar The study participants will be recruited by consecutivepurposive sampling Study design This will be a prospective observational study   Sample size Sample size is 150 Pap smear and colposcopywill be done in all participants   Inclusion criteria Age 21 65 years Not undergone treatment for cervical cancer or andprecancer in the past history of postcoital bleeding postmenopausal bleedingpersistent discharge per vaginum with abnormal looking cervix polyp cervicallacerations leukoplakia erosion chronic cervicitis on examination Consenting patients Exclusion criteria Pregnant women Frank cervical cancer growth Diagnosed case of cervical cancer precancer Women undergoing treatment for gynecological cancer   Primary outcome Colposcopy compared to Pap results in high-risk womenwith histopathology reference   Secondary outcome Prevalence of cervical premalignant and malignantlesions in high risk women     Statistical analysis The clinical records will be entered in the proformasThe proformas used for data collection will be allocated serial numbers fordata entry The data will then be entered in Microsoft access database afterpartial cleaning After partial cleaning it will be migrated to SPSS softwareData analysis will be carried out The results of colposcopy and pap smear willbe recorded separately and compared with histopathology as the gold standardThe results of the study will be compared with prior relevant literature Theprevalence of cervical cancer in women with cervical lesions will be estimated DATA COLLECTION A pre structured questionnaire will be administered toall women aged 21 to 65 years of age visiting AIIMS Deoghar out patientdepartment. In questionnaire proformas detailed clinical history will berecorded regarding symptoms of abnormal bleeding vaginal dischargeabdominal pain demographics sexual history obstetric history and past historyGynecological examination will be done in all women and those with abnormallooking cervix will be identified All high risk women will be explained aboutthe nature and purpose of tests in the local language Subject informationmaterial and consent forms will be read out to the participants beforeobtaining their signature on the consent forms Those women who deny informedconsent will be excluded Allparticipants will undergo pap smear colposcopy and guided biopsy in the samevisit Cervical cytology smearscervical biopsies and endocervical tissue will be processed and diagnosed inthe Department of Pathology AIIMS Deoghar The pap smear examination willbe done according to the standard protocol. The ectocervical smear will becollected by Ayres spatula and endocervical sample will be collected usingcytobrush The monolayer cytology smear will be fixed in 95 ethanol for processing.The cytology smears will be reported according to theBethesda system 2014 The participants with Pap test results of atypicalsquamous cells with undetermined significance ASCUS atypical squamous cellscannot exclude high grade lesion ASCH atypical glandular cells AGC low gradesquamous intraepithelial lesion LSIL high grade squamous intraepithelial lesionHSIL atypical glandular and or atypical endocervical cells will be classifiedas abnormal Pap smear Colposcopy will be performed using a video colposcopeDigital video colposcope Sims and recorded according to 2011 IFCPC nomenclaturenormalabnormal The cervix will be inspected in good light Saline will beapplied to remove any discharge or mucus Any area of leukoplakia present willbe noted Then 5 freshly prepared acetic acid will be applied liberally over thecervix using cotton After 1 minute of application entire cervix will beexamined under magnification ranging 5 25 times Any abnormal acetowhite areaswill be noted. A record will be made of the transformation zone TZ TZ will belabelled as type 1 if new squamocolumnar junction is fully visualized type 2 ifTZ is partially visualized and type 3 if TZ is not visualized After that lugolsiodine will be dabbed onto cervix Any area of nonuptake appearing as mustard orcanary yellow will be noted. Swede scoring will be done with five recordedvariables acetowhite areas margins abnormal vessels iodine negativity andlesion size Biopsy will be taken from most abnormal area using punch biopsyforceps For unhealthy cervical lesionsappropriate treatment as per standard guidelines will be administered in allparticipant women For colposcopythe paticipants with swede score 0 to 4 will be considered low grade lesionsand swede score 510 will be considered high grade lesions or malignancy oncolposcopy  Detailed time line for the project The type of biopsy will be taken as per standard treatment care.Histopathological findings will be described according to OSSN classificationBenign report will be recorded in specimens with no atypia CervicalIntraepithelial neoplasia CIN if mild moderate and severe will be described asCIN1 CIN2 and CIN3 respectively Invasive cancer will include malignant cellsinvading basement membraneThe methodology is summarizedin Figure 1    DATA analysis The clinicalrecords will be entered in the proformas The proformas used for data collectionwill be allocated serial numbers for data entry The data will then be enteredin Microsoft access database after partial cleaning After partial cleaning itwill be migrated to SPSS software Data analysis will be carried out The results will be expressedas mean value plus minus standard deviation or proportions Colposcopy and papsmear will be the two index tests for comparison of diagnostic accuracyparameters Histopathology will be taken as the reference standard test. ROC analysis will be donefor comparing sensitivity specificity predictive values accuracy and otherparameters using histopathology as the gold standard AUC point 9to 1 will indicateexcellent diagnostic accuracy and AUC between point 8 and point 9 very goodaccuracy point7 to point 8 good point 6 to point 7 sufficient and if AUC is less than point 5test will not be useful The results of the study willbe compared with prior relevant literature Additionaly the diagnostic parameters of pap smear andcolposcopy different histopathology, will also be compared separately using 22tables The prevalence of cervical cancer in women with cervical lesions will beestimated  This project is for three years       Limitations  As this is aprospective observational diagnostic accuracy study design involving threeprocedures and reporting the risk of information bias will be there to someextent Clinical reporting and histopathological reporting and statisticalanalysis may be affected by clinical data and symptoms Selection bias may bethere to some extent Both selection and information bias may be overcome byrandomized control study design Adverse events in participants though very rare ifoccur will be managed as per the standard guidelines With 604127 cases every year and 341831 deaths cancercervix is the fourth most common cancer affecting women worldwide 1 Majority ofcases are still reported from developing countries despite widespread screeningand treatment programmes One women dies of cervical cancer every eight minutesin India despite cancer cervix being a largely preventable disease The primaryprevention methods namely vaccination and screening are effective measures toprevent the disease progression Cytology by Papanicolau test High Risk Human PapillomaVirus testing visual inspection by Acetic acid and Visual inspection by Lugols Iodine are commonly used primary screening tests for cancer cervix. Pap smearwas considered to be 80 to 95 accurate for detection of premalignant and earlyinvasive cervical cancer More recently the reported accuracy of Pap smear waschallenged due to false negative Pap reports in cases of unhealthy cervixespecially chronic cervicitis endocervicitis cervical polyps leukoplakiaerosions lacerations and lesions bleeding on touch 2 3 4 The false negativerate of Pap smear had been reported as high as 47 and specificity as 74 inrecent times 5  However till date it isthe most commonly used screening test During the process of collection of smearacetic acid and schillers test without magnification or direct colposcopy canbe planned in case of suspicious or unhealthy cervix This is particularlyimportant in early diagnosis and administration of treatment see triage andtreat in those cases which may result in false negative pap test result The Paptest is the recommended cervical cancer screening test of choice of nationalcolposcopy and cervical pathology organisations worldwide Cervical cytology hasthe added advantage of direct inspection of cervix by health care personnelunlike the HRHPV test Visual inspection tests have limited accuracy and thuslimited to low re source settings HRHPVPV test have the advantage of selfsampling and thus broad coverage but limited specificity especially in youngerwoman Colposcopy has been traditionally used for thediagnosis of precancerous lesions It has been used as an adjunct to screeningas a secondary triage screening tool The purpose of colposcopy is largelylimited to direct biopsies from abnormal areas in screen positive women Women with chronic cervical lesions like chroniccervicitis endocervicitis cervical erosions lacerations polyp leukoplakiaharbor premalignant lesions Exfoliative cytology may be reported as normal inthem The false negative rate of Pap smear had been reported as low as 2 earlierbut as high as 47  in recent times 5 6 Soevaluation under magnification acetic acid application and directed biopsy incolposcopy clinics is of great value in women with unhealthy looking cervixHistopathology has been used as gold standard for comparison of two groups inwomen with unhealthy cervices 7 8 9   REFERENCES 1 Sung H et al Global cancerstatistics 2020 GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36Cancers in 185 Countries CA cancer J Clin 2021 May 2 Singh Ls Dastur NA NanavatiMS A comparison of colposcopy and papanicolaou smear sensitivity specificityand predictive value 3 Gupta SC Evaluation ofcervical erosion in symptomatic women Int J Reprod Contracept Obstet Gynecol2020 4 Fuke RP Sonak M Singh M Roleof colposcopy in the evaluation of unhealthy cervix and cervicalintraepithelial neoplasia J Evid Based Med Healthcare 2020 5 Bhattacharya AK Nath JD DekaH Comparative study between Pap smear and visual inspection with acetic acid inscreening of CIN and early cervical cancer J Midlife Health April  2015 Oglan SC Obut M Comparison ofPap smear and Colposcopy in the absence of HPV test for the diagnosis ofPremalignant and Malignant cervical lesions East J Med 2020 7 Can LBC Completely ReplaceConventional Pap Smear in Developing Countries J obs and Gynae India 2019 8 Rahman Z Yadav G Tripathi U The Diagnostic Efficacy of Swede Score forPrediction of Preinvasive Cervical Lesions A Prospective HospitalBased Study JObstet Gynaecol India 2020 Dec 9 Campos PL Guimares ICCDV Fialho SCAV Martins CAO Rodrigues FR VelardeLGC Monteiro DDSA Association of Swede Score and 2011 IFCPC Nomenclature inWomen with Abnormal Cytology