Screening for Cervical CancerScreening for Cervical Cancer

Max Brinsmead MB BS PhDMax Brinsmead MB BS PhDOctober 2015October 2015

Cervical CytologyCervical Cytology As a screening test for Ca Cx this test has only As a screening test for Ca Cx this test has only ~~75% 75%

sensitivitysensitivity Better at detecting CIN Better at detecting CIN

» but then specificity is a problembut then specificity is a problem

Must sample the squamocolumnar junctionMust sample the squamocolumnar junction More significant if +ve in a high risk individualMore significant if +ve in a high risk individual

» OlderOlder» Early sex, multiple partners, other STDsEarly sex, multiple partners, other STDs» SmokingSmoking» HPV infection with high risk subtypeHPV infection with high risk subtype

Liquid-based cytology can enhance sensitivity by ≈5%Liquid-based cytology can enhance sensitivity by ≈5% Start at age 20 or within 3 years first coitusStart at age 20 or within 3 years first coitus

Cytological TermsCytological Terms

LGEA = Low grade epithelial abnormalityLGEA = Low grade epithelial abnormality» Replaces the older term mild dysplasiaReplaces the older term mild dysplasia» Mostly due to HPVMostly due to HPV» Also called low grade squamous intraepithelial lesion or LSILAlso called low grade squamous intraepithelial lesion or LSIL

HGEA = High grade epithelial abnormalityHGEA = High grade epithelial abnormality» Replaces the older terms moderate & severe dysplasiaReplaces the older terms moderate & severe dysplasia» Arises from CIN1 & CIN2 (but these are histological terms)Arises from CIN1 & CIN2 (but these are histological terms)» Also called high grade squamous intraepithelial lesion or HSILAlso called high grade squamous intraepithelial lesion or HSIL

Both the above have “Possible” variants ieBoth the above have “Possible” variants ie» Possible LGEA = former “nonspecific minor changes”Possible LGEA = former “nonspecific minor changes”» Possible HGEA = former “Inconclusive” reportPossible HGEA = former “Inconclusive” report

ColposcopyColposcopy

Limited by need for expert and equipmentLimited by need for expert and equipment Relatively expensiveRelatively expensive SubjectiveSubjective Limited to visible part of the CxLimited to visible part of the Cx CIN can be masked by HPVCIN can be masked by HPV Of most use in identifying area for biopsyOf most use in identifying area for biopsy Better therefore than previous alternative of cone Better therefore than previous alternative of cone

biopsybiopsy

HistologyHistology

The gold standard for diagnosisThe gold standard for diagnosis Only as good as the sample receivedOnly as good as the sample received

» (except for cone or LLETZ)(except for cone or LLETZ) And still somewhat subjectiveAnd still somewhat subjective But accuracy is increased if stains for high But accuracy is increased if stains for high

risk HPV DNA is usedrisk HPV DNA is used

Natural History of CINNatural History of CIN Progression 1Progression 12233cancer is not inevitablecancer is not inevitable

CIN 1 - 85% spontaneously regressCIN 1 - 85% spontaneously regress

CIN 3 – 50% regress or stay the sameCIN 3 – 50% regress or stay the same

Progression time varies Progression time varies » 6m to 16 years 6m to 16 years

But some will have invasive Ca when Pap smear reports only But some will have invasive Ca when Pap smear reports only LGEALGEA

» Hence the debate about current NH&MRC guidelinesHence the debate about current NH&MRC guidelines

HPV SubtypingHPV Subtyping

90% of Ca Cx is associated with High Risk HPV90% of Ca Cx is associated with High Risk HPV» Subtypes 16,18,45,31,33,35,52,58 etcSubtypes 16,18,45,31,33,35,52,58 etc

Highly sensitive for the detection of HGEAHighly sensitive for the detection of HGEA Does not require equipment or expertiseDoes not require equipment or expertise Equivocal results can occurEquivocal results can occur Of most use in the follow up of treated CINOf most use in the follow up of treated CIN And those patients with persisting LGEA on Pap And those patients with persisting LGEA on Pap

smearsmear

Treatment Options for CINTreatment Options for CIN ObservationObservation

» LGEALGEA» Young womenYoung women» Obvious HPV infectionObvious HPV infection» Chronic LGEA with Low risk HPV subtypeChronic LGEA with Low risk HPV subtype

Targeted destructionTargeted destruction» LaserLaser» DiathermyDiathermy» CryotherapyCryotherapy

Excision of the Squamocolumnar JunctionExcision of the Squamocolumnar Junction» LETZLETZ» Cone BiopsyCone Biopsy

HysterectomyHysterectomy

Follow up ofFollow up of CIN CIN 90 – 95% will be “cured” forever90 – 95% will be “cured” forever Pap smearsPap smears

» Repeated until negativeRepeated until negative» 12 monthly for 2 years12 monthly for 2 years

ColposcopyColposcopy» Ideally at lease once 6m after the procedureIdeally at lease once 6m after the procedure

HPV High Risk subtypingHPV High Risk subtyping» Perform 12m and 24m after the procedurePerform 12m and 24m after the procedure» High negative predictive valueHigh negative predictive value

Obstetric implications of treated CIN Obstetric implications of treated CIN debatabledebatable

Current NH&MRC GuidelinesCurrent NH&MRC Guidelines Repeat Pap once 12m after the first or if no Repeat Pap once 12m after the first or if no

tests tests for 5 years. Thereafter 2 yearlytests tests for 5 years. Thereafter 2 yearly Unsatisfactory PapUnsatisfactory Pap

» Treat as requiredTreat as required» Repeat in 3mRepeat in 3m» Send for colposcopy if 3 consecutive unsatisfactorySend for colposcopy if 3 consecutive unsatisfactory

For LGEAFor LGEA» If <30 years repeat If <30 years repeat in 12 monthsin 12 months» If >30 refer for colposcopy or repeat in 6mIf >30 refer for colposcopy or repeat in 6m

For HGEAFor HGEA» Send for colposcopySend for colposcopy

Current NH&MRC Guidelines (2)Current NH&MRC Guidelines (2) For HSIL on colposcopy and biopsyFor HSIL on colposcopy and biopsy

» LLETZLLETZ For HGEA on Pap but colposcopy For HGEA on Pap but colposcopy

unsatisfactoryunsatisfactory» Cone biopsyCone biopsy

LSIL on colposcopy and biopsyLSIL on colposcopy and biopsy» Review in 12mReview in 12m» Return to normal after 2 negative tests 12m apartReturn to normal after 2 negative tests 12m apart» Send for colposcopy if 3 consecutive unsatisfactorySend for colposcopy if 3 consecutive unsatisfactory

Refer all suspected adenomatous abnormalitiesRefer all suspected adenomatous abnormalities

Proposed Screening Program 2017Proposed Screening Program 2017 To commence at age 25 & offered until age 75To commence at age 25 & offered until age 75 Will primarily consist of HPV testing of cervical Will primarily consist of HPV testing of cervical

samples with partial genotyping (16,18+/-45)samples with partial genotyping (16,18+/-45)» With the option of self collectionWith the option of self collection

Negative HPV is highly predictive of absent CINNegative HPV is highly predictive of absent CIN» Next test after 5 YEARSNext test after 5 YEARS

Liquid based cytology will be done only on HPV Liquid based cytology will be done only on HPV positive samplespositive samples

Colposcope those that are High Risk HPV positive Colposcope those that are High Risk HPV positive (16, 18, +/- 45) (16, 18, +/- 45) andand those with HSIL to cytology those with HSIL to cytology

This protocol proven by RCT to increase detection This protocol proven by RCT to increase detection of CIN2+ and 10 year CIN3 rateof CIN2+ and 10 year CIN3 rate

Prevention of CIN and Genital WartsPrevention of CIN and Genital Warts

Polyvalent vaccines (types 6,11, 16 & 18)Polyvalent vaccines (types 6,11, 16 & 18)» Provide 90 – 100% protection from persistent Provide 90 – 100% protection from persistent

infection, 16/18-related CIN2-3, adenoCa in situ and infection, 16/18-related CIN2-3, adenoCa in situ and Ca CxCa Cx

» Also protects against genital warts caused by the Also protects against genital warts caused by the low risk HPV subtypes 6 & 11low risk HPV subtypes 6 & 11

Therapeutic vaccines also under studyTherapeutic vaccines also under study Optimal age for immunisation and need for Optimal age for immunisation and need for

boosters under evaluationboosters under evaluation ?Male immunisation?Male immunisation

Counselling a Patient with a Positive Counselling a Patient with a Positive Pap SmearPap Smear

This is not cancerThis is not cancer» It is pre cancerIt is pre cancer» It is the whole point of doing Pap tests i.e. to detect and It is the whole point of doing Pap tests i.e. to detect and

treat pre cancer so as to prevent it becoming cancertreat pre cancer so as to prevent it becoming cancer» Just like watching /removing “moles” of the skinJust like watching /removing “moles” of the skin» Not all pre cancer becomes cancerNot all pre cancer becomes cancer

It is a common conditionIt is a common condition» 40 – 50% of 40 – 50% of ♀♀ not immunised at some time in their life not immunised at some time in their life» STD basis not helpful but may need to be addressedSTD basis not helpful but may need to be addressed

The Pap test is not diagnosticThe Pap test is not diagnostic» Only a well-directed biopsy can be used for Rx Only a well-directed biopsy can be used for Rx

decisionsdecisions

Any Questions or Any Questions or Comments?Comments?

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