Screening for Cervical Cancer Max Brinsmead MB BS PhD May 2015

Cervical Cytology As a screening test for Ca Cx this test has only ~75% sensitivity Better at detecting CIN but then specificity is a problem Must sample the squamocolumnar junction More significant if +ve in a high risk individual Older Early sex, multiple partners, other STDs Smoking HPV infection with high risk subtype Liquid-based cytology can enhance sensitivity by ≈5% Start at age 20 or within 3 years first coitus

Cytological Terms LGEA = Low grade epithelial abnormality Replaces the older term mild dysplasia Mostly due to HPV Also called low grade squamous intraepithelial lesion or LSIL HGEA = High grade epithelial abnormality Replaces the older terms moderate & severe dysplasia Arises from CIN1 & CIN2 (but these are histological terms) Also called high grade squamous intraepithelial lesion or HSIL Both the above have “Possible” variants ie Possible LGEA = former “nonspecific minor changes” Possible HGEA = former “Inconclusive” report

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

Histology The gold standard for diagnosis Only as good as the sample received (except for cone or LLETZ) And still somewhat subjective But accuracy is increased if stains for high risk HPV DNA is used

Natural History of CIN Progression 123cancer is not inevitable CIN 1 - 85% spontaneously regress CIN 3 – 50% regress or stay the same Progression time varies 6m to 16 years But some will have invasive Ca when Pap smear reports only LGEA Hence the debate about current NH&MRC guidelines

HPV Subtyping 90% of Ca Cx is associated with High Risk HPV Subtypes 16,18,45,31,33,35,52,58 etc Highly sensitive for the detection of HGEA Does not require equipment or expertise Equivocal results can occur Of most use in the follow up of treated CIN And those patients with persisting LGEA on Pap smear

Treatment Options for CIN Observation LGEA Young women Obvious HPV infection Chronic LGEA with Low risk HPV subtype Targeted destruction Laser Diathermy Cryotherapy Excision of the Squamocolumnar Junction LETZ Cone Biopsy Hysterectomy

Follow up of CIN 90 – 95% will be “cured” forever Pap smears Repeated until negative 12 monthly for 2 years Colposcopy Ideally at lease once 6m after the procedure HPV High Risk subtyping Perform 12m and 24m after the procedure High negative predictive value Obstetric implications of treated CIN debatable

Current NH&MRC Guidelines Repeat Pap once 12m after the first or if no tests tests for 5 years. Thereafter 2 yearly Unsatisfactory Pap Treat as required Repeat in 3m Send for colposcopy if 3 consecutive unsatisfactory For LGEA If <30 years repeat in 12 months If >30 refer for colposcopy or repeat in 6m For HGEA Send for colposcopy

Current NH&MRC Guidelines (2) For HSIL on colposcopy and biopsy LLETZ For HGEA on Pap but colposcopy unsatisfactory Cone biopsy LSIL on colposcopy and biopsy Review in 12m Return to normal after 2 negative tests 12m apart Send for colposcopy if 3 consecutive unsatisfactory Refer all suspected adenomatous abnormalities

Prevention of CIN and Genital Warts Polyvalent vaccines (types 6,11, 16 & 18) Provide 90 – 100% protection from persistent infection, 16/18-related CIN2-3, adenoCa in situ and Ca Cx Also protects against genital warts caused by the low risk HPV subtypes 6 & 11 Therapeutic vaccines also under study Optimal age for immunisation and need for boosters under evaluation ?Male immunisation

Counselling a Patient with a Positive Pap Smear This is not cancer It is pre cancer It is the whole point of doing Pap tests i.e. to detect and treat pre cancer so as to prevent it becoming cancer Just like watching /removing “moles” of the skin Not all pre cancer becomes cancer It is a common condition 40 – 50% of ♀ not immunised at some time in their life STD basis not helpful but may need to be addressed The Pap test is not diagnostic Only a well-directed biopsy can be used for Rx decisions

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