Screening for Cervical Cancer Max Brinsmead MB BS PhD May 2015

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

Cytological Terms n LGEA = Low grade epithelial abnormality »Mostly due to HPV »Also called low grade squamous intraepithelial lesion or LSIL n HGEA = High grade epithelial abnormality »Arises from CIN1 & CIN2 (but these are histological terms) »Also called high grade squamous intraepithelial lesion or HSIL n Both the above have “Possible” variants »That is “Possible LGEA” and “Possible HGEA”

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

Histology n The gold standard for diagnosis n Only as good as the sample received » (except for cone or LLETZ) n And still somewhat subjective n 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 Progression 1  2  3  cancer is not inevitable n CIN % spontaneously regress n CIN 3 – 50% regress or stay the same n Progression time varies » 6m to 16 years n But some will have invasive Ca when Pap smear reports only LGEA

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

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

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

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

Prevention of CIN and Genital Warts n 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 n Therapeutic vaccines also under study n Optimal age for immunisation and need for boosters under evaluation n Male immunisation has started

Counselling a Patient with a Positive Pap Smear n 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 n 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 n The Pap test is not diagnostic »Only a well-directed biopsy can be used for Rx decisions

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