Trreatment of Preinvasive Lesions

1. Trreatment of Preinvasive Lesions Nejat Özgül Assoc. Prof. Hacettepe University Faculty of Medicine Department of Obstetrics and Gynecology

2. The Primary Goal in the Management of Preinvasive Lesions The Primary goal in the management of Preinvasive Lesions is to prevent the development of invasive cervical cancer progression to cancer.

3. Management of Preinvasive Lesions • toselectthewomenwhoare in danger of developingcervicalcancerandtoprotectthosewhoare not risk of cancerfromover-treatment • Colposcopyplays a central role in selection of patients at the risk of developingCervicalCancerandtreatmentmodalities. • Shouldprovide as littleharmtothewomen as possible • Should be cost-effective

4. How can wedecideaboutthechoice of therapyforPreinvasiveLesions ? • Cytologic and colposcopic findings • The patient’s age and further desire for fertility • The type of TZ • The experience of the physician • Guidelines

5. ASCCP Guidelines Massad LS, J Low Gen Tract Dis 2013

6. Management of women with a histological diagnosis of CIN 1 preceded by ASCUS, LSIL, HPV 16/18(+) or Persistent HPV infection Follow-up without treatment *Cytology if age <30 years, cotesting if age ≥30 years £Either ablative or excisional methods Cotesting @ 1Y ≥ASC or HPV (+) Colposcopy HPV (-) and Cytology negative Age appropriate‡ retesting* @ 3 Y No CIN 2,3 CIN 2,3 CIN 1 Cytology Negative+/- HPV (-) Manage per ASCCP Guideline Follow-up or £ Treatment If persists for at least 2 years Routine Screening

7. CIN1 (Preceded by ASC-H or HSIL Cytology) Review of cytological,histological,andcolposcopic findings € Cotesting 1. and 2. Year £ Diagnostic excision procedure or or Manage per ASCCP Guideline HPV (-) and cytology(-) at both visits ≥ASC <HGSIL or HPV (+) HGSIL (at either visit) Age-specific retesting* @ 3 Y Colposcopy €Colposcopy ‘s adequateand ECC (-) £Except in pregnant women and those ages 21-24 *<30 Y cytology, ≥30 Y cotesting

8. CIN 1 (Women Ages 21-24 ) After ASC-US or LGSIL After ASC-H or HGSIL Repeat cytology @ 12 months inadequate colposcopy adequate colposcopy £ Diagnostic Excisional procedure Colposcopy and cytology @ 6 and 12 month Review of cytological,histological,andcolposcopic findings <ASC-H or HGSIL ≥ASC-H or HGSIL Repeat cytology @ 12 months HGSIL (at either visit) Cytology negative (at both visits) Other results Changing results Colposcopy Manage per ASCCP Guideline Routine Screening Negative ≥ASC Routine Screening €No pregnancy

9. Treatment of CIN 1 Ferlay J, GLOBOCAN 2002; IARC Cancer Base 5, IARC Press, 2004; NCCN, Practice Guidelines in Oncology-v.1.2009

10. Management of Women with CIN 2, 3(except pregnant and age 21-24 women) Adequate Colposcopy Inadequate colposcopy or recurrent CIN 2,3 or ECC is CIN2,3 Either excision or ablation of T-zone Diagnostic excisional procedure Cotesting @ 12 and 24 months 2x Negative results Any test abnormal Repeat Cotesting @ 3 Years Colposcopy with ECC Routine Screening

11. Management of Women with CIN 2,3(Age 21-24) If adequate colposcopy; treatment or observation is acceptable. When CIN 2 is specified, observation is preferred. When CIN 3 is spesified, orcolposcopy is inadequate, treatment is preferred. Observation – Colposcopy and cytology (6 months interval for 12 months) Treatment using excision or ablation 2x Cytology (-) and Normal colposcopy Colposcopy worsens or High grade cytology or colposcopy persists for 12 Moths Colposcopy/ Biopsy Recommended Either test abnormal CIN3or CIN 2,3 persists for 24 moths Cotest @ 1Y Both tets negative Treatment recommended Cotesting @ 3 Years

12. Management of Margin (+) patients • Reflex hysterectomy • no desire for future fertility • Possibility of invasive disease: stage ≤1A • Re-excision (in 1-3 months) • CIN2+;ectocervical or endocervical margin(especially age >50) • Complication rates are similar with primary approach • Uncertain effect on pregnancy and fertility • Ablation of excision crater is not recommended • Invasive cancer may be omitted • Benefit ? • Uncertain superiority on fertility or preterm birth Ghaem-Maghami S, Lancet, 2007; Siriaree S, Asian Pac J Cancer Prev, 2006; Kietpeerakool C, J Obstet Gynaecol Res, 2007

13. Hysterectomy in patients with CIN 2-3 • Operation for other gynecological reasons • If there is no possibility for conization, because of cervical structure • CIN (+) : LEEP orconizationmargins [ no desire for future fertility] • Cancer phobia Das N, Gynecol Oncol, 2005

14. Management of Women Diagnosed with AIS during a Diagnostic Excisional Procedure Conservative Management Acceptable if future fertility desired Hysterectomy Preferred Treatment Margin (+) orECC (+) Margin (-) Re-evaluation* @ 6 months Acceptable Long term Follow up Re excision is recommended *Cytology, HPV Testing, Colposcopy and ECC

15. EFC Guidelines-2007 • Whereas there is no obviously superior conservative surgical technique for treating and eradicating cervical intra-epithelial neoplasia (CIN), • Excision is preferred because of better histopathological assessment

16. EFC Guidelines-2007 • Ablative techniques are only suitable when: • The entire transformation zone is visualised • There is no evidence of glandular abnormality • There is no evidence of invasive disease • There is no discrepancy between cytology and histology • Cryocautery should be used only for low grade CIN and a double freeze technique should be used.

17. EFC Guidelines-2007 • When excisional techniques are used for treatment, every effort should be made to remove the lesion in one specimen. • The histology report should record the dimensions of the specimen and the status of the resection margins with regard to intraepithelial or invasive disease. • For ectocervical lesions, treatment techniques should remove tissue to a depth of 6 mm.

18. EFC Guidelines-2007 • A see and treat policy at first visit can be used where audit has identified that CIN is present in the majority of the excised specimens. • A target of CIN in ≥90% of the excised specimens should be achieved. • Treatment at first visit for a referral of borderline or mild dyskaryosis should be used only in exceptional cases to minimise the possibility of over-treatment.

19. EFC Guidelines-2007 • CIN extending to the resection margins at LEEP excision results in a higher incidence of recurrence but does not justify routine repeat excision as long as: • The entire transformation zone is visualised • There is no evidence of glandular abnormality • There is no evidence of invasive disease • The women are under 50 years of age

20. EFC Guidelines-2007 • Women over the age of 50 years with incomplete excision of CIN at the endocervical margin are at high risk for residual disease. • Careful and adequate follow-up endocervical cytology is a minimum requirement. • Re-excision is an alternative.

21. EFC Guidelines-2007 • Women with adenocarcinoma in situ / CGIN can be managed by local excision for women wishing to retain fertility. • Incomplete excision at the endocervical margin requires a further excisional procedure to obtain clear margins and exclude occult invasive disease.

22. EFC Guidelines-2007 • Microinvasive squamous cancer FIGO stage Ia1 can be managed by excisional techniques if: • The excision margins are free of CIN and invasive disease. • If the invasive lesion is excised but CIN extends to the excision margin then a repeat excision should be performed to confirm excision of the CIN and to exclude further invasive disease. • This should be performed even in those cases planned for hysterectomy to exclude an occult invasive lesion requiring radical surgery • The histology has been reviewed by a specialist gynaecologicalpathologist

23. Preinvasivelesion in pregnancy • Treatmentshould be postponeduntil 2 monthsafterdelivery • Invasivediseasemust be excludedbycolposcopy. Looporwedgebiopsy is moreappropriatethanpunchbiopsytoobtain a histologicalspecimenwithsufficientstroma • Cone biopsy during pregnancy should be performed only when there is a strong suspicion of invasive cancer.

24. Conclusions • Excisional treatments are diagnostic and therapeutic procedure for women with HGSIL • Treatment should be performed under colposcopic vision • The technique and the configuration of the cone should be individualized, depending on the specific lesion • TZ should be excised entirely • The most significant perioperative complication of cone biopsy is bleeding, which is generally managed with local measures

25. Conclusions • Theexcisionaltreatment of CIN do not compromisefuturefertility, but is associtedwith an increased risk of pretermlabouraccordingtotype of excision • Theexcisionaltreatment of AIS is regardedto be appropriateıffertility is desired.Butclosefollow-up is important

26. Conclusions • Hysterectomy is not a treatment option for CIN1 • Hysterectomy should not performed with a cytological diagnosis. • Hysterectomy is not primary treatment in patients with HGSIL: possibility of recurrence is similar with hysterectomy andlocal treatment • Long-termfollow-up is essential • Colposcopy is a very important diagnostic tool in the management of cytological abnormalities • The follow-up is easier at centers with HPV testing capability