Management of cin

cervical intraepithelial neoplasia management ASCCP Guidelines 2015

1. Management of Cervical Intraepithelial Neoplasia Dr. Sourav Chowdhury MBBS DGO & Dr. Debraj Mondal MBBS MS Senior Resident IQ City Medical College , Durgapur .

2. Cervical Histology: Squamocolumnar Junction (SCJ): The cervix is composed of columnar epithelium, which lines the endocervical canal, and squamous epithelium, which covers the exocervix. The point at which they meet is called the squamocolumnar junction.

3. Transformation Zone: Transformation zone also called ectropion , an area between original SC junction and new SC junction due to regenerative metaplastic response.

4. Normal Transformation Zone: The Basal Layer The Parabasal Layer The Intermediate layer The superficial layer

5. Formation of TZ: SCJ is a dynamic point and it works in response to puberty, pregnancy, Menopause and hormones. Neonates SCJ located at exocervix. In menarche, SCJ moves inwards and towards external os resulting Transformation Zone. As metaplastic epi . Matures in TZ it resembles to original squamous epithelium.

6. Age-wise Location of SCJ :

7. Columnar Epithelium: Columnar epithelium has a single layer of columnar cells with mucus at the top and a round nucleus at the base. The glandular epithelium is composed of numerous ridges, clefts, and infoldings and when covered by squamous, metaplasia , leads to the appearance of gland openings. Technically, the endocervix is not a gland, but the term gland opening often is used.

8. Metaplastic Epithelium Metaplasia originates at SCJ esp. at subcolumnar cells Begins at tip of columnar villi exposed to acidic pH Metaplastic cells replace columnar epithelium Deeper clefts, however, may not be completely replaced, leaving them trapped below. Gland openings and nabothian cysts mark the original SCJ

9. Satisfactory Colpscopy : Adequate visualisation Entire squamocolumnar junction to be visualized Proximal and distal end of lesion Jennifer E. Frank, MD (2008)  The colposcopic examination,  Available at: http :// www.medscape.com / viewarticle /579947_4  (Accessed: 21st july 2014).

10. Coarse punctation Mosaic Abnormal Vessels Acetowhite

11. Cervical Intraepithelial Neoplasia : CIN I – Abnormal cells confined to lower third of sq. epi . CIN II – Extending to middle third of sq. epi . CIN III- Into upper third as severe dysplasia CIS – Full thickness involvement In contrast being only one cell thick, columnar cells does not demonstrate similar analogous neoplastic disease spectrum, histologic abnormalities limited to AIS or Adenocarcinoma .

12. Why screen for cervical cancer? It’s a highly prevalent condition in Indian population, It has a long latent phase, Its natural history of disease is well understood, There are suitable test for screening, These tests are easily available, cost-effective & well acceptable, Treatment of screen positive patients will stop the disese progression

13. Natural history of disease

14. Whom to screen?

15. ACOG or ACS - AGE Recommendations Before 21 yr No screening (Irrespective of sexual activity). 21 to 29 yrs Screen every 2 years with conventional PAP smear or LBC 30 to 65 yr If 3 consecutive tests in last 10 yr are negative then Screen every 3 yrly with PAP/ LBC Or Every 5 yrly with CO-TESTING (HPV-DNA + Cytology) *ACOG has no upper age limit

16. ACOG & ACS After 65 yr* If 3 consecutive tests in last 10 yr are negative AND There is no h/o CIN2+ in last 20 yr Then DISCONTINUE screening (even if the women report having a new partner) Post- hysterectomised If Cervix is removed AND Hysterectomy was done for benign indication AND There is no h/o CIN2+ in last 20 yr Then DISCONTINUE screening *ACOG has no upper age limit

17. ACOG & ACS - HPV vaccinated women : Women who have been vaccinated should continue to be screened. Screening practices should not change on the basis of HPV vaccination status. *ACOG has no upper age limit

18. More frequent screening History of CIN 2 or greater (screen annually for 20 yr) HIV (Twice in 1st yr then annually after) or immune-suppressed Diethylstilbesterol (DES) daughters.

19. WHO - AGE Recommendations Before 30 yr New programmes should start screening women aged 30 years or more Before 25 yr Existing programmes should not include women < 25 years of age 25−49 years Screen every 3 yrly with Cytology >50 years Screen every 5 yrly with Cytology >65 years Screening NOT necessary provided the last two smears were negative.

20. Methods of screening - Down staging screening Recommended methods Under The National Cancer Control Program, Govt. of India VIA based screening & with Lugol’s Iodine (VILI) Use of Magnascope Single visit approach Cryosurgery for VIA + ve women Self collected samples for cytology and (HPV)-DNA testing Cytology Conventional PAP smear Liquid Based Cytology HPV DNA Visual approach VILI, VIA.

21. PAP smears

22. Sample collection CONVENTIONAL LBC Ayre’s spatula -predominantly samples the ectocervix , The endocervical brush - samples the endocervical canal and is used in combination with a spatula Samples are collected in Koplik jar . The broom - samples both endo and ectocervical epithelia simultaneously. Samples are then collected in a jar containing special preservative solution.

23. HPV DNA testing

24. HPV DNA testing The Hybrid Capture 2, HC2 , test is the most widely used HPV-DNA test Has a very high negative predictive value (approx 99%) Currently tests for 13 high risk HPV types , It screens for the presence of HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68.

25. HPV DNA testing Almost 80% women <30 yr show + ve HPV HC-2. Most women clears of the infection within 10 yr. Due to high prevalence of this temporary infection this test has no diagnostic value <30 yr. so it should not be done <30 yr.

26. TRIAGE Screening It is done to reduce the load on the colposcopy centers. If PAP smear shows atypical cells HPV DNA testing by HC-2 method Positive Go for colposcopy Negative Repeat smear after 1 year

27. Management of CIN I preceeded by ASC-US or LSIL - * Follow-up without treatment Colposcopy Routine Screening Lesser abnormalities include ASC-US or LSIL cytology. HPV16 or 18 + ve persistent HPV Management options would vary if pregnant or age less than 21-24yrs Cytology if less than 30yrs and cotestinf if age≥30yrs Either ablative or excisional Excisional if colposcopy inadequate or CIN II Manage According to ASCCP

28. Management of CIN I preceded by HSIL or ASC-H - * Cotesting at 12 & 24 months Diagnostic Excisional Procedure Review of Cytological or Histological or Colposcopic findings Colposcopy Provided colposcopy is Adequate and EndoCx sampling is – ve Except in special population/pregnant women/age 21-24yrs Cytology if less than 30yrs, Cotesting if age ≥30yrs

29. Management of CIN I in Special Population * Cytology at 12 months Repeat Cytology at 12months

30. Management of Women with Biopsy confirmed CIN II or III Adequate Colposcopy Inadequate Colposcopy or Recurrent CIN 2/3 EndoCx sampling CIN 2/3 Excision or Ablation of the TZ Diagnostic Excisional Procedure Cotesting at 12-24months Any test Abnormal Colposcopy Two consequtive – ve results Repeat Cotesting at 3yrs Routine Screening

31. Management of a Women with Biopsy-confirmed CIN 2or3 in special circumstances - A young women with CIN 2 or 3 Observation-Cytology & Colposcopy 6month interval for 12months Treatment using Excision or Ablation 2x Cytology _ ve & Normal Colposcopy Cotest in 1yr Both tests - ve Cotest in 3yrs Colposcopy worsens or High-grade Cytology or colposcopy persists for 1yr Repeat Biopsy or colposcopy Any test Abnormal If CIN 2 or 3 persists for ≥ 24months Treatment Required

32. Management of Women With AGC or Cytologic AIS Initial Workup :

33. Treatment Modalities : * * Excision Ablation LEEP Laser Vapourization CO2 Electrosurgical Needle Conisation Cryotherapy Laser Conization CO2 Cryopen Cold-Knife Conization Cold Coagulation Hysterectomy Electrocoagulation Electro- cautery

34. Cryotherapy - Criteria CIN I persisted for 2yrs or CIN II Lesion in EctoCx Negative EndoCx sampling Small lesion No EndoCx gland involvement Effective Temperature -20˚to -30˚C Iceball of 5mm from edge of probe=Effective Failure Rate Size EndoCx sample + ve EndoCx Gland + ve *1

35. CO₂ Laser Vapourization : Outline of lesion are demarcated Vapourization to the depth 6-7mm. Advantages- Precise Spare unnecessary damage Ability to destroy coexisting lesions Disadvantage- Increase preocedure time Very expensive Complications Minor discomfort Uterine cramps

36. Long Loop Excision of Transformation Zone(LLETZ)- Tissue effects depends on Size of wire 0.5mm Power (watts) 35-55W Water content of tissue Steam envelope at tissue-wire interface =cutting Zone of 4-5mm beyond the affected area Advantage Specimen for Histopathological diagnosis Less expensive Complications Operative/post-operative haemorrhage Cervical stenosis

37. Conization Conization diagnostic/therapeutic Provides tissue for further evaluation Indications- Microinvasive Carcinoma present in EndoCx currettings Cytolopgy not consistent with tissue diagnosis Entire TZ not visualized Microinvasive Ca diagnosis by biopsy Cytology/Biopsy evidence of Premalignant or Malignant glandular epithelium. Lesions with + ve margins more likely to recur

38. Hysterectomy - Indications: Microinvasion CIN III at the EndoCx limits of conization specimens in selected patients Poor compliance with follow-up Other gynaecologic problems requiring Hysterectomy Histologically confirmed recurrent high-grade CIN

39. Colposcopy -

40. Referrence 1. Jennifer E. Frank, MD (2008)  The colposcopic examination, Available at:  http://www.medscape.com/viewarticle/579947_4 (Accessed: 21st july 2014). 2. berek jonathan s., abaid s. lisa , anderson r. jean, aubuchon mira , baker l. valerie , baram a. david , et el.  Berek and Novak's Gynecology , 15th ed. united states of america : wolters kluwers / lippincott william wilkins ; 2011.  3. Connor P. Joseph, Hartenbach M. Ellen.  Treatment of Cervical Intraepithelial Neoplasia. http://www.glowm.com/section_view/heading/Treatment%20of%20Cervical%20Intraepithelial%20Neoplasia/item/228#9151 (accessed 24th july 2014). 4. Massad Stewart L.,Einstein H. Mark, Huh k. Warner, Katki A. Hormuzd , Kinney K. Walter, Schiffman Mark, et el.  2012 Updated Consensus Guidelines for the Management of Abnormal Cervical Cancer Screening Tests and Cancer Precursors. http://www.omniaeducation.com/images/hpv_resource2.pdf (accessed 20th July 2014).

41. Thank you !