1. MANAGEMENT OF ABNORMAL PAP SMEAR
DR ALIFAH BT MOHD ZIZI
O&G SPECIALIST
SGH

2. BETHESDA SYSTEM 2001
It was designed to provide uniform diagnostic language to facilitate communication between cytologists and clinician
3 general categories
Within Normal Limits
Benign Cellular Changes
Epithelial Cell Abnormality

3. BETHESDA SYSTEM 2001 Adequacy of the sample is paramount
8000 – 12,000 squamous cells for conventional PS/10 HPF
5000 cells/10 HFP for liquid-based sample
Presence of endocervical cells (at least 10) is recommended (not required for women < 40 y.o)

4. WHAT IS ABNORMAL PAP SMEAR?
Abnormal due to inadequacy
Abnormal due to inflammation
Abnormal due to infection
Abnormal due to dysplastic changes

5. 1. INADEQUATE OR UNSATISFACTORY SMEAR

6. SATISFACTORY SPECIMEN..
Appropriate labeling and identifying information
Relevant clinical information
Adequate numbers of well preserved and well visualized squamous epithelial cells.
An adequate endocervical / transformation zone component (from a patient with a cervix).
Quality of the Pap smear will still be noted when:
1. More than 10 well preserved endocervical or metaplatic cells are seen
2. No blood or inflammation obscuring the Pap smear

7. INADEQUATE/UNSATISFACTORY SMEAR
A smear that is unreliable for the detection of cervical epithelial cell abnormalities

8. INADEQUATE/ UNSATISFACTORY SMEAR
1. Sampling Scanty cells Blood, mucous, pus 2.Preparation Too thick due to poor spreading Air drying artifact Broken slide 3.Mainly endocervical cell

9. HOW TO DEAL WITH INADEQUATE/ UNSATISFACTORY SMEAR ??
Correct timing of smear
Do not use cream or gel
Cleaning of excessive mucus
Choice of sampling devices
Correct spreading
Rapid fixation (< 10 second)
Do use cream or gel

10. GIVE A COURSE OF ESTROGEN IF POST MENOPAUSE WITH ATROPHY
PAP SMEAR
UNSATISFACTORY
TX ANY INFECTION
GIVE A COURSE OF ESTROGEN IF POST MENOPAUSE WITH ATROPHY
REPEAT 6/12
NEGATIVE FOR INTRAEPITHELIAL LESSION
2ND SMEAR UNSATISFACTORY
REPEAT 6/12
3RD SMEAR UNSATISFACTORY
ROUTINE SCREENING
COLPOSCOPY

11. 2. INFLAMMATORY SMEAR

12. Inflammation on Pap smear results, does not indicate any particular pathology
Therefore, does not necessitate routine treatment.

13. POSSIBLE CAUSES……
Infection
Chronic cervicitis
Atrophic cervicitis
Chemical or mechanical irritation to cervix- tampoon, douching

14. NEGATIVE FOR MALIGNANT CELL
PAP SMEAR
NEGATIVE FOR MALIGNANT CELL
INFLAMMATORY
TX ANY INFECTION OR ATROPHY
REPEAT 6/12
NORMAL
2ND SMEAR INFLAMMATORY
REPEAT 6/12
ROUTINE SCREENING
3RD SMEAR INFLAMMATORY
COLPOSCOPY

15. 3. ABNORMAL SMEAR DUE TO INFECTION

16. COMMON INFECTIONS…. Tricomonas vaginalis Fungal ie candidiasis
Bacterial Vaginosis
Actinomyces
Herpes Simplex
ORGANISM
TREATMENT
TRICHOMONAS VAGINALIS
T. METRONIDAZOLE 400MG TDS
FUNGAL INFECTION (CANDIDA)
CANNESTAN PESSARY 200MG ON
BACTERIA VAGINOSIS

17. NEGATIVE FOR MALIGNANT CELL
PAP SMEAR
NEGATIVE FOR MALIGNANT CELL
SPECIFIC MICROORGANISM
TREAT ANY INFECTION
REPEAT PAP SMEAR 6/12
NORMAL
ROUTINE SCREENING

18. 4. ABNORMAL SMEAR DUE TO DYSPLASTIC CHANGES

19. SQUAMOUS CELL ABNORMALITY GLANDULAR ABNORMALITY
DYSPLASTIC CHANGES
SQUAMOUS CELL ABNORMALITY
GLANDULAR ABNORMALITY
AGS
AIS
INVASIVE ADENOCARCINOMA
ASCUS
ASC-H
LGSIL
HGSIL
INVASIVE SQUAMOUS CELL CARCINOMA

20. Spectrum of Changes in Cervical Squamous Epithelium Caused by HPV Infection
CIN* 1
CIN 2 / CIN 3 /
Cervical Cancer
Normal Cervix
Key Point
Integration of HPV into the DNA of the infected host cell is commonly associated with high-risk oncogenic HPV types1 and is linked to the activity of E6 and E7 proteins.2
Background
In benign HPV-associated skin lesions, the HPV virus maintains its genome as episomes at low copy numbers (10–200 copies/cell) in the basal cells of the epithelium separate from the host cell DNA. To maintain its viral DNA as an episome, viral E1 and E2 proteins are expressed. Failure to express E1 leads to the integration of the HPV genome into the host cell chromosome.3
Integration of HPV into the DNA of the infected host cell is commonly associated with high-risk oncogenic HPV types1 and is considered an important step in tumor progression.2 In malignant HPV-associated skin lesions, HPV DNA integration into the host cell’s chromosome regularly occurs through a break in the viral genome around the E1/E2 region. Integration-mediated disruption of E2 may trigger uncontrolled expression of E6 and E7, resulting in cellular transformation.2
The E6 protein associates with the tumor suppressor protein p53 and promotes proteolytic destruction of the protein. This leads to malignant transformation and loss of regulated cell growth. The E7 protein associates with the retinoblastoma protein (pRB), which inactivates the cell cycle restriction function of this protein.2
References
1. Gallo G, Bibbo M, Bagella L, et al. Study of viral integration of HPV-16 in young patients with LSIL. J Clin Pathol. 2003;56:532–536.
2. Syrjänen KJ, Syrjänen SM. Molecular biology of papillomaviruses. In: Papillomavirus Infections in Human Pathology. Chichester, United Kingdom: John Wiley & Sons, Inc.; 2000:11–51.
3. Doorbar J. The papillomavirus life cycle. J Clin Virol. 2005;32(suppl):S7–S15.
*CIN = cervical intraepithelial neoplasia
Adapted from Goodman A, Wilbur DC. N Engl J Med. 2003;349:1555–1564.

21. NATURAL HISTORY…….. % Regress Persist Progress to CIS
Progress to Invasion
CIN 1 60 30 10 1
CIN 2 40 35 20 5
CIN 3
<56 -
18 (5y), 36(10y)

22. SQUAMOUS CELL ABNORMALITY…

23. ABNORMAL PAP SMEAR DUE TO DYSPLASTIC CHANGES – SQUAMOUS CELL ABNORMALITIES
1. Atypical Squamous Cells (ASC)
Atypical Squamous Cells-Undetermined Significance (ASC-US)
Atypical Squamous Cells, Cannot Exclude High Grade Lesion (ASC-H)
2. Low-grade Squamous Intraepithelial Lesion (LSIL)
(Mild Dyskaryosis / HPV/CIN 1)
3. High-grade Squamous Intraepithelial Lesion (HSIL)
(Mod or Severe Dyskaryosis / CIN 2,3)
4. Invasive Squamous Cell Carcinoma

24. 1.ATYPICAL SQUAMOUS CELL (ACS)
1. Undetermined Significance (ASC-US)
Cytologic changes suggestive of a low grade squamous lesion but lack criteria for definitive interpretation.
2. Cannot Exclude High Grade Lesion (ASC-H)
Cytologic changes suggestive of a high grade squamous lesion but lack criteria for definitive interpretation.

25. ATYPICAL SQUAMOUS CELL (ASC)
PAP SMEAR
ATYPICAL SQUAMOUS CELL (ASC)
ASCUS
HPV DNA TESTING
POSITIVE
NEGATIVE
REPEAT 6/12
COLPOSCOPY
NEGATIVE FOR INTRAEPITHELIAL LESSION
RESUME NORMAL SCREENING

26. PAP SMEAR
ASC-H
COLPOSCOPY

27. 2. LOW GRADE INTRAEPITHELIAL LESSION (LGSIL) / CIN 1
CIN I being the morphologic manifestation of a self-limited sexually transmitted HPV infection
60% of CIN I regress spontaneously
30% of CIN I persists.
10% of CIN I lesions progress to CIN III,
1% may ultimately progress to invasive cancer.

28. NILM LSIL Immediate colposcopy Colposcopy No yes Assessment of client= No
yes
Assessment of client
Presence of at least 1 criteria:
-Age > 30 yrs
Poor compliance
Immunocompromised Sx
Hx of pre-invasive lesion
+ve for high risk HPV
(16,18,31,33,45,52,58)
Repeat smear in 6/12
60%
NILM
LSIL
Immediate colposcopy
Resume routine screening schedule
Colposcopy

29. MANAGEMENT APPROACH
A lesion that persist after 1-2 years or any progression during follow up suggest need of treatment
If HPV testing is available, +ve HPV: indication for treatment
- Treatment- local ablative/ excission
-Follow up after treatment for CIN1
-repeat smear in 6/12
-repeat smear and colposcopy in 12/12
-If normal, yearly pap smear x 2 years then back to normal routine

30. 3.HIGH GRADE INTRAEPITHELIAL LESSION (HGSIL)/ CIN 2-3
CIN 2-3 is a cervical cancer precursor
1.CIN 2
40% of CIN II regress
30% of CIN II persist
20% of CIN II progress to CIN III
5% of CIN II progress to CIN III
2. CIN 3
33% of CIN III regress
18% of CIN III progress to invasive disease over a 10 years
36% of CIN III progress to invasive disease over a 20 years

31. Subsequent management depends on: Whether lesion identified
PAP SMEAR
HGSIL
COLPOSCOPY AND BIOPSY
Subsequent management depends on:
Whether lesion identified
Whether colposcopy satisfactory
Annual smear following treatment

32. MANAGEMENT APPROACH EXCISION METHOD LLETZ Cold knife cone biopsy
Hysterectomy

33. ABLATIVE METHODS
Cryocautery
Electrodiathermy
Cold coagulation

34. 4. INVASIVE SQUAMOUS CELL CANCER
PAP SMEAR
INVASIVE SQUAMOUS CANCER
COLPOSCOPY AND BIOPSY
Subsequent management depends on:
Stage of the disease

35. GLANDULAR ABNORMALITY

36. ABNORMAL PAP SMEAR DUE TO DYSPLASTIC CHANGES- GLANDULAR CELL ABNORMALITIES
1.Atypical Glandular Cells (AGS) (undetermined or favour neoplastic)
2.Adenocarcinoma in Situ (AIS)
3. Invasive Adenocarcinoma

37. GLANDULAR ABNORMALITIES
The most common significant lesions associated
with AGC (Atypical Glandular Cells) are actually squamous
Management should include colposcopy and endocervical sampling

38. ATYPICAL ENDOMETRIAL CELLS
Always perform endometrial sampling
If endometrial sampling is negative : colposcopy with endocervical sampling

39. GLANDULAR ABNORMALITIES

40. OTHERS…

41. LOCAL ESTROGEN CREAM 1G ON FOR 2 WEEKS THEN TWICE WEEKLY FOR 6 WEEKS
ATROPHY SMEAR
PAP SMEAR
ATROPHY
LOCAL ESTROGEN CREAM 1G ON FOR 2 WEEKS THEN TWICE WEEKLY FOR 6 WEEKS
REPEAT IN 6 MONTHS

42. REACTIVE CELLULAR CHANGES
PAP SMEAR
REACTIVE CELLULAR CHANGES DUE TO RADIATION, REPAIR OR IUCD
REPEAT IN 1 YEAR

43. ABNORMAL PAP SMEAR IN PREGNANCY
Reported abnormal smear during pregnancy 1%- 8%
Follow-up should be similar to non pregnant state-every trimester
Regardless of gestation, suspicious lesion should
be biopsied.
Cervical biopsy does not increase the risk of miscarriage
If evidence of invasive cancer- require excission

44. THANK YOU…….